Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes.

The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.

Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue.

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.

Psychometric Testing of the Newly Developed Competence Scale for Clinical Nurses.

BACKGROUND: Nursing competence is an essential element in ensuring high-quality nursing care and positive patient outcomes. Valid and reliable assessment tools for assessing nurse competence are needed to help nurse supervisors measure whether nurses are performing their job well and to provide a baseline for improving the competences of nurses. PURPOSE: This study was designed to develop and psychometrically validate the Competence Scale for Clinical Nurses (CSCN). METHODS: The CSCN was developed in three steps: (a) generalize assessment items from nursing competence-related scales and a review of the relevant literature, (b) determine the content validity of the developed scale, and (c) psychometrically test the developed scale. Five hundred nurses were recruited from a medical center in southern Taiwan. Exploratory and confirmatory factor analyses were executed to analyze construct validity and internal consistency reliability. RESULTS: The scale-content validity index was .87, as determined by five experts. Two thirds (63.29%) of the variance was explained by three factors: basic care skills (nine items), being dedicated to work (five items), and patient-centered and ethical considerations (four items). A second-order confirmatory factor analysis indicated that the data fit the model well. The Cronbach's alpha coefficients for each of the three factors and the total scale were .84-.91. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The 18-item CSCN is a feasible and time-efficient tool for assessing competence in clinical nurses. Nursing supervisors may use this tool to explore nurses' competency and routinely track the effect of continuing education on competence. Continuous evaluation of nurses' clinical-based competence using the CSCN is recommended.

Determinants Impacting User Behavior towards Emergency Use Intentions of m-Health Services in Taiwan.

Emergency usage intention and behavior are crucial to business service success for m-Health providers and patient healthcare service. This study aimed to identify the factors that influence m-Health acceptance and the effect of emergency use intentions on usage behavior among Taiwanese m-Health users by adopting and extending the Unified Theory of Acceptance and Use of Technology (UTAUT). This study also examines the moderating role of gender and age in the effects of the independent variables on satisfaction with m-Health services. An online questionnaire was used to collect data from 371 participants. The results revealed that performance expectancy, facilitating conditions, and trust had positive effects on user satisfaction. Additionally, m-Health knowledge and user satisfaction had positive effects on emergency use intentions. However, social influence and effort expectancy did not have a significant effect on satisfaction. Moreover, age and gender significantly moderated the effects of some predictors.

From d- to l-Monosaccharide Derivatives via Photodecarboxylation-Alkylation.

Photodecarboxylation-alkylation of conformationally locked monosaccharides leads to inversion of stereochemistry at C5. This allows the synthesis of l-sugars from their readily available d-counterparts. Via this strategy, methyl l-guloside was synthesized from methyl d-mannoside in 21% yield over six steps.

Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice.

Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear 188Re achieved better therapeutic effect on lung cancer. Methods188Re-cetuximab administered by the i.v. route in human NCI-H292 lung tumor-bearing mice was investigated. NanoSPECT/CT images were taken to evaluate the distribution and tumor targeting of 188Re-cetuximab in mice. The anti-tumor effect of 188Re-cetuximab was assessed by the tumor growth inhibition, survival ratio. Results For nanoSPECT/CT imaging, a significant uptake in tumor was observed at 24 and 48 h following the injection of 188Re-cetuximab. The anti-tumor effect of 188Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with 188Re-cetuximab showed a better mean tumor growth inhibition rate (MGI = 0.049) and longer median survival time and lifespan (62.50 d; 70.07%) than those treated with 188Re-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for 188Re-cetuximab (CI = 6.135 and 9.276). Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of 188Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from 188Re-cetuximab for diagnosis and therapy of oncology applications in the future.

Radiolabeling, Characteristics and NanoSPECT/CT Imaging of 188Re-cetuximab in NCI-H292 Human Lung Cancer Xenografts.

BACKGROUND/AIM: Cetuximab has exhibited high EGFR-targeting specificity and clinical promise in previous studies. In this study, we formulated unit dose kits for preparation of high specific activity 188Re-cetuximab for imaging and treatment of EGFR-positive cancer. MATERIALS AND METHODS: 188Re-cetuximab was prepared by adding 0.37-0.74 GBq/0.5 ml of 188Re-perrhenate for 4 h at 37°C. Cell surface expression of EGFR, cell binding and cytotoxic effects were evaluated in vitro using both EGFR-positive (NCI-H292, A431) and EGFR-negative (BT483) tumors. A nanoSPECT/CT imaging study was performed in mice bearing EGFR-expressing NCI-H292 tumors. RESULTS: 188Re-cetuximab bound specifically to EGFR-expressing cells and labeling of radionuclides to cetuximab preserved the binding ability of the antibody. Besides, the cytotoxic effect of 188Re-cetuximab was increased dose-dependently. NanoSPECT/CT imaging revealed that 188Re-cetuximab could continually target the tumor region for at least 48 h. CONCLUSION: The highly specific targeted property of 188Re-cetuximab suggested that it is suitable as a diagnostic tool and maybe a potent radioimmunotherapy agent in EGFR-positive cancers.

A comparison of medication adherence between subsidized and self-paying patients in Malaysia.

BACKGROUND: Limited efforts have been made to evaluate medication adherence among subsidized and self-paying patients. OBJECTIVE: To investigate medication adherence among patients with and without medication subsidies and to identify factors that may influence patients' adherence to medication. Setting: Government healthcare institutions in Kuala Lumpur, Selangor, and Negeri Sembilan and private healthcare institutions in Selangor and Negeri Sembilan, Malaysia. METHODS: This cross-sectional study sampled patients with and without medication subsidies (self-paying patients). Only one of the patient's medications was re-packed into Medication Event Monitoring Systems (MEMS) bottles, which were returned after four weeks. Adherence was defined as the dose regimen being executed as prescribed on 80% or more of the days. The factors that may influence patients' adherence were modelled using binary logistic regression. Main outcome measure: Percentage of medication adherence. RESULTS: A total of 97 patients, 50 subsidized and 47 self-paying, were included in the study. Medication adherence was observed in 50% of the subsidized patients and 63.8% of the self-paying patients (χ2=1.887, df=1, p=0.219). None of the evaluated variables had a significant influence on patients' medication adherence, with the exception of attending drug counselling. Patients who attended drug counselling were found to be 3.3 times more likely to adhere to medication than those who did not (adjusted odds ratio of 3.29, 95% CI was 1.42 to 7.62, p = 0.006). CONCLUSION: There is no significant difference in terms of medication adherence between subsidized and self-paying patients. Future studies may wish to consider evaluating modifiable risk factors in the examination of non-adherence among subsidized and self-paying patients in Malaysia.

Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature.

The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.

Endothelial cell loss in penetrating keratoplasty, endothelial keratoplasty, and deep anterior lamellar keratoplasty.

PURPOSE: To compare endothelial cell density (ECD) loss rates in penetrating keratoplasty (PKP), Descemet's stripping automated endothelial keratoplasty (DSAEK), and deep anterior lamellar keratoplasty (DALK). DESIGN: Single-center, multiple-surgeon, retrospective cohort study. MATERIALS AND METHODS: Patients who received PKP, DSAEK, or DALK from 2009 to 2014 were analyzed (68 vs. 38 vs. 11 patients, respectively). We excluded patients with therapeutic PKP or regraft, infection, endothelial rejection, or uncontrolled glaucoma. Only clear grafts and initial ECD more than 1000 cell/mm2 were included in the study. The main outcome was ECD loss rate. The follow-up time period was divided into five subgroups: 0-1.5 months, 1.5-6 months, 6-12 months, 12-24 months, and longer than 24 months. RESULTS: Average ECD loss rate (cell/mm2/month) declined in all three groups (PKP group: -561.5, -113.2, -36.6, -31.4, and -53.7; DSAEK group: -686.4, -68.3, -21.8, -14.4, and -5.1; DALK group: -576.5, -68, -23.7, 5.9, and 18.3). Although DSAEK group showed faster ECD loss rate in the early postoperative period, it became slower compared to the PKP group within the postoperative 6th month and demonstrated significant difference within 2 years. No ECD loss developed in the DALK group after the 1st postoperative year; this was significantly different from the PKP group. CONCLUSIONS: Although ECD loss rate in the DSAEK group was initially larger than that in the PKP group, the DSAEK group possessed better long-term endothelial cell survival rate. The DALK group had a lower ECD loss rate than that of the other groups and maintained a stable ECD at 1 year after surgery.

Cultural issues in post-disaster reconstruction: the case of Typhoon Morakot in Taiwan.

Most members of Taiwan's indigenous communities live in areas that are prone to natural disasters. Yet, due to their marginalised cultural, economic and political status, each time such calamities strike, any assistance they receive is usually provided without considering their actual needs. The areas hardest hit by Typhoon Morakot in August 2009 were the indigenous villages in the southern and eastern parts of the island. After the initial emergency relief efforts had been completed, there remained the highly challenging task of reconstruction and the resettlement of those who lost their homes and livelihoods. This paper examines the cultural conflicts that arose during the reconstruction process, with special emphasis on the participation of Taiwan's indigenous communities and their capacity for resilience. It was found that community participation and identification are key issues in effective disaster governance.

Biomarkers for Bone Tumors: Discovery from Genomics and Proteomics Studies and Their Challenges.

Diagnosis of bone tumor currently relies on imaging and biopsy, and hence, the need to find less invasive ways for its accurate detection. More recently, numerous promising deoxyribonucleic acid (DNA) and protein biomarkers with significant prognostic, diagnostic and/or predictive abilities for various types of bone tumors have been identified from genomics and proteomics studies. This article reviewed the putative biomarkers for the more common types of bone tumors (that is, osteosarcoma, Ewing sarcoma, chondrosarcoma [malignant] and giant cell tumor [benign]) that were unveiled from the studies. The benefits and drawbacks of these biomarkers, as well as the technology platforms involved in the research, were also discussed. Challenges faced in the biomarker discovery studies and the problems in their translation from the bench to the clinical settings were also addressed.

[The aesthetic practice of care ethics].

Situated between the doctor and the patient, nurses play a central role in the doctor-patient relationship. Nurses attend to patients' exhaustion and take responsibility for the "Other," in Lévinas' sense of the word. In discussions of the doctor-patient relationship, the patient is often regarded as the "Other". This perspective seeks to challenge the traditional contention that the doctor plays the dominant role. In the structure of this relationship, the doctor, responsible for providing diagnoses, is the subject and the patient is the object. The latter constantly feels frustrated and helpless and requires the comfort of the nurse. In this sense, the nurse, having the direct contact with the patient, constantly sees the faces of the patients. In the care relationship, the patient's frustration and helplessness will sometimes be expressed to the nurse if the patient cannot be affectively affirmed. In this type of situation, the nurse bears not simply his / her routine work, but also affective devotion and endurance. On the one hand, the nurse must practice professional medical care in the face of patients' affective feelings and emotions and, on the other hand, he / she must treat the patient as a relative and suppress inner feelings and emotions. How does a nurse situate herself into the doctor-patient relationship? As the nurse is asked to treat the patient as a relative, how does he / she face inner emotions? This paper reflects on the possibility of the aesthetic practice of care ethics.

Successful ageing: the case of Taiwan.

AIM: To investigate the conditions of successful ageing in Taiwan. METHODS: The respondents included two age groups, namely, 45-64 years (n = 1143), and 65 years and older (n = 1309), from a cross-section national representative survey conducted in 2007. RESULTS: Older people faced more problems that cause depression than their counterparts. Eleven per cent of older people were in the labour market. Neither middle-aged people nor older people were actively involved in volunteer services. Those who lived longer had less social support. Over 50% felt their financial preparations for later life were not adequate. Educational levels and family income were the significant factors affecting the levels of successful ageing. CONCLUSIONS: Improvement in the four dimensions of successful ageing must be re-emphasised for both age groups.

Pioglitazone prevents smoking carcinogen-induced lung tumor development in mice.

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p < 0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.

Recovery of metallic copper by integrated chemical reduction and high gradient magnetic separation.

The recovery of metals from waste effluents is necessary for pollution prevention and sustainable practice. High gradient magnetic separation (HGMS) is seen as a viable method. We investigated the capture of valence copper from aqueous copper ion by HGMS in combination with a chemical reduction process. When a copper solution (3.9 or 15.6 mM) was exposed to excess of dithionite (mole ratio of 1:3) in the presence of ammonia (mole ratio of 4) and amended with MnCl2 (2.5 g/L) and the mixture passed through a flow reactor under a strong magnetic field (10000 Gauss), valence copper was obtained and captured in the reactor with well over 95% yields. The chemical reduction reactions were unaffected by the presence of MnCl2 while the amount of MnCl2 (0, 20 and 32 mM) has significantly varied the copper recovery efficiency, especially in the case of high initial copper ion concentration (15.6 mM). Formation of MnO2 flocs was found to have a detrimental effect on copper removal efficiency. The HGMS method offers a tool of resource recovery for copper from waste effluents.

[Reducing patient pressure sore incidence in the surgical intensive care unit].

BACKGROUND: Pressure ulcers were an increasingly significant problem among patients in the authors' ward. The eight patients diagnosed with pressure ulcers (0.42% of all inpatients) during the first half of 2009 represented a 140% increase over the first half of 2008 (0.28% of all inpatients). PURPOSE: This project was designed to reduce pressure ulcer incidence in the surgical intensive care unit (ICU) to 0.05%. METHODS: Intervention measures included: 1) holding professional training on preventing pressure ulcers; 2) specifying appropriate patient turnover tools; 3) creating and distributing to nurses a proper turnover technique and positioning manual; 4) creating and distributing to nurses a comprehensive patient skin inspection checklist; and 5) organizing a permanent pressure ulcer care quality and audit committee. RESULTS: Pressure ulcer incidence fell from 0.42% to 0.04% following implementation of the methods. CONCLUSION: Results demonstrate the effectiveness of using the proposed methods to reduce pressure ulcer incidence and enhance nursing care quality.

Single nucleotide polymorphisms of the maternal Msx2 gene and their association with fetal neural tube defects in Han ethnic group in Shanxi Province, China.

BACKGROUND: Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population. METHODS: We studied 59 mothers with at least one previous child with a neural tube defect (the case group) and 73 case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T polymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests. RESULTS: Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups (CT: 32% vs. 15%, P = 0.0073 and TT 15% vs. 4%, P = 0.013, respectively). Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects (P < 0.05; OR: 3.466; 95%CI: 1.831 - 6.560). Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2. CONCLUSION: Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.