Chronic periodontal disease is related with newly developing hypertension: a nationwide cohort study.

BACKGROUND: Periodontal disease (PD) is a condition that can be treated and managed. This study aimed to determine if chronic PD status is associated with the risk of developing hypertension, utilizing data from the National Health Insurance Database of Korea. METHODS: Participants who received oral health examinations both in 2003 and in 2005-2006 were included. Those with a history of hypertension were excluded. Hypertension was defined as at least one outpatient or inpatient claim diagnosis (primary or secondary) of hypertension (International Classification of Diseases (ICD)-10 codes I10-I11) with prescription for antihypertensive medication or at least one incident of systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg during a health examination. Changes of PD status was determined during two oral examinations. Study participants were divided into 4 groups according to the changes of PD status: PD-free (those consistently free of disease in both exams), PD-recovered (individuals with disease initially but not in the second exam), PD-developed (no disease initially, but present in the second exam), and PD-chronic (disease throughout both exams). The incidence of hypertension after the second oral health examination (index date) was monitored. Participants were observed from the index date until the earliest occurrence of hypertension onset, mortality, or December 2020. RESULTS: The study comprised 706,584 participants: 253,003(35.8%) in the PD-free group, 140,143(19.8%) in the PD-recovered group, 132,397(18.7%) in the PD-developed group, and 181,041(25.6%) in the PD-chronic group. Over a median follow-up duration of 14.3 years, 239,937 (34.0%) cases of hypertension were recorded. The PD-recovered group had a lower risk of hypertension compared to the PD-chronic group, while the PD-developed group had a higher risk of hypertension compared to the PD-free group. CONCLUSION: Chronic PD is associated with an increased risk of developing hypertension. Although the increase in risk is modest, recovery from PD may have beneficial effects in reducing hypertension risk. Further studies are needed to confirm the importance of regular dental examinations and effective management of PD to reduce hypertension risk.

A sexually transmitted sugar orchestrates reproductive responses to nutritional stress.

Seminal fluid is rich in sugars, but their role beyond supporting sperm motility is unknown. In this study, we found Drosophila melanogaster males transfer a substantial amount of a phospho-galactoside to females during mating, but only half as much when undernourished. This seminal substance, which we named venerose, induces an increase in germline stem cells (GSCs) and promotes sperm storage in females, especially undernourished ones. Venerose enters the hemolymph and directly activates nutrient-sensing Dh44+ neurons in the brain. Food deprivation directs the nutrient-sensing neurons to secrete more of the neuropeptide Dh44 in response to infused venerose. The secreted Dh44 then enhances the local niche signal, stimulating GSC proliferation. It also extends the retention of ejaculate by females, resulting in greater venerose absorption and increased sperm storage. In this study, we uncovered the role of a sugar-like seminal substance produced by males that coordinates reproductive responses to nutritional challenges in females.

Effect of Cage Material and Size on Fusion Rate and Subsidence Following Biportal Endoscopic Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is an emerging, minimally invasive technique performed under biportal endoscopic guidance. However, concerns regarding cage subsidence and sufficient fusion during BE-TLIF necessitate careful selection of an appropriate interbody cage to improve surgical outcomes. This study compared the fusion rate, subsidence, and other radiographic parameters according to the material and size of the cages used in BE-TLIF. METHODS: In this retrospective cohort study, patients who underwent single-segment BE-TLIF between April 2019 and February 2023 were divided into 3 groups: group A, regular-sized three-dimensionally (3D)-printed titanium cages; group B, regular-sized polyetheretherketone cages; and group C, large-sized 3D-printed titanium cages. Radiographic parameters, including lumbar lordosis, segmental lordosis, anterior and posterior disc heights, disc angle, and foraminal height, were measured before and after surgery. The fusion rate and severity of cage subsidence were compared between the groups. RESULTS: No significant differences were noted in the demographic data or radiographic parameters between the groups. The fusion rate on 1-year postoperative computed tomography was comparable between the groups. The cage subsidence rate was significantly lower in group C than in group A (41.9% vs. 16.7%, p=0.044). The severity of cage subsidence was significantly lower in group C (0.93±0.83) than in groups A (2.20±1.84, p=0.004) and B (1.79±1.47, p=0.048). CONCLUSION: Cage materials did not affect the 1-year postoperative outcomes of BE-TLIF; however, subsidence was markedly reduced in large cages. Larger cages may provide more stable postoperative segments.

Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Cholinesterase inhibitor use in amyloid PET-negative mild cognitive impairment and cognitive changes.

BACKGROUND: Cholinesterase inhibitors (ChEIs) are prescribed for Alzheimer's disease (AD) and sometimes for mild cognitive impairment (MCI) without knowing underlying pathologies and its effect on cognition. We investigated the frequency of ChEI prescriptions in amyloid-negative MCI and their association with cognitive changes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. METHODS: We included participants with amyloid positron emission tomography (PET)-negative MCI from the ADNI. We analyzed the associations of ChEI use with cognitive changes, brain volume, and cerebrospinal fluid (CSF) total tau (t-tau), hyperphosphorylated tau181 (p-tau181), and p-tau181/t-tau ratio. RESULTS: ChEIs were prescribed in 27.4% of amyloid PET-negative MCI and were associated with faster cognitive decline, reduced baseline hippocampal volume and entorhinal cortical thickness, and a longitudinal decrease in the frontal lobe cortical thickness. CONCLUSIONS: The association between ChEI use and accelerated cognitive decline may stem from underlying pathologies involving reduced hippocampal volume, entorhinal cortical thickness and faster frontal lobe atrophy. We suggest that ChEI use in amyloid PET-negative MCI patients might need further consideration, and studies investigating the causality between ChEI use and cognitive decline are warranted in the future.

Repeatability of Scheimpflug-Placido camera in mild dry eye versus normal eyes according to the topographical position of the cornea.

We aimed to investigate the repeatability of various corneal measurements according to topographical location in the entire cornea measured by dual rotating Scheimpflug-Placido camera and to explore the differences in repeatability between patients with mild dry eye and those with normal eyes. In both the normal and dry eye groups, divided based on BUT or the height of the tear film, there were no statistically significant differences in the ratio of unacceptable variation (RUV) and ICC. The consistency of the examination of the anterior and posterior refractive values and corneal thickness according to the corneal location, measured three times repeatedly using the Galilei anterior segment camera, was high. There was no difference based on the height of the tear film or the tear film break-up time. However, caution is needed when interpreting the values of the anterior corneal refractive values, as there can be changes of more than 0.5D within 3 mm of the central area.

Evidence of small vessel disease in patients with transient global amnesia based on the peak width of skeletonized mean diffusivity.

BACKGROUND AND PURPOSE: The peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. In this study, we aimed to investigate the presence of small vessel disease in patients with transient global amnesia (TGA) using the PSMD. MATERIALS AND METHODS: We enrolled 75 patients newly diagnosed with TGA and included 65 age-and sex-matched healthy controls. Diffusion tensor imaging (DTI) was performed using a 3T magnetic resonance imaging scanner. We measured the PSMD based on DTI using the FSL program. This measure was compared between patients with TGA and healthy controls. Additionally, we conducted a correlation analysis to explore the relationship between PSMD and clinical factors. RESULTS: A significant difference in the PSMD between patients with TGA and healthy controls was observed. Patients with TGA exhibited higher a PSMD compared to healthy controls (2.297±0.232 vs. 2.188±0.216 ×10-4 mm2/s, p=0.005). Additionally, patients with TGA but without any vascular risk factors, such as diabetes, hypertension or dyslipidemia, also exhibited higher a PSMD compared to healthy controls (2.278±0.253 vs. 2.188±0.216 ×10-4 mm2/s, p=0.036). The PSMD positively correlated with age (r=0.248, p=0.032); however, it was not associated with duration of amnesia. CONCLUSIONS: This finding underscores the feasibility of using PSMD as a marker for detecting small vessel diseases in patients with neurological disorders. Furthermore, our study also implies the presence of small vessel disease may be present in patients with TGA. ABBREVIATIONS: TGA=transient global amnesia; TIA= transient ischemic attack; PSMD= peak width of skeletonized mean diffusivity; DTI= diffusion tensor imaging.

Durably Superhydrophobic Magnetic Cobalt Ferrites for Highly Efficient Oil-Water Separation and Fast Microplastic Removal.

Microplastic pollution has become a primary global concern in the 21st century. Recyclable magnetic particles with micro-nanostructures are considered an efficient and economical way to remove microplastics from water. In this study, superhydrophobic magnetic cobalt ferrite particles were prepared by using a simple coprecipitation method combined with surface functionalization. The micromorphology, chemical composition, hysteresis loop, and surface contact angle of the functionalized cobalt ferrite were characterized. The separation efficiency and absorption capacity of cobalt ferrite particles in water-oil separation and microplastic removal were investigated. The results showed that the saturation magnetic field intensity of cobalt ferrite was 65.52 emu/g, the residual magnetization intensity (Mr) was 18.79 emu/g, and the low coercivity was 799.83 Oe. Cobalt ferrites had stable superhydrophobicity in the pH range of 1-13. The separation efficiency of cobalt ferrite powder for four oil-water mixture separations was higher than 94.2%. The separation efficiency was as high as 99.6% in the separation of the hexane and water mixtures. Due to the synergistic effect of the hydrophobic effect and van der Waals force, the functionalized magnetic cobalt ferrite had a high and stable microplastic removal efficiency and capture capacity. The removal efficiency of microplastics was close to 100%, and the capture capacity was 2.56 g/g. After ten microplastic removal cycles, the removal efficiency reached more than 98%, and the surface contact angle was still greater than 150°.

Mechanistic insight into interactive effect of microplastics and arsenic on growth of rice (Oryza sativa L.) and soil health indicators.

Microplastics (MPs) pollution has recently become a major concern for agroecosystems. The interplay between MPs, and heavy metal(loid)s in the soil can intensify the risks to plant growth and human health. The current study investigated the interactive effects of arsenic (As) and biodegradable and petroleum-based conventional MPs on rice growth, As bioavailability, soil bacterial communities, and soil enzyme activities. As-contaminated soil (5 mg kg-1) was treated with conventional MPs i.e., polystyrene (PS) and polyethylene (PE) and biodegradable MPs i.e., polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) at 0.1 % and 1 % rates. In a pot experiment, rice plants were cultivated in soil co-contaminated with As and MPs. PLA-MPs exhibited significant interactions with As, increasing its bioavailability and impairing rice plant growth by enhancing plant oxidative stress. The results illustrated that T2 treatment (PLA-MPs @ 1 % + As 5 mg kg-1) significantly decreased the root and shoot lengths, root and shoot dry weights as well as the rates of photosynthesis, transpiration, intercellular CO2, and stomatal conductance in rice plants. Biodegradable PLA-MPs @ 1 % resulted in increased uptake of As in rice roots, stems, and leaves by 13.4 %, 38.9 %, and 20.6 %, respectively. In contrast, conventional PE-MPs @ 1 % showed contradictory results with As uptake declined by 2.2 %, 5.1 %, and 9.9 % in rice roots, stem and leaves. Soil enzyme kinetics showed that biodegradable MPs increased the activities of soil catalase, dehydrogenase, and phytase enzymes, whereas both conventional PS and PE-MPs decreased their activities. Moreover, As and PLA-MPs combined stress altered soil bacterial communities by increasing the relative abundance of Protobacteria, Acidobacteria, Chloroflexi, and Firmicutes phyla by 49 %, 29 %, 82 %, and 57 %, respectively. This study provides new insights into MPs-As interactions in soil-plant system and ecological risks associated with their coexistence.

Gelatin-based hydrogels with tunable network structure and mechanical property for promoting osteogenic differentiation.

Osteoarthritis (OA) is a joint disease involving all joint components, including cartilage, calcified cartilage, and subchondral bone. The repair of osteochondral defects remains a significant challenge in orthopedics. Development of new strategies is essential for effective osteochondral injury repair. In this study, gelatin (Gel), polyethylene glycol diglycidyl ether (PEGDGE), hydroxyethyl cellulose (HEC) and chitosan (CS) were used to prepare semi-IPNs and IPNs hydrogels. Mechanical properties of Gel based hydrogels significantly improved with the semi-IPN and IPN structures. Tensile strength ranges from 238.7 KPa to 479.5 KPa, and its compressive strength ranges from 35.6 KPa to 112.7 KPa. Additionally, the stress relaxation rate increased with higher CS concentrations, ranging from 25 % to 35 %. The network structure of Gel-based hydrogels was a key factor in regulating stress relaxation. Viscoelasticity was adjusted by its network structures. Swelling and degradation behaviors of Gel based hydrogels were systematically investigated. Gel based hydrogels had good cytocompatibility. Both semi-IPN and IPN structures Gel based hydrogels could promote cell spreading and osteogenic differentiation. G10HEC1 and G10CS1 hydrogels show promise as candidates for osteochondral tissue regeneration, offering a new strategy for osteochondral tissue engineering.

Multifaceted neuroprotective approach of Trolox in Alzheimer's disease mouse model: targeting Aß pathology, neuroinflammation, oxidative stress, and synaptic dysfunction.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aß1 - 42-induced AD mouse model. Aß1 - 42 5µL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aß, phosphorylated tau (p-tau), and ß-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1ß (IL-1ß), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases.

Umbelliferone alleviates impaired wound healing and skin barrier dysfunction in high glucose-exposed dermal fibroblasts and diabetic skins.

Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. KEY MESSAGES: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration.

Dietary ellagic acid blocks inflammation-associated atherosclerotic plaque formation in cholesterol-fed apoE-deficient mice.

BACKGROUND/OBJECTIVES: Atherosclerosis particularly due to high circulating level of low-density lipoprotein is a major cause of cardiovascular diseases. Ellagic acid is a natural polyphenolic compound rich in pomegranates and berries. Our previous study showed that ellagic acid improved functionality of reverse cholesterol transport in murine model of atherosclerosis. The aim of this study is to investigate whether ellagic acid inhibited inflammation-associated atherosclerotic plaque formation in cholesterol-fed apolipoprotein E (apoE)-knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE-KO mice were fed a cholesterol-rich Paigen diet for 10 weeks to induce severe atherosclerosis. Concurrently, 10 mg/kg ellagic acid was orally administered to the apoE-KO mice. Plaque lesion formation and lipid deposition were examined by staining with hematoxylin and eosin, Sudan IV and oil red O. RESULTS: The plasma leukocyte profile of cholesterol-fed mice was not altered by apoE deficiency. Oral administration of ellagic acid attenuated plaque lesion formation and lipid deposition in the aorta tree of apoE-KO mice. Ellagic acid substantially reduced plasma levels of soluble vascular cell adhesion molecule and interferon-γ in Paigen diet-fed apoE-KO mice. When 10 mg/kg ellagic acid was administered to cholesterol-fed apoE-KO mice, the levels of CD68 and MCP-1 were strongly reduced in aorta vessels. The protein expression level of nitric oxide synthase-2 (NOS2) in the aorta was highly enhanced by supplementation of ellagic acid to apoE-KO mice, but the expression level of heme oxygenase-1 (HO-1) in the aorta was reduced. Furthermore, ellagic acid diminished the increased aorta expression of the inflammatory adhesion molecules in cholesterol-fed apoE-KO mice. The treatment of ellagic acid inhibited the scavenger receptor-B1 expression in the aorta of apoE-KO mice, while the cholesterol efflux-related transporters were not significantly changed. CONCLUSION: These results suggest that ellagic acid may be an atheroprotective compound by attenuating apoE deficiency-induced vascular inflammation and reducing atherosclerotic plaque lesion formation.

An Optimized Liquid Chromatography-Mass Spectrometry Method for Ganglioside Analysis in Cell Lines.

Gangliosides are glycosphingolipids composed of a sialylated glycan head group and a ceramide backbone. These anionic lipids form lipid rafts and play crucial roles in regulating various proteins involved in signal transduction, adhesion, and cell-cell recognition. Neuroblastoma, a pediatric cancer of the sympathetic nervous system, is treated with intensive chemotherapy, radiation, and an antibody targeting the GD2 ganglioside. Gangliosides are critical in neuroblastoma development and serve as therapeutic targets, making it essential to establish a reliable, rapid, and cost-effective method for profiling gangliosides, particularly one capable of isomeric separation of intact species. In this study, liquid chromatography-mass spectrometry (LC-MS) was optimized using standard gangliosides, followed by the optimization of sphingolipid extraction methods from cell lines by comparing Folch and absolute methanol extraction techniques. Percent recovery and the number of identified sphingolipids were used to evaluate the analytical merits of these methods. A standard gangliosides calibration curve demonstrated excellent linearity (R2 = 0.9961-0.9975). The ZIC-HILIC column provided the best separation of ganglioside GD1 isomers with a 25 min runtime. GD1a elutes before GD1b on the ZIC-HILIC column. Absolute methanol yielded better percent recovery (96 ± 7) and identified 121 different sphingolipids, the highest number between the two extraction methods. The optimized method was applied to profile gangliosides in neuroblastoma (COG-N-683), pancreatic cancer (PSN1), breast cancer (MDA-MB-231BR), and brain tumor (CRL-1620) cell lines. The ganglioside profile of the neuroblastoma cell line COG-N-683 showed an inverse relationship between GD1 and GD2. Ceramide, Hex1Cer, GM1, and GM3 were highly abundant in CRL-1620, PSN1, and MDA-MB-231BR, respectively. These results suggest that our method provides a sensitive, reliable, and high-throughput workflow for ganglioside profiling across different cell types.

Effect of glymphatic system function on cognitive function in patients with chronic kidney disease.

Objectives: Studies have recently shown an alteration of the structural connectivity and a dysfunctional glymphatic system in patients with chronic kidney disease (CKD). In this study, we aimed to investigate the effects of the structural connectivity and glymphatic system on the cognitive function of patients with CKD. Methods: We prospectively enrolled patients with CKD and healthy controls. The CKD group was divided into two regarding their cognitive function. All patients received brain magnetic resonance imaging, including diffusion tensor imaging (DTI). We calculated the measures of structural connectivity and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, a neuroimaging marker of the glymphatic system function, and compared the indices between groups. Results: The mean clustering coefficient, local efficiency, and small-worldness index in patients with CKD were lower than those in healthy controls (0.125 ± 0.056 vs. 0.167 ± 0.082, p = 0.008; 1.191 ± 0.183 vs. 1.525 ± 0.651, p = 0.002; 0.090 ± 0.043 vs. 0.143 ± 0.102, p = 0.003; respectively). The DTI-ALPS index was lower in patients with CKD than in healthy controls (1.436 vs. 1.632, p < 0.001). Additionally, the DTI-ALPS index differed significantly between CKD patients with and without cognitive impairment. Notably, this index was lower in patients with CKD and cognitive impairment than in patients without cognitive impairment (1.338 vs. 1.494, p = 0.031). However, there were no differences of the structural connectivity between CKD patients with and without cognitive impairment. Conclusion: We found lower DTI-ALPS index in patients with CKD, which could be related with glymphatic system dysfunction. Moreover, those with cognitive impairment in the CKD group had a lower index than those without, indicating a link between the glymphatic system function and cognitive function.

The association between structural connectivity and anti-seizure medication response in patients with temporal lobe epilepsy.

OBJECTIVES: This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response. METHODS: We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders. RESULTS: We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. -0.007, p = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (-0.001 vs. -0.197, p = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, p < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, p = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (r = -0.267, p = 0.049). SIGNIFICANCE: We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS. PLAIN LANGUAGE SUMMARY: This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patients show altered brain connectivity and glymphatic function compared to healthy individuals. A key finding is the strong link between a specific connectivity measure (assortativity coefficient) and antiseizure medication response, providing valuable insights that could influence epilepsy treatment and future research directions.

Incidence and risk factor analysis of neovascular glaucoma following vitrectomy in patients with proliferative diabetic retinopathy.

To investigate the incidence and risk factors for neovascular glaucoma (NVG) after vitrectomy in patients with proliferative diabetic retinopathy (PDR). Patients were categorized into two subgroups based on their treatment regimen: one group received vitrectomy only (Group 1), while the other received combined phacovitrectomy (Group 2). A comparative analysis was conducted to evaluate the distinguishing characteristics of the two groups. Kaplan-Meier survival analysis was used to determine the incidence of NVG following surgery. Furthermore, multivariate analysis using the Cox proportional hazards model was conducted to identify the risk factors associated with the development of NVG after surgery. A total of 484 eyes of 484 patients were included in the study. When comparing Group 1 with Group 2, a significant difference was observed in the occurrence of NVG. In Group 1, there were 10 cases of NVG (3.9%), whereas 29 cases of NVG occurred in Group 2 (12.71%). Male sex, high preoperative intraocular pressure (IOP), and combined phacovitrectomy were found to be associated with the occurrence of NVG following phacovitrectomy. Higher creatinine levels had a protective effect in preventing the development of NVG. Male sex, high preoperative IOP, and combined phacovitrectomy were associated with a high incidence of NVG. Explore strategies to prevent NVG is important when performing combined phacovitrectomy in patients with PDR.

Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity.

Rotavirus considerably threatens global health, particularly for children <5 years. Current, licensed oral attenuated vaccine formulations have limitations including insufficient efficacy in children in low- and middle-income countries, warranting urgent development of novel vaccines with improved efficacy and safety profiles. Herein, we present a novel approach utilizing an encapsulin (ENC) nanoparticle (NP)-based non-replicating rotavirus vaccine. ENC, originating from bacteria, offers a self-assembling scaffold that displays rotavirus VP8* antigens on its surface. To enhance the correct folding and soluble expression of monomeric antigens and their subsequent assembly into NP, we adopted an RNA-interacting domain (RID) of mammalian transfer RNA synthetase as an expression tag fused to the N-terminus of the ENC-VP8* fusion protein. Using the RID-ENC-VP8* tripartite modular design, insertion of linkers of appropriate length and sequence and the universal T cell epitope P2 remarkably improved the production yield and immunogenicity. Cleavage of the RID rendered a homogenous assembly of ENC-P2-VP8* into protein NPs. Immunization with ENC-P2-VP8* induced markedly higher levels of VP8*-specific antibodies and virus neutralization titers in mice than those induced by P2-VP8* without ENC. Altogether, these results highlight the potential of the designed ENC NP-based rotavirus vaccine as an effective strategy against rotavirus disease to address global health challenges.

Targeting Molecular Signaling Pathways and Cytokine Responses to Modulate c-MYC in Acute Myeloid Leukemia.

Overexpression of the MYC oncogene, encoding c-MYC protein, contributes to the pathogenesis and drug resistance of acute myeloid leukemia (AML) and many other hematopoietic malignancies. Although standard chemotherapy has predominated in AML therapy over the past five decades, the clinical outcomes and patient response to treatment remain suboptimal. Deeper insight into the molecular basis of this disease should facilitate the development of novel therapeutics targeting specific molecules and pathways that are dysregulated in AML, including fms-like tyrosine kinase 3 (FLT3) gene mutation and cluster of differentiation 33 (CD33) protein expression. Elevated expression of c-MYC is one of the molecular features of AML that determines the clinical prognosis in patients. Increased expression of c-MYC is also one of the cytogenetic characteristics of drug resistance in AML. However, direct targeting of c-MYC has been challenging due to its lack of binding sites for small molecules. In this review, we focused on the mechanisms involving the bromodomain and extra-terminal (BET) and cyclin-dependent kinase 9 (CDK9) proteins, phosphoinositide-Akt-mammalian target of rapamycin (PI3K/AKT/mTOR) and Janus kinase-signal transduction and activation of transcription (JAK/STAT) pathways, as well as various inflammatory cytokines, as an indirect means of regulating MYC overexpression in AML. Furthermore, we highlight Food and Drug Administration (FDA)-approved drugs for AML, and the results of preclinical and clinical studies on novel agents that have been or are currently being tested for efficacy and tolerability in AML therapy. Overall, this review summarizes our current knowledge of the molecular processes that promote leukemogenesis, as well as the various agents that intervene in specific pathways and directly or indirectly modulate c-MYC to disrupt AML pathogenesis and drug resistance.

Biportal Endoscopic Transforaminal Lumbar Interbody Fusion: How to Improve Fusion Rate?

BACKGROUND: Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is a minimally invasive surgical technique for treating degenerative lumbar spine conditions. It offers advantages such as reduced soft tissue trauma and lower infection rates, but certain technical aspects may be challenging. The current study aims to identify strategies to enhance the fusion rate in BE-TLIF by addressing these specific challenges. METHODS: A literature review was conducted on techniques to improve fusion rates in BE-TLIF. RESULTS: The review suggests that lateral-based portals supplemented with medial portals allowed for safe insertion of interbody cages with large footprint. Direct visualization of the disc space with a 30° endoscope assisted with better disc space preparation. Facetectomies performed with osteotomes, rather than burrs, ensured maximum retrieval of autologous bone graft. Utilizing bone morphogenetic proteins with sustained release carriers such as hydroxyapatite can be useful to increase fusion rates of BE-TLIF. CONCLUSIONS: To our knowledge, the current literature is the first comprehensive review of strategies to enhance fusion rates in BE-TLIF. The proposed techniques and biological adjuncts are effective means to address key challenges associated with the procedure, and such strategies would potentially shorten the learning curve and improve clinical outcomes. Further clinical studies are required to validate these findings and establish standardized protocols. CLINICAL RELEVANCE: These findings provide practical solutions to overcome common challenges in BE-TLIF. The suggested techniques would reduce the incidence of pseudarthrosis, improve patient outcomes, and ultimately offer a safer and more reliable option for lumbar interbody fusion patients.