Gluten dependent activation of CD4+ T cells by MHC class II-expressing epithelium.

BACKGROUND AND AIMS: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T cell interactions in organoid monolayers expressing human MHC class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. METHODS: Epithelial MHC class II (MHCII) was determined in active and treated CeD, and in non-immunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without IFN-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T cell co-cultures were incubated with gluten, pre-digested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. RESULTS: Active CeD patients and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer-T cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T cell activation markers, and the release of IL-2, IFN-γ, and IL-15 in co-culture supernatants. Gluten metabolized by P. aeruginosa, but not the lasB mutant, enhanced CD4+ T cell proliferation and activation. CONCLUSIONS: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten pre-digestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in CeD patients.

BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex-mismatched model with cGVHD-like manifestations, we first examined B-lymphopenic µMT allo-BMT recipients and found that increased BAFF levels in cGVHD mice were not merely a reflection of B-cell number. Mice that later developed cGVHD had significantly increased numbers of recipient fibroblastic reticular cells with higher BAFF transcript levels. Increased BAFF production by donor cells also likely contributed to cGVHD, because BAFF transcript in CD4+ T cells from diseased mice and patients was increased. cGVHD manifestations in mice were associated with high BAFF/B-cell ratios and persistence of B-cell receptor (BCR)-activated B cells in peripheral blood and lesional tissue. By employing BAFF transgenic (Tg) mice donor cells, we addressed whether high BAFF contributed to BCR activation in cGVHD. BAFF increased NOTCH2 expression on B cells, augmenting BCR responsiveness to surrogate antigen and NOTCH ligand. BAFF Tg B cells had significantly increased protein levels of the proximal BCR signaling molecule SYK, and high SYK protein was maintained by BAFF after in vitro BCR activation or when alloantigen was present in vivo. Using T cell-depleted (BM only) BAFF Tg donors, we found that BAFF promoted cGVHD manifestations, circulating GL7+ B cells, and alloantibody production. We demonstrate that pathologic production of BAFF promotes an altered B-cell compartment and augments BCR responsiveness. Our findings compel studies of therapeutic targeting of BAFF and BCR pathways in patients with cGVHD.

Optimizing the Rydberg EIT spectrum in a thermal vapor.

We present Rydberg-state electromagnetically-induced-transparency (EIT) measurements examining the effects of laser polarization, magnetic fields, laser intensities, and the optical density of the thermal 87Rb medium. Two counter-propagating laser beams with wavelengths of 480 nm and 780 nm were employed to sweep the spectrum across the Rydberg states |33D3/2〉 and |33D5/2〉. An analytic transmission expression well fits the Rydberg-EIT spectra with multiple transitions under different magnetic fields and laser polarization after accounting for the relevant Clebsch-Gordan coefficients, Zeeman splittings, and Doppler shifts. In addition, the high-contrast Rydberg EIT can be optimized with the probe laser intensity and optical density. Rydberg EIT peak height was achieved at 13%, which is more than twice as high as the maximum peak height at room temperature. A quantitative theoretical model is employed to represent the spectra properties and to predict well the optimization conditions. A Rydberg EIT spectrum with high contrast in real time can be served as a quantum sensor to detect the electromagnetic field within an environment.

An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan.

BACKGROUND: Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively. METHODS: We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed. RESULTS: A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level (<4.0 g/dL), and hypercalcemia (serum calcium level > 10.2 mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0 g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension. CONCLUSION: Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment.

Superiority of NBI endoscopy to PET/CT scan in detecting esophageal cancer among head and neck cancer patients: a retrospective cohort analysis.

BACKGROUND: Second primary cancer of the esophagus is frequent in head and neck patients, especially in high-risk populations, and has a great impact on the prognosis. Although Positron emission tomography (PET)/computed tomography (CT) scan is commonly conducted in head and neck patients, its ability to detect early esophageal cancer is limited. Narrow-band imaging endoscopy is an accurate and convenient technique for esophageal examination. We aimed to compare PET/CT scan and narrow-band imaging endoscopy for the detection of esophageal cancer in head and neck cancer patients. METHODS: From November 2015 to November 2018, all head and neck cancer patients who underwent both PET/CT scan and narrow-band imaging endoscopy at Changhua Christian Hospital were retrospectively enrolled. Descriptive statistics, receiver operating characteristic curve analysis, logistic regression analysis, independent Student's t-test, and Kaplan-Meier survival analysis were conducted with MedCalc Statistical Software. RESULTS: A total of 147 subjects were included in the analysis; suspicious esophageal lesions were identified by PET/CT scan in 8 (5.44%) and by narrow-band imaging in 35 (23.81%). The final pathologic diagnoses were esophageal squamous cell carcinoma in 10 and high-grade dysplasia in 5. The respective sensitivity, specificity, and area under the curve for detecting suspicious esophageal lesions were 33.33, 97.73%, and 0.655 for PET/CT scan, and 100.0, 84.85%, and 0.924 for narrow-band imaging endoscopy. Hypopharyngeal or laryngeal location of the primary head and neck cancer was the only risk factor for developing second primary esophageal cancer. CONCLUSIONS: PET/CT scan was inferior to narrow-band imaging endoscopy in detecting second primary esophageal cancer in head and neck cancer patients. In addition to PET/CT scan, narrow-band imaging endoscopy should be considered in head and neck patients at high risk for developing second primary esophageal cancer.

Patients' preferences and factors influencing initial advance care planning discussions' timing: A cross-cultural mixed-methods study.

BACKGROUND: Although advance care planning discussions are increasingly accepted worldwide, their ideal timing is uncertain and cultural factors may pertain. AIM: To evaluate timing and factors affecting initiation of advance care planning discussions for adult patients in Japan and Taiwan. DESIGN: Mixed-methods questionnaire survey to quantitatively determine percentages of patients willing to initiate advance care planning discussions at four stages of illness trajectory ranging from healthy to undeniably ill, and to identify qualitative perceptions underlying preferred timing. SETTING/PARTICIPANTS: Patients aged 40-75 years visiting outpatient departments at four Japanese and two Taiwanese hospitals were randomly recruited. RESULTS: Overall (of 700 respondents), 72% (of 365) in Japan and 84% (of 335) in Taiwan (p < 0.001) accepted discussion before illness. In Japan, factors associated with willingness before illness were younger age and rejection of life-sustaining treatments; in Taiwan, older age, stronger social support, and rejection of life-sustaining treatments. Four main categories of attitudes were extracted: the most common welcomed discussion as a wise precaution, responses in this first category outnumbered preference for postponement of discussion until imminent end of life, acceptance of the universal inevitability of death, and preference for discussion at healthcare providers' initiative. CONCLUSION: The majority of patients are willing to begin discussion before their health is severely compromised; about one out of five patients are unwilling to begin until clearly facing death. To promote advance care planning, healthcare providers must be mindful of patients' preferences and factors associated with acceptance and reluctance to initiate advance care planning.

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD.

B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we found that BCR-NOTCH activation significantly increased the proximal BCR adapter protein BLNK. BCR-NOTCH activation also enabled persistent NOTCH2 surface expression, suggesting a positive feedback loop. Specific NOTCH2 blockade eliminated NOTCH-BCR activation and significantly altered NOTCH downstream targets and B-cell maturation/effector molecules. Examination of the molecular underpinnings of this "NOTCH2-BCR axis" in cGVHD revealed imbalanced expression of the transcription factors IRF4 and IRF8, each critical to B-cell differentiation and fate. All-trans retinoic acid (ATRA) increased IRF4 expression, restored the IRF4-to-IRF8 ratio, abrogated BCR-NOTCH hyperactivation, and reduced NOTCH2 expression in cGVHD B cells without compromising viability. ATRA-treated cGVHD B cells had elevated TLR9 and PAX5, but not BLIMP1 (a gene-expression pattern associated with mature follicular B cells) and also attained increased cytosine guanine dinucleotide responsiveness. Together, we reveal a mechanistic link between NOTCH2 activation and robust BCR responses to otherwise suboptimal amounts of surrogate antigen. Our findings suggest that peripheral B cells in cGVHD patients can be pharmacologically directed from hyperactivation toward maturity.

What influences patients' decisions regarding palliative care in advance care planning discussions? Perspectives from a qualitative study conducted with advanced cancer patients, families and healthcare professionals.

BACKGROUND: The concept of advance care planning is largely derived from Western countries. However, the decision-making process and drivers for choosing palliative care in non-Western cultures have received little attention. AIM: To explore the decision-making processes and drivers of receiving palliative care in advance care planning discussions from perspectives of advanced cancer patients, families and healthcare professionals in northern Taiwan. METHOD: Semi-structured qualitative interviews with advanced cancer patients, their families and healthcare professionals independently from inpatient oncology and hospice units. Thematic analysis with analytical rigour enhanced by dual coding and exploration of divergent views. RESULTS: Forty-five participants were interviewed (n = 15 from each group). Three main decision-making trajectories were identified: (1) 'choose palliative care' was associated with patients' desire to reduce physical suffering from treatments, avoid being a burden to families and society, reduce futile treatments and donate organs to help others; (2) 'decline palliative care' was associated with patients weighing up perceived benefits to others as more important than benefits for themselves; and (3) 'no opportunity to choose palliative care' was associated with lack of opportunities to discuss potential benefits of palliative care, lack of staff skill in end-of-life communication, and cultural factors, notably filial piety. CONCLUSION: Choice for palliative care among advanced cancer patients in Taiwan is influenced by three decision-making trajectories. Opinions from families are highly influential, and patients often lack information on palliative care options. Strategies to facilitate decision-making require staff confidence in end-of-life discussions, working with the patients and their family while respecting the influence of filial piety.

The Power Law of Learning in Transumbilical Single-Port Laparoscopic Subtotal Hysterectomy.

STUDY OBJECTIVE: To analyze the surgical outcomes and learning curve of transumbilical single-port laparoscopic subtotal hysterectomy, which requires sutures of the cervical stump. DESIGN: A prospective observational study (Canadian Task Force classification II-2). SETTING: A university-affiliated center. PATIENTS: From the first (July 2012) and consecutive patients of benign uterine disease scheduled for subtotal hysterectomy until October 2013. INTERVENTIONS: All single-port laparoscopies were performed using straight instruments by 1 gynecologist. An ancillary port was added whenever technical difficulties could endanger surgical quality. MEASUREMENT AND MAIN RESULTS: Seventy-five patients were recruited for intention-to-treat analysis with a mean (±SD) age of 44.7 ± 3.8 years and a body mass index of 24.2 ± 3.7 kg/m2. No major complication was noted. The mean uterine weight was 432.5 ± 344.0 g with 24 (32%) uteri ≧500 g. The patients' sequential order, or gradually increasing experience, was the determining factor in progressively decreasing operative time. Furthermore, most cases that required an additional ancillary port (67%) were clustered in the first 20 cases, whereas 4 were scattered after the 47th patient because of severe pelvic adhesion. The mean operative time decreased in the power law function of the patients' sequential order with a plateau achieved at the 20th patient. CONCLUSION: The patients' sequential order was identified as an independent factor of achieving purely single-port access, and the trend of decreasing operative time delineated the existence of a learning curve. Approximately 20 patients were needed for an experienced multiport laparoscopist to reach technical competency in the current series.

[Nursing Care of Patients With Carotid Artery Stenosis Who Receive Carotid Artery Stent].

Atherosclerosis, a major cause of carotid artery stenosis, has a high correlation to stroke, which may induce transient ischemic attack (TIA) and/or permanent brain damage. The main treatment of carotid artery stenosis includes medication, carotid endarterectomy (CEA), and carotid artery stenting (CAS). However, when artery stenosis becomes severe, CEA or CAS is the most-often recommended intervention. CAS, a type of revascularization, is considered less invasive than CEA and is associated with a higher successful rate. CAS not only treats carotid stenosis effectively and reduces the incidence of stroke and myocardial infarction but also may increase the survival rate. Because CAS may lead to in-stent restenosis, an eluting stent has been developed to prevent this adverse event. However, the effectiveness of the eluting stent has yet to be adequately verified. As patients who receive CAS remain at risk of recurrent stroke, intravascular restenosis, TIA, and mortality, post-procedure medical and nursing care for this population must be appropriately applied in order to maximize the rate of long-term success. Therefore, we recommend that clinical physicians and nurses regularly evaluate and monitor post-CAS patients in order to prevent complications. Moreover, they should educate patients before discharge on post-CAS wound care and medicine-taking regimens as well as on the importance of smoking cessation, controlling blood sugar and blood pressure, exercising regularly, reducing body weight, maintaining a healthy diet, and controlling the risk factors of atherosclerosis in order to prevent the recurrence of complications.

[The Promotion of Resources Integration in Long-Term Care Service: The Experience of Taipei City Hospital].

The home-based medical care integrated plan under Taiwan National Health Insurance has changed from paying for home-based medical care, home-based nursing, home-based respiratory treatment, and palliative care to paying for a single, continuous home-based care service package. Formerly, physician-visit regulations limited home visits for home-based nursing to providing medical related assessments only. This limitation not only did not provide practical assistance to the public but also caused additional problems for those with mobility problems or who faced difficulties in making visits hospital. This 2016 change in regulations opens the door for doctors to step out their 'ivory tower', while offering the public more options to seek medical assistance in the hope that patients may change their health-seeking behavior. The home-based concept that underlies the medical service system is rooted deeply in the community in order to set up a sound, integrated model of community medical care. It is a critical issue to proceed with timely job handover confirmation with the connecting team and to provide patients with continuous-care services prior to discharge through the discharge-planning service and the connection with the connecting team. This is currently believed to be the only continuous home-based medical care integrated service model in the world. This model not only connects services such as health literacy, rehabilitation, home-based medical care, home-based nursing, community palliative care, and death but also integrates community resources, builds community resources networks, and provides high quality community care services.

An Application of NGS for WDR36 Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma.

Primary open-angle glaucoma (POAG) is one of the most important disease in ophthalmology with high prevalence and risk of irreversible blindness. If diagnosed before the age of 35, it is usually categorized as juvenile open-angle glaucoma (JOAG). The WDR36 gene is reckoned as one of the major causative genes of POAG, and had been studied to be related to the pathogenesis of POAG in the literature. We have selected 61 JOAG patients and 61 JOAG-free individuals, and by next-generation sequencing method, the WDR36 gene of the subjects were analyzed. We identified 26 variations exclusively in JOAG group. Among these 26 variations, there were 3 noteworthy variations. First, a novel variation c.460-650A>G was found in our study which might cause premature termination of splicing of the conserved domain in WDR36; second, c.1494+1111G>T (rs13178997) had significantly different frequency in our JOAG patients compared to the reference frequency on NCBI; third, a variation c.710+30C>T (rs10038177) was found in our study, which had already been reported to be related to high-pressure glaucoma. We offer the profile of WDR36 in JOAG in Taiwan population, and we suggest that WDR36 gene is involved in the pathogenesis of JOAG as a subordinate modifier gene.

Deep Dermatophytosis Caused by Zoophilic Strain of Trichophyton interdigitale with Successful Treatment of Itraconazole.

We report a 66-year-old female patient with deep dermatophytosis caused by zoophilic strain of Trichophyton interdigitale, a rare granulomatous presentation of Trichophyton species infection in patients with underlying systemic diseases, and she was successfully cured by itraconazole. Since the identification of Trichophyton mentagrophytes complex had been misused for years, a brief discussion of molecular diagnosis and taxonomy of T. mentagrophytes complex is given. The pathogenesis and comparison with cases reported in the literature are also discussed.

Acute Effects of Foam Rolling, Static Stretching, and Dynamic Stretching During Warm-ups on Muscular Flexibility and Strength in Young Adults.

CONTEXT: Foam rolling has been proposed to improve muscle function, performance, and joint range of motion (ROM). However, whether a foam rolling protocol can be adopted as a warm-up to improve flexibility and muscle strength is unclear. OBJECTIVES: To examine and compare the acute effects of foam rolling, static stretching, and dynamic stretching used as part of a warm-up on flexibility and muscle strength of knee flexion and extension. DESIGN: Crossover study. SETTING: University research laboratory. PARTICIPANTS: 15 male and 15 female college students (age 21.43 ± 1.48 y, weight 65.13 ± 12.29 kg, height 166.90 ± 6.99 cm). MAIN OUTCOME MEASURES: Isokinetic peak torque was measured during knee extension and flexion at an angular velocity of 60°/second. Flexibility of the quadriceps was assessed by the modified Thomas test, while flexibility of the hamstrings was assessed using the sit-and-reach test. The 3 interventions were performed by all participants in random order on 3 days separated by 48-72 hours. RESULTS: The flexibility test scores improved significantly more after foam rolling as compared with static and dynamic stretching. With regard to muscle strength, only knee extension peak torque (pre vs. postintervention) improved significantly after the dynamic stretching and foam rolling, but not after static stretching. Knee flexion peak torque remained unchanged. CONCLUSIONS: Foam rolling is more effective than static and dynamic stretching in acutely increasing flexibility of the quadriceps and hamstrings without hampering muscle strength, and may be recommended as part of a warm-up in healthy young adults.

Pattern Recognition to Prognosticate Endometrial Cancer: The Science Behind the Art of Office Hysteroscopy-A Retrospective Study.

OBJECTIVE: This study aimed to evaluate a specific glomerular pattern for prognostication of endometrial cancer (EC). MATERIALS AND METHODS: The office hysteroscopy's picture and video of 4197 women were reviewed, 48 women who were suspected of type I EC were analyzed: 26 have glomerular pattern (group 1) and 22 without it (group 2). RESULTS: The histopathological grading after hysterectomy with glomerular pattern had grade 2 or grade 3 disease on final histology (n = 25; 96%). The sensitivity and specificity of this test were 84.6% and 81.8%, respectively, with a likelihood ratio of 4:6 in predicting and prognosticating those women who have high-grade tumor or invasive disease. CONCLUSIONS: This hysteroscopic picture might be used as a novel marker for risk stratification of EC.

Establishment of a renal supportive care program: Experience from a rural community hospital in Taiwan.

Renal supportive care (RSC) denotes a care program dedicated for patients with acute, chronic renal failure, and end-stage renal disease (ESRD), aiming to offer maximal symptom relief and optimize patients' quality of life. The uncertainty of prognosis for patients with chronic kidney disease and ESRD, the sociocultural issues inherent to the Taiwanese society, and the void of structured and practical RSC pathway, contributes to the underrecognition and poor utilization of RSC. Taiwanese patients rarely receive information regarding RSC as part of a standardized care and are not commonly offered this option. In National Taiwan University Hospital Jinshan branch, we started a RSC subprogram, supported by the community-based palliative/hospice care main program. We focused on understanding the need and providing the choice of RSC to suitable candidates. A three-step and four-phase protocol was designed and implemented to identify appropriate patients and to enhance the applicability of the RSC. We harnessed family visit and home-based family meeting as a vehicle to understand the patients' preferences, to discover what ESRD patients and their family value most, and to introduce the option of RSC. In the current review, we described our pilot experience of establishing a RSC program in Taiwan, and discuss its potential advantage.

Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery for nonprolapsed uteri.

BACKGROUND: Natural orifice transluminal endoscopic surgery has shown its prospection as a minimally invasive endoscopic surgery. This study aimed to examine the safety and feasibility of transvaginal natural orifice transluminal endoscopic hysterectomy (tVNOTEH) for nonprolapsed uteri in the management of benign gynecological diseases. METHODS: Records were reviewed for the 147 consecutive tVNOTEH procedures between April 2011 and October 2013. Age, body mass index, number of vaginal delivery, and specimen weight were used to select comparable patient who had undergone laparoscopically assisted vaginal hysterectomy (LAVH). RESULTS: A total of 512 patients were recruited in this study (147 tVNOTEHs and 365 LAVHs, respectively). These patients were stratified into six subgroups according to the uterine weight and type of hysterectomy. There was no incidence of switching to abdominal laparatomy. Length of operation, estimated blood loss (EBL), requirement of blood transfusion, and length of postoperative stay were significantly greater in the LAVH group than in the tVNOTEH group but total hospital charges were higher in the tVNOTEH group (p < 0.001). There was no difference in overall incidence of operative complications between the two groups but more complications in LAVH for uterine weight more than 500 g (4.3 vs. 0 %, p < 0.001); this likely reflects higher hospital charges in this subgroup. Significant linear correlations of uterine weight with operating time and EBL existed in both groups. CONCLUSION: tVNOTEH can be safely performed for large and nonprolapsed uterus. Besides, as uterine weight increased, the operative efficiency of tVNOTEH increases compared with LAVH.

[The present and future of community/home-based palliative care in Taiwan].

In Taiwan, the Department of Health (DOH) has implemented regulations and policies related to hospice and palliative care since 1995. Taiwan is the first country in Asia to have a Natural Death Act, promulgated in 2000. Although recognition of the need for palliative care in non-cancer terminally ill patients is increasing, at present, the needs of these patients are often not met. Moreover, while a majority of the population prefers to die at home, the percentage of patients who die in the home setting remains small. The palliative care system should be adjusted to improve the accessibility and continuity of care based on the needs of patients. Therefore, the Jin-Shan Branch of the National Taiwan University Hospital has run a pilot community palliative care service model since 2012. National Health Insurance reimbursement was introduced in 2014 for community-based palliative care services. Establishing a formal system of community-based palliative care should be encouraged in order to improve the quality of care at the end of life and to allow more patients to receive end-of-life care and die in their own communities. This system will require that skilled nurses provide discharge planning, symptoms control, end-of-life communications, social-resources integration, and social-support networks in order to achieve a high quality of end-of-life care.