The Hippo pathway drives the cellular response to hydrostatic pressure.

Cells need to rapidly and precisely react to multiple mechanical and chemical stimuli in order to ensure precise context-dependent responses. This requires dynamic cellular signalling events that ensure homeostasis and plasticity when needed. A less well-understood process is cellular response to elevated interstitial fluid pressure, where the cell senses and responds to changes in extracellular hydrostatic pressure. Here, using quantitative label-free digital holographic imaging, combined with genome editing, biochemical assays and confocal imaging, we analyse the temporal cellular response to hydrostatic pressure. Upon elevated cyclic hydrostatic pressure, the cell responds by rapid, dramatic and reversible changes in cellular volume. We show that YAP and TAZ, the co-transcriptional regulators of the Hippo signalling pathway, control cell volume and that cells without YAP and TAZ have lower plasma membrane tension. We present direct evidence that YAP/TAZ drive the cellular response to hydrostatic pressure, a process that is at least partly mediated via clathrin-dependent endocytosis. Additionally, upon elevated oscillating hydrostatic pressure, YAP/TAZ are activated and induce TEAD-mediated transcription and expression of cellular components involved in dynamic regulation of cell volume and extracellular matrix. This cellular response confers a feedback loop that allows the cell to robustly respond to changes in interstitial fluid pressure.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

BACKGROUND: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. OBJECTIVE: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). METHODS: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. RESULTS: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. CONCLUSION: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

Caffeine-induced protein kinase A activation restores cognitive deficits induced by sleep deprivation by regulating O-GlcNAc cycling in adult zebrafish.

Sleep deprivation (SD) is widely acknowledged as a significant risk factor for cognitive impairment. In this study, intraperitoneal caffeine administration significantly ameliorated the learning and memory (L/M) deficits induced by SD and reduced aggressive behaviors in adult zebrafish. SD led to a reduction in protein kinase A (PKA) phosphorylation, phosphorylated-cAMP response element-binding protein (p-CREB), and c-Fos expression in zebrafish brain. Notably, these alterations were effectively reversed by caffeine. In addition, caffeine mitigated neuroinflammation induced by SD, as evident from suppression of the SD-mediated increase in glial fibrillary acidic protein (GFAP) and nuclear factor-κB (NF-κB) activation. Caffeine restored normal O-GlcNAcylation and O-GlcNAc transferase (OGT) levels while reversing the increased expression of O-GlcNAcase (OGA) in zebrafish brain after SD. Intriguingly, rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, effectively mitigated cognitive deficits, restored p-CREB and c-Fos levels, and attenuated the increase in GFAP in brain induced by SD. In addition, rolipram reversed the decrease in O-GlcNAcylation and OGT expression as well as elevation of OGA expression following SD. Treatment with H89, a PKA inhibitor, significantly impaired the L/M functions of zebrafish compared with the control group, inducing a decrease in O-GlcNAcylation and OGT expression and, conversely, an increase in OGA expression. The H89-induced changes in O-GlcNAc cycling and L/M dysfunction were effectively reversed by glucosamine treatment. H89 suppressed, whereas caffeine and rolipram promoted O-GlcNAc cycling in Neuro2a cells. Our collective findings underscore the interplay between PKA signaling and O-GlcNAc cycling in the regulation of cognitive function in the brain, offering potential therapeutic targets for cognitive deficits associated with SD.NEW & NOTEWORTHY Our observation highlights the intricate interplay between cAMP/PKA signaling and O-GlcNAc cycling, unveiling a novel mechanism that potentially governs the regulation of learning and memory functions. The dynamic interplay between these two pathways provides a novel and nuanced perspective on the molecular foundation of learning and memory regulation. These insights open avenues for the development of targeted interventions to treat conditions that impact cognitive function, including SD.

Contrast-Enhanced Ultrasound With Perfluorobutane for Hepatocellular Carcinoma Diagnosis: Comparison of Imaging Phases and Diagnostic Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) with perfluorobutane has used varying protocols and diagnostic criteria for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of this article was to assess diagnostic performance for HCC of CEUS with perfluorobutane in high-risk patients using various criteria. METHODS. This retrospective post hoc study evaluating individual patient data from three earlier prospective studies from one hospital included 204 patients (136 men, 68 women; mean age, 63 ± 11 [SD] years) at high risk of HCC with 213 liver observations. Patients underwent CEUS using perfluorobutane from March 2019 to June 2022. Three radiologists (the examination's operator and two subsequent reviewers) independently interpreted examinations, assessing arterial, portal venous (arterial phase completion through 2 minutes), transitional (2-5 minutes after injection), and Kupffer (≥ 10 minutes after injection) phase findings. Six criteria for HCC were tested: 1, any arterial phase hyperenhancement (APHE) with Kupffer phase hypoenhancement; 2, nonrim APHE with Kupffer phase hypoenhancement; 3, nonrim APHE with portal venous washout; 4, nonrim APHE with portal venous washout and/or Kupffer phase hypoenhancement; 5, nonrim APHE with portal venous and/or transitional washout; 6, nonrim APHE with any of portal venous washout, transitional washout, or Kupffer phase hypoenhancement. Depending on the criteria, observations were instead deemed to be a non-HCC malignancy if showing rim APHE, early washout (at < 1 minute), or marked washout (at 2 minutes). Reference was pathology for malignant observations and pathology or imaging follow-up for benign observations. Diagnostic performance was assessed, pooling readers' data. RESULTS. Criterion 1 (no recognized features of non-HCC malignancy) had highest sensitivity (86.9%) but lowest specificity (43.2%) for HCC. Compared with nonrim APHE and portal venous washout (criterion 3), the addition of Kupffer phase hypoenhancement (criterion 4), transitional washout (criterion 5), or either feature (criterion 6) significantly increased sensitivity (34.4% vs 62.6-64.2%) and accuracy (61.8% vs 75.1-76.5%), but significantly decreased specificity (98.5% vs 91.9-94.1%). Criteria 2, 4, 5, and 6 (all incorporating transitional washout and/or Kupffer phase hypoenhancement) showed no significant differences in sensitivity (62.6-64.2%), specificity (91.9-94.1%), or accuracy (75.1-76.5%). CONCLUSION. Recognition of features of non-HCC malignancy improved specificity for HCC. Incorporation of the findings of transitional washout and/or Kupffer phase hypoenhancement improved sensitivity and accuracy, albeit lowered specificity, versus arterial and portal venous findings alone, without further performance variation among criteria incorporating those two findings. CLINICAL IMPACT. Kupffer phase acquisition may be optional for observations classified as HCC or non-HCC malignancy by arterial, portal venous, and transitional phases.

High-level production and purification of bioactive recombinant human activin A in Chinese hamster ovary cells.

Activin A, a member of the TGF-ß superfamily, is a homodimer of the inhibin ßΑ subunit that plays a diversity of roles in biological processes. Because of its multiple functions, significant efforts have been made to produce activin A, however, unsatisfactory results were obtained due to its low level of expression. In this study, a stable CHO cell line exhibiting high expression of rhActivin A was isolated and production of rhActivin A was achieved using the cell line from 11-day fed-batch cultures in a 7.5 L bioreactor. The production rate was 0.22 g/L, substantially higher than those reported in previous studies. The culture supernatant of the bioreactor was used to purify rhActivin A (purity: >99%, recovery rate: 47%). The purified rhActivin A exhibited biological activity, with an EC50 of 3.893 ng/mL and a specific activity of 1.38 × 103 IU/mg. The control of process-related impurities in the purified rhActivin A was successful and met the USP recommendations for use in cell therapy. Thus, our production and purification methods were appropriate for large-scale GMP-grade rhActivin A production, which can be used for various purposes including cell therapy.

Hexosamine biosynthetic pathway and O-GlcNAc cycling of glucose metabolism in brain function and disease.

Impaired brain glucose metabolism is considered a hallmark of brain dysfunction and neurodegeneration. Disruption of the hexosamine biosynthetic pathway (HBP) and subsequent O-linked N-acetylglucosamine (O-GlcNAc) cycling has been identified as an emerging link between altered glucose metabolism and defects in the brain. Myriads of cytosolic and nuclear proteins in the nervous system are modified at serine or threonine residues with a single N-acetylglucosamine (O-GlcNAc) molecule by O-GlcNAc transferase (OGT), which can be removed by ß-N-acetylglucosaminidase (O-GlcNAcase, OGA). Homeostatic regulation of O-GlcNAc cycling is important for the maintenance of normal brain activity. Although significant evidence linking dysregulated HBP metabolism and aberrant O-GlcNAc cycling to induction or progression of neuronal diseases has been obtained, the issue of whether altered O-GlcNAcylation is causal in brain pathogenesis remains uncertain. Elucidation of the specific functions and regulatory mechanisms of individual O-GlcNAcylated neuronal proteins in both normal and diseased states may facilitate the identification of novel therapeutic targets for various neuronal disorders. The information presented in this review highlights the importance of HBP/O-GlcNAcylation in the neuronal system and summarizes the roles and potential mechanisms of O-GlcNAcylated neuronal proteins in maintaining normal brain function and initiation and progression of neurological diseases.

Impact of Treatment on Long-Term Survival of Patients With Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Whether antimicrobial treatment improves long-term survival in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) is unclear. METHODS: We analyzed survival in patients aged ≥18 years who were treated for MAC-PD at a tertiary referral center in South Korea between 1 January 2009 and 31 December 2020. Treatment exposure was divided into 4 time intervals: <6, ≥6 to <12, ≥12 to <18, and ≥18 months. Time-varying multivariable Cox proportional hazards models were used to calculate the all-cause mortality risk in each time interval. The model was adjusted for major clinical factors related to mortality including age, sex, body mass index, presence of cavities, erythrocyte sedimentation rate, positive acid-fast bacilli (AFB) smear, clarithromycin resistance, and comorbid conditions. RESULTS: A total of 486 patients treated for MAC-PD were included in the analysis. A significant inverse correlation was observed between mortality and duration of treatment (P for trend = .007). Long-term treatment (≥18 months) was significantly associated with reduced mortality (adjusted hazard ratio, 0.32 [95% confidence interval, .15-.71]). In subgroup analyses, patients with cavitary lesions (adjusted hazard ratio, 0.17 [95% confidence interval, .05-.57]) or positive AFB smears (0.13 [.02-.84]) at baseline maintained this significant inverse relationship between treatment duration and mortality. CONCLUSIONS: Long-term antimicrobial treatment should be actively considered in patients with progressive MAC-PD, especially in the presence of cavities or positive AFB smears indicative of high mycobacterial burden.

Repeated sleep deprivation decreases the flux into hexosamine biosynthetic pathway/O-GlcNAc cycling and aggravates Alzheimer's disease neuropathology in adult zebrafish.

This study investigated chronic and repeated sleep deprivation (RSD)-induced neuronal changes in hexosamine biosynthetic pathway/O-linked N-acetylglucosamine (HBP/O-GlcNAc) cycling of glucose metabolism and further explored the role of altered O-GlcNAc cycling in promoting neurodegeneration using an adult zebrafish model. RSD-triggered degenerative changes in the brain led to impairment of memory, neuroinflammation and amyloid beta (Aß) accumulation. Metabolite profiling of RSD zebrafish brain revealed a significant decrease in glucose, indicating a potential association between RSD-induced neurodegeneration and dysregulated glucose metabolism. While RSD had no impact on overall O-GlcNAcylation levels in the hippocampus region, changes were observed in two O-GlcNAcylation-regulating enzymes, specifically, a decrease in O-GlcNAc transferase (OGT) and an increase in O-GlcNAcase (OGA). Glucosamine (GlcN) treatment induced an increase in O-GlcNAcylation and recovery of the OGT level that was decreased in the RSD group. In addition, GlcN reversed cognitive impairment by RSD. GlcN reduced neuroinflammation and attenuated Aß accumulation induced by RSD. Repeated treatment of zebrafish with diazo-5-oxo-l-norleucine (DON), an inhibitor of HBP metabolism, resulted in cognitive dysfunction, neuroinflammation and Aß accumulation, similar to the effects of RSD. The pathological changes induced by DON were restored to normal upon treatment with GlcN. Both the SD and DON-treated groups exhibited a common decrease in glutamate and γ-aminobutyric acid compared to the control group. Overexpression of OGT in zebrafish brain rescued RSD-induced neuronal dysfunction and neurodegeneration. RSD induced a decrease in O-GlcNAcylation of amyloid precursor protein and increase in ß-secretase activity, which were reversed by GlcN treatment. Based on the collective findings, we propose that dysregulation of HBP and O-GlcNAc cycling in brain plays a crucial role in RSD-mediated progression of neurodegeneration and Alzheimer's disease pathogenesis. Targeting of this pathway may, therefore, offer an effective regulatory approach for treatment of sleep-associated neurodegenerative disorders.

Risk of fracture according to temporal changes of low body weight changes in adults over 40 years: a nationwide population-based cohort study.

BACKGROUND: Low body weight is associated with an increased risk of fractures. However, the effect of temporal changes in the low body weight status on the risk of fracture remains unknown. This study aimed to evaluate the relationships between temporal changes in low body weight status and the risk of fractures in adults over the age of 40 years. METHODS: This study included data on adults over 40 years old who underwent two biannual consecutive general health examinations between January 1, 2007 and December 31, 2009 extracted from the National Health Insurance Database, a large nationwide population database. Fracture cases in this cohort were monitored from the time of the last health examination to the end of the designated follow-up period (from January 1, 2010 to December 31, 2018) or the participant's death. Fractures were defined as any fracture resulting in hospitalization or outpatient treatment claim after the date of general health screening. The study population was then separated into four groups based on the temporal changes in low body weight status as follows: low body weight to low body weight (L-to-L), low body weight to non-low body weight (L-to-N), non-low body weight to low body weight (N-to-L), and non-low body weight to non-low body weight (N-to-N). The hazard ratios (HRs) for new fractures, depending on weight changes over time, were calculated using Cox proportional hazard analysis. RESULTS: Adults in the L-to-L, N-to-L, and L-to-N groups had a substantially increased risk of fractures after multivariate adjustment (HR, 1.165; 95% confidence interval [CI], 1.113-1.218; HR, 1.193; 95% CI, 1.131-1.259; and HR, 1.114; 95% CI, 1.050-1.183, respectively). Although the adjusted HR was greater in participants who changed into having a low body weight, followed by those with consistently low body weight, those with low body weight remained to have an elevated risk of fracture independent of weight fluctuation. Elderly men (aged over 65 years), high blood pressure, and chronic kidney disease were significantly associated with an increase in fractures (p < 0.05). CONCLUSION: Individuals aged over 40 years with low body weight, even after regaining normal weight, had an increased risk of fracture. Moreover, having a low body weight after having a normal body weight increased the risk of fractures the most, followed by those with consistently low body weight.

Spinal epidural abscess as predicting factor for the necessity of early surgical intervention in patients with pyogenic spondylitis.

BACKGROUND: Pyogenic spondylitis is a condition with low incidence that can lead to neurological sequelae and even life-threatening conditions. While conservative methods, including antibiotics and bracing, are considered the first-line treatment option for pyogenic spondylitis, it is important to identify patients who require early surgical intervention to prevent progressive neurologic deficits or deterioration of the systemic condition. Surgical treatment should be considered in patients with progressive neurologic deficits or deteriorating systemic condition. However, currently, there is a lack of treatment guidelines, particularly with respect to whether surgical treatment is necessary for pyogenic spondylitis. This study aims to analyze the radiological epidural abscess on MRI and clinical factors to predict the need for early surgical intervention in patients with pyogenic spondylitis and provide comprehensive insight into the necessity of early surgical intervention in these patients. METHODS: This study retrospectively reviewed 47 patients with pyogenic spondylitis including spondylodiscitis, vertebral osteomyelitis, epidural abscess, and/or psoas abscess. All patients received plain radiographs, and a gadolinium-enhanced magnetic resonance imaging (MRI) scan. All patients have either tissue biopsies and/or blood cultures for the diagnosis of a pathogen. Demographic data, laboratory tests, and clinical predisposing factors including comorbidities and concurrent other infections were analyzed. RESULTS: We analyzed 47 patients, 25 of whom were female, with a mean age of 70,7 years. MRI revealed that 26 of 47 patients had epidural abscesses. The surgical group had a significantly higher incidence of epidural abscess than the non-surgical group (p = 0.001). In addition, both CRP and initial body temperature (BT) were substantially higher in the surgical group compared to the non-surgical group. There was no significant difference between the surgical group and the non-surgical group in terms of age, gender, comorbidities, and concurrent infectious disorders, as well as the number of affected segments and affected spine levels. However, the surgical group had lengthier hospital stays and received more antibiotics. CONCLUSION: The presence of an epidural abscess on MRI should be regarded crucial in the decision-making process for early surgical treatment in patients with pyogenic spondylitis in order to improve clinical outcomes.

The Impact of Persistent Low Weight Status on the Occurrence of Vertebral Fractures: A Nationwide Population-Based Cohort Study.

BACKGROUND: Although, being underweight is commonly associated with osteoporosis and sarcopenia, its association with vertebral fractures (VFs), is less well researched. We investigated the influence of cumulative, chronic periods of low weight and changes in body weight on VF development. METHODS: We used a nationwide, population-based database with data on people (> 40 years) who attended three health screenings between January 1, 2007, and December 31, 2009 to assess the incidence of new VFs. Cox proportional hazard analyses were used to establish the hazard ratios (HRs) for new VFs based on the degree of body mass index (BMI), the cumulative numbers of underweight participants, and temporal change in weight. RESULTS: Of the 561,779 individuals in this analysis, 5,354 (1.0%) people were diagnosed three times, 3,672 (0.7%) were diagnosed twice, and 6,929 (1.2%) were diagnosed once. The fully adjusted HR for VFs in underweight individuals was 1.213. Underweight individuals diagnosed only once, twice, or three times had an adjusted HR of 0.904, 1.443, and 1.256, respectively. Although the adjusted HR was higher in adults who were consistently underweight, there was no difference in those who experienced a temporal change in body weight. BMI, age, sex, and household income were significantly associated with VF incidence. CONCLUSION: Low weight is a risk factor for VFs in the general population. Given the significant correlation between cumulative periods of low weight and the risk of VFs, it is necessary to treat underweight patients before a VF to prevent its development and other osteoporotic fractures.

Could Natural Products Help in the Control of Obesity? Current Insights and Future Perspectives.

Obesity is a global issue faced by many individuals worldwide. However, no drug has a pronounced effect with few side effects. Green tea, a well-known natural product, shows preventive effects against obesity by decreasing lipogenesis and increasing fat oxidation and antioxidant capacity. In contrast, other natural products are known to contribute to obesity. Relevant articles published on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus. The search was conducted by entering keywords such as "obesity", "natural product", and "clinical trial". The natural products were classified as single compounds, foods, teas, fruits, herbal medicines-single extract, herbal medicines-decoction, and herbal medicines-external preparation. Then, the mechanisms of these medicines were organized into lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis. This review aimed to assess the efficacy and mechanisms of effective natural products in managing obesity. Several clinical studies reported that natural products showed antiobesity effects, including Coffea arabica (coffee), Camellia sinensis (green tea), Caulerpa racemosa (green algae), Allium sativum (garlic), combined Ephedra intermedia Schrenk, Thea sinensis L., and Atractylodes lancea DC extract (known as Gambisan), Ephedra sinica Stapf, Angelica Gigantis Radix, Atractylodis Rhizoma Alba, Coicis semen, Cinnamomi cortex, Paeoniae radix alba, and Glycyrrhiza uralensis (known as Euiiyin-tang formula). Further studies are expected to refine the pharmacological effects of natural products for clinical use.

Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Photo-Curable Lacquer Sap Resin Based on Urushiol-Mimicking, Tyrosine-Containing Additive.

Oriental lacquer sap is attracting considerable attention as a renewable and eco-friendly natural resin with high durability, heat resistance, insulation, insect repellency, and antiseptic and antibacterial properties. However, to ensure excellent coating performance, it is necessary to improve the drying/curing process of lacquer sap with a time-consuming drying time at high humidity [relative humidity (RH), 70-90%] and ambient temperature (20-30 °C). Drawing on an understanding of the polymerization mechanism of urushiol, the main component of the lacquer sap consisted of a water-in-oil (W/O) emulsion, and this study presents an eco-friendly additive that mimics the structure-function of urushiol composed of a polar catechol head group and a nonpolar hydrocarbon tail. A photo-curable lacquer sap was thus developed by adding a tyrosine amino acid-based lipid agent (denoted as Y-ADDA), which allows faster and more effective drying/curing at lower humidity while maintaining the nature-derived properties of lacquer sap. Y-ADDA easily coassembles with urushiol in the W/O emulsion droplets, thereby significantly accelerating the formation of a polymer network along with urushiol during water evaporation leading to fast drying/curing under ultraviolet (UV) light irradiation at low humidity (∼50% RH). The UV-cured lacquer sap resins showed higher performance in terms of film processing and physicochemical properties compared with that of the lacquer containing only tyrosine amino acids without aliphatic tail conjugation, N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-l-tyrosine Fmoc-Tyr(tBu)-OH. Furthermore, the drying and curing times, film morphology, transmittance, hardness, and adhesion strength of the UV-cured lacquer were markedly superior compared to those of shellac, a general eco-friendly fast-drying primer. The study provides useful strategies and insights to promote the industrial application of lacquer sap resins by employing biocompatible nanoagents developed with an understanding of the curing mechanism of natural resins and from the viewpoint of green and sustainable chemistry perspective.

DSCR1 upregulation enhances dural meningeal lymphatic drainage to attenuate amyloid pathology of Alzheimer's disease.

Highly developed meningeal lymphatics remove waste products from the brain. Disruption of meningeal lymphatic vessels in a mouse model of amyloid pathology (5XFAD) accelerates the accumulation of amyloid plaques in the meninges and brain, and causes learning and memory deficits, suggesting that clearance of toxic wastes by lymphatic vessels plays a key role in neurodegenerative diseases. Here, we discovered that DSCR1 (Down syndrome critical region 1, known also as RCAN1, regulator of calcineurin 1) facilitates the drainage of waste products by increasing the coverage of dorsal meningeal lymphatic vessels. Furthermore, upregulation of DSCR1 in 5XFAD mice diminishes Aß pathology in the brain and improves memory defects. Surgical ligation of cervical lymphatic vessels afferent to dcLN blocks the beneficial effects of DSCR1 on Aß accumulation and cognitive function. Interestingly, intracerebroventricular delivery of AAV1-DSCR1 to 5XFAD mice is sufficient to rebuild the meningeal lymphatic system and re-establish cognitive performance. Collectively, our data indicate that DSCR1 facilitates the growth of dorsal meningeal lymphatics to improve drainage efficiency and protect against Alzheimer's disease (AD) pathologies, further highlighting that improving meningeal lymphatic function is a feasible treatment strategy for AD. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Successful delayed delivery of the second twin by evacuating the cord prolapsed first fetus and emergent cerclage: a report of 2 cases.

BACKGROUND: In twin pregnancies, the cord prolapse of either fetus during the pre-viable period leads to fetal death but can also cause an intrauterine infection, leading to death or prematu-re birth of the remaining fetus. However, there are no validated protocols to prolong the gestational period or decrease the morbidity and mortality of the remaining fetus. CASE PRESENTATION: The present cases were PPROM and cord prolapse very early during the second trimester (around 17 weeks in the first case and 19 weeks in the second case). The first fetus was evacuated, and cervical cerclage was performed at 23 and 20 weeks in the two cases, respectively. After maintaining the pregnancy, the second baby was born around 27 and 39 weeks in the first and second cases, respectively. The delivery interval between the first and second fetuses was 46 days in the first case and 126 days in the second case. CONCLUSION: If cord prolapse is identified at a pre-viable time in twin fetuses, evacuation and cerclage should be performed as soon as possible after the cord prolapse to reduce intrauterine infection and increase the survival chances of the remaining fetus.

Women's attitudes toward certification logos, labels, and advertisements for organic disposable sanitary pads: results from a multi-city cross-sectional survey.

BACKGROUND: This cross-sectional study evaluated women's attitudes toward the certification logos, labels, and advertisements for organic disposable sanitary pads (OSPs) and investigated what could be the main reason for them. Additionally, the present study examined whether a relationship could be found between these attitudes and OSPs purchasing behavior. METHODS: This study was conducted using a self-reported online survey of Korean adult women who have purchased OSPs. The study questionnaire had four sections, covering (1) characteristics of OSP purchasing behavior, (2) attitudes toward OSP certification logos, labels, and advertisements, (3) demand on government and companies for proper management, and (4) respondent's sociodemographic information. The Cronbach's alpha value of the questionnaire was 0.857. RESULTS: A total of 500 respondents completed the questionnaire. Overall, high reliability was found for the certification logos (3.73 ± 0.61), labels on the product packaging (3.71 ± 0.63), and advertisements of OSPs (3.41 ± 0.62). Respondents indicated that these had fairly positive effects on their decision-making regarding product reliability, product image, and their own purchasing behavior. The aspects most frequently affected from the informants were safety to human health. All attitudes toward OSP certification logos, labels, and advertisements that were evaluated in this study became more positive in the direction from non-buyers to occasional buyers and to habitual buyers (all P < 0.05). The most significant demand from the respondents for OSP companies and the government was to clearly indicate hazardous ingredients on the OSP packaging (42.0%) and to strengthen the sanctions for false advertising (37.8%), respectively. CONCLUSIONS: The results of this study clearly indicate the importance of using certification logos, labels, and advertisements in the OSP market. These results can be utilized by OSP companies to improve the effectiveness of their marketing strategies or by policy makers and certifying bodies to manage the informants properly in the OSP market.

Effects of preoperative spinopelvic compensation states on the patient-reported outcomes of adult spinal deformity surgery: three-dimensional motion analysis results.

PURPOSE: This study aimed to investigate how preoperative motion analysis results affect the postoperative clinical outcomes of patients undergoing surgery for adult spinal deformity (ASD). METHODS: Patients who underwent surgery for ASD and whose motion analysis results were available were included. All patients underwent preoperative three-dimensional gait analysis using a motion analysis system. Univariate and multivariate regression analyses were performed to determine the predictive parameters of the 12-month postoperative Oswestry Disability Index (ODI). According to the mean anterior pelvic tilt (Ant-PT) angle in the motion analysis, the patients were divided into two groups: small and high Ant-PT angle groups. The 12-month postoperative ODI between the two groups was compared. RESULTS: A total of 111 patients who met the inclusion criteria were enrolled in the study. In the multivariate regression analysis, the preoperative sacral slope and mean Ant-PT angle were significant predictors of the 12-month postoperative ODI (p = 0.013 and p = 0.009, respectively). The high Ant-PT angle group showed a poorer 12-month postoperative ODI than did the small Ant-PT angle group, with a mean ODI of 21.9 ± 8.4 and 16.7 ± 8.5, respectively (p = 0.002). Simple linear regression analysis revealed that the Ant-PT angle was positively correlated with the postoperative sagittal vertical axis in all follow-up periods. CONCLUSION: The study highlights that a high preoperative Ant-PT angle in motion analyses is associated with poor clinical outcomes after surgery for ASD. Therefore, it is necessary to observe and consider the dynamic gait pattern related to the compensatory mechanism for sagittal imbalance in the decision-making process for ASD surgery.

functional mobility tests for evaluation of functionalities in patients with adult spinal deformity.

STUDY DESIGN: Retrospective cohort study. BACKGROUND: Current evaluation of patients with adult spinal deformity (ASD) is mainly based on radiographic parameters derived from X-rays. However, due to their static nature, X-rays fall short of assessing the dynamic functionalities including balance, gait, and the risk of falling. This study aimed to determine the functionalities of ASD patients by measuring functional mobility tests (FMTs) and compared the relationships between patient-reported outcomes (PROs) with FMTs and radiographic parameters to determine whether FMTs are useful evaluation tools for the evaluation of patients with ASD. METHODS: This age- and sex-matched case-control study included 66 patients with ASD and 66 patients with LSS, all of whom were scheduled to undergo spinal surgery. All patients were evaluated with four FMTs including alternate step test (AST), six-meter walk test (SMT), sit-to-stand test (STS), and timed up and go test (TUGT). Correlations of the PROs with FMTs and static radiographic parameters were analyzed. RESULTS: The baseline characteristics were not significantly different between the two groups. However, compared with patients with LSS, those with ASD showed significantly poorer performance on all four FMTs, spending significantly more time performing the SMT, STS, and TUGT (P = 0.046, 0.045, and 0.015, respectively). The results of the four FMTs were significantly correlated with the ODI (Oswestry Disability Index) scores only in the ASD group and not in the LSS group. CONCLUSIONS: FMTs were appropriate tools for assessing the dynamic functionalities of patients with ASD. FMTs might play a bridging role between static radiographic parameters and subjective PROs when treating patients with ASD.

Bias-Repeatability Analysis of Vacuum-Packaged 3-Axis MEMS Gyroscope Using Oven-Controlled System.

The performance of microelectromechanical system (MEMS) inertial measurement units (IMUs) is susceptible to many environmental factors. Among different factors, temperature is one of the most challenging issues. This report reveals the bias stability analysis of an ovenized MEMS gyroscope. A micro-heater and a control system exploiting PID/PWM were used to compensate for the bias stability variations of a commercial MEMS IMU from BOSCH "BMI 088". A micro-heater made of gold (Au) thin film is integrated with the commercial MEMS IMU chip. A custom-designed micro-machined glass platform thermally isolates the MEMS IMU from the ambient environment and is vacuum sealed in the leadless chip carrier (LCC) package. The BMI 088 built-in temperature sensor is used for temperature sensing of the device and the locally integrated heater. The experimental results reveal that the bias repeatability of the devices has been improved significantly to achieve the target specifications, making the commercial devices suitable for navigation. Furthermore, the effect of vacuum-packaged and non-vacuum-packaged devices was compared. It was found that the bias repeatability of vacuum-packaged devices was improved by more than 60%.