The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation.

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.

Vimentin-mediated buffering of internal integrin ß1 pool increases survival of cells from anoikis.

BACKGROUND: The intermediate filament protein vimentin is widely recognized as a molecular marker of epithelial-to-mesenchymal transition. Although vimentin expression is strongly associated with cancer metastatic potential, the exact role of vimentin in cancer metastasis and the underlying mechanism of its pro-metastatic functions remain unclear. RESULTS: This study revealed that vimentin can enhance integrin ß1 surface expression and induce integrin-dependent clustering of cells, shielding them against anoikis cell death. The increased integrin ß1 surface expression in suspended cells was caused by vimentin-mediated protection of the internal integrin ß1 pool against lysosomal degradation. Additionally, cell detachment was found to induce vimentin Ser38 phosphorylation, allowing the translocation of internal integrin ß1 to the plasma membrane. Furthermore, the use of an inhibitor of p21-activated kinase PAK1, one of the kinases responsible for vimentin Ser38 phosphorylation, significantly reduced cancer metastasis in animal models. CONCLUSIONS: These findings suggest that vimentin can act as an integrin buffer, storing internalized integrin ß1 and releasing it when needed. Overall, this study provides insights regarding the strong correlation between vimentin expression and cancer metastasis and a basis for blocking metastasis using this novel therapeutic mechanism.

Association Between Risk Perceptions of COVID-19, Political Ideology, and Mask-Wearing Behavior After the Outbreak: A Cross-Sectional Survey in South Korea.

Purpose: After the declaration by the World Health Organization signaling the conclusion of the COVID-19 pandemic, most countries lifted mandatory mask-wearing regulations. This study aimed to investigate factors such as risk perception and political ideology associated with continued adherence to mask-wearing among specific populations, particularly when it is no longer deemed necessary. Methods: We conducted a cross-sectional study including a sample of 1001 respondents stratified by sex, age (≥ 18 years), and region from January 31 to February 2, 2023, after the mandatory mask regulation was lifted in South Korea. Multivariate logistic regression models were applied to estimate the relationships between risk perceptions, political ideology, and mask-wearing maintenance, adjusting for factors such as sex, age, occupation, and trust in the government. Results: Our results indicated significant associations between age, self-reported household economic status, political ideology, affective risk perception, and perceived effectiveness of the government's COVID-related measures with indoor mask-wearing. Specifically, liberals were more likely to keep mask-wearing indoors than conservatives (adjusted odds ratio [aOR]: 2.19; 95% confidence interval [CI]: 1.33-3.59); and those who perceived a greater affective risk of COVID-19 (aOR: 2.47; 95% CI: 1.96-3.10), along with those who perceived the government's countermeasures as inadequate, were more inclined to maintain the habit of wearing masks indoors (aOR: 1.90; 95% CI: 1.19-3.03). Conclusion: Our study highlighted the multifaceted factors influencing mask-wearing behavior in the post-COVID-19 era. Even after adjusting for various confounding factors, such as age, sex, and trust in the government, an association remained between affective risk perception, political ideology, and mask-wearing behavior. However, further research for psychological mechanisms is needed to foster a culture of preventive behaviors proportional to the risk of infection.

Overactive bladder and cognitive impairment in middle-aged women: A cross-sectional study.

BACKGROUND: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. MATERIALS AND METHODS: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. RESULTS: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52-2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50-2.65), 2.12 (1.66-2.58), and 1.75 (1.17-2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55-19.44 %] of the relationship between OAB and cognitive impairment. CONCLUSIONS: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.

Relationship between crustacean consumption and serum perfluoroalkyl substances (PFAS): the Korean National Environmental Health Survey (KoNEHS) cycle 4.

Background: Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental toxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, immunotoxicity, and hormone toxicity. PFASs are used in the production of disposable food packages, aircraft and automobile devices, cooking utensils, outdoor gear, furniture and carpets, aqueous film forming foam (AFFF), cables and wires, electronics, and semiconductors. This study aimed to determine the association between crustacean consumption and serum PFASs. Methods: Adult participants (2,993) aged ≥ 19 years were extracted from the 4th cycle data of the Korean National Environmental Health Survey (KoNEHS). Based on the 50th percentile concentrations of serum PFASs, participants were divided into the low-concentration group (LC) and the high-concentration group (HC). General characteristics, dietary factors, coated product usage, and personal care product usage, an independent t-test and χ2 test were analyzed. The odds ratio (OR) of serum PFAS concentration against crustacean consumption was estimated via logistic regression analysis adjusting for general characteristics, dietary factors, coated product usage, and personal care product usage. Results: The OR for the HC of serum PFASs was higher in individuals with ≥once a week crustacean consumption than in those with < once a week crustacean consumption. Estimated ORs were perfluorohexanesulfonic acid 2.15 (95% confidence interval [CI]: 1.53-3.02), perfluorononanoic acid (PFNA) 1.23 (95% CI: 1.07-1.41), and perfluorodecanoic acid (PFDeA) 1.42 (95% CI: 1.17-1.74) in males, and perfluorooctanoic acid 1.48 (95% CI: 1.19-1.84), perfluorooctanesulfonic acid 1.39 (95% CI: 1.27-1.52), PFNA 1.70 (95% CI: 1.29-2.26) and PFDeA 1.43 (95% CI: 1.32-1.54) in females. Conclusions: This study revealed the association between the crustacean consumption and concentrations of serum PFASs in general Korean population.

Identification of novel biomarkers for anti-Toxoplasma gondii IgM detection and the potential application in rapid diagnostic fluorescent tests.

Toxoplasmosis, while often asymptomatic and prevalent as a foodborne disease, poses a considerable mortality risk for immunocompromised individuals during pregnancy. Point-of-care serological tests that detect specific IgG and IgM in patient sera are critical for disease management under limited resources. Despite many efforts to replace the T. gondii total lysate antigens (TLAs) by recombinant antigens (rAgs) in commercial kits, while IgG detection provides significant specificity and sensitivity, IgM detection remains comparatively low in sensitivity. In this study, we attempted to identify novel antigens targeting IgM in early infection, thereby establishing an IgM on-site detection kit. Using two-dimensional gel electrophoresis (2DE) and mouse serum immunoblotting, three novel antigens, including EF1γ, PGKI, and GAP50, were indicated to target T. gondii IgM. However, rAg EF1γ was undetectable by IgM of mice sera in Western blotting verification experiments, and ELISA coated with PGKI did not eliminate cross-reactivity, in contrast to GAP50. Subsequently, the lateral flow reaction employing a strip coated with 0.3 mg/mL purified rAg GAP50 and exhibited remarkable sensitivity compared with the conventional ELISA based on tachyzoite TLA, which successfully identified IgM in mouse sera infected with tachyzoites, ranging from 103 to 104 at 5 dpi and 104 at 7 dpi, respectively. Furthermore, by using standard T. gondii-infected human sera from WHO, the limit of detection (LOD) for the rapid fluorescence immunochromatographic test (FICT) using GAP50 was observed at 0.65 IU (international unit). These findings underline the particular immunoreactivity of GAP50, suggesting its potential as a specific biomarker for increasing the sensitivity of the FICT in IgM detection.

Electromagnetic Interference Shielding Properties of Highly Flexible Poly(styrene-co-butyl acrylate)/PEDOT:PSS Films Fabricated by Latex Technology.

As the use of stretchable electronic devices increases, the importance of flexible electromagnetic interference (EMI) shielding films is emerging. In this study, a highly flexible shielding film was fabricated using poly(styrene-co-butyl acrylate) (p(St-co-BA)) latex as a matrix and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as a conductive filler, and then the mechanical properties and EMI shielding performance of the film were examined. Styrene and butyl acrylate were copolymerized to lower the high glass transition temperature and increase the ductility of brittle polystyrene. The latex blending technique was used to produce a shielding film in which the aqueous filler dispersion was uniformly dispersed in the emulsion polymerized resin. To determine the phase change in the copolymer matrix with temperature, the storage modulus was measured, and a time-temperature superposition master curve was constructed. The drying temperature of water-based copolymer resin suitable for film fabrication was set based on this curve. The glass transition temperature and flexibility of the blends were determined by evaluating the thermomechanical analysis and tensile tests. The EMI shielding effectiveness (SE) of the films was analyzed at frequencies from 50 MHz to 1.5 GHz, covering the VHF and UHF ranges. As the filler content increased, the SE of the blend film increased, but the elongation increased until a certain content and then decreased. The optimal content of PEDOT:PSS that satisfied both the ductility and shielding performance of the film was found to be 10 wt%. In this case, the elongation at break reached 300%, and the SE of a 1.6 mm thick film was about 35 dB. The film developed in this study can be used as an EMI shielding material that requires high flexibility.

Sex-based differences in the association of resistance training levels with the risk of hypertension.

Introduction: Hypertension is a primary risk factor for cardiovascular disease and all-cause mortality. This study investigated sex-based differences in the association between the risk of hypertension and resistance training (RT) levels, including training frequency and period. Methods: We enrolled 162,102 participants from nationwide Korean cohorts. The training period (months) and frequency (per week) of RT were used to investigate the presence of an inverse dose-response relationship between RT levels and the risk of hypertension. Multiple logistic regression models were used to evaluate the risk of hypertension in relation to RT levels. Results: The prevalence of hypertension in the study population was 36.28% in men and 26.94% in women. Performing RT was associated with an 8% reduction in the risk of hypertension in women but not in men. In women, performing RT for 3-4 days/week, compared with not performing RT, reduced the risk of hypertension by 11%, even after adjusting for covariates, including RT time per week and period. However, in men, no significant association was observed between training frequency and the risk of hypertension. We also evaluated the risk of hypertension by simultaneously considering both the RT frequency and period. Performing RT for 3-4 days/week and ≥5 days/week were markedly related to 14 and 11% hypertension risk reduction, respectively, in women who had been performing RT for at least 6 months. Conclusion: Given that no inverse dose-response association was observed between RT frequency and hypertension risk, engaging in RT for 3-4 days/week for at least 6 months is recommended for women. Further longitudinal studies are needed to verify sex-based differences in the antihypertensive effects of regular RT.

Pharmacokinetic evaluation of paclitaxel, albumin-binding paclitaxel, and liposomal-encapsulated albumin-binding paclitaxel upon gastric subserosal administration.

Introduction: Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Results: Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. Conclusion: These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.

Prognostic Factors for Recurrent Rhegmatogenous Retinal Detachment after Silicone Oil Removal.

Purpose: To Investigate the prognostic factors for recurrent rhegmatogenous retinal detachment (RRD) following silicone oil removal. Methods: This retrospective review included 147 consecutive patients with RRD treated with silicone-oil tamponade at a high-volume referral-based tertiary hospital between January 2012 and May 2022. All patients underwent follow-up for a minimum of 6 months after subsequent silicone oil removal. The primary outcome measure was the rate of recurrent retinal detachment following silicone oil removal, and the secondary outcome was best-corrected visual acuity after silicone oil removal. Results: The mean silicone oil tamponade duration was 4.7  5.01 months (range: 1-38 months; median: 3 months), and the recurrent retinal detachment rate after silicone oil removal was 15.6%. Logistic regression analysis revealed that argon endolaser photocoagulation during silicone oil removal (odds ratio [OR]: 0.31;95% confidence interval [CI]: 0.106-0.898; p = 0.031) was associated with a lower rate of anatomical success after silicone oil removal. Demographics, preoperative ocular characteristics, proliferative vitreoretinopathy, previous scleral encircling or buckling, previous retinectomy, concomitant phacoemulsification, duration of silicone-oil tamponade, and gas tamponade after silicone oil removal were not significantly associated with recurrent retinal redetachment r after silicone oil removal. Duration of silicone-oil tamponade (OR: 1.23; 95% CI: 1.07-1.40; p = 0.003) and recurrent retinal detachment after silicone oil removal (OR, 3.40; 95% CI, 1.31-8.82; p = 0.012) were associated with poor visual outcomes after silicone oil removal. Conclusions: Among all factors examined in this study, including the duration of silicone-oil tamponade, laser retinopexy was the only significant prognostic factor for recurrent retinal detachment after silicone oil removal. A longer duration of silicone oil tamponade was associated with worse visual outcomes and a lower rate of visual improvement after silicone oil removal.

Topological Learning Approach to Characterizing Biological Membranes.

Biological membranes play key roles in cellular compartmentalization, structure, and its signaling pathways. At varying temperatures, individual membrane lipids sample from different configurations, a process that frequently leads to higher-order phase behavior and phenomena. Here, we present a persistent homology (PH)-based method for quantifying the structural features of individual and bulk lipids, providing local and contextual information on lipid tail organization. Our method leverages the mathematical machinery of algebraic topology and machine learning to infer temperature-dependent structural information on lipids from static coordinates. To train our model, we generated multiple molecular dynamics trajectories of dipalmitoyl-phosphatidylcholine membranes at varying temperatures. A fingerprint was then constructed for each set of lipid coordinates by PH filtration, in which interaction spheres were grown around the lipid atoms while tracking their intersections. The sphere filtration formed a simplicial complex that captures enduring key topological features of the configuration landscape using homology, yielding persistence data. Following fingerprint extraction for physiologically relevant temperatures, the persistence data were used to train an attention-based neural network for assignment of effective temperature values to selected membrane regions. Our persistence homology-based method captures the local structural effects, via effective temperature, of lipids adjacent to other membrane constituents, e.g., sterols and proteins. This topological learning approach can predict lipid effective temperatures from static coordinates across multiple spatial resolutions. The tool, called MembTDA, can be accessed at https://github.com/hyunp2/Memb-TDA.

Successful Treatment of Refractory or Relapsed Hepatoblastoma With Autologous Hematopoietic Stem Cell Transplantation in Children.

BACKGROUND: The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma. METHODS: We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen. RESULTS: We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy. CONCLUSION: This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.

APACE: AlphaFold2 and advanced computing as a service for accelerated discovery in biophysics.

The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The advent of AI models, such as AlphaFold, is revolutionizing applications that depend on robust protein structure prediction algorithms. To maximize the impact, and ease the usability, of these AI tools we introduce APACE, AlphaFold2 and advanced computing as a service, a computational framework that effectively handles this AI model and its TB-size database to conduct accelerated protein structure prediction analyses in modern supercomputing environments. We deployed APACE in the Delta and Polaris supercomputers and quantified its performance for accurate protein structure predictions using four exemplar proteins: 6AWO, 6OAN, 7MEZ, and 6D6U. Using up to 300 ensembles, distributed across 200 NVIDIA A100 GPUs, we found that APACE is up to two orders of magnitude faster than off-the-self AlphaFold2 implementations, reducing time-to-solution from weeks to minutes. This computational approach may be readily linked with robotics laboratories to automate and accelerate scientific discovery.

Comparison of the transcranial approach and transsphenoidal approach based on the anatomical location of origin in pediatric craniopharyngiomas.

BACKGROUND: Various clinical classifications of craniopharyngiomas (CRPs) have been proposed to suggest optimal surgical planning. We aimed to evaluate the clinical outcomes of pediatric CRPs and the clinical significance of anatomical classification in relation to the diaphragm sellae. METHODS: A retrospective review was conducted on patients under 18 years of age who underwent surgery for CRPs from July 1998 to August 2022. The patients were divided into transcranial approach (TCA), and transsphenoidal approach (TSA) groups, which included microscopic TSA and endoscopic endonasal approach (EEA) groups. EEA has been adopted at our institute since 2011. CRPs were classified by their origin and relationship with the diaphragm sellae. RESULTS: A total of 132 pediatric CRP patients were included in this study, 117 of whom underwent surgery for primary CRP and 15 for recurrent CRP. Among them, 89 (67.4%) underwent TCA, 9 (6.8%) had microscopic TSA, and 34 (25.8%) had EEA. In subdiaphragmatic CRPs with competent diaphragm sellae, TSA tended to yield better outcomes than did TCA in terms of stalk preservation and ophthalmological outcomes. After the introduction of EEA, the proportion of supradiaphragmatic CRPs treated via the TSA increased from 0% to 50% (p < 0.001). Gross total resection (HR=0.194; 95% CI=0.102-0.367, p < 0.001) and adjuvant therapy (HR=0.208; 95% CI=0.048-0.897, p = 0.035) were found to be positive prognostic factors for long-term tumor control. CONCLUSIONS: Over time, with the adoption of EEA at our institute, the impact of anatomical classification on the surgical apprpoach has decreased. Nevertheless, an individualized surgical approach should be employed to improve long-term outcomes and minimize complications for pediatric CRPs.

Neurosurgical treatment of spasticity: a potential return to the cerebellum.

OBJECTIVE: Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders. METHODS: In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity. RESULTS: Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity. CONCLUSIONS: Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.

Surgical Treatment of Ruptured Aneurysms of Lateral Spinal Artery Presenting as Intracranial Subarachnoid Hemorrhage : Case Series and Literature Review.

Lateral spinal artery (LSA) aneurysms are extremely rare lesions that can rupture and cause subarachnoid hemorrhage (SAH) even though the spinal arteries communicate directly with the subarachnoid space. To date, six cases of LSA aneurysms have been reported in the literature. (Table 1) Herein, three such cases are reported. All patients presented to the emergency department with headaches. The patients in the first two cases were confirmed to have SAH and LSA aneurysms on a brain computed tomography (CT) angiography performed at the hospital. Two patients had prior instances of cerebral infarction and coronary disease, respectively, and were undergoing antiplatelet therapy. The antiplatelet medication was halted for 2 weeks and 1 weeks, respectively, while conservative care was provided. Subsequently, a suboccipital craniectomy was performed, followed by aneurysm clipping. Following the surgery, both patients were discharged without any significant neurological deficits. Regarding the third patient, no aneurysm was found on brain CT angiography, and cerebral angiography was performed during the patient's hospital stay. She was hospitalized, where she received medication and conservative care, and was discharged with an improvement in bleeding without neurological symptoms. Subsequently, an LSA aneurysm was identified on a brain CT angiography performed at an outpatient clinic; however, the patient opted for treatment and was transferred to another hospital. LSA aneurysms are difficult to visualize using CT angiography; therefore, careful angiographic studies are required. Surgical clipping is the treatment of choice if the aneurysm is inaccessible by the endovascular treatment.

Nurse-led remote digital support for adults with chronic conditions: A systematic synthesis without meta-analysis.

AIM: The systematic review aims to synthesize the literature examining the effectiveness of nurse-led remote digital support on health outcomes in adults with chronic conditions. BACKGROUND: Adults with chronic diseases have increased rates of mortality and morbidity and use health care resources at a higher intensity than those without chronic conditions-placing strain on the patient, their caregivers and health systems. Nurse-led digital health disease self-management interventions have potential to improve outcomes for patients with chronic conditions by facilitating care in environments other that the hospital setting. DESIGN AND METHODS: We searched PubMed/MEDLINE, Embase, PsycINFO and Cochrane Central databases from inception to 7 December 2022. We included randomized controlled trials assessing the impact of nurse-led remote digital support interventions compared to usual care on health-related outcomes in adults with chronic illness. The Cochrane risk-of-bias tool was used to assess bias in studies. Outcomes were organized into four categories: self-management, clinical outcomes, health care resource use and satisfaction with care. Results are presented narratively based on statistical significance. RESULTS: Forty-four papers pertaining to 40 unique studies were included. Interventions most targeted diabetes (n = 11) and cardiovascular disease (n = 8). Websites (n = 10) and mobile applications (n = 10) were the most used digital modalities. Nurses supported patients either in response to incoming patient health data (n = 14), virtual appointment (n = 8), virtual health education (n = 5) or through a combination of these approaches (n = 13). Positive impacts of nurse-led digital chronic disease support were identified in each outcome category. Mobile applications were the most effective digital modality. CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Results show that nurse-led remote digital support interventions significantly improve self-management capacity, clinical health outcomes, health care resource use and satisfaction with care. Such interventions have potential to support overall health for adults with chronic conditions in their home environments.

One-hit kill: On the inactivation of RNA viruses by ultraviolet (UV)-C-induced genomic damage.

Large scale outbreaks of infectious respiratory disease have repeatedly plagued the globe over the last 100 years. The scope and strength of the outbreaks are getting worse as pathogenic RNA viruses are rapidly evolving and highly evasive to vaccines and anti-viral drugs. Germicidal UV-C is considered as a robust agent to disinfect RNA viruses regardless of their evolution. While genomic damage by UV-C has been known to be associated with viral inactivation, the precise relationship between the damage and inactivation remains unsettled as genomic damage has been analyzed in small areas, typically under 0.5 kb. In this study, we assessed genomic damage by the reduced efficiency of reverse transcription of regions of up to 7.2 kb. Our data seem to indicate that genomic damage was directly proportional to the size of the genome, and a single hit of damage was sufficient for inactivation of RNA viruses. The high efficacy of UV-C is already effectively adopted to inactivate airborne RNA viruses.

Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves' orbitopathy.

Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves' orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1ß to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1ß, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1ß-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.

Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.