Urban people's preferences for life-sustaining treatment or artificial nutrition and hydration in advance decisions.

BACKGROUND: The Patient Right to Autonomy Act (PRAA), implemented in Taiwan in 2019, enables the creation of advance decisions (AD) through advance care planning (ACP). This legal framework allows for the withholding and withdrawal of life-sustaining treatment (LST) or artificial nutrition and hydration (ANH) in situations like irreversible coma, vegetative state, severe dementia, or unbearable pain. This study aims to investigate preferences for LST or ANH across various clinical conditions, variations in participant preferences, and factors influencing these preferences among urban residents. METHODS: Employing a survey of legally structured AD documents and convenience sampling for data collection, individuals were enlisted from Taipei City Hospital, serving as the primary trial and demonstration facility for ACP in Taiwan since the commencement of the PRAA in its inaugural year. The study examined ADs and ACP consultation records, documenting gender, age, welfare entitlement, disease conditions, family caregiving experience, location of ACP consultation, participation of second-degree relatives, and the intention to participate in ACP. RESULTS: Data from 2337 participants were extracted from electronic records. There was high consistency in the willingness to refuse LST and ANH, with significant differences noted between terminal diseases and extremely severe dementia. Additionally, ANH was widely accepted as a time-limited treatment, and there was a prevalent trend of authorizing a health care agent (HCA) to make decisions on behalf of participants. Gender differences were observed, with females more inclined to decline LST and ANH, while males tended towards accepting full or time-limited treatment. Age also played a role, with younger participants more open to treatment and authorizing HCA, and older participants more prone to refusal. CONCLUSION: Diverse preferences in LST and ANH were shaped by the public's current understanding of different clinical states, gender, age, and cultural factors. Our study reveals nuanced end-of-life preferences, evolving ADs, and socio-demographic influences. Further research could explore evolving preferences over time and healthcare professionals' perspectives on LST and ANH decisions for neurological patients..

Multi-needle blow-spinning technique for fabricating collagen nanofibrous nerve guidance conduit with scalable productivity and high performance.

Nerve guidance conduits (NGCs) have been widely accepted as a promising strategy for peripheral nerve regeneration. Fabricating ideal NGCs with good biocompatibility, biodegradability, permeability, appropriate mechanical properties (space maintenance, suturing performance, etc.), and oriented topographic cues is still current research focus. From the perspective of translation, the technique stability and scalability are also an important consideration for industrial production. Recently, blow-spinning technique shows great potentials in nanofibrous scaffolds fabrication, possessing high quality, high fiber production rates, low cost, ease of maintenance, and high reliability. In this study, we proposed for the first time the preparation of a novel NGC via blow-spinning technique to obtain optimized performances and high productivity. A new collagen nanofibrous neuro-tube with the bilayered design was developed, incorporating inner oriented and outer random topographical cues. The bilayer structure enhances the mechanical properties of the conduit in dry and wet, displaying good radial support and suturing performance. The porous nature of the blow-spun collagen membrane enables good nutrient delivery and metabolism. The in vitro and in vivo evaluations indicated the bilayer-structure conduit could promoted Schwann cells growth, neurotrophic factors secretion, and axonal regeneration and motor functional recovery in rat.

External magnetic field non-invasively stimulates spinal cord regeneration in rat via a magnetic-responsive aligned fibrin hydrogel.

Magnetic stimulation is becoming an attractive approach to promote neuroprotection, neurogenesis, axonal regeneration, and functional recovery in both the central nervous system and peripheral nervous system disorders owing to its painless, non-invasive, and deep penetration characteristics. Here, a magnetic-responsive aligned fibrin hydrogel (MAFG) was developed to import and amplify the extrinsic magnetic field (MF) locally to stimulate spinal cord regeneration in combination with the beneficial topographical and biochemical cues of aligned fibrin hydrogel (AFG). Magnetic nanoparticles (MNPs) were embedded uniformly in AFG during electrospinning to endow it magnetic-responsive feature, with saturation magnetization of 21.79 emu g-1. It is found that the MNPs under the MF could enhance cell proliferation and neurotrophin secretion of PC12 cellsin vitro. The MAFG that was implanted into a rat with 2 mm complete transected spinal cord injury (SCI) effectively enhanced neural regeneration and angiogenesis in the lesion area, thus leading to significant recovery of motor function under the MF (MAFG@MF). This study suggests a new multimodal tissue engineering strategy based on multifunctional biomaterials that deliver multimodal regulatory signals with the integration of aligned topography, biochemical cues, and extrinsic MF stimulation for spinal cord regeneration following severe SCI.

Factors Impacting Advance Decision Making and Health Care Agent Appointment among Taiwanese Urban Residents after the Passage of Patient Right to Autonomy Act.

In recent years, advance care planning (ACP) promotion in Taiwan has expanded beyond clinical practice to the broader population. This study aims to investigate people's attitudes toward ACP and to identify factors influencing their signing of advance directives (ADs) and appointment of health care agents (HCAs). METHODS: We identified 2337 ACP participants from consultation records between 2019 and 2020. The relationships among the participants' characteristics, AD completion, and HCA appointment were investigated. RESULTS: Of 2337 cases, 94.1% completed ADs and 87.8% were appointed HCAs. Welfare entitlement (OR = 0.47, p < 0.001), the place ACP progressed (OR = 0.08, p < 0.001), the participation of second-degree relatives (OR = 2.50, p < 0.001), and the intention of not being a family burden (OR = 1.65, p = 0.010) were significantly correlated with AD completion. The probability of appointing HCAs was higher in participants with family caregiving experience (OR = 1.42, p < 0.05), who were single (OR = 1.49, p < 0.05), and who expected a good death with dignity (OR = 1.65, p < 0.01). CONCLUSIONS: Our research shows that adopting ACP discussion in Taiwan is feasible, which encourages ACP conversation and facilitates AD completion. IMPLICATIONS: Male and younger adults may need extra encouragement to discuss ACP matters with their families. LIMITATIONS: due to sampling restrictions, our data were chosen from an urban district to ensure the integrity of the results. Furthermore, interview data could be collected in future research to supplement the quantitative results.

3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of living constructs have been bioprinted for in vitro applications, while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury (SCI) has been relatively overlooked. Herein, living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy. The living nerve-like fibers are comprised of neural stem cells (NSCs) embedded within a designed hydrogel that mimics the extracellular matrix (ECM), assembled into a highly spatial ordered architecture, similar to densely arranged bundles of the nerve fibers. The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model. Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation, angiogenesis, neurogenesis, neural relay formations, and neural circuit remodeling, leading to outstanding functional reconstruction, revealing an evolution process of this living construct after implantation. This effective strategy, based on biomimetic living constructs, opens a new perspective on SCI therapies.

Demographics, employment, and proximity to covid-19 as predictors of preparedness among Taiwanese health social workers.

COVID-19 struck the world violently and cause negative psychological consequences on health professionals. The preparedness of social workers for the pandemic is critical while facing these challenges and pressures. The study aimed to explore what are the roles of demographic, employment, and proximity to Covid-19 in predicting preparedness for the next wave of COVID among social workers in Taiwan. A total of 158 participants were conveniently sampled and multiple regression, univariate analysis, and two-way ANOVA were conducted. The results demonstrated that the demographic and employment variables significantly predicted preparedness, and there were significant differences among demographics on preparedness and an interaction effect between seniority and age. Consequently, middle-aged social workers with junior seniority years may have more difficulties in their preparation for the current situation. The implication of our findings is also discussed.

Active-site cysteine 215 sulfonation targets protein tyrosine phosphatase PTP1B for Cullin1 E3 ligase-mediated degradation.

Reactive oxygen species (ROS), released as byproducts of mitochondrial metabolism or as products of NADPH oxidases and other processes, can directly oxidize the active-site cysteine (Cys) residue of protein tyrosine phosphatases (PTPs) in a mammalian cell. Robust degradation of irreversibly oxidized PTPs is essential for preventing accumulation of these permanently inactive enzymes. However, the mechanism underlying the degradation of these proteins was unknown. In this study, we found that the active-site Cys215 of endogenous PTP1B is sulfonated in H9c2 cardiomyocytes under physiological conditions. The sulfonation of Cys215 led PTP1B to exhibit a conformational change, and drive the subsequent ubiquitination and degradation of this protein. We then discovered that Cullin1, an E3 ligase, interacts with the Cys215-sulfonated PTP1B. The functional impairment of Cullin1 prevented PTP1B from oxidation-dependent ubiquitination and degradation in H9c2 cells. Moreover, delivery of the terminally oxidized PTP1B resulted in proteotoxicity-caused injury in the affected cells. In conclusion, we elucidate how sulfonation of the active-site Cys215 can direct turnover of endogenous PTP1B through the engagement of ubiquitin-proteasome system. These data highlight a novel mechanism that maintains PTP homeostasis in cardiomyocytes with constitutive ROS production.

Advance Care Planning Among Adult Patients and Their End-of-Life Care Preferences.

To explore people's intentions to opt for a good death when planning for their end-of-life care, this study examined the type of end-of-life care preferred by patients receiving advance care planning (ACP) consulting services for five specified clinical and disability conditions and possible factors affecting their decision-making. This cross-sectional study analyzed 1303 hospital patients and 1032 nonhospital patients who attended a clinic providing ACP consulting services. This study revealed the following two results. First, patients who were older, were female, did not have an appointed surrogate decision-maker, and were nonhospital patients had a higher intention of not receiving life-sustaining treatments (LST) or artificial nutrition and hydration (ANH) under the five specified clinical and disability conditions. Second, people who were the least willing to receive LST or ANH under the following conditions (in descending order): permanent vegetative state, severe dementia, irreversible coma, other disease conditions recognized by the central competent authority, and end-of-life stage.

Prompt successful response to a COVID-19 outbreak: Performance of community-based rapid screening station.

An outbreak occurred in Wanhua District of Taipei City. It was traced to a cluster infection originating from a teahouse. To prevent further large-scaled community spread, the Taipei City Government established the first community rapid test screening station. This report describes the station's strategy and performance and key factors that contributed to its operation. The project involves collaboration among various departments of Taipei City Government, including the health, environmental, police, transportation, and fire departments. The station provides rapid screening, polymerase chain reaction (PCR) testing, and immediate isolation and follow-up medical services upon the detection of a positive case. These services are accessible to local residents and are intended to ease hospitals' burdens. In 36 days, a total of 8532 people were tested, and 419 confirmed cases were identified. Over the same period, the weekly number of positive cases in Wanhua District decreased from 356 to 40, and the PCR positive rate decreased from 21.7% to 1.2%. The policy of establishing rapid screening station, contact tracing and mask wearing policy are key strategies for interrupting chains of transmission of COVID-19. This intervention has become a model for preventing the spread of the epidemic and establishing community rapid screening stations in Taiwan.

Blow-Spun Collagen Nanofibrous Spongy Membrane: Preparation and Characterization.

Fibrous biotextiles are very popular structural forms that are widely used in medical products and devices ranging from sutures, bandages, wound dressing, and patches to all kinds of artificial grafts such as ligaments, tendons, blood vessels, heart valves, and tissue engineered scaffolds. Blow-spinning is a recently developed technique that enables the large-scale and efficient production of ultrathin fibers with diameters ranging from micrometer to nanometer. In this study, the blow-spinning process and parameters were optimized to steadily fabricate collagen nanofibers by ejecting a collagen solution with constant airflow with precisely controlled diameter and alignment. Different from the electrospun collagen nanofibrous membrane, the blow-spun one was fluffy and spongy with high porosity. It was observed that the blow-spun collagen membrane could better maintain the fiber structure after chemical crosslinking in comparison with the electrospun membrane crosslinked in the same condition, which probably attributed to the good porosity and permeability of crosslinking agent within the membranes. The in vitro cell culture of Schwann cells on the blow-spun collagen nanofibrous spongy membrane showed its good biocompatibility for cell attachment, growth, and migration into the membrane, implying its potential in biomedical applications. Besides, there is no requirement for electroconductivity of the polymer solution and collector in blow-spinning. In brief, our results indicated that blow-spinning is an accessible and efficient technique to prepare nanofibers of synthetic and natural polymers, which has a great prospect in the large-scale production of biotextile medical devices and tissue engineered scaffolds. Impact statement Solution blow-spinning is a recently developed fiber fabrication technology with efficient and large-scale production. In this study, we successfully prepared collagen nanofibrous membrane with precisely controlled diameter and alignment by blow-spinning. The blow-spun collagen nanofibrous spongy membrane could better maintain the fiber structure after chemical crosslinking, which showed good biocompatibility for cell spreading and migration inward.

Biodegradable aniline-derived electroconductive film for the regulation of neural stem cell fate.

Neural stem cells (NSCs) represent significant potential and promise in the treatment of neurodegenerative diseases and nerve injuries. An efficient methodology or platform that can help in specifically directing the stem cell fate is important and highly desirable for future clinical therapy. In this study, a biodegradable electrical conductive film composed of an oxidative polymerized carboxyl-capped aniline pentamer (CCAP) and ring-opening polymerized tetra poly(d,l-lactide) (4a-PLA) was designed with the addition of the dopant, namely chondroitin sulfate. This conductive film acts as a biological substrate for the exogenous/endogenous electric field transmission in tissue, resulting in the control of NSC fate, as well as improvement in neural tissue regeneration. The results show that CCAP is successfully synthesized and then conjugated onto 4a-PLA to form a network structure with electrical conductivity, cell adhesion capacity, and biodegradability. The neuronal differentiation of NSCs can be induced on 4a-PLAAP, and the neuronal maturation process can be facilitated by the manipulation of the electrical field. This biocompatible and electroactive material can serve as a platform to determine the cell fate of NSCs and be employed in neural regeneration. For future perspectives, its promising performance shows potential in applications, such as electrode-tissue integration interfaces, coatings on neuroprosthetics devices and neural probes, and smart drug delivery system in neurological systems.

Neural tissue engineering: the influence of scaffold surface topography and extracellular matrix microenvironment.

During nervous system development, an extracellular matrix (ECM) plays a pivotal role through surface topography and microenvironment signals in neurons and neurites maturation. Topography and microenvironment signals act as physical and chemical guiding cues, respectively, for neural tissue formation and reconstruction. Imposed surface topography can affect neural stem cells by promoting adhesion, spreading, alignment, morphological changes, and specific gene expression. Therefore, fabrication of a biomimetic construct or scaffold to support neurite outgrowth and axon extension is a crucial and common strategy for neural tissue regeneration. Here, we review recent developments in biomaterials modification for simulating the microenvironment to promote neural cell adhesion and growth. The subtopics include those of potential cellular mechanisms of topographical response, topography on cellular organization and function, contact guidance in neurite outgrowth and axon growth, ECM microenvironment as regulatory cues, as well as challenges and future perspectives of nerve conduits that are now in clinical trials and usage.

[Efficiency of Magnesium Hydroxide Capping and Amendment to Control Phosphorus Release from Sediments].

Eutrophication of freshwater bodies has become a global environmental problem, and phosphorus (P) has been identified as one of the key limiting factors responsible for this eutrophication problem. Reducing internal P release is crucial to the control of the eutrophication of freshwater bodies besides reducing the input of external P. To control sedimentary P release, magnesium hydroxide[Mg(OH)2] was applied as a capping and amendment material in this study. The adsorption performance of phosphate on Mg(OH)2 was investigated in batch mode, and the effect of Mg(OH)2 capping and amendment on the mobilization of P in sediments was studied using sediment incubation experiments. Results showed that Mg(OH)2 exhibited good adsorption performance toward phosphate. The phosphate removal efficiency of Mg(OH)2 increased with increasing adsorbent dosage. The adsorption equilibrium data of phosphate on Mg(OH)2 could be better described by the Freundlich and Dubinin-Radushkevich isotherm models compared to the Langmuir isotherm model. Mg(OH)2 capping and addition both could effectively control the release of reactive soluble P (SRP) from sediments into the overlying water, resulting in a low concentration of SRP in the overlying water under Mg(OH)2 capping and amendment conditions. Mg(OH)2 capping and amendment both could reduce pore water SRP in the uppermost sediment (0-10 mm), which played a key role in the control of the release of SRP from sediments into the overlying water. The as-prepared Mg(OH)2 possessed a much higher phosphate adsorption ability than commercial Mg(OH)2, and the former also had a higher controlling efficiency of sedimentary P release than the latter. In summary, Mg(OH)2 is a promising capping and amendment material for the control of internal phosphorus release in freshwater bodies.

Targeting protein tyrosine phosphatase PTP-PEST (PTPN12) for therapeutic intervention in acute myocardial infarction.

AIMS: The myocardial ischaemia/reperfusion (I/R) injury is almost inevitable since reperfusion is the only established treatment for acute myocardial infarction (AMI). To date there is no effective strategy available for reducing the I/R injury. Our aim was to elucidate the mechanisms underlying myocardial I/R injury and to develop a new strategy for attenuating the damage it causes. METHODS AND RESULTS: Using a mouse model established by ligation of left anterior descending artery, we found an increase in activity of protein tyrosine phosphatases (PTPs) in myocardium during I/R. Treating the I/R-mice with a pan-PTP inhibitor phenyl vinyl sulfone attenuated I/R damage, suggesting PTP activation to be harmful in I/R. Through analysing RNAseq data, we showed PTPs being abundantly expressed in mouse myocardium. By exposing primary cardiomyocytes ablated with specific endogenous PTPs by RNAi to hypoxia/reoxygenation (H/R), we found a role that PTP-PEST (PTPN12) plays to promote cell death under H/R stress. Auranofin, a drug being used in clinical practice for treating rheumatoid arthritis, may target PTP-PEST thus suppressing its activity. We elucidated the molecular basis for Auranofin-induced inactivation of PTP-PEST by structural studies, and then examined its effect on myocardial I/R injury. In the mice receiving Auranofin before reperfusion, myocardial PTP activity was suppressed, leading to restored phosphorylation of PTP-PEST substrates, including ErbB-2 that maintains the survival signalling of the heart. In line with the inhibition of PTP-PEST activity, the Auranofin-treated I/R-mice had smaller infarct size and better cardiac function. CONCLUSIONS: PTP-PEST contributes to part of the damages resulting from myocardial I/R. The drug Auranofin, potentially acting through the PTP-PEST-ErbB-2 signalling axis, reduces myocardial I/R injury. Based on this finding, Auranofin could be used in the development of new treatments that manage I/R injury in patients with AMI.

Fasting but not changes of plasma metabolome during oral glucose tolerance tests improves the diagnosis of severe coronary arterial stenosis.

BACKGROUND: Noninvasive stress tests for the diagnosis of significant coronary arterial stenosis requiring intervention are not perfect. We investigated whether plasma metabolome during the oral glucose tolerance test (OGTT) can improve the diagnosis. METHODS: A total of 117 subjects with positive stress test results who received coronary angiography were recruited. After excluding subjects with a history of myocardial infarction and subjects who did not receive OGTT, the 18 subjects without significant stenosis were selected as controls. Another 18 age- and sex-matched subjects with significant stenosis were selected as cases. Plasma metabolome from samples obtained in fasting, 30 and 120 min after OGTT was measured using liquid chromatography combined with time-of-flight mass spectrometry. RESULTS: We found five metabolites which can identify patients with significant stenosis independent to clinical risk factors, including diabetes, hypertension, hypercholesterolaemia, smoking and history of percutaneous coronary intervention (all P < 0·05). The area under the receiver operating characteristic (AUROC) curve of these metabolites was 0·799-0·818 at fasting and 30 min after OGTT. The addition of metabolites to clinical factors increases the AUROC (0·616, 95%CI 0·429-0·803 for model with clinical factors only; 0·824, 95%CI 0·689-0·959 for model with four metabolites and clinical factors). The changes of plasma metabolite levels during OGTT did not significantly improve the diagnostic performance. CONCLUSIONS: Fasting plasma metabolome, but not change of plasma metabolome during OGTT, can improve the diagnosis of significant stenosis in patients with positive noninvasive stress test results.

Mass spectrometry-based quantitative proteomics for dissecting multiplexed redox cysteine modifications in nitric oxide-protected cardiomyocyte under hypoxia.

AIMS: Distinctive states of redox-dependent cysteine (Cys) modifications are known to regulate signaling homeostasis under various pathophysiological conditions, including myocardial injury or protection in response to ischemic stress. Recent evidence further implicates a dynamic interplay among these modified forms following changes in cellular redox environment. However, a precise delineation of multiplexed Cys modifications in a cellular context remains technically challenging. To this end, we have now developed a mass spectrometry (MS)-based quantitative approach using a set of novel iodoacetyl-based Cys-reactive isobaric tags (irreversible isobaric iodoacetyl Cys-reactive tandem mass tag [iodoTMT]) endowed with unique irreversible Cys-reactivities. RESULTS: We have established a sequential iodoTMT-switch procedure coupled with efficient immunoenrichment and advanced shotgun liquid chromatography-MS/MS analysis. This workflow allows us to differentially quantify the multiple redox-modified forms of a Cys site in the original cellular context. In one single analysis, we have identified over 260 Cys sites showing quantitative differences in multiplexed redox modifications from the total lysates of H9c2 cardiomyocytes experiencing hypoxia in the absence and presence of S-nitrosoglutathione (GSNO), indicative of a distinct pattern of individual susceptibility to S-nitrosylation or S-glutathionylation. Among those most significantly affected are proteins functionally implicated in hypoxic damage from which we showed that GSNO would protect. INNOVATION: We demonstrate for the first time how quantitative analysis of various Cys-redox modifications occurring in biological samples can be performed precisely and simultaneously at proteomic levels. CONCLUSION: We have not only developed a new approach to map global Cys-redoxomic regulation in vivo, but also provided new evidences implicating Cys-redox modifications of key molecules in NO-mediated ischemic cardioprotection.

Systems biology of meridians, acupoints, and chinese herbs in disease.

Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM). They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.