Screening and purification of antimicrobial materials from coelomic fluid of sea urchin, Heliocidaris crassispina.

Marine organisms, such as sea urchins like Heliocidaris crassispina, produce bioactive substances with antimicrobial activity to protect themselves from the high density of microorganisms in their habitats. One such substance, Echinochrome A (Ech A), has been isolated from various sea urchins' shells and spines using strong acidic solutions and organic solvents. Ech A, however, has not been reported from the coelomic fluid of H. crassispina. In this study, we report the antimicrobial activity of H. crassispina coelomic fluid extract against various microbes, evaluating its potential for purifying potent antimicrobial materials. Upon confirming the extract as a promising source of antimicrobial materials, we isolated antimicrobial compounds from the extract. A series of HPLC steps were taken to purify antimicrobial materials from the H. crassispina coelomic fluid extract, resulting in the isolation of two single absorbance peaks showing antimicrobial activity against Staphylococcus aureus. One peak consisted of a single antimicrobial compound with a molecular weight (MW) corresponding to Ech A, while the other peak comprised five MWs inferred to be those of Ech A and its oxidative products. The elution of Ech A in two separate peaks may be attributable to the presence of Ech A's isomer, as reported in several previous studies. The use of the environmentally friendly extraction method in procurement of Ech A from the coelomic fluid would contribute to the implementation of risk-reducing extraction method for researchers studying Ech A from sea urchins.

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.

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.

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.

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.

Elucidating Structural Configuration of Lipid Assemblies for mRNA Delivery Systems.

The development of mRNA delivery systems utilizing lipid-based assemblies holds immense potential for precise control of gene expression and targeted therapeutic interventions. Despite advancements in lipid-based gene delivery systems, a critical knowledge gap remains in understanding how the biophysical characteristics of lipid assemblies and mRNA complexes influence these systems. Herein, we investigate the biophysical properties of cationic liposomes and their role in shaping mRNA lipoplexes by comparing various fabrication methods. Notably, an innovative fabrication technique called the liposome under cryo-assembly (LUCA) cycle, involving a precisely controlled freeze-thaw-vortex process, produces distinctive onion-like concentric multilamellar structures in cationic DOTAP/DOPE liposomes, in contrast to a conventional extrusion method that yields unilamellar liposomes. The inclusion of short-chain DHPC lipids further modulates the structure of cationic liposomes, transforming them from multilamellar to unilamellar structures during the LUCA cycle. Furthermore, the biophysical and biological evaluations of mRNA lipoplexes unveil that the optimal N/P charge ratio in the lipoplex can vary depending on the structure of initial cationic liposomes. Cryo-EM structural analysis demonstrates that multilamellar cationic liposomes induce two distinct interlamellar spacings in cationic lipoplexes, emphasizing the significant impact of the liposome structures on the final structure of mRNA lipoplexes. Taken together, our results provide an intriguing insight into the relationship between lipid assembly structures and the biophysical characteristics of the resulting lipoplexes. These relationships may open the door for advancing lipid-based mRNA delivery systems through more streamlined manufacturing processes.

Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping.

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.

Daily vitality fluctuations in older adults with depressive symptoms: A multilevel location-scale model.

BACKGROUND: Examining the daily experiences of older adults with depression facilitates the development and application of personalized effective treatments for them. In previous clinical research on depression, traditional mean-based approaches have mainly been employed. However, the within-person residual variance as a random effect provides greater insight into the heterogeneity of daily experiences among geriatric samples. OBJECTIVE: This study aimed to examine the relationship between depression and daily vitality in older adults. Specifically, it focused on the mean and residual variance of daily vitality measured by the Ecological Momentary Assessment (EMA). METHODS: Data from 64 older adults aged 65 years or more, who participated in community welfare centers or retirees' associations, were used. Daily vitality was examined using EMA surveys for seven consecutive days (four random surveys per day). The data were analyzed using a location-scale model. RESULTS: The intraclass correlation computed from the empty model for the EMA data was 0.488, indicating significant variances in daily vitality across time between individuals. Older adults with higher levels of depressive symptoms showed low mean levels of daily vitality and a large log-residual variance of daily vitality. CONCLUSIONS: The findings from the current study suggest that individuals experiencing depression not only exhibit low vitality in their daily lives but also struggle to maintain stable levels of vitality in their lives. These insights could contribute to the facilitation and advancement of personalized interventions tailored for older adults.

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.

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.

SPATA20 deficiency enhances the metastatic and angiogenic potential of cancer cells by promoting HIF-1α synthesis.

Hypoxia-inducible factors (HIFs) regulate cellular oxygen balance and play a central role in cancer metastasis and angiogenesis. Despite extensive research on HIFs, successful therapeutic strategies remain limited due to the intricate nature of their regulation. In this study, we identified SPATA20, a relatively understudied protein with a thioredoxin-like domain, as an upstream regulator of HIF-1α. Depleting SPATA20 induced HIF-1α expression, suggesting a tumor-suppressive role for SPATA20 in cancer cells. SPATA20 depletion increased HIF-1α protein levels and transcriptional activity without affecting its degradation. It appears that SPATA20 inhibits the de novo synthesis of HIF-1α, possibly by repressing the cap-dependent translation process involving AKT phosphorylation. Additionally, depletion of SPATA20 promoted cancer cell migration and invasion, which can be reversed by pharmacological inhibition of HIF-1α. Clinical data analysis revealed an inverse correlation between SPATA20 expression and colorectal cancer progression, providing evidence of its role as a potential biomarker. Utilizing SPATA20 as an indicator for HIF-1α-targeting therapy may be an attractive strategy for treating patients with hypoxia-driven cancers. In conclusion, this study demonstrates that SPATA20 deficiency promotes cancer progression by activating the HIF-1α signaling pathway.

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.

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.

Infection Control Experiences and Educational Needs of Geriatric Care Workers in Long-Term Care Facilities: A Pilot Study.

BACKGROUND: In the post-COVID-19 condition, infection control education is important for geriatric care workers who care for the elderly and are vulnerable to emerging infectious diseases. This study was conducted to enhance the insight into the experiences of geriatric care workers in managing novel infectious diseases (COVID-19) and to identify the newly required educational requirements necessary to effectively implement infectious disease control. METHODS: This is a qualitative and pilot study using focus group interviews. Data from 10 participants were collected using a focus group interview. The data were analyzed using Qualitative content analysis. RESULTS: The findings showed that geriatric healthcare workers experienced difficulties following infection control protocols and emotional distress related to visitor restrictions and had an increased workload. The participants requested further education regarding general knowledge of infectious diseases to decrease their fears of infection and reported that visual and practical teaching methods were preferable. CONCLUSIONS: Further attention is needed regarding the education of infection control to strengthen infection prevention in long-term care facilities vulnerable to the spread of emerging infectious diseases.

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.

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.

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.

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.

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study.

OBJECTIVE: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). METHODS: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. RESULTS: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. CONCLUSIONS: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia.