Paeonol Derivative, 6'-Methyl Paeonol, Attenuates Aß-Induced Pathophysiology in Cortical Neurons and in an Alzheimer's Disease Mice Model.

Herbs themselves and various herbal medicines are great resources for discovering therapeutic drugs for various diseases, including Alzheimer's disease (AD), one of the common neurodegenerative diseases. Utilizing mouse primary cortical neurons and DiBAC4(3), a voltage-sensitive indicator, we have set up a drug screening system and identified an herbal extraction compound, paeonol, obtained from Paeonia lactiflora; this compound is able to ameliorate the abnormal depolarization induced by Aß42 oligomers. Our aim was to further find effective paeonol derivatives since paeonol has been previously studied. 6'-Methyl paeonol, one of the six paeonol derivatives surveyed, is able to inhibit the abnormal depolarization induced by Aß oligomers. Furthermore, 6'-methyl paeonol is able to alleviate the NMDA- and AMPA-induced depolarization. When a molecular mechanism was investigated, 6'-methyl paeonol was found to reverse the Aß-induced increase in ERK phosphorylation. At the animal level, mice injected with 6'-methyl paeonol showed little change in their basic physical parameters compared to the control mice. 6'-Methyl paeonol was able to ameliorate the impairment of memory and learning behavior in J20 mice, an AD mouse model, as measured by the Morris water maze. Thus, paeonol derivatives could provide a structural foundation for developing and designing an effective compound with promising clinical benefits.

Improved Symptom Change Enhances Quality of Dying in Patients With Advanced Cancer: An East Asian Cross-Cultural Study.

BACKGROUND: Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death. METHODS: This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores. RESULTS: Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (ß = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores. CONCLUSIONS: Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner.

Glycative Stress, Glycated Hemoglobin, and Atherogenic Dyslipidemia in Patients with Hyperlipidemia.

(1) Background: Diabetes mellitus (DM) is a significant health problem and is associated with dyslipidemia; however, the association between glycative stress, in terms of glycated hemoglobin (HbA1c), and atherogenic dyslipidemia in hyperlipidemic patients with and without DM has rarely been reported. (2) Methods: We prospectively recruited 949 hyperlipidemic patients from the Lipid Clinic of the National Taiwan University Hospital. HbA1c and fasting serum lipids, including total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), small dense LDL-C (sdLDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, and advanced glycation end-products (AGEs), were measured. After fasting for 10-14 h, all subjects except those with DM underwent a standard oral glucose tolerance test (OGTT) with 75 g of glucose loading. All subjects were asked to discontinue the use of lipid-lowering agents for 8 weeks before recruitment. (3) Results: Patients with DM had a higher prevalence of hypertension and higher levels of triglyceride, TC/HDL-C ratio, AGEs, VLDL-C, and sdLDL-C. Among patients with higher HbA1c, the serum VLDL-C, AGEs, and TC/HDL-C ratio were significantly higher than those with lower HbA1c. After adjustment for covariates, multiple logistic regression analyses revealed different groups of dysglycemia with higher HbA1c had a higher odds ratio for TC/HDL-C ≥ 5, sdLDL-C ≥ 75th percentile, VLDL-C ≥ 75th percentile and AGEs ≥ 75th percentile. (4) Conclusions: A higher HbA1c was associated with a significant increase in the risk of atherogenic dyslipidemia and AGEs levels in patients with hyperlipidemia. The findings can be very promising in clinical application.

Sodium thiosulfate through preserving mitochondrial dynamics ameliorates oxidative stress induced renal apoptosis and ferroptosis in 5/6 nephrectomized rats with chronic kidney diseases.

Chronic kidney disease (CKD) progression may be evoked through dysregulated mitochondrial dynamics enhanced oxidative stress and inflammation contributing to high cardiovascular morbidity and mortality. Previous study has demonstrated sodium thiosulfate (STS, Na2S2O3) could effectively attenuate renal oxidative injury in the animal model of renovascular hypertension. We explored whether the potentially therapeutic effect of STS is available on the attenuating CKD injury in thirty-six male Wistar rats with 5/6 nephrectomy. We determined the STS effect on reactive oxygen species (ROS) amount in vitro and in vivo by an ultrasensitive chemiluminescence-amplification method, ED-1 mediated inflammation, Masson's trichrome stained fibrosis, mitochondrial dynamics (fission and fusion) and two types of programmed cell death, apoptosis and ferroptosis by western blot and immunohistochemistry. Our in vitro data showed STS displayed the strongest scavenging ROS activity at the dosage of 0.1 g. We applied STS at 0.1 g/kg intraperitoneally 5 times/week for 4 weeks to these CKD rats. CKD significantly enhanced the degree in arterial blood pressure, urinary protein, BUN, creatinine, blood and kidney ROS amount, leukocytes infiltration, renal 4-HNE expression, fibrosis, dynamin-related protein 1 (Drp1) mediated mitochondrial fission, Bax/c-caspase 9/c-caspase 3/poly (ADP-ribose) polymerase (PARP) mediated apoptosis, iron overload/ferroptosis and the decreased xCT/GPX4 expression and OPA-1 mediated mitochondrial fusion. STS treatment significantly ameliorated oxidative stress, leukocyte infiltration, fibrosis, apoptosis and ferroptosis and improved mitochondrial dynamics and renal dysfunction in CKD rats. Our results suggest that STS as drug repurposing strategy could attenuate CKD injury through the action of anti-mitochondrial fission, anti-inflammation, anti-fibrosis, anti-apoptotic, and anti-ferroptotic mechanisms.

Traveler's knowledge, attitude, and practice about travel health insurance: A community-based questionnaire study.

BACKGROUND: Travel, especially international travel, has become one of the most popular leisure activities in the world. The risk of accidents and travel-related illnesses, including infectious and non-communicable diseases, should not be neglected. To provide a more comprehensive pre-travel consultation to international travelers, this study aimed to investigate the knowledge, attitude, and practice of travelers about travel health insurance. METHODS: This was a cross-sectional study. Anonymous structured questionnaires were distributed to 1000 visitors to the Taiwan International Travel Fair in May 2019. RESULTS: The top three important travel health insurances were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%), and 24-hour emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel health insurances and the willingness of pre-travel consultation. CONCLUSIONS: Most travelers would buy travel health insurance; however, disproportional respondents understood the content of travel health insurance. Most travelers considered travel clinics to be the most reliable information source regarding travel health insurance. Therefore, travel medicine specialists are encouraged to offer more information about travel health insurance during pre-travel consultation.

Association between Wakeup Frequency at Night and Atherogenic Dyslipidemia: Evidence for Sex Differences.

AIM: This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences. METHODS: A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis. RESULTS: A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively. CONCLUSION: A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.

Negative air ions through the action of antioxidation, anti-inflammation, anti-apoptosis and angiogenesis ameliorate lipopolysaccharide induced acute lung injury and promote diabetic wound healing in rat.

Negative air ions (NAIs) being bioactive and negative charged molecules may confer antioxidant and anti-inflammatory activity. We assessed the effect of NAIs on two inflammatory diseases in animal models including lipopolysaccharide (LPS) induced acute lung injury (ALI) and wound healing in diabetic rats. We used intra-tracheal infusion of LPS to induce ALI and made a full-thickness cutaneous wound in streptozotocin-induced diabetic female Wistar rats. We evaluated NAIs effects on reactive oxygen species amount, leukocyte infiltration, wound healing rate, western blot, and immunohistochemistry in the lungs of ALI and skin sections of wounds. Our data found NAIs exposed saline displayed higher antioxidant activity vs. non-exposed saline. NAIs exposure did not significantly affect arterial blood pressure and respiratory frequency in control and LPS treated groups. LPS increased leukocyte infiltration, caspase 3/Poly-ADP-ribose-polymerase-mediated apoptosis formation and decreased Beclin-1/LC3-II-mediated autophagy in lungs. NAIs exposure conferred pulmonary protection by depressed leukocyte infiltration and caspase 3/Poly-ADP-ribose-polymerase mediated apoptosis and enhanced LC3-II-mediated autophagy in LPS induced ALI. NAIs treatment resulted in a significantly accelerated wound closure rate, decreased erythrocyte accumulation and leukocyte infiltration mediated oxidative stress and inflammation, and upregulated expression of skin collagen, vascular endothelial growth factor receptor-2 (VEGFR-2) and factor transforming growth factor-beta 1 (TGF-ß1) vs non-treated group. Based on these results, it is suggested that NAIs conferred a protection through the upregulating LC3-II-dependent autophagy mechanism and downregulating leukocyte infiltration mediated inflammation and caspase 3/Poly-ADP-ribose-polymerase signaling in the LPS-treated ALI and promoted diabetic wound healing through the enhancing skin collagen synthesis, VEGFR-2 and TGF-ß1 pathways.

Telehealth-Based Family Conferences with Implementation of Shared Decision Making Concepts and Humanistic Communication Approach: A Mixed-Methods Prospective Cohort Study.

Smartphone-enabled, telehealth-based family conferences represent an attractive and safe alternative to deliver communication during the COVID-19 pandemic. However, some may fear that the therapeutic relationship might be filtered due to a lack of direct human contact. The study aims to explore whether shared decision-making model combining VALUE (Value family statements, Acknowledge emotions, Listen, Understand the patient as a person, Elicit questions) and PLACE (Prepare with intention, Listen intently and completely, Agree on what matters most, Connect with the patient's story, Explore emotional cues) framework can help physicians respond empathetically to emotional cues and foster human connectedness in a virtual context. Twenty-five virtual family conferences were conducted in a national medical center in Taiwan. The expression of verbal emotional distress was noted in 20% of patients and 20% of family members, while nonverbal distress was observed in 24% and 28%, respectively. On 10-point Likert scale, the satisfaction score was 8.7 ± 1.5 toward overall communication and 9.0 ± 1.1 on meeting the family's needs. Adopting SDM concepts with VALUE and PLACE approaches helps physicians foster connectedness in telehealth family conferences. The model has high participant satisfaction scores and may improve healthcare quality among the pandemic.

Smartphone-Enabled, Telehealth-Based Family Conferences in Palliative Care During the COVID-19 Pandemic: Pilot Observational Study.

BACKGROUND: In the palliative care setting, infection control measures implemented due to COVID-19 have become barriers to end-of-life care discussions (eg, discharge planning and withdrawal of life-sustaining treatments) between patients, their families, and multidisciplinary medical teams. Strict restrictions in terms of visiting hours and the number of visitors have made it difficult to arrange in-person family conferences. Phone-based telehealth consultations may be a solution, but the lack of nonverbal cues may diminish the clinician-patient relationship. In this context, video-based, smartphone-enabled family conferences have become important. OBJECTIVE: We aimed to establish a smartphone-enabled telehealth model for palliative care family conferences. Our model integrates principles from the concept of shared decision making (SDM) and the value, acknowledge, listen, understand, and elicit (VALUE) approach. METHODS: Family conferences comprised three phases designed according to telehealth implementation guidelines-the previsit, during-visit, and postvisit phases. We incorporated the following SDM elements into the model: "team talk," "option talk," and "decision talk." The model has been implemented at a national cancer treatment center in Taiwan since February 2020. RESULTS: From February to April 2020, 14 telehealth family conferences in the palliative care unit were analyzed. The patients' mean age was 73 (SD 10.1) years; 6 out of 14 patients (43%) were female and 12 (86%) were married. The primary caregiver joining the conference virtually comprised mostly of spouses and children (n=10, 71%). The majority of participants were terminally ill patients with cancer (n=13, 93%), with the exception of 1 patient with stroke. Consensus on care goals related to discharge planning and withdrawal of life-sustaining treatments was reached in 93% (n=13) of cases during the family conferences. In total, 5 families rated the family conferences as good or very good (36%), whereas 9 were neutral (64%). CONCLUSIONS: Smartphone-enabled telehealth for palliative care family conferences with SDM and VALUE integration demonstrated high satisfaction for families. In most cases, it was effective in reaching consensus on care decisions. The model may be applied to other countries to promote quality in end-of-life care in the midst of the COVID-19 pandemic.

Correction: Yao, C.A., et al. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide. Nutrients 2016, 8, 192.

The authors wish to make the following correction to their published paper [...].

Shared decision making with oncologists and palliative care specialists effectively increases the documentation of the preferences for do not resuscitate and artificial nutrition and hydration in patients with advanced cancer: a model testing study.

BACKGROUND: Communication in do not resuscitate (DNR) and artificial nutrition and hydration (ANH) at the end of life is a key component of advance care planning (ACP) which is essential for patients with advanced cancer to have cares concordant with their wishes. The SOP model (Shared decision making with Oncologists and Palliative care specialists) aimed to increase the rate of documentation on the preferences for DNR and ANH in patients with advanced cancer. METHODS: The SOP model was implemented in a national cancer treatment center in Taiwan from September 2016 to August 2018 for patients with advanced cancer visiting the oncology outpatient clinic. The framework was based on the model of shared decision making as "choice talk" initiated by oncologists with "option talk" and "decision talk" conducted by palliative care specialists. RESULTS: Among 375 eligible patients, 255 patients (68%) participated in the model testing with the mean age of 68.5 ± 14.7 years (mean ± SD). Comparing to 52.3% of DNR documentation among patients with advanced cancer who died in our hospital, the rate increased to 80.9% (206/255) after the decision talk in our model. Only 6.67% (n = 17) of the participants documented their preferences on ANH after the model. A worse Eastern Cooperative Oncology Group Performance Status was the only statistically significant associating factor with a higher rate of DNR documentation in the multiple logistic regression model. CONCLUSIONS: The SOP model significantly increased the rate of DNR documentation in patients with advanced cancer in this pilot study. Dissemination of the model could help the patients to receive care that is concordant with their wishes and be useful for the countries having laws on ACP.

Treatment with the herbal formulation Eefooton slows the progression of chronic kidney disease: A case report.

RATIONALE: Patients with end-stage kidney disease (ESKD) receiving maintenance dialysis experience an overall burden of physical and emotional symptoms. However, there were limited alternative treatments to dialysis. PATIENT CONCERNS: A 79-year-old woman with chronic kidney disease stage 5 (CKD5) and gout had refused to be on dialysis. She also had hypoglycemia, hypertension, and heart disease. DIAGNOSES: The patient had received the ultrasonography, the renal biopsy and biochemical examinations, confirming the diagnosis of renal impairment, primary hypertension, and chronic nephritic syndrome with unspecified morphologic changes. INTERVENTIONS: She was administered with 20 mL Eefooton (a liquid formula of herbal extracts: Astragalus membranaceus 3 g, Codonopsis pilosula 3 g, Ligustrum lucidum 3 g, Panax quinquefolius 1.3 g, and Rhodiola sacra 1.3 g) orally twice a day for 6 months in addition to her regular medications. OUTCOMES: The patient was followed up for 3 months after the completion of the Eefooton adjuvant treatment. The patient's renal function was improved, and CKD progression was alleviated. After Eefooton treatment, the sizes of both kidneys in the patient increased by 8% while blood urea nitrogen (BUN) and serum creatinine concentrations were decreased. In addition, further reduction in BUN concentration was observed 2 months posttreatment. LESSONS: This case demonstrated that Eefooton has potential therapeutic significance in patients with CKD5 who chose conservative treatment over dialysis.

Gender Differences with Dose⁻Response Relationship between Serum Selenium Levels and Metabolic Syndrome-A Case-Control Study.

Few studies have investigated the association between selenium and metabolic syndrome. This study aimed to explore the associations between the serum selenium level and metabolic syndrome as well as examining each metabolic factor. In this case-control study, the participants were 1165 adults aged ≥40 (65.8 ± 10.0) years. Serum selenium was measured by inductively coupled plasma-mass spectrometry. The associations between serum selenium and metabolic syndrome were examined by multivariate logistic regression analyses. The least square means were computed by general linear models to compare the serum selenium levels in relation to the number of metabolic factors. The mean serum selenium concentration was 96.34 ± 25.90 µg/L, and it was positively correlated with waist circumference, systolic blood pressure, triglycerides, fasting glucose, and homeostatic model assessment insulin resistance (HOMA-IR) in women, but it was only correlated with fasting glucose and HOMA-IR in men. After adjustment, the odds ratios (ORs) of having metabolic syndrome increased with the selenium quartile groups (p for trend: <0.05), especially in women. The study demonstrated that the serum selenium levels were positively associated with metabolic syndrome following a non-linear dose⁻response trend. Selenium concentration was positively associated with insulin resistance in men and women, but it was associated with adiposity and lipid metabolism in women. The mechanism behind this warrants further confirmation.

Ginkgolide A Prevents the Amyloid-ß-Induced Depolarization of Cortical Neurons.

Utilizing the N-methyl-d-aspartate (NMDA) receptor antagonist as a strategy, memantine is the only agent available for clinically treating mild to severe Alzheimer's disease (AD). Our aim was to develop novel similar herb-based drugs. Using a screening platform, ginkgolide A (GA), a pure compound extracted from Ginkgo biloba, was found to attenuate amyloid ß (Aß)-induced abnormal depolarization in mouse primary cortical neurons. Using receptor agonists, it was determined that GA inhibits both NMDA receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Furthermore, the Aß-induced increase in c-Jun N-terminal kinase phosphorylation in neurons was prevented by GA. Body weight, glutamate oxaloacetate transaminase, glutamic-pyruvic transaminase, liver histology, and kidney histology were similar when the wild-type/AD animal model mice with and without GA treatment were compared. This pure compound improves the memory of wild-type mice. Our findings indicate that GA has great potential clinically for the treatment of AD because it might target NMDA receptors just like memantine.

Prevailing Ethical Dilemmas Encountered by Physicians in Terminal Cancer Care Changed After the Enactment of the Natural Death Act: 15 Years' Follow-up Survey.

CONTEXT: Advance directive laws have influences on ethical dilemmas encountered by physicians caring for terminal cancer patients. OBJECTIVES: To identify the prevailing ethical dilemmas among terminal care physicians 15 years after the Natural Death Act was enacted in Taiwan. METHODS: This study is a cross-sectional survey from April 2014 to February 2015 using the clustering sampling method and a well-structured questionnaire. Targeted participants included physicians at oncology and related wards or palliative care units where terminal cancer care may be provided in Taiwan. RESULTS: Among the 500 physicians surveyed, 383 responded (response rate 76.6%) and 346 valid questionnaires were included in the final analysis (effective response rate 69.2%). The most frequently identified ethical dilemma was "place of care," followed by "use of antimicrobial agents" and "artificial nutrition and hydration." The dilemma of "truth telling," which ranked first in the 2005-2006 survey, now ranked at the fourth place. Stepwise logistic regression analysis revealed that female gender and knowledge of palliative care were negatively correlated with the extent of dilemmas regarding issues of "life and death." CONCLUSION: The prevailing ethical dilemmas have changed in Taiwan 15 years after the enactment of the Natural Death Act, supporting that some previous strategies had worked. Our results suggest that education on the core values of palliative care, improvement of community-based hospice care program, and creating treatment guidelines with prognostication may resolve the current dilemmas. This type of survey should be adapted by individual countries to guide policy decisions on end-of-life care.

Association of mSin1 with mTORC2 Ras and Akt reveals a crucial domain on mSin1 involved in Akt phosphorylation.

mSin1 is a unique component within the mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which is responsible for cellular morphology and glucose metabolism. The association between mSin1 and other mTORC2 components, as well as their functions, has been explored previously; nevertheless, the mapping of the various binding domains of the components is lacking. Based on an evolutionary analysis of the gene, we constructed various fragments and truncated-forms of mSin1. We characterized the individual binding sites of mSin1 with its various partners, including mTOR, Rictor, Ras, and Akt. mTOR and Rictor bind to the amino acid (aa) 100-240 region of mSin1, which is different to the Ras binding site, the aa 260-460 region. A reciprocal examination found that mSin1 associated with the aa 2148-2300 region of mTOR, which is within the kinase domain, and with the carboxyl terminus of Rictor. Interestingly, Akt was found to associate with mSin1 in a region that slightly overlapped with the mTOR/Rictor complex binding site, namely aa 220-260. When only the Akt binding site was deleted from mSin1, phosphorylation of Akt S473 was greatly reduced. Furthermore, the association between Akt and mTOR can be regulated by serum, insulin and LY294002, but not by rapamycin or MAPK kinase inhibitors. Taken together, mSin1 would seem to act as a hub that allows mTORC2 to phosphorylate Akt S473. Our findings should facilitate future proteomic and crystallographic studies, help the development of dominant inhibitors and promote the identification of new drug targets.

National Policies Fostering Hospice Care Increased Hospice Utilization and Reduced the Invasiveness of End-of-Life Care for Cancer Patients.

BACKGROUND: In 2011, two national policies aiming to foster hospice services for terminal cancer patients took effect in Taiwan. The single-payer National Health Insurance of Taiwan started to reimburse full hospice services. The national hospital accreditation program, which graded all hospitals, incorporated hospice utilization in its evaluation. We assessed the impact of these national policies. METHODS: A cohort of 249,394 patients aged ≥18 years who died of cancer between 2008 and 2013 were identified from the National Death Registry. We retrieved utilization data of medical services and compared the health care utilization in the final month of life before and after the implementation of the new policies. RESULTS: After the policy changes, hospice utilization increased from 20.8% to 36.2%. In a multivariate analysis adjusting for patient demographics, cancer features, and hospital characteristics, hospice utilization significantly increased after 2011 (adjusted odds ratio [AOR] 2.35, p < .001), accompanied by a decrease in intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV), and cardiopulmonary resuscitation (CPR; AORs 0.87, 0.75, and 0.80, respectively; all p < .001). The patients who received hospice services were significantly less likely to receive ICU admissions, IMV, and CPR (AORs 0.20, 0.12, and 0.10, respectively; all p < .001). Hospice utilization was associated with an adjusted net savings of U.S. $696.90 (25.2%, p < .001) per patient in the final month of life. CONCLUSION: The national policy changes fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients. IMPLICATIONS FOR PRACTICE: National policies fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients.

Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide.

The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids' oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis.

The Changes of Ethical Dilemmas in Palliative Care. A Lesson Learned from Comparison Between 1998 and 2013 in Taiwan.

The current ethical dilemmas met by healthcare professionals were never compared with those 15 years ago when the palliative care system was newly developing in Taiwan. The aim of the study was to investigate the ethical dilemmas met by palliative care physicians and nurses in 2013 and compare the results with the survey in 1998. This cross-sectional study surveyed 213 physicians and nurses recruited from 9 representative palliative care units across Taiwan in 2013. The compared survey in 1998 studied 102 physicians and nurses from the same palliative care units. All participants took a questionnaire to survey the "frequency" and "difficulty" of 20 frequently encountered ethical dilemmas, which were grouped into 4 domains by factor analysis. The "ethical dilemma" scores were calculated and then compared across 15 years by Student's t tests. A general linear model analysis was used to identify significant factors relating to a high average "ethical dilemma" score in each domain. All of the highest-ranking ethical dilemmas in 2013 were related to insufficient resources. Physicians with less clinical experience had a higher average "ethical dilemma" score in clinical management. Physicians with dissatisfaction in providing palliative care were associated a higher average "ethical dilemma" score in communication. Nurses reported higher "ethical dilemma" scores in all items of resource allocation in 2013. Further analysis confirmed that, in 2013, nurses had a higher average "ethical dilemma" score in resource allocation after adjustment for other relating factors. Palliative care nursing staff in Taiwan are more troubled by ethical dilemmas related to insufficient resources than they were 15 years ago. Training of decision making in nurses under the framework of ethical principles and community palliative care programs may improve the problems. To promote the dignity of terminal cancer patients, long-term fundraising plans are recommended for countries in which the palliative care system is in its early stages of development.