Red blood cell tension protects against severe malaria in the Dantu blood group.

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Development and psychometric testing of the safety climate instrument suitable for nurses handling chemotherapy drugs.

AIM: To develop and test the psychometric properties of the Taiwanese safety climate instrument suitable for nurses handling chemotherapy drugs. DESIGN: This is an instrument development study. METHOD: All four stages, including questionnaire design, expert consultation, cognitive testing and psychometric validation, were used in this study. The data were collected between August and December 2018. Nurses with experience in handling chemotherapy drugs (N = 484) at one medical centre and two regional hospitals in Taiwan completed this instrument. Data were randomly split into two groups: one group (N = 237) for exploratory factor analysis and the other (N = 247) for confirmatory factor analysis. RESULTS: The instruments' items were based on qualitative research, and the content validity index levels exceeded the acceptable value. An exploratory factor analysis revealed 43 items remaining in six factors, which accounted for 74.4% of variance. The result of the confirmatory factor analysis verified the acceptability of a 43-item model. The composite reliability values, Cronbach's alpha values, convergent validity and discriminant validity for each factor exceeded the acceptable value. CONCLUSION: Most climate safety instruments used in the health care sector focus mainly on patient safety outcomes. Furthermore, there is no safety climate instrument for handling chemotherapy drugs, and there is a cultural difference. Through the development and validation process, we have developed a new instrument suitable for nurses handling chemotherapy drugs, which has good psychometric properties. IMPACT: This instrument is valuable as its development was based on the concept of a safety climate for health care perceptions and qualitative survey findings. Hospital managers can use this instrument regularly to evaluate nurses' perceptions of the safety climate to determine the strengths and weaknesses of their workplace, thereby assisting organizational managers in proposing concrete actions.

Differences between Gamblers and Non-Gamblers on Sports Betting Websites.

Online sports gambling is a popular recreational activity. Using the Theory of Planned Behaviour as the theoretical foundation, the aim of this study was to examine for differences between gamblers and non-gamblers in terms of their attitudes, subjective norms and perceived behavioral control towards online sports gambling. 173 male students from a tertiary educational institution were recruited for this study of which 56 respondents (32%) were gamblers. A series of regression analysis revealed differences between gamblers and non-gamblers. While subjective norms and perceived behavioural control were significant predictors of gambling intentions for the gamblers group, only attitude was a significant predictor for the non-gamblers group. Further analysis showed that subjective norms had a larger effect on the gamblers group in comparison to the non-gamblers group. Physiological data from an eye tracker provided further empirical evidence that there were differences between gamblers and non-gamblers. Gamblers, perhaps because they are more familiar with gambling websites, take less time to process information. The findings from this study suggests that there are differences between gamblers and non-gamblers. To prevent problem gambling, there is a need to develop different communication messages for gamblers and non-gamblers.

Experience of the use of hydroxychloroquine on patients with COVID-19: A perspective on viral load and cytokine kinetics.

Until now, there are no approved treatment against COVID-19. Hydroxychloroquine (HCQ) was hypothesized to be active against SARS-CoV2 via antiviral and anti-inflammatory effect; however, HCQ for COVID-19 in clinical use remained debating. In this preliminary report, we presented six patients with mild to moderate COVID-19. They were treated with HCQ for 14 days from the day of COVID-19 diagnosis. Serial viral load from respiratory specimens were performed every other day. Cytokine profile was checked before HCQ initiation and on the 14th day of HCQ treatment. All patients receiving HCQ completed 14-day course without complication. Among the six patients, the mean duration from symptom onset to last detectable viral load was 34 ± 12 days, which was similar to those without specific treatment in previous reports. Low level of interferon-gamma was noted in all patients of different stage of infection and three patients had elevation of IL-17 level. Prolonged virus shedding is still observed regardless HCQ. The impact of HCQ on cytokine kinetics remained unclear; however, IL-17 could be an inflammatory marker for disease status monitor and a potential therapeutic target.

Visual, sensitive and rapid event-specific detection of genetically modified potato EH92-527-1 by loop-mediated isothermal amplification method.

To date, studies on the application of loop-mediated isothermal amplification (LAMP) in the detection of genetically modified organisms (GMOs) are stably increasing and demonstrates LAMP is a potential and promising method for on spot identification of GMOs. However, little information is known for detection of GM potato events by LAMP. In this report, we developed an optimized and visual LAMP assay with high specificity and sensitivity to rapidly amplify genomic DNA of potato EH92-527-1 within 45 min. The limit of detection of LAMP in our study is 10-fold higher than the conventional PCR. Furthermore, LAMP products can be directly observed via naked eyes by addition of SYBR Green I without gel electrophoresis analysis and PCR-based equipment. Therefore, the LAMP assay developed in this paper provides an efficient, convenient and cost-effective tool for the detection of GM potato EH92-527-1.

Synergistic malaria vaccine combinations identified by systematic antigen screening.

A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

Effects of the biopsychosocial functional activity program on cognitive function for community older adults with mild cognitive impairment: A cluster-randomized controlled trial.

Early preventive interventions may delay the onset of dementia for people with mild cognitive impairment. This study was designed to examine the effects of the biopsychosocial functional activity program on the cognitive function of community middle to older adults with mild cognitive impairment. A cluster-randomized controlled trial was conducted. The experimental group received a 12-month biopsychosocial functional activity program intervention that contained two phases. The first phase was a 6-week teaching program followed by a second-phase home follow-up phase. The measurement was carried out at baseline, 6 months and 12 months after the biopsychosocial functional activity program. The measurement tool was the Chinese version of the Saint Louis University Mental Status Examination. The Generalized Estimating Equations statistical approach was used to analyze the data. The experimental group showed significant short-term and continuous improvement in overall cognitive function in the immediate- and short-term memory domain while the domain of attention and executive function showed improvement on the 12-month measurement compared to the control group. Yet, there was no significant improvement overall and in the three domains of cognitive function for the control group. The findings may become references for advancing the dementia prevention program for communities as well as the national policies for dementia prevention programs.

Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates.

The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more "western" lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends.

Progressive multifocal leukoencephalopathy in a 27-year-old lady with systemic lupus erythematosus - rheumatoid arthritis overlap syndrome.

Progressive multifocal leukoencephalopathy (PML) is a rare viral demyelinating disease of central nervous system. Immunosuppression is a significant risk factor for the disease. Previously, PML developed more commonly in patients of hematological malignancy and acquired immune deficiency syndrome (AIDS). In the era of biological disease modifying anti-rheumatic drugs, PML is more frequently reported in patients of autoimmune diseases. However, for its rarity and unspecific clinical presentations, accurate diagnosis and immediate immune restoration might be difficult in clinical practice, and the outcome might thus be miserable. Herein we present a 27-year-old lady of systemic lupus erythematosus (SLE) - rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system. Neuropsychiatric SLE was suspected first. However, after intensive immunosuppressive treatment, the condition kept deteriorating. An alternative diagnosis was thus considered. PML was suspected for her immunosuppressive status and suggestive radiological findings, and the diagnosis was confirmed by a polymerase chain reaction of JC virus from cerebrospinal fluid. After restoring the immune status by decreasing the dose of immunosuppressants, the condition of the patient improved significantly. We report this case to raise the importance of clinical alertness for the rare but possibly underdiagnosed disease.

Evidence against a Role of Elevated Intracellular Ca2+ during Plasmodium falciparum Preinvasion.

Severe malaria is primarily caused by Plasmodium falciparum parasites during their asexual reproduction cycle within red blood cells. One of the least understood stages in this cycle is the brief preinvasion period during which merozoite-red cell contacts lead to apical alignment of the merozoite in readiness for penetration, a stage of major relevance in the control of invasion efficiency. Red blood cell deformations associated with this process were suggested to be active plasma membrane responses mediated by transients of elevated intracellular calcium. Few studies have addressed this hypothesis because of technical challenges, and the results remained inconclusive. Here, Fluo-4 was used as a fluorescent calcium indicator with optimized protocols to investigate the distribution of the dye in red blood cell populations used as P. falciparum invasion targets in egress-invasion assays. Preinvasion dynamics was observed simultaneously under bright-field and fluorescence microscopy by recording egress-invasion events. All the egress-invasion sequences showed red blood cell deformations of varied intensities during the preinvasion period and the echinocytic changes that follow during invasion. Intraerythrocytic calcium signals were absent throughout this interval in over half the records and totally absent during the preinvasion period, regardless of deformation strength. When present, calcium signals were of a punctate modality, initiated within merozoites already poised for invasion. These results argue against a role of elevated intracellular calcium during the preinvasion stage. We suggest an alternative mechanism of merozoite-induced preinvasion deformations based on passive red cell responses to transient agonist-receptor interactions associated with the formation of adhesive coat filaments.

PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

Prostaglandin E2 (PGE2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE2 /prostaglandin E receptor 4 (EP4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFß signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP4 ) antagonism. EP4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFß and PI3K/Akt pathways. EP4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE2 /EP4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444.

[Self-Supporting Care Model for Older Adults].

Self-supporting care is an emerging concept in the geriatric care system of Taiwan. The traditional care model tends to prioritize aspects such as "safety" and "convenient and effective". For older adult patients, this situation has led to excessive restrictions, enforced bedrest, and the use of adult diapers, which seriously deteriorate quality of life. The present article introduces the development and current status of self-supporting care and international empirical research results from the perspective of holistic care for older adults as well as describes the intervention strategies that are currently used in Taiwan. We look forward to the caregivers of older adults being able to apply self-supporting care in their care settings, which is expected to enhance quality of life and dignity for older adults.

APOA5 Gene Polymorphisms and Cardiovascular Diseases: Metaprediction in Global Populations.

BACKGROUND: Apolipoprotein A5 (APOA5) 1131 is one of the most investigated gene polymorphisms in association with cardiovascular diseases (CVD) for its roles in epigenetics pathways. OBJECTIVES: The major objective of this metaprediction study was to comprehensively examine the association of polymorphism risk subtypes of APOA5 1131 gene and potential contributing factors of CVD risks in global populations. METHODS: This study is a meta-analysis to determine APOA5 gene polymorphisms as risk factors for CVDs. Following the guidelines of meta-analyses, we applied big data analytics including the recursive partition tree, nonlinear association curve fit, and heat maps for data visualization-in addition to the conventional pooled analyses. RESULTS: A total of 17,692 CVD cases and 23,566 controls from 50 study groups were included. The frequency of APOA5 1131 CC and TC polymorphisms in Asian populations (22.2%-52.6%) were higher than that in other populations, including Caucasians and Eurasians (10.0%-25.0%). The homozygous CC and heterozygous TC genotypes (both p < .0001) were associated with increased risks for CVD and were higher in many Western nations, including Canada, Spain, the Czech Republic, Hungary, Turkey, Egypt, France, and Iran. The CC genotype was associated with greater risks (RR > 2.00, p < .0001) for dyslipidemia and myocardial infarction, whereas RR > 1.00 was associated with metabolic syndrome, coronary artery disease, and stroke. Air pollution was significantly associated with APOA5 1131 CC and TC polymorphisms. DISCUSSION: The findings of this study provided novel insight to further understand the associations among APOA5 1131 polymorphisms, air pollution, and the development of CVDs. Methylation studies are needed to examine epigenetic factors associated with APOA5 1131 polymorphisms and CVD and to suggest potential prevention strategies for CVD.

Autologous Serum Eye Drops Combined With Silicone Hydrogen Lenses for the Treatment of Postinfectious Corneal Persistent Epithelial Defects.

OBJECTIVE: To evaluate the clinical effect of combined topical autologous serum eye drops (ASEs) and silicone hydrogel contact lens (CLs) for the treatment of corneal persistent epithelial defects (PEDs) after infectious corneal ulcers. METHODS: We conducted a retrospective chart review of 12 patients with postinfectious corneal PEDs who were unsuccessfully treated with conventional medical management and were then treated with combined topical 20% (v/v) ASEs and silicone hydrogel CLs from July 1, 2011, to June 30, 2014. The corneal ulcers were all initially managed with antibiotic eye drops until the infiltrates resolved but the lesions failed to epithelialize. The clinical effects of the combined treatment were evaluated. RESULTS: The PEDs healed in all 12 patients within 2 weeks. The combined treatment was associated with an improvement of best-corrected visual acuity (BCVA) at the final 3-month follow-up examination. All patients responded well to the combined treatment and no adverse events were noted in any patient. CONCLUSIONS: The combined use of silicone hydrogel CLs and ASEs can successfully treat postinfectious corneal PEDs and prevent continuous corneal melting during acute disease.

Concept analysis of safety climate in healthcare providers.

AIM AND OBJECTIVE: To report an analysis of the concept of safety climate in healthcare providers. BACKGROUND: Compliance with safe work practices is essential to patient safety and care outcomes. Analysing the concept of safety climate from the perspective of healthcare providers could improve understanding of the correlations between safety climate and healthcare provider compliance with safe work practices, thus enhancing quality of patient care. DESIGN: Concept analysis. DATA SOURCES: The electronic databases of CINAHL, MEDLINE, PubMed and Web of Science were searched for literature published between 1995-2015. Searches used the keywords 'safety climate' or 'safety culture' with 'hospital' or 'healthcare'. METHOD: The concept analysis method of Walker and Avant analysed safety climate from the perspective of healthcare providers. RESULTS: Three attributes defined how healthcare providers define safety climate: (1) creation of safe working environment by senior management in healthcare organisations; (2) shared perception of healthcare providers about safety of their work environment; and (3) the effective dissemination of safety information. Antecedents included the characteristics of healthcare providers and healthcare organisations as a whole, and the types of work in which they are engaged. Consequences consisted of safety performance and safety outcomes. Most studies developed and assessed the survey tools of safety climate or safety culture, with a minority consisting of interventional measures for improving safety climate. CONCLUSION: More prospective studies are needed to create interventional measures for improving safety climate of healthcare providers. This study is provided as a reference for use in developing multidimensional safety climate assessment tools and interventional measures. RELEVANCE TO CLINICAL PRACTICE: The values healthcare teams emphasise with regard to safety can serve to improve safety performance. Having an understanding of the concept of and interventional measures for safety climate allows healthcare providers to ensure the safety of their operations and their patients.

[The Application of Grief Theories to Bereaved Family Members].

Loss is an inevitable experience for humans for which grief is a natural response. Nurses must have an adequate understanding of grief and bereavement in order to be more sensitive to these painful emotions and to provide appropriate care to families who have lost someone they love deeply. This article introduces four important grief theories: Freud's grief theory, Bowlby's attachment theory, Stroebe and Schuts' dual process model, and Neiyemer's meaning reconstruction model. Freud's grief theory holds that the process of grief adaptation involves a bereaved family adopting alternative ways to connect with the death of a loved one and to restore their self-ego. Attachment theory holds that individuals who undergo grieving that is caused by separation from significant others and that triggers the process of grief adaptation will fail to adapt if they resist change. The dual process model holds that bereaved families undergo grief adaptation not only as a way to face their loss but also to restore normality in their lives. Finally, the meaning reconstruction model holds that the grief-adaptation strength of bereaved families comes from their meaning reconstruction in response to encountered events. It is hoped that these theories offer nurses different perspectives on the grieving process and provide a practical framework for grief assessment and interventions. Additionally, specific interventions that are based on these four grief theories are recommended. Furthermore, theories of grief may help nurses gain insight into their own practice-related reactions and healing processes, which is an important part of caring for the grieving. Although the grieving process is time consuming, nurses who better understand grief will be better able to help family members prepare in advance for the death of a loved one and, in doing so, help facilitate their healing, with a view to the future and to finally returning to normal daily life.

[Implementing and Promoting Advance Care Planning for Community Older Adults].

Advance care planning (ACP) is an emerging issue in the primary care system of Taiwan. Previous studies have attributed benefits to various types of ACP in diverse ranges of healthcare settings and populations. However, few older adults in Taiwan have had the opportunity to discuss ACP or to complete their advance directives. The present article takes the perspective of community health nursing to describe the international development and current status of ACP in the community in Taiwan. Furthermore, the intervention models and available resources of ACP are described. We look forward to healthcare professionals using ACP to assist greater numbers of community older adults, thus enhancing their terminal-stage quality of life.

Clickable 5'-γ-ferrocenyl adenosine triphosphate bioconjugates in kinase-catalyzed phosphorylations.

Clickable co-substrate: A tri-functional 5'-γ-ferrocenyl adenosine triphosphate (Fc-ATP) derivative containing a clickable site was synthesized. This compound is an effective co-substrate in kinase-catalyzed phosphorylation reactions, which can be detected by both electrochemical and immunoassay detection methods. The clickable reaction site makes direct modification possible, which greatly expands its application.

Comparison of senhance and da vinci robotic radical prostatectomy: short-term outcomes, learning curve, and cost analysis.

BACKGROUND: The Senhance® Robotic System is a new laparoscopy-based platform that has been increasingly used in radical prostatectomy (RP) procedures. The purpose of this study is to compare the outcome of Senhance RP (SRP) with da Vinci RP (DRP) cases. METHODS: From August 2019 to April 2022, we prospectively recruited 63 cases of SRP. We compared the perioperative data, postoperative complication rates, short-term surgical outcomes (3-month postoperative undetectable prostate-specific antigen (PSA) and incontinence rates), learning curves, and cost analysis with data from 63 matched da Vinci Xi RP cases. RESULTS: There was no difference in BL (180 versus 180 ml, p = 0.86) and postoperative surgical complication rate (Clavient -Dindo grade I-IV, 25.3 versus 22.2%, p = 0.21) between the SRP cases and the DRP. Regarding the oncologic and continence function, there was no difference between positive margin rate (36.5% versus 41.3%, p = 0.58), rate of undetectable PSA level at postoperative 3 months (68.3 versus 66.7%, p = 0.85), and incontinence rate (14.3 versus 15.9%, p = 1.0) at postoperative 3 months between the two cohorts. The learning curve showed a quick downward slope for laparoscopic experienced surgeons. The median pocket cost for SRP patients in our hospital was $4170, which was lower than $7675 for the DRP patients. CONCLUSIONS: Safety and short-term outcomes are comparable between SRP and DRP. For experienced LRP surgeons, using the Senhance system to perform RP is straightforward. With a more affordable price as its biggest advantage, the Senhance system may serve as a safe and effective alternative for robotic RP.

Generation of induced pluripotent stem cells from an HLA-B27 positive ankylosing spondylitis patient with syndesmophyte formation.

Human leukocyte antigen (HLA)-B27 is the genetic marker for ankylosing spondylitis (AS). Here, we generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a male AS patient carrying HLA-B27 with syndesmophyte formation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, expressed pluripotent markers, and could differentiate into three germ layers. This cellular model will provide a platform for studying pathological mechanisms of new bone formation in HLA-B27 positive AS patients.