Multifactorial drug carrier system bringing both chemical and physical therapeutics to the treatment of tumor heterogeneity.

Tumor heterogeneity and drug resistance have been invincible features of cancer for its complete cure. Despite the advent of immunotherapy, the expansion and diversification of cancer cells evolved even in the absence or presence of drug treatment discourage additional therapeutic interventions. For the eradication of cancer cells, therefore, an 'all-at-once' strategy is required, which exploits both target-selective chemotherapy and non-selective physicotherapy. Multifactorial microcapsules comprising gold nanoparticles (AuNPs) and a self-assembly protein of α-synuclein (αS) were fabricated, in which hydrophobic and hydrophilic drugs could be separately encapsulated by employing lipid-based inverted micelles (IMs). Their combined physico-chemical therapeutic effects were examined since they also contained both membrane-disrupting IMs and heat-generating AuNPs upon irradiation as physicotherapeutic agents. For the optimal enclosure of IMs containing hydrophilic drugs, a porous inner skeleton made of poly(lactic-co-glycolic acid) was introduced, which would play the roles of not only compartmentalizing the internal space but also enhancing proteolytic disintegration of the microcapsules to discharge and stabilize IMs to the outside. In fact, hydrophobic paclitaxel and hydrophilic doxorubicin showed markedly enhanced drug efficacy when delivered in the IM-containing microcapsules exhibiting the 'quantal' release of both drugs into the cells whose integrity could be also affected by the IMs. In addition, the remnants of αS-AuNP microcapsules produced via proteolysis also caused cell death through photothermal effect. The multifactorial microcapsules are therefore considered as a promising anti-cancer drug carrier capable of performing combinatorial selective and non-selective chemical and physical therapies to overcome tumor heterogeneity and drug resistance.

The National Hospice and Palliative Care registry in Korea.

The National Hospice and Palliative Care (NHPC) registry is a nationwide database in Korea that systematically collects information on terminally ill cancer patients receiving inpatient hospice care. From 2018 to 2020, a total of 47,911 patients were enrolled in the NHPC registry from hospitals providing inpatient hospice care. The NHPC database mainly contains the socio-demographic and clinical information of the registered patients. Among these patients, approximately 75% were 60 years or older, and the ratio of males to females was 1:1.41. Lung, liver, colorectal, pancreatic, and gastric cancer made up nearly 90% of the cancer sites among the registered patients. Upon their initial admission to the hospice ward, around 80% of the patients were aware of their terminal illness. About half of the patients had mild pain at the time of the initial admission to the hospice ward, and the duration of hospice care was 14 days (interquartile range, 6-30) in 2019 and 2020. The NHPC registry aims to provide national statistics on inpatient hospice care to assist health policy-making.

Disulfide-Mediated Elongation of Amyloid Fibrils of α-Synuclein For Use in Producing Self-Healing Hydrogel and Dye-Absorbing Aerogel.

Due to their mechanical robustness, biocompatibility, and nanoscale size, amyloid fibrils (AFs) have been considered as a potential nanomaterial for biological applications. Unfortunately, however, AFs are usually not fully extended because of their pre-mature breakage, which hampers their use to generate biocompatible suprastructures, although the amounts of AFs could be amplified via their self-propagation property. Here, we have demonstrated the full extension of AFs of α-synuclein (αS) by introducing a cysteine residue to its C-terminus which prevents the shear-induced fragmentation of AFs via site-directed disulfide bond formation on the exposed surface of AFs. These heat- and cold-resistant elongated AFs were entangled into self-healable hydrogels through a mild disulfide-exchange process in the presence of tris(2-carboxyethyl) phosphine, which subsequently developed into dye-absorbing aerogels upon freeze-drying without collapsing the three-dimensional internal fibrillar network. The resulting αS aerogel with high porosity and increased surface area was shown to be capable of absorbing both hydrophilic and hydrophobic substances. In addition, the aerogel was further engineered with 8-arm polyethylene glycol containing a sulfhydryl group to increase its drug loading capacity and protease susceptibility for drug unloading. The elongated AFs, therefore, have been suggested to play a pivotal component for the development of bio-nano-matrix for diverse biological applications including drug delivery, tissue engineering, and environmental remediation. STATEMENT OF SIGNIFICANCE: Due to accurate protein self-assembly process, α-synuclein forms an amyloid fibril which are the major component of Lewy bodies. In general, α-synuclein amyloid fibrils break under thermal fluctuations as these nanofibrils elongate to reach certain length. In this study, we have demonstrated the full extension of α-synuclein amyloid fibrils by introducing a cysteine residue to its C-terminus by forming site-directed disulfide bonds on the exposed surface of amyloid fibrils for the first time. The resulting elongated amyloid fibrils were mechanically robust and stable. By using elongated amyloid fibrils, we have made self-healable amyloid fibril hydrogel and dye-absorbing aerogel.

Fabrication of a Dual Stimuli-Responsive Assorted Film Comprising Magnetic- and Gold-Nanoparticles with a Self-Assembly Protein of α-Synuclein.

Development of sensing elements for controllable soft materials is crucial to improve their responsiveness toward remotely provided external stimuli. Magnetic nanoparticles (MNPs) and gold nanoparticles (AuNPs) have been coassembled into a flexible free-floating 2D film to produce a shape deformable mobile structure in the presence of magnetic field and light irradiation by employing a self-assembly protein of α-synuclein (αS). αS was demonstrated to be essential for the preparation of a multisensory system because the intrinsically disordered protein led to a complete dispersion of MNPs to an average size of 10 nm in aqueous solution, pH-dependent closely packed single layer adsorption of αS-MNPs, and α-helix-mediated free-floating MNP monolayer film formation upon dissolving the underlying polycarbonate substrate with chloroform. As AuNPs were incorporated into the assorted hybrid film in the presence of MNPs, however, the ß-sheet component became prominent. By placing the assorted film between a spin-coated thin layer of thermoresponsive P(AAc-co-NIPAAm) hydrogel comprising acrylic acid and N-isopropylacrylamide and a passive layer of silicone elastomer, the resulting triply structure exhibited not only magnet-induced locomotion but also shape deformation due to asymmetric contraction of the sandwiching two layers caused by the heat generated by AuNPs upon near IR irradiation. In fact, two adjoining planar layers of another triply structure were shown to form a three-dimensional lotus flower with the light. This multisensory system is suggested to be further functionalized by modifying the αS molecules and incorporating additional nanoparticles to react to diverse stimuli, which would make the system be utilized in the areas of not only soft robotics but also foldable electronics, high-performance sensors/actuators, and medical/wearable applications.

Mediating Effects of Social Support on Depression and Suicidal Ideation in Older Korean Adults With Hypertension Who Live Alone.

BACKGROUND: Older adults who live alone are less physically and emotionally healthy and report higher levels of depression relative to those who do not live alone. Suicide is the most problematic health issue reported by older adults who live alone. In particular, vulnerable older adults who live alone experience difficulty obtaining self-care and medical services; therefore, early detection of depression is difficult, and there are few opportunities to implement suicide prevention strategies in this population. In addition, social support for depression is an important factor affecting illness and economic vulnerability in older adults who live alone. PURPOSE: This study aimed to examine the relationship between depression and suicidal ideation in vulnerable older Korean adults with hypertension and to explore the mediating effect of social support on this relationship. METHODS: The study used a cross-sectional design. Vulnerable older adults who were 65 years old or older with hypertension and who received home visit services from a public health center were invited to participate. The participants completed structured questionnaires, including the 15-item Short-Form Geriatric Depression Scale, 12-item Multidimensional Scale of Perceived Social Support, and 19-item Scale for Suicidal Ideation, and provided information regarding their demographic characteristics, health status, and economic status. Descriptive and correlation analyses were performed to examine the correlations among these variables. The three-step regression analysis method proposed by Baron and Kenny was used to examine the mediating effect of social support. RESULTS: The mean depression, social support, and suicidal ideation scores of participants were 23.64 (± 2.04), 35.94 (± 15.40), and 7.80 (± 7.73), respectively. In addition, depression was negatively correlated with social support (r = -.27) and positively correlated with suicidal ideation (r = .21), whereas social support was negatively correlated with suicidal ideation (r = -.35). Social support mediated the relationship between depression and suicidal ideation (Z = 2.69). CONCLUSIONS: Social support was identified as an important variable for older adults with chronic illness who lived alone. Interventions that include social support hold the potential to reduce depression and suicidal ideation in this population.

Factors Related with Utilizing Hospice Palliative Care Unit among Terminal Cancer Patients in Korea between 2010 and 2014: a Single Institution Study.

BACKGROUND: Establishing and designating specialized hospice palliative care units (HPCUs) has been an important part of national policy to promote hospice palliative care in Korea in the recent decade. However, few studies have sought to identify patterns and barriers for utilizing HPCU over the period of national policy implementation. We aimed to investigate factors related with utilizing HPCU for terminal cancer patients after consultation with a palliative care team (PCT). METHODS: We reviewed medical records for 1,028 terminal cancer patients who were referred to the PCT of the National Cancer Center in 2010 and 2014. We compared the characteristics of the patients who decided to utilize HPCU and those who did not. We also analyzed factors influencing choices for a medical institution and reasons for not selecting an HPCU. RESULTS: The patients' mean age was 61.0 ± 12.2, with lung cancer patients (24.3%) comprising the largest percentage of these patients. The percentage of referred patients who utilized an HPCU was 53.9% in 2014, increasing from 44.6% in 2010. Older age and awareness of terminal illness were found to be positively associated with utilization of an HPCU. The most common reason for not selecting an HPCU was "refusing hospice facility" (34.9%), followed by "near death," "poor accessibility to an HPCU," and "caregiving problems." CONCLUSION: Compared to 2010, HPCU utilization by terminal cancer patients increased in 2014. Improving awareness of terminal condition among patients and family members and earlier discussion of end-of-life care would be important to promote utilization of HPCU.

Knowledge, practices, and perceived barriers regarding cancer pain management among physicians and nurses in Korea: a nationwide multicenter survey.

PURPOSE: Medical professionals' practices and knowledge regarding cancer pain management have often been cited as inadequate. This study aimed to evaluate knowledge, practices and perceived barriers regarding cancer pain management among physicians and nurses in Korea. METHODS: A nationwide questionnaire survey was administered to physicians and nurses involved in the care of cancer patients. Questionnaire items covered pain assessment and documentation practices, knowledge regarding cancer pain management, the perceived barriers to cancer pain control, and processes perceived as the major causes of delay in opioid administration. RESULTS: A total of 333 questionnaires (149 physicians and 284 nurses) were analyzed. Nurses performed pain assessment and documentation more regularly than physicians did. Although physicians had better knowledge of pain management than did nurses, both groups lacked knowledge regarding the side effects and pharmacology of opioids. Physicians working in the palliative care ward and nurses who had received pain management education obtained higher scores on knowledge. Physicians perceived patients' reluctance to take opioids as a barrier to pain control, more so than did nurses, while nurses perceived patients' tendency to under-report of pain as a barrier, more so than did physicians. Physicians and nurses held different perceptions regarding major cause of delay during opioid administration. CONCLUSIONS: There were differences between physicians and nurses in knowledge and practices for cancer pain management. An effective educational strategy for cancer pain management is needed in order to improve medical professionals' knowledge and clinical practices.