Dysfunction of Emotion Regulation in Mild Cognitive Impairment Individuals Combined With Depressive Disorder: A Neural Mechanism Study

Depression increases the risk of progression from mild cognitive impairment (MCI) to dementia, where impaired emotion regulation is a core symptom of depression. However, the neural mechanisms underlying the decreased emotion regulation in individuals with MCI combined with depressive symptoms are not precise. We assessed the behavioral performance by emotion regulation tasks and recorded event-related electroencephalography (EEG) signals related to emotion regulation tasks simultaneously. EEG analysis, including event-related potential (ERP), event-related spectral perturbation (ERSP), functional connectivity and graph theory, was used to compare the difference between MCI individuals and MCI depressed individuals in behavioral performance, the late positive potential (LPP) amplitudes, neural oscillations and brain networks during the processing of emotional stimuli. We found that MCI depressed individuals have negative preferences and are prone to allocate more attentional resources to negative stimuli. Results suggested that theta and alpha oscillations activity is increased, and gamma oscillations activity is decreased during negative stimulus processing in MCI depressed individuals, thus indicating that the decreased emotion regulation in MCI depressed individuals may be associated with enhanced low-frequency and decreased high-frequency oscillations activity. Functional connectivity analysis revealed a decrease in functional connectivity in the left cerebral hemisphere of the alpha band and an increase in functional connectivity in the right cerebral hemisphere of the alpha band in MCI depressed individuals. Graph theory analysis suggested that global network metrics, including clustering coefficients and disassortative, decreased, while nodal and modular network metrics regarding local nodal efficiency, degree centrality, and betweenness centrality were significantly increased in the frontal lobe and decreased in the parieto-occipital lobe, which was observed in the alpha band, further suggesting that abnormal alpha band network connectivity may be a potential marker of depressive symptoms. Correlational analyses showed that depressive symptoms were closely related to emotion regulation, power oscillations and functional connectivity. In conclusion, the dominant processing of negative stimuli, the increased low-frequency oscillations activity and decreased high-frequency activity, so as the decrease in top-down information processing in the frontal parieto-occipital lobe, results in the abnormality of alpha-band network connectivity. It is suggested that these factors, in turn, contribute to the declined ability of MCI depressed individuals in emotion regulation

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Undiagnosed cardiovascular risk factors including elevated lipoprotein(a) in patients with ischaemic heart disease

ObjectivesThis study aims to investigate the prevalence of undiagnosed cardiovascular risk factors in patients with ischaemic heart disease (IHD).MethodsWe assessed the prevalence of previously undiagnosed cardiovascular risk factors, including elevated lipoprotein(a) [Lp(a)], among consenting patients with IHD who were admitted to hospital. Clinical information, including dietary history, from patients with newly diagnosed IHD and known IHD were compared.ResultsOf the 555 patients, 82.3% were males and 48.5% of Chinese ethnicity. Overall, 13.3% were newly diagnosed with hypertension, 14.8% with hypercholesterolemia, and 5% with type 2 diabetes (T2DM). Patients with newly diagnosed IHD, compared to those with known IHD, had a higher prevalence of new diagnoses of hypercholesterolemia (29.1% vs. 2.0%, p < 0.001), hypertension (24.5% vs. 3.4%, p < 0.001) and T2DM (7.3% vs. 3.1%, p = 0.023). Active smoking was prevalent in 28.3% of patients, and higher in newly diagnosed IHD (34.1% vs. 23.2%, p = 0.005). Elevated Lp(a) of ≥120 nmol/L was detected in 15.6% of all patients, none of whom were previously diagnosed. Dietary habits of >50% of patients in both groups did not meet national recommendations for fruits, vegetables, wholegrain and oily fish intake. However, patients with known IHD had a more regular omega-3 supplement intake (23.4% vs. 10.3%, p = 0.024).ConclusionIncreased detection efforts is necessary to diagnose chronic metabolic diseases (hypertension, hypercholesterolemia, T2DM) especially among patients at high risk for IHD. Cardiovascular risk factors, in particular elevated Lp(a), smoking, and suboptimal dietary intake in patients with IHD deserve further attention

Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation

Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively

The autism advantage: a communications campaign to combat the autism employment gap in Singapore

Running from 14 December 2022 to 22 March 2023, The Autism Advantage is a communications campaign that aims to advocate for more holistic support for the employment of persons with autism (PWAs) in Singapore. As laid out in the Autism Enabling Plan drafted by Autism Network Singapore (2021), the employment continuum is a high priority area, with many PWAs either unemployed or underemployed. Given that most employees and employers hold existing misconceptions on PWAs abilities and lack knowledge and professional guidance on employing PWAs, the team aimed to raise knowledge levels, receptiveness towards inclusive hiring as well as behavioural intention to hiring PWAs. Anchored on an abilities-centered messaging approach, the campaign utilised a mix of online and offline activations to educate the business community on autism and increase positive perception towards the abilities of PWAs, by spotlighting their strengths through real-life testimonies. Developed in partnership with SG Enable, Singapore’s focal disability organisation, prominent executions include an inclusive hiring playbook and a week-long public exhibition that managed to amass over 1000 visitors and a total of 388 pledges to make the workplace more inclusive. The campaign managed to increase the target audiences’ knowledge by an average of 42.9%, increase attitudes towards PWAs by 13% and increase behavioural intention by 8.5%. The discussion and recommendations of The Autism Advantage show how a targeted campaign across online and offline channels can be effective in targeting the business community and has implications for future communication campaigns in Singapore and abroad.Bachelor of Communication Studie

Structural durability of early-generation Transcatheter aortic valve replacement valves compared with surgical aortic valve replacement valves in heart valve surgery: a systematic review and meta-analysis

10.1186/s13019-020-01170-7JOURNAL OF CARDIOTHORACIC SURGERY15

Fragment-based whole cell screen delivers hits against M. tuberculosis and non-tuberculous mycobacteria

Reactive multi-target ‘fragment drugs’ represent critical components of current tuberculosis regimens. These compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside Mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. Based on the success of small ‘dirty’ drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacterial drug discovery efforts. Here, we carried out such a screen and characterized bactericidal activity, selectivity and spectrum of hits we obtained. A library of 1725 fragments was tested at a single concentration for growth inhibitory activity against M. bovis BCG as screening strain and 38 of 116 primary hits were confirmed in dose response analyses to be active against virulent M. tuberculosis. Bacterial kill experiments showed that most hits displayed bactericidal activity at their minimal inhibitory concentration. Cytotoxicity assays established that a large proportion of hits displayed a favorable selectivity index for mammalian cells. Importantly, one third of M. tuberculosis active fragments were also active against M. abscessus and M. avium, two emerging non-tuberculous mycobacterial pathogens, opening the opportunity to develop broad spectrum antimycobacterials. Activity determination against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa) bacteria, as well as fungi (Candida albicans, Cryptococcus neoformans) showed only a small overlap indicating a generally narrow spectrum of these novel antimicrobial hits for mycobacteria. In conclusion, we carried out the first fragment-based whole cell screen against bacteria and identified a substantial number of hits with excellent physicochemical properties and dual activity against M. tuberculosis and non-tuberculous mycobacterial pathogens. These hits will now be evaluated in animal models of mycobacterial infection to determine whether any of them can be moved forward as a new antimycobacterial fragment drug candidate

Relationship between Food Habits and Tooth Erosion Occurrence in Malaysian University Students

Background: Tooth erosion is a growing dental problem; however, the role of diet in the aetiology of tooth erosion is unclear. A cross-sectional study was conducted to determine the association between tooth erosion occurrence and the consumption of acidic foods and drinks among undergraduate university students. Methods: A total of 150 undergraduate students (33 males and 117 females) aged 19 to 24 years at Universiti Kebangsaan Malaysia participated in this study. The Basic Erosive Wear Examination was used to assess the occurrence of tooth erosion. Information regarding dental hygiene practices, usual dietary habits, and consumption of acidic foods and drinks was obtained through a structured questionnaire. Results: In all, 68% of subjects had tooth erosion. Subjects who reported having received information about healthy eating were less likely to have tooth erosion (χ2 [1, N = 150] = 7.328, P = 0.007). The frequencies of milk (OR = 0.29, 95% CI = 0.13–0.67) and tea/coffee (adjusted OR = 0.42, 95% CI = 0.19–0.95) consumption were negatively associated with tooth erosion. Dental hygiene practice, the frequency and amount of acidic food and drink intake, and body mass index classification were not significantly associated with the risk of tooth erosion (P > 0.05). Conclusion: A high prevalence of tooth erosion was observed among this group of students. Preventive measures, such as dietary advice and increased consumption of milk at a younger age, may reduce the occurrence of tooth erosion among this age group