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This systematic review examined the associations of dietary factors such as nutrients, food intake, dietary patterns and dietary biomarkers with structural and functional brain MRI biomarkers, focusing on macrostructural, microstructural, lesion and perfusion measures, and functional activity/connectivity. Articles published in English were systematically searched in PubMed, Embase and PsycInfo up to 19 July 2024. A total of thirty-eight prospective cohort studies (twenty-three cross-sectional and fifteen longitudinal analyses) and thirteen intervention studies were included. Cross-sectional analyses revealed heterogenous associations: baked fish correlated with larger hippocampal volumes (β = 0·21), while oily fish, dairy products and tofu adversely related to ventricle grade. Pro-inflammatory dietary patterns were positively associated with silent infarct risk (DII Q4 v. Q1, OR = 1·77), whereas anti-inflammatory patterns tended to favour brain preservation. Longitudinal studies demonstrated more consistent protective associations: green tea consumption (+100 mL/d) reduced hippocampal atrophy by 0·024%/year, prudent dietary patterns preserved +203 mm3 left hippocampal volume over 4 years and higher plasma carotenoids decreased medial temporal lobe loss by 0·02 cm3/year. However, null findings were common across multiple dietary factors. Interventions showed limited structural benefits (effective in only two of six studies), while polyphenol-rich supplements more consistently improved cerebral perfusion and functional connectivity. Longitudinal and intervention studies demonstrated more consistent patterns than cross-sectional analyses; however, current evidence remains limited for clinical translation. Findings from cross-sectional analyses, despite being from prospective cohorts, require careful interpretation. Further replication across diverse populations and standardised long-term studies are needed before translating these associations into clinical practice.
How psychotic symptoms, depressive symptoms, cognitive deficits, and functional impairment may interact with one another in schizophrenia or bipolar disorder is unclear.
Methods
This study explored these interactions in a discovery sample of 339 Chinese, of whom 146 had first-episode schizophrenia and 193 had bipolar disorder. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale; depressive symptoms, using the Hamilton Depression Rating Scale; cognitive deficits, using tests of processing speed, executive function, and logical memory; and functional impairment, using clinical assessments. Network models connecting the four types of variables were developed and compared between men and women and between disorders. Potential causal relationships among the variables were explored through directed acyclic graphing. The results in the discovery sample were compared to those obtained for a validation sample of 235 Chinese, of whom 138 had chronic schizophrenia and 97 had bipolar disorder.
Results
In the discovery and validation cohorts, schizophrenia and bipolar disorder showed similar networks of associations, in which the central hubs included ‘disorganized’ symptoms, depressive symptoms, and deficits in processing speed during the digital symbol substitution test. Directed acyclic graphing suggested that disorganized symptoms were upstream drivers of cognitive impairment and functional decline, while core depressive symptoms (e.g. low mood) drove somatic and anxiety symptoms.
Conclusions
Our study advocates for transdiagnostic, network-informed strategies prioritizing the mitigation of disorganization and depressive symptoms to disrupt symptom cascades and improve functional outcomes in schizophrenia and bipolar disorder.
Previous studies highlighted the health benefits of coffee and tea, but they only focused on the comparisons between different consumptions. Consequently, the association estimate lacked a clear interpretation, as the substitution of beverages and distribution of doses were not explicitly prescribed. We focused on the ‘relative association’ to ascertain the optimal consumption strategy (including total intake and optimal allocation strategy) for coffee, tea and plain water associated with decreased mortality. Self-reported coffee, tea and plain water intake were used from the UK Biobank. Within a compositional data analysis framework, a multivariate Cox model was used to assess the relative associations after adjusting for a range of potential confounders. The lower mortality risk was observed with at least approximately 7–8 drinks/d of total consumption. When the total intake > 4 drinks/d, substituting plain water with coffee or tea was linked to reduced mortality; nevertheless, the benefit was not seen for ≤ 4 drinks/d. Besides, a balanced consumption of coffee and tea (roughly a ratio of 2:3) associated with the lowest hazard ratios of 0·55 (95 % CI 0·47, 0·64) for all-cause mortality, 0·59 (95 % CI 0·48, 0·72) for cancer mortality, 0·69 (95 % CI 0·49, 0·99) for CVD mortality, 0·28 (95 % CI 0·15, 0·52) for respiratory disease mortality and 0·35 (95 % CI 0·15, 0·82) for digestive disease mortality than other combinations. These results highlight the importance of the rational combination of coffee, tea and plain water, with particular emphasis on ensuring adequate total intake, offering more comprehensive and explicit guidance for individuals.
Introduction: We propose to develop a Unique Device Identification (UDI) barcode tracking system for surgical instruments. This system aims to enhance hospital processes, thereby benefiting both patients and staff members. Methods: The UDI barcode tracking system for surgical instruments was implemented in March 2023: 1. Each surgical instrument underwent laser engraving with a UDI barcode, encompassing relevant data such as instrument name, image, model, specifications, origin, license, Instructions for Use (IFU), and total distribution quantity. 2. Upon scanning the engraved serial number, the system automatically discerns whether the instrument belongs to the designated set. 3. Mechanical, chemical, and biological monitoring indicators are integrated into the tracking system, with automatic adjudication for release into storage if criteria are met; otherwise, notifications are issued for review and retrieval by personnel. Results: 1. Between March 2023 and February 2024, a total of 157,614 instrument sets were equipped with this system, enabling staff to achieve a zero-error rate in rapid and precise instrument identification. 2.During this period, 4,026 cycles of high-temperature sterilization monitoring and 380 cycles of low- temperature H2O2 plasma sterilization monitoring were recorded. 3.Each monitoring cycle was digitally recorded, obviating the necessity for paper-based documentation and saving a total of 4,406 A4 paper sheets. 4. In the same timeframe, a total of 85,899 packages were dispensed, each linked to patient medical record numbers. Conclusions: The adoption of the surgical instrument UDI barcode tracking system by our institution’s central sterilization supply department has garnered participation from 622 individuals. It not only reduces the time spent by staff searching for items and conducting educational training but also automatically identifies whether the instrument belongs to the package, thereby enhancing inventory efficiency and reducing the incidence of errors. Sterilization monitoring indicators are automatically uploaded and intercepted to uphold patient safety.
Metabolic syndrome (MetS) is associated with an increased risk of CVD, type 2 diabetes and death from all causes. Dietary factors correlate with MetS, making diet a potential target for intervention. We used data from the 2012–2016 Korea National Health and Nutrition Examination Survey (KNHANES, n 12 122) to identify a dietary pattern (DP) using thirty-nine predefined food groups as predictors. MetS components were used as the response variable with the food groups in reduced rank regression followed by stepwise linear regression analyses. We then verified the Korean status of the DP externally in the Cardiovascular Disease Association Study (CAVAS) (n 8277) and the Health EXAminees (HEXA) study (n 48 610). The DP score, which included twenty food groups, showed significant positive associations with all MetS components and a higher prevalence ratio in KNHANES participants (P < 0·0001). Although the score was NS in CAVAS (P = 0·0913), it showed a strong positive association with MetS prevalence in HEXA (P < 0·0001). We identified and tested a DP associated with MetS in Korean populations. This DP may be a useful tool for assessing MetS risk. Although the score was linked to higher MetS risk, particularly in the predominantly urban population of the HEXA study, further validation in more diverse populations is needed.
Compelling evidence claims that gut microbial dysbiosis may be causally associated with major depressive disorder (MDD), with a particular focus on Alistipes. However, little is known about the potential microbiota–gut–brain axis mechanisms by which Alistipes exerts its pathogenic effects in MDD.
Methods
We collected data from 16S rDNA amplicon sequencing, untargeted metabolomics, and multimodal brain magnetic resonance imaging from 111 MDD patients and 102 healthy controls. We used multistage linked analyses, including group comparisons, correlation analyses, and mediation analyses, to explore the relationships between the gut microbiome (Alistipes), fecal metabolome, brain imaging, and behaviors in MDD.
Results
Gut microbiome analysis demonstrated that MDD patients had a higher abundance of Alistipes relative to controls. Partial least squares regression revealed that the increased Alistipes was significantly associated with fecal metabolome in MDD, involving a range of metabolites mainly enriched for amino acid, vitamin B, and bile acid metabolism pathways. Correlation analyses showed that the Alistipes-related metabolites were associated with a wide array of brain imaging measures involving gray matter morphology, spontaneous brain function, and white matter integrity, among which the brain functional measures were, in turn, associated with affective symptoms (anxiety and anhedonia) and cognition (sustained attention) in MDD. Of more importance, further mediation analyses identified multiple significant mediation pathways where the brain functional measures in the visual cortex mediated the associations of metabolites with behavioral deficits.
Conclusion
Our findings provide a proof of concept that Alistipes and its related metabolites play a critical role in the pathophysiology of MDD through the microbiota–gut–brain axis.
Temperature is the most significant abiotic factor that affects the growth and behaviour of insects. However, the mechanism by which the olfactory system senses thermal stimulus and combines temperature and chemical signals to trigger certain behavioural outputs is unclear. This study aimed to clarify the mechanism by which environmental temperature affects olfactory perception in Apis cerana cerana (Hymenoptera: Apidae). We used quantitative reverse-transcriptase polymerase chain reaction and western blotting to analyse the expression of AcerOr1 and AcerOr2. We also used electroantennography (EAG) assays to detect bee antennal responses to odorants at different temperatures. The results revealed that the mRNA expression of AcerOr1 and AcerOr2 was significantly influenced by temperature. These genes exhibited both increases and decreases in expression over time, with the most significant differential observed at 25 °C. Protein expression was similarly affected at 2 hours after different temperature treatments. Electroantennography responses from the antennae revealed that six odorant volatiles – N-(4-ethylphenyl)-2-((4-ethyl-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)thio)acetamide (VUAA1), linolenic acid, eugenol, hexyl acetate, 1-nonanol, and lauroleic acid – had the most dramatic effect at 25 °C. The results indicate that environmental factors affecting the expression of AcerOr1 and AcerOr2 modulate olfactory recognition behaviour in A. cerana cerana, suggesting that changes in environmental temperature can affect bees’ olfactory preferences.
Drawing upon research on the visual complexity effect and Dual Coding Theory, this research examined the influence of character properties and the role of individual learner differences in Chinese character acquisition. The participants included 248 Chinese-speaking children in grades 1 through 3 in Taiwan. The study extended the scope of previous research by concurrently examining two types of cognitive processing: activation of verbal codes with nonverbal codes (activation of word form) and activation of nonverbal codes with verbal codes (activation of meaning). Results revealed the asymmetry in the two types of cognitive processing. Regarding the influence of character properties, while characters with less visual complexity and with radical presence are generally more acquirable, the interaction between these two properties was only present in the activation of meaning but not the activation of word form. Individual differences contributing to character acquisition did not mirror each other in the two directions of cognitive processing either. The contribution of radical awareness and visual skills remained the same across grade levels in the activation of meaning but varied with grades and the properties of the characters in the activation of word form. The methodological and theoretical contributions of the study were discussed.
Parkinson disease (PD) is a neurological disorder that affects more than 10 million people worldwide, impacting both quality of life and marital relationships. Divorce rates are higher in Western compared to Eastern countries. However, it is unclear if there are differences in marital status after PD onset between the two regions.
Methods:
We searched MEDLINE and Embase from inception to March 31, 2024. Original studies discussing marital status in participants with PD were included. An unmarried status includes single, widowed, divorced or separated. Outcomes included the prevalence of being unmarried, measured as proportions, and the risk ratio (RR) of being unmarried in participants with PD relative to controls.
Results:
Out of 567 studies screened initially, 55 studies involving 3,723,966 participants were included. The prevalence of being unmarried was evaluated in 55 studies (25.16%; 95% CI: 21.52–29.18). The prevalence of being unmarried was significantly higher in countries in the West compared to the East (28.83%; 95% CI: 25.09–32.89 vs 17.47%; 95% CI: 12.10–24.57, p < 0.01). Compared to controls, the risk of being unmarried in PD participants after the onset of PD was significantly higher in the East (RR: 1.21, 95% CI: 0.91–1.60) compared to the West (RR: 0.87, 95% CI: 0.65–1.15).
Conclusions:
Our meta-analysis showed significantly higher rates of being unmarried in Western compared to Eastern countries. After PD onset, participants in the East were at significantly higher risk of being unmarried compared to participants in the West, suggesting that differences in cultural practices, societal norms and healthcare systems may affect marital status outcomes in PD participants.
To speed up the construction of grassroots medical and health teams in China, free training of rural order-oriented medical students was launched in June 2010. Based on the theory of policy tools, a quantitative analysis of policy texts at the national level was conducted to explore the use of policy tools and to put forward corresponding suggestions for adjustments.
Methods
From January to February 2023, the research team searched the Peking University Treasure Database and the official websites of the State Council, the National Health Commission, the Ministry of Education, and other ministries for national policy documents related to free training of order-oriented medical students published from June 2010 to May 2023. A policy tool and policy target analysis framework were used to quantitatively analyze the policy documents.
Results
A total of 16 policy documents were included and 213 policy provisions were extracted. From the perspective of policy tools, the proportion of policy provisions using imperative policy tools was the highest (63.4%), followed by advisory policy tools (18.8%). and reward-based policy tools (13.6%). Functional expansion tools (2.8%) and authoritative restructuring tools (1.4%) accounted for a relatively low proportion. The institutional education stage is the main policy target, with provisions accounting for 75 percent (162 articles), followed by the continuing education stage (17.6%; 38 articles), and the postgraduate education stage (7.4%; 16 articles).
Conclusions
The distribution of policy tools for the free training policy of rural order-oriented medical students in China needs to be balanced, and the internal combination of the same policy tools needs to be optimized. The policy targets were mainly concentrated in the education stage of universities.
With the aging population, chronic diseases have become a serious threat to public health in China. Adhering to the doctor’s advice is an effective strategy for controlling chronic diseases, and the preferences of patients with chronic disease has an important impact on compliance with medication. However, there is insufficient research exploring this aspect.
Methods
In this study patients with chronic disease were selected by stratified random sampling to participate in a survey carried out in three cities of a province in eastern China. The discrete choice experiment used a questionnaire of D-efficiency experimental design to measure the medication choices of patients with chronic disease. The main attributes included drug price, onset of action, adverse reactions, traditional Chinese or Western medicine, domestic drug, and reimbursed by medical insurance. The data were analyzed using a mixed logit model.
Results
A total of 1,062 valid questionnaires were received. The 1,045 questionnaires that passed the consistency test covered three prefecture-level cities, nine counties, and 216 villages. All drug attributes were statistically significant for selection preferences. The preference of patients in rural areas with chronic disease was “quick onset of action” (β=2.491), “Western medicine” (β=0. 826), “medical insurance” (β=0.556), “domestic drugs” (β=0.286), and “very few adverse reactions” (β=0.170). “Drug price” also had an impact on medication preferences among patients in rural areas with chronic disease (β=−0.013).
Conclusions
Onset of action is the attribute of medications that is of most concern for patients in rural areas with chronic disease. Subgroup analysis showed that these patients were predominantly female, had a primary school education or lower, were younger than 69 years, were unemployed, and had an annual income between CNY10,000 (USD1,396.78) and CNY50,000 (USD6,983.92). They were willing to pay more for drugs with a quick onset of action, Western medicines, and drugs with reimbursed by medical insurance.
With increased global navigation satellite system (GNSS) signals and degraded observation environments, the correctness of ambiguity resolution is disturbed, causing unexpected real-time kinematic (RTK) positioning solutions. This paper presents an improved fault detection and exclusion (FDE) method based on the generalized least squares (GLS) model. The correlated GLS model is constructed by regarding double-differencing (DD) integer ambiguities as the known parameters. Meanwhile, the validity of residuals as crucial components of fault detection could be enhanced by the iterative re-weighted least squares (IRLS) method rather than the least squares (LS) without robustness. A static test with artificial faults and a dynamic test with natural faults were carried out, respectively. By analyzing test statistics of the enhanced FDE algorithm and comparing its positioning errors with those from the classical LS, it is shown that our method can provide high-precision and high-reliability RTK solutions facing wrong DD fixed ambiguities due to observation faults.
The maser instability associated with the loss-cone distribution has been widely invoked to explain the radio bursts observed in the astrophysical plasma environment, such as aurora and corona. In the laboratory plasma of a tokamak, events reminiscent of these radio bursts have also been frequently observed as an electron cyclotron emission (ECE) burst in the microwave range ($\mathrm{\sim }2{f_{\textrm{ce}}}$ near the last closed flux surface) during transient magnetohydrodynamic events. These bursts have a short duration of ~10 μs and display a radiation spectrum corresponding to a radiation temperature ${T_{e,\textrm{rad}}}$ of over $30\ \textrm{keV}$ while the edge thermal electron temperature ${T_e}$ is only in the range of $1\ \textrm{keV}$. Suprathermal electrons can be generated through magnetic reconnection, and a loss-cone distribution can be generated through open stochastic field lines in the magnetic mirror of the near-edge region of a tokamak plasma. Radiation modelling shows that a sharp distribution gradient $\partial f/\partial {v_ \bot } > 0$ at the loss-cone boundary can cause a negative absorption of ECE radiation through the maser instability. The negative absorption then amplifies the radiation so that the microwave intensity is significantly stronger than the thermal value. The significant ${T_{e,\textrm{rad}}}$ from the simulations suggests the potential role of the loss-cone maser instability in generating the ECE burst in a tokamak.
Isolated multi-MeV $\gamma$-rays with attosecond duration, high collimation and beam angular momentum (BAM) may find many interesting applications in nuclear physics, astrophysics, etc. Here, we propose a scheme to generate such $\gamma$-rays via nonlinear Thomson scattering of a rotating relativistic electron sheet driven by a few-cycle twisted laser pulse interacting with a micro-droplet target. Our model clarifies the laser intensity threshold and carrier-envelope phase effect on the generation of the isolated electron sheet. Three-dimensional numerical simulations demonstrate the $\gamma$-ray emission with 320 attoseconds duration and peak brilliance of $9.3\times 10^{24}$ photons s${}^{-1}$ mrad${}^{-2}$ mm${}^{-2}$ per 0.1$\%$ bandwidth at 4.3 MeV. The $\gamma$-ray beam carries a large BAM of $2.8 \times 10^{16}\mathrm{\hslash}$, which arises from the efficient BAM transfer from the rotating electron sheet, subsequently leading to a unique angular distribution. This work should promote the experimental investigation of nonlinear Thomson scattering of rotating electron sheets in large laser facilities.
Compacted bentonite, used as an engineering barrier for permanent containment of high-level radioactive waste, is susceptible to mineral evolution resulting in compromise of the expected barrier performance due to alkaline–thermal chemical interaction in the near-field. To elucidate the mineral-evolution mechanisms within bentonite and the transformation of the nuclide adsorption properties during that period, experimental evolution of bentonite was conducted in a NaOH solution with a pH of 14 at temperatures ranging from 60 to 120°C. The results showed that temperature significantly affects the stability of minerals in bentonite under alkali conditions. The dissolution rate of fine-grained cristobalite in bentonite exceeds that of smectite, with the phase-transition products of smectite being temperature-dependent. As the temperature rises, smectite experiences a three-stage transformation: initially, at 60°C, the lattice structure thins due to the collapse of the octahedral sheets; at 80°C, the lattice disintegrates and reorganizes into a loose framework akin to albite; and by 100°C, it further reorganizes into a denser framework resembling analcime. The adsorption properties of bentonite exhibit a peak inflection point at 80°C, where the dissolution of the smectite lattice eliminates interlayer pores and exposes numerous polar or negatively charged sites which results in a decrease in specific surface area and an increase in cation exchange capacity and adsorption capacity of Eu3+. This research provides insights into the intricate evolution of bentonite minerals and the associated changes in radionuclide adsorption capacity, contributing to a better understanding of the stability of bentonite barriers and the effective long-term containment of nuclear waste.
Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial.
This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n = 41; 8.6%) and cardiac manifestations (n = 31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796–0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.
Increasing social concern surrounds the potential adverse health effects of precarious employment (PE). In this study, we explored the association between PE and the onset of depressive symptoms.
Methods
A total of 11,555 Korean waged workers (5700 females) contributed 62,217 observations from 2009 to 2022. PE was operationalized as a multidimensional construct, including employment insecurity, income inadequacy and lack of rights and protection. Depressive symptoms were evaluated using the Center for Epidemiological Studies-Depression Scale (11-item version). The association between PE and the onset of depressive symptoms in the subsequent year was estimated using generalized estimating equations. Effect sizes were reported as odds ratio (OR) and 95% confidence interval (CI).
Results
The overall incidence of depressive symptoms was 8.3% during the study period. In cross-sectional analysis, daily employment, disguised employment, lower monthly wages and lack of social insurance coverage were associated with concurrent depressive symptoms in both men and women. Longitudinally, fixed-term employment (OR: 1.17, 95% CI: 1.07–1.29), daily employment (OR: 1.64, 95% CI: 1.45–1.85) and disguised employment (OR: 1.36, 95% CI: 1.17–1.57) were associated with the onset of depressive symptoms among the overall sample. Among men, the lowest quartiles of wage were associated with the onset of depressive symptoms (OR: 1.34, 95% CI: 1.13–1.60), while the absence of a trade union was associated among women (OR: 1.18, 95% CI: 1.01–1.39).
Conclusions
Employment insecurity, inadequate income and lack of rights and protection may contribute to depressive symptoms. Therefore, PE serves as a significant social determinant of mental health among workers in Korea. Active policy efforts are warranted to improve the overall quality of employment in the workforce.
OBJECTIVES/GOALS: Donor hearts are transported in cold storage (CS) and undergo ischemia-reperfusion injury (IRI) when transplanted. IRI injures microvascular endothelial cells (EC), heightens the immune response, and has been associated with increased autophagy. We aim to understand the changes in autophagy during CS and IRI and its impact on EC immunogenicity. METHODS/STUDY POPULATION: To study autophagy changes during IRI, immunoblotting for autophagy markers was performed in mouse cardiac ECs (MCECs) lysates. MCECs were in a cold preservation solution in a hypoxic chamber for 6 hours(h) and warm conditions with culture medium for 24 h. MCECs, under standard conditions, served as controls. Secreted interferon-gamma (IFN-γ) levels were quantified via ELISA to study autophagy and EC immunogenicity. MCEC-sensitized CD8+ T-cells were isolated from C57BL/6 spleens and co-cultured with MCECs pre-treated for 16 h with rapamycin or starvation, autophagy inducers, or chloroquine, an autophagy inhibitor under normal or IRI conditions. MCECs without any treatment served as controls. RESULTS/ANTICIPATED RESULTS: To determine autophagy levels in IRI, immunoblotting of MCEC lysates revealed a significant increase (P<0.01) in the established autophagy marker, LC3, at early time points post-reperfusion compared to NT conditions, indicating more autophagosome formation during CS and IRI. To assess the role of autophagy in EC immunogenicity, the co-culture experiment revealed that autophagy induction in MCECs under NT and HCS conditions with rapamycin had a 74.9-fold and 51.5-fold reduction of IFN-γ (pg/mL), resepectively, compared to the non-treated controls. In contrast, autophagy inhibition in MCECs with chloroquine resulted in 1.82-fold increase of IFN-γ compared to untreated controls. This suggests a protective role of autophagy in ECs during IRI. DISCUSSION/SIGNIFICANCE: We observed that autophagy may be protective during IRI by mitigating EC immunogenicity. Thus, pharmacologically modulating microvascular EC autophagy in donor hearts prior to transplantation may mitigate insults incurred during CS and IRI.
Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients.
Methods
We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention.
Results
Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group.
Conclusions
These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.