Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aß burden and restores memory functions in 5xFAD mice.

Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer's disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer's disease. High levels of YKL-40 are associated with either advanced Alzheimer's disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer's disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer's disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aß1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aß1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aß1-42 peptides, increased rate of Aß1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer's disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer's disease patients.

Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models.

PTEN hamartoma tumour syndrome is characterised by mutations in the human PTEN gene. We performed transcriptomic and proteomic analyses of neural tissues and primary cultures from heterozygous and homozygous Pten-knockout mice. The somatosensory cortex of heterozygous Pten-knockout mice was enriched in immune response and oligodendrocyte development Gene Ontology (GO) terms. Parallel proteomic analysis revealed differentially expressed proteins (DEPs) related to dendritic spine development, keratinisation and hamartoma signatures. However, primary astrocytes (ASTs) from heterozygous Pten-knockout mice were enriched in the extracellular matrix GO term, while primary cortical neurons (PCNs) were enriched in immediate-early genes. In ASTs from homozygous Pten-knockout mice, cilium-related activity was enriched, while PCNs exhibited downregulation of forebrain neuron generation and differentiation, implying an altered excitatory/inhibitory balance. By integrating DEPs with pre-filtered differentially expressed genes, we identified the enrichment of traits of intelligence, cognitive function and schizophrenia, while DEPs in ASTs were significantly associated with intelligence and depression.

Factors affecting nursing students' intention to use a 3D game to learn field triage skills: a structural equation modelling analysis.

BACKGROUND: As mass casualty incidents are low-probability events, students often do not have the chance to practise field triage skills during their clinical placement. This study used a 3D game to engage participants in experiential learning in a realistic virtual environment. The purpose of the study was to explore factors affecting nursing students' intention to use a 3D game to learn field triage skills. METHODS: This was a cross-sectional survey study. The technology acceptance model augmented by computer self-efficacy was used as a research model and a questionnaire was used to evaluate students' intention to use the 3D game to learn field triage. Data was collected from nursing students of a degree-awarding higher education institution in Hong Kong. RESULTS: A total of 177 valid questionnaires were returned, and structural equation modeling was used to test the research model and hypotheses. Consistent with the technology acceptance model, perceived usefulness (0.21, p < 0.05) and perceived ease of use (0.91, p < 0.001) had a positive effect on the behavioral intention to use the 3D game. Computer self-efficacy positively influenced both perceived usefulness (0.66, p < 0.001) and perceived ease of use (0.73, p < 0.001). The research model explained 42 percent of the variance in the behavioral intention to use the 3D game. CONCLUSION: Students believed that using the 3D game would enhance their field triage skills and found the game easy to use. Using 3D games to facilitate learning is a worthwhile educational approach for preparing healthcare professionals to handle low-probability clinical tasks, such as field triage in mass casualty incidents. Insights provided by findings of this study included the best way to design and promote interactive education programmes in a virtual environment.

Nursing students' experiences and perceptions of learner-centred education in a disaster nursing course: A qualitative study.

Learner-centred education has been shown to be an effective teaching method in the healthcare disciplines that integrate practical skills and theoretical knowledge. However, the elements of learner-centred education that influence students' motivation and engagement in learning remain unclear. In this descriptive qualitative research study, 43 nursing students in a baccalaureate nursing programme in Hong Kong who enrolled in a disaster and trauma nursing course were recruited through purposive sampling. Data were collected through semi-structured, face-to-face, focus group interviews. The transcribed interviews were interpreted through the use of qualitative analysis. This study revealed that adopting learner-centred education techniques in a disaster nursing course could cater to the hedonic nature and practical nature of learning disaster nursing, which consequently strengthens student's motivation and engagement in learning. The findings also suggested that learner-centred education could improve nursing students' learning experience and promote their transformation from passive and receptive students into proactive learners. The present study provides a greater and more focused understanding of the elements of learner-centred education that promote motivation and engagement in learning among nursing students. This study could offer insights into the development and evaluation of disaster nursing courses and other subjects in the undergraduate nursing curriculum.

Antecedents and Contextual Factors Affecting Occupational Turnover among Registered Nurses in Public Hospitals in Hong Kong: A Qualitative Descriptive Study.

Global increases in both population size and ageing have led to a drastic expansion in the demand for healthcare services. The shortage of nursing workforce capacity continues, posing immense challenges for the global healthcare system. We aimed to identify the antecedents and contextual factors that contribute to the decisions of occupational turnover from the clinical duties of registered nurses in public hospitals in Hong Kong. A qualitative descriptive design was used in this study. A total of 18 registered nurses who had resigned from public hospitals in Hong Kong and changed their occupations were recruited via convenience and snowball sampling methods. Data were collected through individual, semi-structured, and face-to-face interviews and were analyzed according to the content analysis approach. The antecedents and contextual factors that contributed to the registered nurses' decisions regarding occupational turnover were identified from the collected data. These factors were classified into three overarching categories: (1) job dissatisfaction due to a tense work environment, (2) low motivation due to limited career opportunities, and (3) inadequate communication due to ineffective leadership. The identification of these antecedents and contextual factors could help healthcare service providers to develop strategies to enhance nurses' commitment and engagement in their positions and eventually improve their retention. Based on these factors, healthcare sector policy makers could consider incorporating appropriate strategies into healthcare system policy.

Investigating the Strategies Adopted by Emergency Nurses to Address Uncertainty and Change in the Event of Emerging Infectious Diseases: A Grounded Theory Study.

Emergency nurses frequently encounter uncertainty and changes during the management of emerging infectious diseases, which challenge their capability to perform their duties in a well-planned and systematic manner. To date, little is known about the coping strategies adopted by emergency nurses in addressing uncertainty and changes during an epidemic event. The present study explored emergency nurses' behaviours and strategies in handling uncertainty and practice changes during an epidemic event. A qualitative study based on the Straussian grounded theory approach was established. Semi-structured, face-to-face, individual interviews were conducted with 26 emergency nurses for data collection. Adapting protocol to the evolving context of practice was revealed as the core category. Four interplaying subcategories were identified: (1) Completing a comprehensive assessment, (2) continuing education for emerging infectious disease management, (3) incorporating guideline updates and (4) navigating new duties and competencies. The nurses demonstrated the prudence to orientate themselves to an ambiguous work situation and displayed the ability to adapt and embrace changes in their practice and duties. These findings offer insights into the need for education and training schemes that allow emergency nurses to acquire and develop the necessary decision-making and problem-solving skills to handle a public health emergency.

A qualitative descriptive study of the contextual factors influencing the practice of emergency nurses in managing emerging infectious diseases.

Purpose: Emergency nurses are engaged in the management of epidemic events that unfold along with the evolution of diseases. The goal of this study was to explore the contextual factors that inhibited the ability of emergency nurses to perform their duties in response to an outbreak. Methods: A qualitative descriptive design was used to explore the experiences and perceptions of emergency nurses. Participants were purposively recruited from 12 emergency departments in Hong Kong. Semi-structured face-to-face individual interviews were conducted with 26 emergency nurses. The audio-recorded interviews were transcribed verbatim and interpreted with a thematic analysis approach. Results: Four intertwined themes emerged from the analysis: resource constraints, threats of infection, ubiquitous changes and lingering uncertainties. These themes portrayed the constraints and challenges surrounding the work environment of emergency nurses. Conclusion: This study described the instabilities and vulnerabilities of the circumstances in which the emergency nurses were situated in during epidemic events. The findings shed light on the importance of hospitals and emergency departments in addressing both the technical problems and adaptive challenges that face emergency nurses during epidemic events.

Evaluation of multiplex tandem PCR (MT-PCR) assays for the detection of bacterial resistance genes among Enterobacteriaceae in clinical urines.

Background: Increasing resistance drives empirical use of less potent and previously reserved antibiotics, including for urinary tract infections (UTIs). Molecular profiling, without culture, might better guide early therapy. Objectives: To explore the potential of AusDiagnostics multiplex tandem (MT) PCR UTI assays. Methods: Two MT-PCR assays were developed successively, seeking 8 or 16 resistance genes. Amplification was tracked in real time, with melting temperatures used to confirm product identity. Assays were variously performed on: (i) extracted DNA; (ii) cultured bacteria; (iii) urine spiked with reference strains; and (iv) bacteria harvested from clinical urines. Results were compared with those from sequencing, real-time SybrGreen PCR or phenotypic susceptibility. Results: Performance was similar irrespective of whether DNA, cultures or urines were used, with >90% sensitivity and specificity with respect to common ß-lactamases, dfr genes and aminoglycoside resistance determinants except aadA1/A2/A3, for which carriage correlated poorly with streptomycin resistance. Fluoroquinolone-susceptible and -resistant Escherichia coli (but not other species) were distinguished by the melting temperatures of their gyrA PCR products. The time from urine to results was <3 h. Conclusions: The MT-PCR assays rapidly identified resistance genes from Gram-negative bacteria in urines as well as from cultivated bacteria. Used directly on urines, this assay has the potential to guide early therapy.

Effects of Resveratrol and Morin on Insoluble Tau in Tau Transgenic Mice.

Tauopathies are neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal dementia (FTD), in which tau protein aggregates within neurons. An effective treatment is lacking and is urgently needed. We evaluated two structurally similar natural compounds, morin and resveratrol, for treating tauopathy in JNPL3 P301L mutant human tau overexpressing mice. Rotarod tests were performed to determine effects on motor function. After treatment from age 11 to 14 months, brains of 26 mice were collected to quantify aggregated hyperphosphorylated tau by Thioflavin T and immunohistochemistry (IHC) and to quantify total tau (HT7 antibody) and hyperphosphorylated tau (AT8 antibody) in homogenates and a fraction enriched for paired helical filaments. Resveratrol reduced the level of total hyperphosphorylated tau in IHC sections (p=0.036), and morin exhibited a tendency to do so (p=0.29), while the two drugs tended to increase the proportion of solubilizable tau that was hyperphosphorylated, as detected in blots. Neither resveratrol nor morin affected motor function. One explanation of these results is that the drugs might interrupt a late stage in tau aggregation, after small aggregates have formed but before further aggregation has occurred. Further animal studies would be informative to explore the possible efficacy of morin or resveratrol for treating tauopathies.

Nurses' preparedness for infectious disease outbreaks: A literature review and narrative synthesis of qualitative evidence.

AIMS AND OBJECTIVES: To explore the core components that constitute nurses' preparedness in an epidemic event. BACKGROUND: Healthcare service providers have worked to augment efforts to protect the public from the impact of epidemic events. While constituting the major healthcare taskforce, nurses are frequently tasked with fronting the response to an infectious disease outbreak. Given the crucial role of nurses in the management of prevailing epidemics, the constituents of their preparedness in epidemic events should be identified. DESIGN: A systematic search was undertaken to identify eligible studies from the literature. A narrative synthesis approach was employed to extract and synthesise findings of the reviewed qualitative studies. METHODS: Seven qualitative studies on nurses' experience and perceptions of epidemic events were examined for scientific quality using the Critical Appraisal Skills Programme Qualitative Checklist. Findings of these studies were synthesised adopting a narrative synthesis approach. RESULTS: Three interplaying themes were identified as follows: (i) personal resources, (ii) workplace resources and (iii) situational influences. The findings suggest that an effective epidemic outbreak response would require further effort to reinforce the interplay between individual nurses, healthcare institutions and the governments. CONCLUSIONS: The practical interplay among individual nurses, healthcare institutions and the governments is crucial in establishing an effective epidemic response. Further research on the understanding of the dynamic process of preparedness development is recommended to set future directions in research. RELEVANCE TO CLINICAL PRACTICE: This study offers important insights for devising future strategies in enhancing nurses' preparedness and response to an epidemic event. These include recommendations on providing education and training to nurses regarding infectious diseases, fostering institutional assistance and support in an outbreak and revising government policies and planning.

Backbone and side-chain ¹H, ¹³C and ¹5N assignments of the PPIase domain of macrophage infectivity potentiator (Mip) protein from Coxiella burnetii.

Coxiella burnetii is an obligate intracellular gram-negative bacterium uniquely evolved to thrive in the inhospitable phagolysosome of macrophage. C. burnetii causes Q fever in humans and animals, which is emerging as a global public health concern. It is highly infectious and designated as a category B biowarfare agent because of its ubiquitous nature, abundant natural reservoirs, high resistance to environmental conditions, ease of transmission and low infectious dose. The lack of knowledge and awareness of C. burnetii leads to under-reporting and under-diagnosing of Q fever cases. Therefore, further understanding of the interactions between the infected host and the bacteria is necessary. C. burnetii macrophage infectivity potentiator (cb-Mip) is a secreted protein of 230 amino acids involving in intracellular survival of the pathogen. cb-Mip belongs to the family of FK506 binding protein, which possesses peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a PPIase, Mip protein homolog has been identified as virulence factor of many intracellular pathogenic microorganisms. In the present study, we report the near complete resonance assignments of the PPIase domain-containing region of Mip protein of C. burnetii. Secondary structure prediction based on chemical shift index analysis indicates that the protein adopts a predominately beta-strand structure, which is consistent with the crystal structure of homologous Mip protein in Legionella pneumophila.

The Canadian experience with Durata and Riata ST Optim defibrillator leads: a report from the Canadian Heart Rhythm Society Device Committee.

BACKGROUND: The St. Jude Medical Riata family of implantable cardioverter-defibrillator (ICD) leads has demonstrated a high rate of externalized conductors and electrical failure. OBJECTIVE: Given similar design elements of Durata to Riata, the purpose of this study was to assess the rates of failure of the Riata ST Optim and Durata lead families in Canada. METHODS: All Canadian ICD-implanting centers were invited to submit follow-up information on all Optim-coated ICD leads implanted. Electrical failure was defined as a rapid change in impedance or pacing capture threshold leading to lead revision, or oversensing due to noise. Externalized conductors were defined as appearance of conductor wires outside the lead body. Systematic fluoroscopic screening for externalized conductors was not performed. RESULTS: As of December 1, 2012, 15 of 25 centers provided data on 3981 leads (44% of those sold in Canada during the same timeframe): 3477 Durata and 504 Riata ST Optim leads. The most common model numbers were 7122 (1516 leads [38%]), 7121 (707 leads [18%]), and 7120 (622 leads [16%]). Mean follow-up duration from implant to December 1, 2012, was 4.47 ± 0.48 years for Riata ST Optim leads and 2.00 ± 1.10 years for Durata leads. The annual rate of lead failure was 0.27% per year for Riata ST Optim leads and 0.24% per year for Durata leads. No instances of externalized conductors were identified in the failed leads. No deaths were attributed to lead failure; however, 2 patients experienced inappropriate shocks due to lead failure. CONCLUSION: The overall electrical failure rates of the Riata ST Optim and Durata leads appear to be low, and no instances of externalized conductors were observed.

Real-time transmission to real-time patient care: a tale of 4 devices.

We report a case in which a patient with dilated cardiomyopathy presented with syncope, terminated by a shock from his implantable cardioverter defibrillator. However, subsequent interrogation of the device revealed no tachycardia detection or treatment parameters. The mystifying details of the case were unravelled by remote consultation with the staff electrophysiologist and the use of smart phone-transmitted live images. This case highlights the use of mobile phone-facilitated video conferencing in urgent management of intracardiac device therapy. Judicious use of this technology has the potential to deliver effective and cost-effective solutions for many device-related emergencies in patients at remote settings.

Using left-ventricular-only pacing to eliminate T-wave oversensing in a biventricular implantable cardiac defibrillator.

A man aged 75 years and with nonischemic cardiomyopathy had implantation of a biventricular implantable cardiac defibrillator (ICD). Consistent biventricular pacing was limited by intermittent T-wave oversensing (TWOS). A strategy of left-ventricular-only pacing was used to eliminate TWOS. This strategy obviates the need to reduce ventricular sensitivity and thus may be an effective alternative to biventricular pacing complicated by TWOS.

Production of 2-aminophenoxazin-3-one by Staphylococcus aureus causes false-positive results in ß-galactosidase assays.

Staphylococcus aureus can be distinguished from similar coagulase-positive staphylococci by its absence of ß-galactosidase activity. This is commonly tested using o-nitrophenyl-ß-D-galactopyranoside (ONPG) as the substrate. Unexpectedly, 111 and 58 of 123 isolates displayed apparent ß-galactosidase activity in the ONPG assay and on the Vitek 2 system, respectively. Compositional analysis showed that the yellow coloration of the positive ONPG assay resulted from production of 2-aminophenoxazin-3-one. Alternative ß-galactosidase substrates like X-Gal (5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside) should be used for testing staphylococci.

An Exploration of the Burnout Situation on Teachers in Two Schools in Macau.

To explore the burnout situation of teachers in two schools in Macau and to investigate any differences made of demographic characteristics. The relation of burnout on social problem solving and holistic health of teachers is also studied. A self reported questionnaire with the Chinese Maslach Burnout Inventory (C-MBI), Chinese Social Problem Solving Inventory (C-SPSI) and the Body-Mind-Spirit Well-Being Inventory (BMSWBI) were used. Totally 138 teachers participated in the study. With Hong Kong data as a reference, Macau teachers scored in the average range of burnout in emotional exhaustion and depersonalization but scored in the low range of burnout in personal accomplishment. Significance differences were found in some dimensions of burnout in age, marital status, teaching experiences, education background and satisfaction with income. Both C-SPSI and BMSWBI were found to be significantly negative correlated with emotional exhaustion and depersonalization and positive correlated with personal achievement. The findings identified those with greater degree of burnout, to whom more attention should be paid. The study also contributed to the limited literature on the quality of life of teachers in Macau. Finally, the findings added on the data base for comparison internationally among the Chinese population.

Long-term efficacy of cardiac pacemakers and implantable cardioverter/defibrillators.

Cardiac pacemakers and implantable cardioverter/defibrillators are becoming more common due to expanded indications and increasing patient survival. In addition, these device systems are being implanted in younger patients, which increases their necessity for long-term durability. Device adverse events can be seen early, during or following implantation (perforation, lead dislodgement, infection), or late (lead fraction, insulation failure or device system infection). These adverse events can, at least in part, be attributed to intrinsic device system structure. Since the initial pacemakers and implantable cardioverter/defibrillators, many modifications in both device system hardware and software have been made to enhance both their durability and function. The current era of devices appear to have made adjustments for previous inadequacies and promise to be reliable and to function well. Despite this, however, it is necessary for clinicians to be aware of possible malfunctions, their warning signs, and the appropriate course of action should these malfunctions be encountered. In this review we describe the common device system malfunctions and device system insertion complications.

Curcumin effects on blood lipid profile in a 6-month human study.

Studies in animals and a short-term human study have suggested that curcumin, a polyphenolic compound concentrated in the curry spice turmeric, decreases serum cholesterol concentration. However, no controlled human trials have examined the effect of curcumin on cholesterol. This study investigated the effects of consuming curcumin on the serum lipid profile in men and women. Elderly subjects (n=36) consumed 4 g/d curcumin, 1g/d curcumin, or placebo in a 6-month, randomized, double-blind trial. Plasma curcumin and its metabolites were measured at 1 month, and the serum lipid profile was measured at baseline, 1 month, and 6 months. The plasma curcumin concentration reached a mean of 490 nmol/L. The curcumin concentration was greater after capsule than powder administration. Consumption of either dose of curcumin did not significantly affect triacylglycerols, or total, LDL, and HDL cholesterol over 1 month or 6 months. However, the concentrations of plasma curcumin and serum cholesterol were positively and significantly correlated. Curcumin consumption does not appear to have a significant effect on the serum lipid profile, unless the absorbed concentration of curcumin is considered, in which case curcumin may modestly increase cholesterol.

A quasi-experimental study on a community-based stroke prevention programme for clients with minor stroke.

AIM: The aim of this study was to determine the effectiveness of a community-based stroke prevention programme in (1) improving knowledge about stroke; (2) improving self-health-monitoring practice; (3) maintaining behavioural changes when adopting a healthy lifestyle for stroke prevention. BACKGROUND: People with minor stroke (or transient ischaemic attack) tend to under-estimate the long-term impact of this on their health. The challenge for nurses is to prevent subsequent strokes by finding ways to promote and sustain appropriate behaviours. Educational intervention is of paramount importance in equipping those at risk with relevant knowledge and self-care strategies for secondary stroke prevention. DESIGN: This study adopted a quasi-experimental design. METHOD: One hundred and ninety subjects were recruited, of whom 147 (77 in the intervention group and 70 in the control group) completed the study. Data were obtained at three time points: baseline (T0); one week after (T1) and three months after (T2) the intervention. The intervention programme consisted of eight weekly two-hour sessions, with the aims of improving the participants' awareness of their own health signals and of actively involving them in self-care management of their own health for secondary stroke prevention. RESULTS: Significant positive changes were found among participants of the intervention group in the knowledge on stroke warning signs (P < 0.001); treatment seeking response in case of a stroke (P < 0.001); medication compliance (P < 0.001); self blood pressure monitoring (P < 0.001) as well as lifestyle modification of dietary habits (reduction in salted food intake, P = 0.004). No significant improvement was found in walking exercise participation in the intervention group, yet a significant decrease was detected among the control group. CONCLUSION: This study found a three-month-sustained effect of positive changes in knowledge and skill from participants who undertook a nurse-led community-based stroke prevention programme. RELEVANCE TO CLINICAL PRACTICE: Effective educational intervention by professional nurses helped clients integrate their learned knowledge into their real-life practice. This empowering, that is, the taking of responsibility by clients for their own self-care management on a daily basis, affirms that patient education has moved beyond teaching people facts.