Development of a deep-learning phenotyping tool for analyzing image-based strawberry phenotypes.

Introduction: In strawberry farming, phenotypic traits (such as crown diameter, petiole length, plant height, flower, leaf, and fruit size) measurement is essential as it serves as a decision-making tool for plant monitoring and management. To date, strawberry plant phenotyping has relied on traditional approaches. In this study, an image-based Strawberry Phenotyping Tool (SPT) was developed using two deep-learning (DL) architectures, namely "YOLOv4" and "U-net" integrated into a single system. We aimed to create the most suitable DL-based tool with enhanced robustness to facilitate digital strawberry plant phenotyping directly at the natural scene or indirectly using captured and stored images. Methods: Our SPT was developed primarily through two steps (subsequently called versions) using image data with different backgrounds captured with simple smartphone cameras. The two versions (V1 and V2) were developed using the same DL networks but differed by the amount of image data and annotation method used during their development. For V1, 7,116 images were annotated using the single-target non-labeling method, whereas for V2, 7,850 images were annotated using the multitarget labeling method. Results: The results of the held-out dataset revealed that the developed SPT facilitates strawberry phenotype measurements. By increasing the dataset size combined with multitarget labeling annotation, the detection accuracy of our system changed from 60.24% in V1 to 82.28% in V2. During the validation process, the system was evaluated using 70 images per phenotype and their corresponding actual values. The correlation coefficients and detection frequencies were higher for V2 than for V1, confirming the superiority of V2. Furthermore, an image-based regression model was developed to predict the fresh weight of strawberries based on the fruit size (R2 = 0.92). Discussion: The results demonstrate the efficiency of our system in recognizing the aforementioned six strawberry phenotypic traits regardless of the complex scenario of the environment of the strawberry plant. This tool could help farmers and researchers make accurate and efficient decisions related to strawberry plant management, possibly causing increased productivity and yield potential.

Impact of Systolic Blood Viscosity on Deep White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

BACKGROUND: Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. METHODS AND RESULTS: We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). CONCLUSIONS: Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.

How to determine the focus of emergent medical care in healthcare policy: Proposal of treatable death.

INTRODUCTION: The global provision of essential healthcare stands as a critical concern. Consequently, healthcare policies play a pivotal role in determining the allocation of resources. However, the optimal indicators for prioritizing such policies remain uncertain. This study proposes that employing the concept of treatable mortality in a stepwise manner could serve as a viable approach to setting healthcare policy priorities. Furthermore, it aims to demonstrate this concept through the application of real-world data. METHODS: A model was developed to assess treatable mortality at a national level focusing on severe emergency conditions. We established stepwise targets, encompassing short-term, mid-term, and long-term goals to reduce mortality rates and enhance healthcare efficiency. The short-term target consists of directing attention to regions exhibiting in-hospital mortality rates surpassing the national average within a specific disease category and reducing them to the national average. The mid-term objective entails decreasing the in-hospital mortality rate of the specific disease group to match that of the region with the lowest rate nationwide. As for long-term target, it aligns the in-hospital mortality rate with that of OECD countries possessing average or lowest rates. The model was applied using data from South Korea's National Emergency Department Information System, specifically analyzing acute myocardial infarction (AMI), stroke, and sepsis. RESULTS: Reaching the short-term target resulted in the treatable deaths for AMI numbered 191, for stroke 249, and for sepsis 546. Meeting the mid-term target led to treatable deaths for AMI at 749, for stroke at 958, and for sepsis at 1552. Finally, achieving the long-term target yielded the treatable deaths for AMI at 2606, for stroke at 1642, and for sepsis at 2619. Consequently, a reallocation of more healthcare resources to sepsis over AMI or stroke is recommended. CONCLUSIONS: This study proposes the utilization of treatable mortality as a metric for establishing healthcare policies. The stepwise approach provides valuable insights for policymaking at various levels. Despite limitations, the model offers a foundation for resource allocation and international mortality rate comparisons, aiming for achievable rates worldwide.

Assessing the Impact of Nutritional Support Teams on Clinical Outcomes: Compliance and Feasibility of Micronutrient Supplementation.

Background: Micronutrient (MN) supplementation has a positive impact on clinical outcomes. However, the evidence for the impact of MN supplementation remains controversial. Therefore, our study aims to assess the impact on nutritional outcomes according to exploring the implementation of MN support with multidisciplinary collaboration. Methods: This retrospective cohort study was conducted at a university hospital in Incheon, Korea. All patients referred to a nutrition support team (NST) between July and November 2022 were included. The NST reviews the MN protocol, which includes multivitamins and trace elements, based on international nutrient guidelines. All patients who were on nothing per oral and did not meet ≥70% of their nutritional requirements within 1 week were recommended MN supplements. Compliance with the MN protocol was evaluated, alterations in nutritional status based on the Nutrition Risk Screening 2002 (NRS 2002) scoring system and clinical outcomes were assessed after 7 day and at discharge. Multiple logistic regression analysis was used to identify factors associated with high nutritional risk in discharged patients. In addition, a sub-analysis was performed on changes in the nutritional of patients on the ward and in the ICU. Results: A total of 255 patients were eligible for analysis, with many patients requiring an MN supply of nothing per oral. The rate of implementation of MN supplementation was 50.2%. The findings indicate a significant decrease in the NRS 2002 score in the good compliance group with MN supplementation. No significant differences in protocol compliance were observed in terms of mortality, hospital stay, or length of stay in the intensive care unit. However, bad compliance with MN supplementation was correlated with risk factors for malnutrition at discharge. In subgroup analysis, nutritional status in the ICU and wards improved, with a significant difference between the two groups. Conclusions: The implementation of a MN supplementation protocol by a multidisciplinary NST is a feasible approach for improving the nutritional status of inpatients. Ensuring high compliance with this protocol is crucial, as poor compliance has been identified as a risk factor for malnutrition at discharge. Active intervention by the NST is essential to achieve optimal nutritional outcomes.

Non-destructive assessment of cannabis quality during drying process using hyperspectral imaging and machine learning.

Cannabis sativa L. is an industrially valuable plant known for its cannabinoids, such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), renowned for its therapeutic and psychoactive properties. Despite its significance, the cannabis industry has encountered difficulties in guaranteeing consistent product quality throughout the drying process. Hyperspectral imaging (HSI), combined with advanced machine learning technology, has been used to predict phytochemicals that presents a promising solution for maintaining cannabis quality control. We examined the dynamic changes in cannabinoid compositions under diverse drying conditions and developed a non-destructive method to appraise the quality of cannabis flowers using HSI and machine learning. Even when the relative weight and water content remained constant throughout the drying process, drying conditions significantly influenced the levels of CBD, THC, and their precursors. These results emphasize the importance of determining the exact drying endpoint. To develop HSI-based models for predicting cannabis quality indicators, including dryness, precursor conversion of CBD and THC, and CBD : THC ratio, we employed various spectral preprocessing methods and machine learning algorithms, including logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and Gaussian naïve Bayes (GNB). The LR model demonstrated the highest accuracy at 94.7-99.7% when used in conjunction with spectral pre-processing techniques such as multiplicative scatter correction (MSC) or Savitzky-Golay filter. We propose that the HSI-based model holds the potential to serve as a valuable tool for monitoring cannabinoid composition and determining optimal drying endpoint. This tool offers the means to achieve uniform cannabis quality and optimize the drying process in the industry.

Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

Consideration of the diameter of superficial temporal arteries related to filler injections in the temporal region.

BACKGROUND: The concavity of the temple due to adipose tissue atrophy from aging accentuates the zygomatic arch and lateral orbital rim, leading to an aged appearance. The use of hyaluronic acid filler in the temporal region has gained popularity due to its procedural simplicity and consistent outcomes. OBJECTIVE: To evaluate the safety of administering hyaluronic acid filler in the temporal region concerning the frontal branch of the superficial temporal artery, which is at risk of injury. METHODS: Empirical observations were conducted on the internal diameter of the frontal branch of the superficial temporal artery, a critical anatomical site for potential injury. RESULTS: A significant proportion of the artery segments exhibited an internal diameter below 1 mm. Given that the outer diameter of an 18-gauge cannula is 1.27 mm, this method can be considered a relatively secure approach for enhancing the temporal region. CONCLUSION: The use of an 18-gauge cannula for hyaluronic acid filler administration in the temporal region appears to be a safe and effective method, with the potential risk to the frontal branch of the superficial temporal artery being minimal.

Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

COVID-19, Influenza, and RSV in Children and Adults: A Clinical Comparative Study of 12,000 Cases.

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.

The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Skin-whitening effects of Spergularia marina by suppressing MITF translocation.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.

Investigation of factors regarding the effects of COVID-19 pandemic on college students' depression by quantum annealer.

Diverse cases regarding the impact, with its related factors, of the COVID-19 pandemic on mental health have been reported in previous studies. In this study, multivariable datasets were collected from 751 college students who could be easily affected by pandemics based on the complex relationships between various mental health factors. We utilized quantum annealing (QA)-based feature selection algorithms that were executed by commercial D-Wave quantum computers to determine the changes in the relative importance of the associated factors before and after the pandemic. Multivariable linear regression (MLR) and XGBoost models were also applied to validate the QA-based algorithms. Based on the experimental results, we confirm that QA-based algorithms have comparable capabilities in factor analysis research to the MLR models that have been widely used in previous studies. Furthermore, the performance of the QA-based algorithms was validated through the important factor results from the algorithms. Pandemic-related factors (e.g., confidence in the social system) and psychological factors (e.g. decision-making in uncertain situations) were more important in post-pandemic conditions. Although the results should be validated using other mental health variables or national datasets, this study will serve as a reference for researchers regarding the use of the quantum annealing approach in factor analysis with validation through real-world survey dataset analysis.

Current insights into genome-based personalized nutrition technology: a patent review.

Unlike general nutritional ranges that meet the nutritional needs essential for maintaining the life of an entire population, personalized nutrition is characterised by maintaining health through providing customized nutrition according to individuals' lifestyles or genetic characteristics. The development of technology and services for personalized nutrition is increasing, owing to the acquisition of knowledge about the differences in nutritional requirements according to the diversity of individuals and an increase in health interest. Regarding genetics, technology is being developed to distinguish the various characteristics of individuals and provide customized nutrition. Therefore, to understand the current state of personalized nutrition technology, understanding genomics is necessary to acquire information on nutrition research based on genomics. We reviewed patents related to personalized nutrition-targeting genomics and examined their mechanisms of action. Using the patent database, we searched 694 patents on nutritional genomics and extracted 561 highly relevant valid data points. Furthermore, an in-depth review was conducted by selecting core patents related to genome-based personalized nutrition technology. A marked increase was observed in personalized nutrition technologies using methods such as genetic scoring and disease-specific dietary recommendations.

Case report: Tolosa-Hunt syndrome-expanding the neuromyelitis optica spectrum disorder phenotype?

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by the autoantibody of aquaporin-4 (AQP4). Herein, we report a case of Tolosa-Hunt syndrome presenting with abducens palsy and AQP4 antibodies. This was a rare case of AQP4-immunoglobulin G seropositivity in a patient with Tolosa-Hunt syndrome. Our findings may expand the clinical phenotype of NMOSD and indicate that clinicians should consider testing for AQP4 antibodies in patients with Tolosa-Hunt syndrome.

Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence.

Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

Barrier Abnormalities in Type 1 Diabetes Mellitus: The Roles of Inflammation and Ceramide Metabolism.

Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.