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αβ-tubulin dimers need to convert between a 'bent' conformation observed for free dimers in solution and a 'straight' conformation required for incorporation into the microtubule lattice. Here, we investigate the free energy landscape of αβ-tubulin using m

A new coarse-grained model of the E. coli cytoplasm is developed by describing the proteins of the cytoplasm as flexible units consisting of one or more spheres that follow Brownian dynamics (BD), with hydrodynamic interactions (HI) accounted for by a mean

Background: and Purpose: With mindfulness being increasingly recognized for its potential to address psychological challenges related to advanced or terminal illnesses, palliative care professionals are incorporating mindfulness-based interventions into their practice. However, there is limited understanding of the practical applications of mindfulness in clinical settings, particularly for end-of-life patients. This study explored palliative care professionals' experiences in delivering mindfulness-based therapy to end-of-life patients, thereby aiming to inform the development of effective interventions., Materials and Methods: Semi-structured interviews were conducted with 15 palliative care professionals. Participants were asked to describe their memorable experiences in applying mindfulness in a clinical setting. Data were analyzed following Moustakas's transcendental phenomenology approach., Results: The interviews produced three themes: clinicians' mindfulness experiences form the cornerstone of their clinical application of mindfulness; creating an optimal healing environment is essential for mindfulness practice; and patient-centric mindfulness guidance should be implemented., Conclusion: This study underscores the critical role of mindfulness in end-of-life care, highlighting its integration into daily life by palliative care professionals. By drawing upon their own mindfulness experiences, palliative care professionals facilitated a therapeutic environment tailored to the unique needs of end-of-life patients. This patient-centered approach not only enhanced the quality of care but also fostered a healing connection rooted in compassion and empathy. The findings advocate for further education and development of mindfulness-based interventions, including group therapies, to support the holistic well-being of patients in collectivist cultures. Future research should further explore the practical applications and benefits of mindfulness in end-of-life care settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The illness experiences of advanced cancer patients are discussed in a Taiwanese cultural context, using an interpretive ethnographic approach (interviews and participant observations) emphasizing holism and symbolic interactionism. A total of 23 advanced cancer patients from different counties in Taiwan were recruited over a 42-month period. The researcher followed their progress as they approached death to better understand their terminal cancer experiences. An interpretive analysis guided by Agar's hermeneutic cycle approach revealed five emic dimensions: feeling the oppression of death, fighting alongside family, intensifying bodily healing efforts, settling unfinished business, and ending the struggle to control pain. Implications for caregivers are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Philippines has an increasingly aging population thereby increasing the demand for healthcare and support from families. Studies showed that the family is the main caregiver of elderly parents/adults as dictated by the Filipino culture of filial piety and respectful behavior towards older people. However, this caring culture is now slowly declining, and Filipino older adults also experience abuse, exploitation, and other forms of neglect from their families. This special article described that the declining caring culture was due to deteriorating family values and societal influences brought about by modernization. This paper also highlights the crucial role of the family and the community in inculcating the preservation of this valued caring Filipino culture, especially among the youth. In cases where senior citizens are being abused and neglected by their families, the state steps in to safeguard the welfare and protection of Filipino senior citizens. Enacted and promulgated laws ensure social justice and protection of human dignity among Filipino older adults as well as the provision of socioeconomic and health needs. In conclusion, the preservation of a caring culture through educating the youth coupled with the implementation of enacted and promulgated laws of the country ensures the quality of aging life among Filipino older adults., Competing Interests: All authors declared no conflicts of interest. The views and opinions expressed by the authors in this paper do not necessarily reflect the stance of any of the institutions to which they are affiliated., (© 2024 Acta Medica Philippina.)

Purpose: The aim of this study was to explore the essence of the lived experiences of palliative care professionals in cultivating mindfulness, with a focus on the meaning of mindfulness in their lives and how mindfulness is experienced throughout their process of caring for others. Design: This was a qualitative study using a phenomenological approach. Methods: Eleven palliative care professionals (three physicians, four nurses, three psychologists, and one spiritual care provider) partook in in-depth interviews. Data were collected from the in-depth interviews and analyzed according to the method of Giorgi. Findings: Two major themes emerged from this study. First, the palliative care professionals realized the need for self-care amid emotional burden, including recognizing their feelings of guilt and self-doubt, emotional contagion of grief, reflections of others' fragility on themself, and their self-imposed limitations. Second, they noticed the transformative impact of mindfulness on them, including detecting reconnection with their body, changes in their personal values, self-acceptance, and liberation. Conclusion: Palliative care professionals can cultivate self-acceptance and facilitate entirely new life experiences through the practice of mindfulness. For them, mindfulness is not merely a self-regulation technique but an existential epiphany, offering hope for self-care and empowerment.

This study investigated the development and optimization of a flexible printed circuit board-based glucose biosensor with an emphasis on high sensitivity, selectivity, and overall performance. Advances in glucose biosensing have highlighted its importance in medical diagnostics, especially diabetes management. The fabrication process involves depositing a RuO2 sensing film on a flexible printed circuit board (FPCB) by radio frequency sputtering. Enzyme-based modification using glucose oxidase (GOx), (3-aminopropyl) triethoxysilane (APTES), and glutaraldehyde (GA) to enhance selectivity and catalytic reactions. And through Scanning Electron Microscopy and electrochemical impedance spectroscopy, the sensing film, and the effect of modification on the charge transfer rate and performance improvement were analyzed. This glucose biosensor has excellent linearity, sensitivity, and reproducibility. The study also assessed response time and selectivity. The response time efficiency of the biosensor solidified its utility in point-of-care monitoring, while selectivity experiments validated its ability to distinguish glucose from interfering substances, ensuring accuracy in practical applications. According to the experimental results, the enzymatic glucose biosensor has the best average sensitivity and linearity of 44.42 mV/mM and 0.999 with a response time of 6 seconds.

Bacteria contribute to many physiological functions of coral holobionts, including responses to bleaching. The bacterial genus, Endozoicomonas , dominates the microbial flora of many coral species and its abundance appears to be correlated with coral bleaching. However, evidences for decoupling of bleaching and Endozoicomonas abundance changes have also been reported. In 2020, a severe bleaching event was recorded at reefs in Taiwan, providing a unique opportunity to re-examine bleaching- Endozoicomonas association using multiple stony corals in natural environments. In this study, we monitored tissue color and microbiome changes in three coral species ( Montipora sp., Porites sp., and Stylophora pistillata ) in Kenting National Park, following the bleaching event. All tagged Montipora sp. and Porites sp. recovered from bleaching within 1 year, while high mortality occurred in S. pistillata . Microbiome analysis found no correlation of Endozoicomonas relative abundance and bleaching severity during the sampling period, but found a stronger correlation when the month in which bleaching occurred was excluded. Moreover, Endozoicomonas abundance increased during recovery months in Montipora sp. and Porites sp., whereas in S. pistillata it was nearly depleted. These results suggest that Endozoicomonas abundance may represent a gauge of coral health and reflect recovery of some corals from stress. Interestingly, even though different Endozoicomonas strains predominated in the three corals, these Endozoicomonas strains were also shared among coral taxa. Meanwhile, several Endozoicomonas strains showed secondary emergence during coral recovery, suggesting possible symbiont switching in Endozoicomonas. These findings indicate that it may be possible to introduce Endozoicomonas to non-native coral hosts as a coral probiotic., Competing Interests: On behalf of all authors, the corresponding author states that there are no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background: The World Health Organization officially declared an end to the COVID-19 Public Health Emergency three years after the initial outbreak of COVID-19. Healthcare providers worldwide were overwhelmed during the pandemic, which greatly affected the mental health and turnover intention of nurses. Conducting a systematic review of psychological distress in first-line nurses during the pandemic may facilitate future research on pandemic-related resilience., Purpose: A systematic review of the literature on psychological distress among first-line nurses caring for patients with COVID-19 was conducted., Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. We searched the CINAHL, PubMed, Embase, and Airiti Library databases using the English and Chinese keywords ("COVID-19 first-line nurse" OR "COVID-19 frontline nurse") AND ("psychological distress" OR "PTSD" OR "depression" OR "anxiety" OR "insomnia" OR "stress" OR "burnout" OR "fear") to identify Chinese and English articles published between December 2019 and March 2023. The quality of the included studies was assessed using tools from the Joanna Briggs Institute., Results: A total of 20 articles covering 16 quantitative studies and 4 qualitative studies were included in the analysis. The quantitative findings revealed that first-line nurses experienced high task load and moderate or above-average burnout. Between 19.1% and 72.3% of the first-line nurses reported stress, and more than 30% experienced insomnia. At the peak of the pandemic, anxiety and distress levels were high. At 8-week follow-ups, while anxiety had decreased, distress levels had not. Qualitative findings included the identification of fear as a common symptom of psychological distress in first-line nurses., Conclusions / Implications for Practice: Further research is needed to better support frontline caregivers and facilitate their recovery from the moderate to severe psychological distress associated with pandemics.

Taiwan has been an aging society since 2018. As a result, long-term care, end-of-life autonomy, and hospice care have received increasing attention. The government of Taiwan promotes home-based healthcare through the National Health Insurance System to enable the efficient utilization of medical resources and reduce overall medical costs. Taiwan's community hospice and palliative care network is expected to serve as the main care model supplementing partial hospitalization and institutional care. In this article, we review the history of and policies related to hospice and palliative care in Taiwan using a literature review and examining Pingtung County as a case study. The implementation of home-based palliative care is also outlined and policy revisions are proposed. The results are intended to provide a reference for healthcare authorities and medical institutions to promote community hospice and palliative care policies. The integrated care model can enhance the capacity of community-based palliative care, support patients receiving palliative care and their family members and caregivers, and ensure physical and psychological comfort for patients. This model contributes to the realization of older adults' preference for dying at home, which is especially pronounced in cultures where traditional Chinese ideas are deeply rooted.

Background: Midwives have been frontline health professionals at the grassroots level, especially in rural communities. Their role was expanded from maternal and child healthcare providers to primary healthcare services providers. Despite their expanded functions, there have been limited studies investigating the professional practice of midwifery in the Philippines in a rural setting., Objective: This study aimed to investigate the professional practice of midwives in selected rural areas in the Cordillera Administrative Region, Philippines., Methods: This research is a qualitative pilot study using a semi-structured interview guide to collect the data. Key informant interviews were conducted through mobile phone calls convenient for the participants from September to October 2021. Data were analyzed through qualitative content analysis., Results: A total of seven rural health midwives participated in this study. From the data analysis, six themes emerged related to the professional functions of rural Filipino midwives: 1) antenatal and postnatal care, 2) basic emergency obstetrical and newborn care, 3) health education and counseling, 4) treating common children and adult infections, 5) health promotion, and 6) beyond midwifery role., Conclusion: Rural midwives play a role in providing several primary healthcare services mandated by the government and the profession. They also offer health services beyond their scope as midwives because of geographical difficulties and logistic issues. The findings inform the policymaker to review and amend the expanded roles of practicing midwives so that they will be empowered in providing quality and legal healthcare services. The study results will also be important in preparing midwives for rural midwifery practice., Competing Interests: All authors declared that they have no conflicts of interest., (© 2023 Acta Medica Philippina.)

Background: Ethical dilemmas that arise in the clinical setting often require the collaboration of multiple disciplines to be resolved. However, medical and nursing curricula do not prioritize communication among disciplines regarding this issue. A common teaching strategy, problem-based learning, could be used to enhance communication among disciplines. Therefore, a university in southern Taiwan developed an interprofessional ethics education program based on problem-based learning strategies. This study described tutors' experience teaching in this program., Aim: To explore the phenomenon of teaching and learning in interprofessional ethics education for medical and nursing students from the perspectives of tutors., Design: Phenomenological qualitative research., Methods: Medical and nursing students completed a 6-week interprofessional ethics education program moderated by either physician or nurse tutors. At the conclusion of the ethics education program, all 14 tutors were invited to participate in focus group interviews. Among them, six tutors (three nursing tutors and three physician tutors) participated in additional individual interviews. All of the contents from the focus group interviews and individual interviews were recorded and transcribed. Using the phenomenological approach, the phenomenon of teaching and learning in interprofessional ethics education were generated., Ethical Consideration: The study was approved by the Institutional Review Board., Findings: Three themes emerged from the tutors' teaching perspectives, including the instructor's motivation to teach, the use of narrative case scenarios, and the emphasis on improving interprofessional ethics communication., Discussion: Problem-based learning creates an interprofessional communication platform in interprofessional ethics education. The phenomenon of value convergence between tutors and students, between different students' professions, and between different students' professional maturities is observed., Conclusion: Problem-based learning is an effective teaching strategy for creating a communication platform for interprofessional ethics education. Ethic curriculum should emphasize motivating instructor, use narrative case scenarios, and focus on interprofessional communication.

A novel method for the preparation of tetrahydropentaleno[1,2- c ]pyrroles ( 8 ) is described via the reaction of anilines with 1-en-4-yn-3-ols in the presence of Lewis acid. Oxidation of 8 with Br 2 gave pentaleno[1,2- c ]pyrroles ( 10 ), which is the first reported tricyclic 5/5/5 ring with a fully conjugated system. Structures of these obtained compounds were characterized by spectroscopic methods, and compounds 8a , b and 10c were further confirmed by X-ray crystallographic determination.

Cancer-related fatigue is the most common and longest-lasting symptom of discomfort experienced by cancer patients. Its effects on patients include physical, psychological, emotional, and cognitive stress, which greatly reduce quality of life. The field of mind-body integrated medicine has improved gradually in recent years, with many evidence-based studies supporting the efficacy of mindfulness as a symptom management strategy for cancer-related fatigue. Based on a review of the literature, this paper introduces the definition of cancer-related fatigue and related assessments and treatments, describes the origin of mindfulness and related concepts, and introduces mindfulness-based empirical treatment strategies for cancer-related fatigue, including mindfulness-based stress reduction and mindfulness-based cognitive therapy, and their effects. The findings are intended to provide clinicians with a reference for the future care of patients with cancer-related fatigue.

Multiple myeloma is a hematologic malignancy of monoclonal plasma cells that accumulate in the bone marrow. Despite their clinical and pathophysiologic relevance, the roles of bone marrow-infiltrating T cells in treatment-naïve patients are incompletely understood. We investigated whether clonally expanded T cells (i) were detectable in multiple myeloma bone marrow, (ii) showed characteristic immune phenotypes, and (iii) whether dominant clones recognized antigens selectively presented on multiple myeloma cells. Single-cell index sorting and T-cell receptor (TCR) αβ sequencing of bone marrow T cells from 13 treatment-naïve patients showed dominant clonal expansion within CD8+ cytolytic effector compartments, and only a minority of expanded T-cell clones expressed the classic immune-checkpoint molecules PD-1, CTLA-4, or TIM-3. To identify their molecular targets, TCRs of 68 dominant bone marrow clones from five selected patients were reexpressed and incubated with multiple myeloma and non-multiple myeloma cells from corresponding patients. Only 1 of 68 TCRs recognized antigen presented on multiple myeloma cells. This TCR was HLA-C-restricted, self-peptide-specific and could be activated by multiple myeloma cells of multiple patients. The remaining dominant T-cell clones did not recognize multiple myeloma cells and were, in part, specific for antigens associated with chronic viral infections. In conclusion, we showed that dominant bone marrow T-cell clones in treatment-naïve patients rarely recognize antigens presented on multiple myeloma cells and exhibit low expression of classic immune-checkpoint molecules. Our data provide experimental context for experiences from clinical immune-checkpoint inhibition trials and will inform future T cell-dependent therapeutic strategies., (©2022 The Authors; Published by the American Association for Cancer Research.)

Purpose: This study aimed to explore the experience and views of mothers with children who have been diagnosed with retinoblastoma., Design and Methods: A descriptive qualitative study was conducted in the period of 2019-2021. Interviews were conducted with 21 mothers of children diagnosed with retinoblastoma in Indonesia. Data were collected by semi-structured interviews and examined by content analysis., Results: Mothers evolved from a sense of unacceptability to accepting challenges and gaining inner strength. Three themes were identified: 1) physical and psychological suffering, 2) awareness of changes and demands, and 3) keep moving forward. Mothers developed positive adaptive mechanisms for coping with the problems associated with having a child with retinoblastoma. Psychological adjustment and religious beliefs were key elements in their journeys toward embracing life in the moment., Conclusion: Findings illuminated psychological adaptation and coping strategies of mothers with seriously ill children and highlighted how difficulties and cultural norms shaped the adaptative process. Religion and health beliefs played varied and important roles in helping mothers to manage their stress and enhance their coping strategies., Practice Implications: Our findings revealed that it is important to routinely assess social support, traditional health beliefs, and spirituality on mothers, facilitate mentoring to help mothers find their inner strengths, and develop intervention programs designed to promote psychological adjustment without delaying treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bacteria in the coral microbiome play a crucial role in determining coral health and fitness, and the coral host often restructures its microbiome composition in response to external factors. An important but often neglected factor determining this microbiome restructuring is the ability of microbiome members to respond to changes in the environment. To address this issue, we examined how the microbiome structure of Acropora muricata corals changed over 9 months following a reciprocal transplant experiment. Using a combination of metabarcoding, genomics, and comparative genomics approaches, we found that coral colonies separated by a small distance harbored different dominant Endozoicomonas -related phylotypes belonging to two different species, including a novel species, " Candidatus Endozoicomonas penghunesis" 4G, whose chromosome-level (complete) genome was also sequenced in this study. Furthermore, the two dominant Endozoicomonas species had different potentials to scavenge reactive oxygen species, suggesting potential differences in responding to the environment. Differential capabilities of dominant members of the microbiome to respond to environmental change can (i) provide distinct advantages or disadvantages to coral hosts when subjected to changing environmental conditions and (ii) have positive or negative implications for future reefs. IMPORTANCE The coral microbiome has been known to play a crucial role in host health. In recent years, we have known that the coral microbiome changes in response to external stressors and that coral hosts structure their microbiome in a host-specific manner. However, an important internal factor, the ability of microbiome members to respond to change, has been often neglected. In this study, we combine metabarcoding, culturing, and genomics to delineate the differential ability of two dominant Endozoicomonas species, including a novel " Ca. Endozoicomonas penghunesis" 4G, to respond to change in the environment following a reciprocal transplant experiment.

Background: Using conventional esophagogastroduodenoscopy (EGD) to evaluate the infrapapillary area is not feasible. The use of sedative EGD may enable endoscopists to investigate the infrapapillary condition of the duodenum. In this study, we aimed to evaluate lesions in the infrapapillary regions by using sedative EGD., Methods: In this retrospective observational study, we used the data of patients who underwent sedative EGD examinations at a tertiary hospital in southern Taiwan. The endoscopists evaluated the esophagus, stomach, and proximal duodenum and then attempted to explore the infrapapillary portion of the duodenum as deeply as possible. We assessed the success rate for the exploration of infrapapillary areas. Furthermore, we analyzed specific clinical findings of sedative EGD examination., Results: In total, 2973 patients underwent sedative EGD between November 1, 2010, and December 31, 2011. For 2632 of these patients, it was their first sedative EGD examination. In 2511 patients (95.4%), the exploration of the infrapapillary areas was successful. In approximately 10% of the patients, specific findings were detected over the infrapapillary region, and 7 of these patients exhibited clinically significant findings (i.e., gallbladder cancer with metastasis, periampullary Vater adenoma, natural killer cell enteropathy, villous adenoma with moderate dysplasia, infrapapillary duodenal adenoma with dysplasia, duodenal perforation with tumor-like formation, and follicular lymphoma). No patient experienced minor or major adverse reactions during the sedative EGD procedure., Conclusions: The current study provided evidence that sedative EGD examination enables a safe, comfortable, and effective endoscopic examination of deeper sections of the duodenum to evaluate the papillary and infrapapillary regions., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ming-Tse Hsu et al.)

Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome-assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas -dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont.

SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal-lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis.

Relatively warm environments caused by global warming enhance the productivity of aquaculture activities in tropical/subtropical regions; however, the intermittent cold stress (ICS) caused by negative Arctic Oscillation can still result in major economic losses. In contrast to endotherms, ectothermic fishes experience ambient temperature as an abiotic factor that is central to performance and survival. Therefore, the occurrence of extreme temperatures caused by climate change has ignited a surge of scientific interest from ecologists, economists and physiologists. In this study, we test the transgenerational effects of rearing cold-experienced (CE) and cold-naïve (CN) strains of tropical tilapia. Our results show that compared to CN tilapia, the CE strain preferentially converts carbohydrates into lipids in liver at a regular temperature of 27 °C. Besides, at a low temperature of 22 °C, the CE strain exhibits a broader aerobic scope than CN fish, and their metabolite profile suggests a metabolic shift towards the utilization of glutamate derivatives. Therefore, in response to thermal perturbations, this transgenerational metabolic adjustment provides evidence into the adaptive trade-off mechanisms in tropical fish. Nevertheless, global warming may result in less thermal variation each year, and the stabilized ambient temperature may cause tropical tilapia to gradually exhibit lower energy deposits in liver. In addition to those habitants in cold and temperate regions, a lack of cold exposure to multiple generations of fish may decrease the native cold-tolerance traits of subtropical/tropical organisms; this notion has not been previously explored in terms of the biological effects under anthropogenic climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Exosomes participate in cell-cell communication by transferring molecular components between cells. Previous studies have shown that exosomal molecules derived from cancer cells and liquid biopsies can serve as biomarkers for cancer diagnosis and prognosis. The exploration of the molecules transferred by lung cancer-derived exosomes can advance the understanding of exosome-mediated signaling pathways and mechanisms. However, the molecular characterization and functional indications of exosomal proteins and lipids have not been comprehensively organized. This review thoroughly collected data concerning exosomal proteins and lipids from various lung cancer samples, including cancer cell lines and cancer patients. As potential diagnostic and prognostic biomarkers, exosomal proteins and lipids are available for clinical use in lung cancer. Potential therapeutic targets are mentioned for the future development of lung cancer therapy. Molecular functions implying their possible roles in exosome-mediated signaling are also discussed. Finally, we emphasized the importance and value of lung cancer stem cell-derived exosomes in lung cancer therapy. In summary, this review presents a comprehensive description of the protein and lipid composition and function of lung cancer-derived exosomes for lung cancer diagnosis, prognosis, and treatment.

Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94-0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25-0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15-3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04-2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20-2.45, p = 0.003).

Summary: Drug discovery targeting G protein-coupled receptors (GPCRs), the largest known class of therapeutic targets, is challenging. To facilitate the rapid discovery and development of GPCR drugs, we built a system, PanGPCR, to predict multiple potential GPCR targets and their expression locations in the tissues, side effects and possible repurposing of GPCR drugs. With PanGPCR, the compound of interest is docked to a library of 36 experimentally determined crystal structures comprising of 46 docking sites for human GPCRs, and a ranked list is generated from the docking studies to assess all GPCRs and their binding affinities. Users can determine a given compound's GPCR targets and its repurposing potential accordingly. Moreover, potential side effects collected from the SIDER (Side-Effect Resource) database and mapped to 45 tissues and organs are provided by linking predicted off-targets and their expressed sequence tag profiles. With PanGPCR, multiple targets, repurposing potential and side effects can be determined by simply uploading a small ligand., Availability and Implementation: PanGPCR is freely accessible at https://gpcrpanel.cmdm.tw/index.html., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neuronal GABAergic responses switch from excitatory to inhibitory at an early postnatal period in rodents. The timing of this switch is controlled by intracellular Cl- concentrations, but factors determining local levels of cation-chloride cotransporters remain elusive. Here, we report that local abundance of the chloride importer NKCC1 and timely emergence of GABAergic inhibition are modulated by proteasome distribution, which is mediated through interactions of proteasomes with the adaptor Ecm29 and the axon initial segment (AIS) scaffold protein ankyrin G. Mechanistically, both the Ecm29 N-terminal domain and an intact AIS structure are required for transport and tethering of proteasomes in the AIS region. In mice, Ecm29 knockout (KO) in neurons increases the density of NKCC1 protein in the AIS region, a change that positively correlates with a delay in the GABAergic response switch. Phenotypically, Ecm29 KO mice showed increased firing frequency of action potentials at early postnatal ages and were hypersusceptible to chemically induced convulsive seizures. Finally, Ecm29 KO neurons exhibited accelerated AIS developmental positioning, reflecting a perturbed AIS morphological plastic response to hyperexcitability arising from proteasome inhibition, a phenotype rescued by ectopic Ecm29 expression or NKCC1 inhibition. Together, our findings support the idea that neuronal maturation requires regulation of proteasomal distribution controlled by Ecm29., (© 2020 Lee et al.)

Background: As moral action could help nurses reduce moral distress, it is necessary to carry out qualitative research to present the experiences in which nurses apply moral action., Aim: To describe and analyze the phronesis applied by nurses in the face of moral distress., Research Design: The research participants were invited to participate in in-depth interviews. The research materials were based on the stories described by the research participants and recorded by means of first-person narrative. Narrative analysis was applied to interpret the nurses' phronesis., Participants: Twenty-seven nurses from Taiwan., Ethical Considerations: The Institutional Review Board of the Kaohsiung Medical University Hospital in Taiwan confirmed that this study passed the research ethical review., Findings: According to the narrative analysis results, the phenomenon of moral distress contains difficulty, action, and idea transformation. The difficulty is the source of moral distress, action is the practice of moral courage, and idea transformation is the nurse's emotional movement. Action and idea transformation are collectively called phronesis in this study., Discussion: Moral distress refers to a state of suffering caused by situations in which nurses cannot carry out their ethical intentions. Phronesis is the process through which nurses take actions and relocate the subjects and is an ethical way to find relief from moral distress. Starting with empathy and respectful attitudes arising from self-reflection, nurses may be helped to get relief from the suffering of moral distress., Conclusion: Phronesis can help nurses positively face the emotional strain of moral distress. This article puts forward a narrative method to complete the four steps of phronesis: write about the care experience, identify the difficulties in the stories, seek the possibility of action, and form a new care attitude, which could help nurses learn to reduce their moral distress.

Breathomics is a special branch of metabolomics that quantifies volatile organic compounds (VOCs) from collected exhaled breath samples. Understanding how breath molecules are related to diseases, mechanisms and pathways identified from experimental analytical measurements is challenging due to the lack of an organized resource describing breath molecules, related references and biomedical information embedded in the literature. To provide breath VOCs, related references and biomedical information, we aim to organize a database composed of manually curated information and automatically extracted biomedical information. First, VOCs-related disease information was manually organized from 207 literature linked to 99 VOCs and known Medical Subject Headings (MeSH) terms. Then an automated text mining algorithm was used to extract biomedical information from this literature. In the end, the manually curated information and auto-extracted biomedical information was combined to form a breath molecule database-the Human Breathomics Database (HBDB). We first manually curated and organized disease information including MeSH term from 207 literatures associated with 99 VOCs. Then, an automatic pipeline of text mining approach was used to collect 2766 literatures and extract biomedical information from breath researches. We combined curated information with automatically extracted biomedical information to assemble a breath molecule database, the HBDB. The HBDB is a database that includes references, VOCs and diseases associated with human breathomics. Most of these VOCs were detected in human breath samples or exhaled breath condensate samples. So far, the database contains a total of 913 VOCs in relation to human exhaled breath researches reported in 2766 publications. The HBDB is the most comprehensive HBDB of VOCs in human exhaled breath to date. It is a useful and organized resource for researchers and clinicians to identify and further investigate potential biomarkers from the breath of patients. Database URL: https://hbdb.cmdm.tw., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Most previous studies on moral distress focused on the factors that cause moral distress, paying inadequate attention to the moral conflict of nurses' values, the physician-nurse power hierarchy, and the influence of the culture., Research Objective: To analyze the main causes for moral distress with interpretive interactionism., Research Design: A qualitative study was adopted., Participants: Through purposeful sampling, 32 nurses from 12 different departments were chosen as the samples., Ethical Considerations: Approval from the Institutional Review Board of the Kaohsiung Medical University Hospital., Findings: Moral distress is likely to occur in the following clinical situations: patients have no idea about their diseases; the medical decisions fail to meet the optimum benefit of patients; and patients with terminal cancers are not given a proper death. The reason why nurses become trapped in moral distress is that they fail to achieve moral goodness. Inadequate confidence, the physician-nurse power hierarchy, and the Oriental culture affect nurses' goodness-based intention for patients, which deteriorates moral distress., Discussion: The main cause for moral distress is the moral goodness of nurses. If nurses' goodness-based intention for patients is inconsistent with the moral objective of achieving optimum benefit for patients, it leads to moral distress. Culture is an essential background factor of care for patients. In the Oriental culture, family members influence patients' right to know about their diseases, the choice of treatment, and patients' autonomy of not receiving cardio-pulmonary resuscitation. This results in moral distress in medical care., Conclusion: The occurrence of moral distress demonstrates that nurses have moral characteristics such as goodness and caring. It is suggested that appropriate educational strategies can be adopted to weaken the power hierarchy between physicians and nurses and enhance nurses' confidence and cultural sensitivity, so as to reduce the moral distress of nurses.

The aim of this study is to examine aging well (AW) terminology in Taiwan in its local and global contexts, and to suggest ways of communication by Taiwanese professionals that is sensitive to the lay public's preferences. Researchers conducted a systematic review using Khan et al.'s strategy, and Harden and Thomas' method, to sift through seven databases and synthesize diverse studies on AW. Primary aging well terms used in English and Chinese, their usage frequency in Taiwanese academia, and one term uniquely used by lay people in Taiwan were identified. The synthesized literature illustrated commonality as well as diversity in use and interpretation of aging well terms within Taiwanese society and compared with the Western-based research. More qualitative research is needed to explore how AW is experienced, interpreted, and expected from lay perspectives in Taiwan and other countries have primarily relied on translation and adaptation of Western terms in their scientific research.

Background: Aging leads to decreased skeletal muscle function in mammals and is associated with a progressive loss of muscle mass, quality and strength. Age-related muscle loss (sarcopenia) is an important health problem associated with the aged population., Results: We investigated the alteration of genome-wide transcription in mouse skeletal muscle tissue (rectus femoris muscle) during aging using a high-throughput sequencing technique. Analysis revealed significant transcriptional changes between skeletal muscles of mice at 3 (young group) and 24 (old group) months of age. Specifically, genes associated with energy metabolism, cell proliferation, muscle myosin isoforms, as well as immune functions were found to be altered. We observed several interesting gene expression changes in the elderly, many of which have not been reported before., Conclusions: Those data expand our understanding of the various compensatory mechanisms that can occur with age, and further will assist in the development of methods to prevent and attenuate adverse outcomes of aging.

Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.

Aims and Objectives: To explore the meaning of rituals that women and their families perform after a stillbirth., Background: A cultural taboo in Taiwan prohibits discussing death; thus, parents of stillborn babies have no established public mourning or burial ceremonies to perform for their stillborn children. Stillbirths are often treated as if they had never happened., Design: Qualitative descriptive study., Methods: In-depth interviews, which were transcribed and content analysed, were conducted with a purposive sample of 16 women discharged from two teaching hospitals in Taiwan after they had a stillbirth., Results: Families engaged in rituals for two underlying reasons: to benefit the deceased child and the immediate family. The meanings of the rituals for the child are presented through three themes: (i) sending the baby's spirit to a safe place, (ii) protecting it from suffering and (iii) preparing it for a better reincarnation. The meanings of rituals for the families are presented through four themes: (i) releasing parental guilt by doing their best for the deceased child, (ii) cutting bonds with the child, (iii) avoiding additional misfortune should they mishandle the funeral and (iv) praying for a successful subsequent pregnancy., Conclusions: Death-related rituals are highly culturally diverse. This study fills a gap about Asian cultures. Participating in rituals permits a mother to do something for her deceased child, helps relieve her guilt and lets her cope with the stillbirth. Rituals after a stillbirth can help a woman recover from grieving and allow her to hope for a successful subsequent pregnancy., Relevance to Clinical Practice: Health professionals should discuss with bereaved parents what rituals they would like to perform and then respect their decisions. A continuum of care and support that exists from the prenatal diagnosis through the stillbirth and beyond is recommended for parents and families during this difficult time., (© 2017 John Wiley & Sons Ltd.)

Background: The problems of nurse burnout and manpower shortage relate to moral distress. Thus, having a good understanding of moral distress is critical to developing strategies that effectively improve the clinical ethical climate and improve nursing retention in Taiwan., Purpose: The aim of this study was to reconstruct the model of moral distress using the grounded theory., Methods: Twenty-five staff nurses at work units who attend to the needs of adult, pediatric, acute, and critical disease or end-of-life-care patients were recruited as participants using theoretical sampling from three teaching hospitals in Taiwan. Data were collected using intensive, 2- to 3-hour interviews with each participant. Audio recordings of the interviews were made and then converted into transcripts. The data were analyzed using the grounded theory., Results: In the clinical setting, the perspective that nurses take toward clinical moral events reflects their moral values, which trigger moral cognition, provocation, and appraisal. The moral barriers that form when moral events that occur in clinical settings contradict personal moral values may later develop into moral distress. In handling moral barriers in the clinical environment, nurses make moral judgments and determine what is morally correct. Influenced by moral efficacy, the consequence may either be a moral action or an expression of personal emotion. Wasting National Health Insurance resources and Chinese culture are key sources of moral distress for nurses in Taiwan. The role of self-confidence in promoting moral efficacy and the role of heterodox skills in promoting moral actions represent findings that are unique to this study., Conclusions: The moral distress model was used in this study to facilitate the development of future nursing theories. On the basis of our findings, we suggested that nursing students be encouraged to use case studies to establish proper moral values, improve moral cognition and judgment capabilities, and promote moral actions to better handle the regular pressures of moral distress in future clinical or workplace settings. Moreover, a better understanding of moral distress may help retain staff nurses.

Introduction: Determining the optimal time for performing a tracheostomy and weaning a patient off a ventilator is typically challenging for physicians, respiratory therapists, patients and patients' families., Purpose: This study examined the factors influencing tracheostomy timing and ventilator weaning and described the transition-care placement of patients who experience unsuccessful ventilator weaning., Methods: A retrospective design was employed, and 2 years of data were collected through a medical chart review performed at a hospital in Northern Taiwan. Sixty patients who received tracheostomies in the intensive care unit (ICU) or respiratory care center were enrolled. The data included each patient's demographic information, disease diagnosis, and Glasgow Coma Scale score and Acute Physiology and Chronic Health Evaluation II scores., Results: For patients on a ventilator in an ICU, the tracheostomy rate was 2.7%. Early (within 21 days) and late (>21 days) tracheostomies accounted for 36.7% and 63.3%, respectively. Of the patients who had received tracheostomies, 36.7% experienced ventilator weaning. The factors related to tracheostomy timing were disease diagnosis (P = 0.036) and days of ventilator use (P = 0.003). The factors related to ventilator weaning included disease diagnosis (P = 0.010) and tracheostomy timing (P = 0.001). Early tracheostomies were 10.9 times more likely than late tracheostomies to result in ventilator weaning (95%CI =2.5-47.7, P = 0.002)., Conclusions: Tracheostomy timing was strongly correlated with ventilator weaning. Early tracheostomy was higher successful ventilator weaning rates. The surgical patients were more likely to receive an early tracheostomy. However, the number of patients in Taiwan who received tracheostomies was lower than that in other countries. Further study maybe need to understand cultural variations in the acceptance of tracheostomies by patients., (© 2016 John Wiley & Sons Ltd.)

There has been an increased emphasis on nurses' mental health and well-being in the workplace. Psychologists have established a correlative link between individual's beliefs on luck and mental health. The pineapple taboo has been observed among Taiwanese hospital nurses as a prevalent superstitious belief for bringing luck or warding off increased clinical workloads, but how and why the ritual persists in the hospital workplace remains unknown. This article aims to explore the latent meaning of observance of the taboo and how it is related to nurses' clinical practice and possibly affects their mental health at work. A qualitative research was designed in line with the hermeneutic phenomenological method. Through purposive sampling, 18 nurse participants were recruited for in-depth semistructured interviews. Resulting from the ensuing analysis, 3 modalities were identified as constituting the spectrum of observance of the taboo: (a) "strictly not eating pineapple"; (b) "not eating pineapple at work"; and (c) "eating pineapple without admitting to doing so." Each reflects the position of nurses revealed in relation to the pineapple taboo in clinical settings. Based on the subjective narratives of nurses, it may be understood as an active moral attempt at "being right" rather than a passive avoidance of bad luck in the taboo observation. The findings facilitate an appropriate understanding of the embedded meaning of nurses' workplace-related belief and its seminal function of empowerment for nurses in holistic nursing practice.

Fragile X syndrome (FXS) is a generally hereditary form of human mental retardation that is caused by triplet repeat expansion (CGG) mutation in fragile X mental retardation 1 (fmr1) gene promoter and that results in the absence of the fragile X mental retardation protein (FMRP) expression. The common symptoms of FXS patients include learning disabilities, anxiety, autistic behaviors, as well as other behavioral abnormalities. Our previous results demonstrated the behavioral abnormalities in fmr1 knockout (KO) zebrafish such as fear memory impairment and autism-like behavior. Here, we studied the functional role of fmr1 gene on the development of social behavior by behavioral experiments, including shoaling behavior, shoaling preference, light/dark test, and novel tank task. Our results demonstrated that precocious development of shoaling behavior is found in fmr1 KO zebrafish without affecting the shoaling preference on conspecific zebrafish. The shoaling behavior appeared after 14 days postfertilization (dpf), and the level of shoaling elevated in fmr1 KO zebrafish. Furthermore, the fmr1 KO zebrafish at 28 dpf expressed higher anxiety level in novel tank task. These results suggest that the change of shoaling behavior in fmr1 KO zebrafish may result from hyperactivity and an increase of anxiety.

Background: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology., Methods: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing. At the same time, we carried out total RNA sequencing (RNA-seq) to analyze the transcriptomes of brain regions and liver tissues., Results: Our results reveal preferential 5hmC enrichment in the gene bodies of expressed genes, and 5hmC levels of many protein-coding genes are positively correlated with RNA expression intensity. However, more than 75% of genes with low or no 5hmC enrichment are genes encode for mitochondrial proteins and ribosomal proteins despite being actively transcribed, implying different transcriptional regulation mechanisms of these housekeeping genes. Brain regions developed from the same embryonic structures have more similar 5hmC profiles. Also, the genic 5hmC enrichment pattern is highly tissue-specific, and 5hmC marks genes involving in tissue-specific biological processes. Sex chromosomes are mostly depleted of 5hmC, and the X inactive specific transcript (Xist) gene located on the X chromosome is the only gene to show sex-specific 5hmC enrichment., Conclusions: This is the first report of the whole-genome 5hmC methylome of five major brain structures and liver tissues in mice of both sexes. This study offers a comprehensive resource for future work of mammalian cytosine methylation dynamics. Our findings offer additional evidence that suggests 5hmC is an active epigenetic mark stably maintained after the global reprogramming event during early embryonic development., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study focuses on the participants' lived experience of addiction., Design and Methods: The study presents a qualitative method. The use of the fieldwork-based participant observation and in-depth interviews guided the data collection and analysis., Findings: Three major themes of addiction emerge from the analysis: incorrigible conduct, inexcusable compromise, and inevitable corruption., Practice Implications: This study provides a better understanding of what the world is like for people struggling with addiction and also enhances the healthcare professionals' knowledge of the individual's experience of addiction. This knowledge is essential for clinicians to understand this experience as a framework for planning and implementing appropriate treatment., (© 2015 Wiley Periodicals, Inc.)

Background: There has been a dramatic increase in autism around the world. However, little is known about the impact of the Taiwanese primogeniture system on mothers of children with ASD. Greater knowledge is needed to understand the life experiences of Taiwanese mothers with ASD children when a healthy male descendent is expected., Materials and Methods: Research follows the hermeneutic phenomenological approach with in-depth interviews and participant observation (Agar, Speaking of Ethnography. Sage, California, 1986). The researchers collected and analysed stories from seven mothers who are the major caregivers of their school-aged autistic children., Results: The data revealed the following themes that represented the mothers' experiences: taking the blame, my world was turned upside down, a child-centred life and two lives as one., Conclusions: The findings provide a deeper understanding of common expectations of, and behaviours directed towards, Taiwanese mothers of children with autism. This offers healthcare professionals ways of reconceptualizing therapeutic practice, thus benefitting these mothers., (© 2015 John Wiley & Sons Ltd.)

Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Recurrence and metastasis are common in hepatocellular carcinoma (HCC) and correlate with poor prognosis. We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in HCC metastasis. Overexpression of FNDC3B in HCC cell lines enhanced cell migration and invasion. On the other hand, knockdown of FNDC3B using short-hairpin RNA reduced tumor nodule formation in both intra- and extra-hepatic metastasis. High levels of FNDC3B were observed in metastatic HCCs and correlated with poor patient survival and shorter recurrence time. Mutagenesis and LC-MS/MS analyses showed that FNDC3B promotes cell migration by cooperating with annexin A2 (ANXA2). Furthermore, FNDC3B and ANXA2 expression correlated negatively with patient survival. Our results indicate that FNDC3B behaves like an oncogene by promoting cell migration. This suggests FNDC3B could serve as a biomarker and therapeutic target for HCC metastasis., Competing Interests: No conflicts of interest to disclose.

A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.

Telomeres are capped at the ends of eukaryotic chromosomes and are composed of TTAGGG repeats bound to the shelterin complex. Here we report that a replication-dependent histone H2A isotype, H2ac, was associated with telomeres in human cells and co-immunoprecipitates with telomere repeat factor 2 (TRF2) and protection of telomeres protein 1 (POT1), whereas other histone H2A isotypes and mutations of H2ac did not bind to telomeres or these two proteins. The amino terminal basic domain of TRF2 was necessary for the association with H2ac and for the recruitment of H2ac to telomeres. Depletion of H2ac led to loss of telomeric repeat sequences, the appearance of dysfunctional telomeres, and chromosomal instability, including chromosomal breaks and anaphase bridges, as well as accumulation of telomere-associated DNA damage factors in H2ac depleted cells. Additionally, knockdown of H2ac elicits an ATM-dependent DNA damage response at telomeres and depletion of XPF protects telomeres against H2ac-deficiency-induced G-strand overhangs loss and DNA damage response, and prevents chromosomal instability. These findings suggest that the H2A isotype, H2ac, plays an essential role in maintaining telomere functional integrity.

Chronic inflammation may promote development of coronary heart disease. Studies on the relationship between chronic pancreatitis (CP) and cardiovascular diseases are scant.We conducted a nationwide retrospective cohort study to determine the risk of acute coronary syndrome (ACS) in patients with CP.We randomly selected a comparison cohort of individuals without CP from the Taiwan National Health Insurance Research Database (N = 23.74 million) and frequency-matched them with patients with CP from 2000 to 2010 in a 1:4 ratio according to age, sex, and index year. The follow-up period lasted from the index date of the new CP diagnosis to the date of ACS diagnosis, censoring, or the end of 2011. We analyzed the risk of ACS by using Cox proportional-hazard models.In total, 17,405 patients with CP and 69,620 individuals without CP were followed for 84,430 and 417,426 person-years. Most patients with CP were men, and the mean age of the patients was 48.3 ± 15.0 years. The overall ACS incidence was 2.15-fold higher in the CP cohort than in the non-CP cohort (4.89 vs 2.28 per 10,000 person-years) with an adjusted hazard ratio (aHR) of 1.40 (95% confidence interval [CI] 1.20-1.64). Compared with individuals without CP, patients with CP aged ≤39 years exhibited the highest risk of ACS (aHR 2.14, 95% CI 1.13-4.02), followed by those aged 40 to 54 years (aHR 1.66, 95% CI 1.23-2.24) and those aged 55 to 69 years (aHR 1.53, 95% CI 1.15-2.03).CP may become an independent risk factor for ACS.

Axon extension at the growing tip requires elevated local protein supply, with a capability sustainable over long axons in varying environments. The exact mechanisms, however, remain elusive. Here we report that axon-promoting factors elicited a retrograde transport-dependent removal of proteasomes from nascent axon terminals, thereby increasing protein stability at axon tips. Such an effect occurred through phosphorylation of a dynein-interacting proteasome adaptor protein Ecm29. During the transition from immature neurites to nascent axons in cultured hippocampal neurons, live-cell imaging revealed a significant increase of the retrograde axonal transport of fluorescently labeled 20S proteasomes. This retrograde proteasome transport depended on neuron stage and increased with axon lengths. Blockade of retrograde transport caused accumulation of proteasomes, reduction of axon growth, and attenuation of growth-associated Par6 at the axon tip of newly polarized neurons. Our results delineate a regulatory mechanism that controls proteasome abundance via preferential transport required for axon development in newborn neurons., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Recombinant human thyrotropin (rhTSH) can be used to enhance radioiodine therapy for shrinking multinodular goitre. The aim of this meta-analysis was to compare the effectiveness of rhTSH pretreatment and radioiodine therapy with that of radioiodine alone for treating benign nodular goitre., Methods: The PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov databases were searched to identify studies published before September 2014. A meta-analysis was performed to calculate the pooled effect size using random-effects models. The primary outcome was the reduction in thyroid volume. Secondary outcomes included thyroid function, extent of tracheal compression, radioactive iodine uptake, incidence of hypothyroidism and other complications., Results: Nine RCTs including 416 patients were selected. The reductions in thyroid volume were significantly greater in the rhTSH pretreatment groups than those in the radioiodine alone groups at 12 months (weighted mean difference: 14·42%; 95% CI: 4·51-24·34% in high-dose rhTSH vs radioiodine alone; weighted mean difference: 19·66%; 95% CI: 3·67-35·65% in low-dose rhTSH vs radioiodine alone). The incidence of hypothyroidism in the high-dose rhTSH groups was significantly higher than that in the radioiodine alone groups. No significant difference in the incidence of hypothyroidism occurred between the low-dose rhTSH groups and the radioiodine alone groups., Conclusions: The overall results indicated that using rhTSH before radioiodine therapy resulted in a greater thyroid volume reduction than radioiodine therapy alone. An increased incidence of hypothyroidism was observed in patients receiving high-dose rhTSH. Low-dose rhTSH before radioiodine therapy is more efficacious than radioiodine therapy alone for treating nontoxic benign thyroid nodules., (© 2014 John Wiley & Sons Ltd.)

Background: Sliding-scale insulin has been widely used in treating inpatient hyperglycemia. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and possible adverse effects of sliding-scale insulin in hospitalized patients., Methods: PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov registry were searched for studies published up to May 2015. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size using random effects models., Results: Eleven RCTs containing a total of 1322 patients were identified. Among eight studies in which the RISS was compared with other regimens, no significant difference was observed in the percentage of patients who achieved the mean blood glucose level between the two groups, which was determined according to the numbers of blood samples (RR: 2.84; 95% CI: 0.94 to 8.59) and patients (RR: 1.75; 95% CI: 0.86 to 3.55). The mean blood glucose level (weighted mean difference=27.33, 95% CI: 14.74 to 39.92) and incidence of hyperglycemic events were significantly higher in the RISS group than in the non-sliding-scale group. No significant difference in the incidence of severe hypoglycemia and length of hospitalization between the groups was identified., Conclusions: The overall results of the meta-analysis indicated that applying the RISS alone or in combination with other antidiabetic medications did not provide any benefits in blood glucose control, but was accompanied by an increased incidence of hyperglycemic events. Therefore, we suggest that the use of sliding-scale insulin be discontinued in hospitals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims and Objectives: To gain an in-depth understanding of women's experiences of performing pelvic floor muscle exercises for urinary incontinence and the impact on their sexuality., Background: Urinary incontinence is not a life-threatening disorder; however, it has been shown to have detrimental effects on quality of life in terms of psychological, social and sexual dysfunction. Pelvic floor muscle exercises is the first recommended strategy for managing mild to moderate urinary incontinence as it is noninvasive and cost effective. Pelvic floor muscle exercises reduce incontinence and strengthen the pelvic floor muscles, which positively affects sexual function in women. Currently, the data are scarce for qualitative literature regarding the subjective experiences of Taiwanese women undergoing pelvic floor muscle exercises and the impact on their urinary incontinence and sexuality., Design: Qualitative exploratory study., Methods: Semi-structured in depth interviews were undertaken with twelve women who had completed a pelvic floor muscle exercises program in Taiwan. Data were analysed using thematic analysis., Results: Themes were related to Taiwanese women's initial feelings that urinary incontinence was inevitable and the effects on their sexuality. Three core themes were identified: perceptions of inevitability, developing awareness and gaining control and sexual taboo. Through developing awareness and control of their pelvic floor muscles women expressed improvement in urinary incontinence. Sexual enjoyment, body image, self confidence and sexuality were also enhanced., Conclusion: Pelvic floor muscle exercises had a positive effect on urinary incontinence and sexuality. The findings demonstrated that sex is a taboo topic for many Taiwanese women. With the sensitive management of pelvic floor muscle exercises programs this issue can be addressed., Relevance to Clinical Practice: This study raises awareness of healthcare professionals by identifying how Taiwanese women perceive pelvic floor muscles. The positive impact of pelvic floor muscle exercises upon both urinary incontinence and sexuality within the Taiwanese context are addressed. Nurses may also, with greater confidence initiate discussion of women's sexual concerns as part of managing urinary incontinence., (© 2015 John Wiley & Sons Ltd.)