Wernicke encephalopathy in a patient with medullary infarctions: a case report.

Wernicke encephalopathy (WE) is an acute life-threatening neurological condition caused by thiamine (vitamin B1) deficiency. Patients with WE often present with a triad of symptoms consisting of ophthalmoplegia, gait ataxia, and mental confusion. If WE is not treated in a timely manner, it can lead to serious complications such as confusion, coma, or death. Although alcohol abuse is the most commonly reported cause of WE, nonalcoholic causes-although rare-do exist. Herein, we present the case of a nonalcoholic woman with medullary infarctions who presented with intractable vomiting. Her clinical state subsequently progressed to include ophthalmoplegia and gait ataxia. A diagnosis of WE was suspected based on her clinical presentation; this was confirmed by brain magnetic resonance imaging (MRI) and the finding of decreased serum thiamine levels. Brain magnetic resonance imaging demonstrated the complete resolution of abnormal hyperintensities during a follow-up visit, 6 months after treatment.

Elasticity of the HIV-1 core facilitates nuclear entry and infection.

HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid. Recent studies have shown that HIV-1 cores enter the nucleus prior to capsid disassembly. Interactions of the viral capsid with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown. Here we show that the HIV-1 core is highly elastic and that this property is linked to nuclear entry and infectivity. Using atomic force microscopy-based approaches, we found that purified wild type cores rapidly returned to their normal conical morphology following a severe compression. Results from independently performed molecular dynamic simulations of the mature HIV-1 capsid also revealed its elastic property. Analysis of four HIV-1 capsid mutants that exhibit impaired nuclear entry revealed that the mutant viral cores are brittle. Adaptation of two of the mutant viruses in cell culture resulted in additional substitutions that restored elasticity and rescued infectivity and nuclear entry. We also show that capsid-targeting compound PF74 and the antiviral drug Lenacepavir reduce core elasticity and block HIV-1 nuclear entry at concentrations that preserve interactions between the viral core and the nuclear envelope. Our results indicate that elasticity is a fundamental property of the HIV-1 core that enables nuclear entry, thereby facilitating infection. These results provide new insights into the role of the capsid in HIV-1 nuclear entry and the antiviral mechanisms of HIV-1 capsid inhibitors.

Geometric evaluation and quantifying dosimetric impact of diverse deformable image registration algorithms on abdomen images with biomechanically modeled deformations.

PURPOSE: Deformable image registration (DIR) has been increasingly used in radiation therapy (RT). The accuracy of DIR algorithms and how it impacts on the RT plan dosimetrically were examined in our study for abdominal sites using biomechanically modeled deformations. METHODS: Five pancreatic cancer patients were enrolled in this study. Following the guidelines of AAPM TG-132, a patient-specific quality assurance (QA) workflow was developed to evaluate DIR for the abdomen using the TG-132 recommended virtual simulation software ImSimQA (Shrewsbury, UK). First, the planning CT was deformed to simulate respiratory motion using the embedded biomechanical model in ImSimQA. Additionally, 5 mm translational motion was added to the stomach, duodenum, and small bowel. The original planning CT and the deformed CT were then imported into Eclipse and MIM to perform DIR. The output displacement vector fields (DVFs) were compared with the ground truth from ImSimQA. Furthermore, the original treatment plan was recalculated on the ground-truth deformed CT and the deformed CT (with Eclipse and MIM DVF). The dose errors were calculated on a voxel-to-voxel basis. RESULTS: Data analysis comparing DVF from Eclipse versus MIM show the average mean DVF magnitude errors of 2.8 ± 1.0  versus 1.1 ± 0.7 mm for stomach and duodenum, 5.2 ± 4.0  versus 2.5 ± 1.0 mm for small bowel, and 4.8 ± 4.1  versus 2.7 ± 1.1 mm for the gross tumor volume (GTV), respectively, across all patients. The mean dose error on stomach+duodenum and small bowel were 2.3 ± 0.6% for Eclipse, and 1.0 ± 0.3% for MIM. As the DIR magnitude error increases, the dose error range increase, for both Eclipse and MIM. CONCLUSION: In our study, an initial assessment was conducted to evaluate the accuracy of DIR and its dosimetric impact on radiotherapy. A patient-specific DIR QA workflow was developed for pancreatic cancer patients. This workflow exhibits promising potential for future implementation as a clinical workflow.

Analysis of Fatty Acid Compositions and Acid Values of Krill Oil Supplementary Products from the Korean Market.

In order to provide the qualitative data for the 20 commercially available krill oil supplementary products ,the levels of omega-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid ( DHA) and eicosapentaenoic acid (EPA),fatty acid compositions, and chemical indices, including acid values , of the supplements , were determined . The acid values ranged from 7.4 to 43 .7 mg of potassium hydroxide (KOH)/ g of oil. The relative percentages of EPA andDHA in the oils ranged from 14.2 to 34.8 % (w/w).Although all 20 krill oil supplements used 100% krill oil as raw material,the fatty acid composition of 4 samples differed from typical krill oil in terms ofthe content of myristic acid (C14:0), palmitic acid (C16:0), palmitoleic acid (C16:1), linoleic acid (C18:2, n-6), and eicosenoic acid (C20:1, n-9). Accordingly, the Ministry of Food and Drug Safety recently standardized linoleic acid (3% orless) and myristic acid (5-13%) as part ofthe fatty acid components of krill oil. This study provides a reference for analyzing the chemical and nutritional properties and evaluating the adulteration of krill oil supplements in theKorean market.

Minimally invasive technique facilitates early extubation after cardiac surgery: a single-center retrospective study.

BACKGROUND: Postoperative time to extubation plays a role in prognosis after heart valve surgery; however, its exact impact has not been clarified. This study compared the postoperative outcomes of minimally invasive surgery and conventional sternotomy, focusing on early extubation and factors influencing prolonged mechanical ventilation. METHODS: Data from 744 patients who underwent heart valve surgery at the Zhejiang Provincial People's Hospital between August 2019 and June 2022 were retrospectively analyzed. The outcomes in patients who underwent conventional median sternotomy (MS) and minimally invasive (MI) video-assisted thoracoscopic surgery were compared using inverse probability of treatment weighting (IPTW) and Kaplan-Meier curves. Clinical data, including surgical data, postoperative cardiac function, postoperative complications, and intensive care monitoring data, were analyzed. RESULTS: After propensity score matching and IPTW, 196 cases of conventional MS were compared with 196 cases of MI video-assisted thoracoscopic surgery. Compared to patients in the conventional MS group, those in the MI video-assisted thoracoscopic surgery group in the matched cohort had a higher early postoperative extubation rate (P < 0.01), reduced incidence of postoperative pleural effusion (P < 0.05), significantly shorter length of stay in the intensive care unit (P < 0.01), shorter overall length of hospital stay (P < 0.01), and lower total cost of hospitalization (P < 0.01). CONCLUSIONS: Successful early tracheal extubation is important for the intensive care management of patients after heart valve surgery. The advantages of MI video-assisted thoracoscopic surgery over conventional MS include significant reductions in the duration of use of mechanical ventilation support, reduced length of intensive care unit stay, reduced total length of hospitalization, and a favorable patient recovery rate.

Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface.

Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.

Leisure-time activities and disability among Chinese community-dwelling oldest old: evidence from the Chinese Longitudinal Healthy Longevity Study.

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

Bullying Involvement and Subtypes of Disabilities: Who is Likely to be Affected by What?

The current study uses latent class analysis (LCA) and binary logistic regression analysis to explore profiles of bullying and how they might be associated with the types of disabilities. LCA was used to determine a categorization of involvement in bullying among youth with various types of disabilities. Binary logistic regression analysis was conducted to explore how profiles of bullying involvement might be associated with types of disabilities. The study uses the 2016 National Survey of Children's Health, a large-scale survey completed on children's health, ages 0-17, in the United States. A total of 139,923 households were screened for eligibility. The study participants consisted of 50,212 caregivers of a child who completed the survey. Findings revealed that among caregivers of children without disabilities, 79.5% reported that their child was uninvolved, and 20.5% reported that their child was a victim of bullying. Children in the developmental disabilities, speech and/or language disorders, and learning disabilities groups, showed significant odds of being in the bullying victim group compared to those without any disabilities. The study did not find that children in any disability groups were likely to be in the perpetrator group.

The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6). However, the molecular mechanism by which the capsid promotes reverse transcription is undefined. Here we show that wild type HIV-1 virions can undergo efficient reverse transcription in vitro in the absence of a membrane-permeabilizing agent. This activity, originally termed "natural endogenous reverse transcription" (NERT), depends on expression of the viral envelope glycoprotein during virus assembly and its incorporation into virions. Truncation of the gp41 cytoplasmic tail markedly reduced NERT activity, suggesting that gp41 licenses the entry of nucleotides into virions. By contrast to reverse transcription in permeabilized virions, NERT required neither the addition of IP6 nor a mature capsid, indicating that an intact viral membrane can substitute for the function of the viral capsid during reverse transcription in vitro. Collectively, these results demonstrate that the viral capsid functions as a nanoscale container for reverse transcription during HIV-1 infection.

Biosensor Based on ZIF-67-HRP and MWCNTs Nanocomposite Modified Glass Carbon Electrode for the Detection of Luteolin in Vegetables.

Luteolin has various pharmacological properties, including anti-inflammatory, antioxidant, and antitumor characteristics. Due to its potential value in drugs and functional foods, it is important to develop an efficient method for detecting luteolin. In this work, the poor selectivity of existing luteolin nonenzymatic sensors was solved by translating the enzyme-catalyzed reaction from bulk solution to the surface of a horseradish peroxidase (HRP) modified electrode through an electrocatalytic oxidation process. Here, we modified the surface of a glassy carbon electrode (GCE) with metal-organic frameworks (MOFs; ZIF-67 here, abbreviated as ZIF), functional nanomaterials, and HRP and finally covered it with Nafion (NF). In this case, luteolin acts as a hydrogen donor, and the electrode acts as a hydrogen acceptor; the oxidation reaction occurs on the electrode surface. The use of ZIF-67 ensured the conformational stability of HRP to ensure the selectivity and anti-interference property, and SDS-dispersed multiwalled carbon nanotubes (MWCNTs) enhanced the electrode conductivity. The use of NF avoids shedding of the electrode material during the testing process. A UV-vis spectrophotometer was used to study the selectivity of luteolin by HRP and the compatibility between HRP and ZIF. The materials were characterized and analyzed by scanning electron microscopy and transmission electron microscopy. Due to the synergistic effect of these nanomaterials, the linear range of NF/ZIF-HRP/MWCNTs-SDS/GCE was 1.0 × 10-2 to 6.0 µM, with detection limits of 25.3 nM (S/N = 3). The biosensor showed long-term stability and reproducibility, with a relative standard deviation of 4.2% for the peak current (n = 5). Finally, the biosensor was successfully used to detect luteolin in carrots, celery, and cauliflower.

IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages.

BACKGROUND: Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown. METHODS: In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified. RESULTS: IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Development of message passing-based graph convolutional networks for classifying cancer pathology reports.

BACKGROUND: Applying graph convolutional networks (GCN) to the classification of free-form natural language texts leveraged by graph-of-words features (TextGCN) was studied and confirmed to be an effective means of describing complex natural language texts. However, the text classification models based on the TextGCN possess weaknesses in terms of memory consumption and model dissemination and distribution. In this paper, we present a fast message passing network (FastMPN), implementing a GCN with message passing architecture that provides versatility and flexibility by allowing trainable node embedding and edge weights, helping the GCN model find the better solution. We applied the FastMPN model to the task of clinical information extraction from cancer pathology reports, extracting the following six properties: main site, subsite, laterality, histology, behavior, and grade. RESULTS: We evaluated the clinical task performance of the FastMPN models in terms of micro- and macro-averaged F1 scores. A comparison was performed with the multi-task convolutional neural network (MT-CNN) model. Results show that the FastMPN model is equivalent to or better than the MT-CNN. CONCLUSIONS: Our implementation revealed that our FastMPN model, which is based on the PyTorch platform, can train a large corpus (667,290 training samples) with 202,373 unique words in less than 3 minutes per epoch using one NVIDIA V100 hardware accelerator. Our experiments demonstrated that using this implementation, the clinical task performance scores of information extraction related to tumors from cancer pathology reports were highly competitive.

Fabrication of thermo-responsive microcapsule pesticide delivery system from maleic anhydride-functionalized cellulose nanocrystals-stabilized pickering emulsion template.

The overuse of pesticides has shown their malpractices. Novel and sustainable formulations have consequently attracted abundant attention but still appear to have drawbacks. Here, we use a maleic anhydride-functionalized cellulose nanocrystals-stabilized Pickering emulsions template to prepare thermo-responsive microcapsules for a pesticide delivery system via radical polymerization with N-isopropyl acrylamide. The microcapsules (MACNCs-g-NIPAM) are characterized by the microscope, SEM, FTIR, XRD, TG-DTG, and DSC techniques. Imidacloprid (IMI) is loaded on MACNCs-g-NIPAM to form smart release systems (IMI@MACNCs-g-NIPAM) with high encapsulation efficiency (~88.49%) and loading capability (~55.02%). The IMI@MACNCs-g-NIPAM present a significant thermo-responsiveness by comparing the release ratios at 35°C and 25°C (76.22% vs 50.78%). It also exhibits advantages in spreadability, retention and flush resistance on the leaf surface compared with the commercial IMI water-dispersible granules (CG). IMI@MACNCs-g-NIPAM also manifest a significant advantage over CG (11.12 mg/L vs 38.90 mg/L for LC50) regarding activity tests of targeted organisms. In addition, IMI@MACNCs-g-NIPAM has shown excellent biocompatibility and low toxicity. All the benefits mentioned above prove the excellent potential of IMI@MACNCs-g-NIPAM as a smart pesticide formulation.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study.

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (ß: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.

Integrative Effects of Transcutaneous Electrical Acustimulation and Autonomic-Endocrine Mechanisms on Postprocedural Recovery in Patients With Endoscopic Retrograde Cholangio-Pancreatography.

OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.

Mitofusin 1 and 2 overexpression reduces AßO-mediated ER stress and apoptosis in N2a APPswe cells.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AßO), which are pathological markers of AD, are known to be highly toxic. AßO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AßO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that  amyloid beta (Aß) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AßO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AßO-mediated ER stress and the pathogenesis of AD.

Single Neuroform Atlas stent: a reliable approach for treating complex wide-neck bifurcated aneurysms.

Background: Treating wide-neck bifurcated cerebral aneurysms (WNBAs) using various techniques and new devices has shown favorable outcomes. However, endovascular coiling can be technically challenging when the aneurysm neck is incorporated into the parent vessel. Furthermore, although recent research has reported favorable outcomes of Neuroform Atlas stent (NAS)-assisted coiling, broad inclusion criteria have hampered precise evaluations of their effectiveness and safety for treating complex WNBAs. Therefore, this study evaluated whether the use of a single NAS is a safe and effective approach for treating complex WNBAs. Methods: We treated 76 complex WNBAs (unruptured, n = 49; ruptured, n = 27) using single NAS-assisted coil embolization and retrospectively analyzed the clinical and angiographic outcomes. Results: In a cohort of 68 patients (mean age, 58.3 ± 11.6 years; males n = 20, 29.4%; females, n = 48, 70.6%), 76 stents were successfully delivered to the target aneurysms, yielding a technical success rate of 98.6%. Complete occlusion was evident in 59 (77.6%) of 76 aneurysms, with neck remnants found in 16 (21.1%) and partial occlusion in 1 (1.3%). Treatment-related morbidities comprised one branch occlusion and one parenchymal hemorrhage. However, no new neurological symptoms of unruptured aneurysms were evident at discharge. The outcomes of 20 of the 27 ruptured aneurysms were favorable (Glasgow Outcome Scale scores of 4 or 5) at the final follow-up assessment (mean 12.2 [6-29] months), except for one initial subarachnoid hemorrhage. Post-treatment angiography revealed complete occlusion in 89.1%, neck remnants in 7.8%, and incomplete occlusion in 3.1% of the aneurysms. Approximately 88.2% of the patients were assessed at least once by follow-up diagnostic or magnetic resonance angiography (mean, 12.5 ± 4.3 [range, 6-29] months), with five (7.8%) minor and two (3.1%) major recurrences. Conclusion: A single NAS is safe and effective for treating WNBAs incorporated into parent vessels.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. PATIENT CONCERNS: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. DIAGNOSES: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. INTERVENTIONS: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. OUTCOMES: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. LESSONS: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

A novel treatment strategy targeting cellular pathways with natural products to alleviate sarcopenia.

Sarcopenia is a condition marked by a significant reduction in muscle mass and strength, primarily due to the aging process, which critically impacts muscle protein dynamics, metabolic functions, and overall physical functionality. This condition leads to increased body fat and reduced daily activity, contributing to severe health issues and a lower quality of life among the elderly. Recognized in the ICD-10-CM only in 2016, sarcopenia lacks definitive treatment options despite its growing prevalence and substantial social and economic implications. Given the aging global population, addressing sarcopenia has become increasingly relevant and necessary. The primary causes include aging, cachexia, diabetes, and nutritional deficiencies, leading to imbalances in protein synthesis and degradation, mitochondrial dysfunction, and hormonal changes. Exercise remains the most effective intervention, but it is often impractical for individuals with limited mobility, and pharmacological options such as anabolic steroids and myostatin inhibitors are not FDA-approved and are still under investigation. This review is crucial as it examines the potential of natural products as a novel treatment strategy for sarcopenia, targeting multiple mechanisms involved in its pathogenesis. By exploring natural products' multi-targeted effects, this study aims to provide innovative and practical solutions for sarcopenia management. Therefore, this review indicates significant improvements in muscle mass and function with the use of specific natural compounds, suggesting promising alternatives for those unable to engage in regular physical activity.