Bacteriophage-cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice.

Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds.

Development of an activity-based ratiometric electrochemical probe of the tumor biomarker γ-glutamyl transpeptidase: Rapid and convenient sensing in whole blood, urine and live-cell samples.

γ-Glutamyl transpeptidase (GGT) is a key biomarker for cancer diagnosis and post-treatment surveillance. Currently available methods for sensing GGT show high potential, but face certain challenges including an inability to be used to directly sense analytes in turbid biofluid samples such as whole blood without tedious sample pretreatment. To overcome this issue, activity-based electrochemical probes (GTLP and GTLPOH) were herein developed for a convenient and specific direct targeting of GGT activity in turbid biosamples. Both probes were designed to have GGT catalyze the hydrolysis of the gamma-glutamyl amide moiety of the probe, and result in a self-immolative reaction and concomitant ejection of the masked amino ferrocene reporter. The GTLPOH probe, delivered distinctive key results including high sensitivity, high affinity, a wide detection range of 2-100 U/L, and low LOD of 0.38 U/L against GGT. This probe delivered a precise target for sensing GGT and was free of interference from other electroactive biological species. Furthermore, the GTLPOH probe was employed to monitor and quantify the activity of GGT on the surfaces of tumor cells. The designed sensing method was also validated by the direct quantitative measurement of GGT activity in whole blood and urine samples, and the results were found to be consistent with those of the standard fluorometric assay kit. Thus, GTLPOH is of great significance for its promise as a point-of-care tool for early-stage cancer diagnosis as well as a new drug screening method.

Fourteen-year trends in the prescribing patterns of pediatric bipolar patients discharged from two public mental hospitals in Taiwan.

INTRODUCTION: The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019. METHODS: PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased. DISCUSSIONS: Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required.

Daptomycin area under the curve to minimum inhibitory concentration ratio by broth microdilution for predicting the outcome of vancomycin-resistant Enterococcus bloodstream infection.

OBJECTIVES: Different methods are used to determine the minimum inhibitory concentration (MIC) for daptomycin. The threshold is unknown for the free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) of daptomycin using broth microdilution (BMD) to predict outcome of vancomycin-resistant enterococcus (VRE) bacteremia. The MIC testing method which is best for predicting the outcome remains unclear. METHODS: This is a retrospective cohort study. The inclusion criterion was VRE bacteremia treated with ≥ 8 mg/kg of daptomycin. As we aimed to compare different daptomycin MIC testing methods for predicting the clinical outcome of VRE bacteremia, the inclusion criteria included the availability of MIC values for BMD, Etest, and automated antimicrobial susceptibility testing (AST). The primary end point was 28-day mortality. The fAUC/MIC was dichotomized using classification and regression tree analysis for predicting survival. RESULTS: A total of 393 patients were included; 215 survived and 178 died. In the multivariable logistic model for predicting mortality, the dichotomized fAUC/MICs for Etest and AST were 0.508 and 0.065 times as probable, respectively, as that for BMD to minimize information loss. An fAUC/MIC > 75.07 for BMD significantly predicted lower mortality (adjusted odds ratio, 0.53, 95% confidence interval, 0.30-0.95; P = 0.03) after adjusting for underlying disease and bacteremia severity. Using Monte Carlo simulation, none of the doses had a probability of target attainment of ≥ 50% with an MIC of ≥ 2 mg/L. CONCLUSION: The dichotomized threshold for fAUC/MIC for BMD was the best predictor of mortality. An fAUC/MIC > 75.07 for BMD independently predicted better survival.

Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile.

Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

The relation between second-generation antipsychotics and laxative use in elderly patients with schizophrenia.

BACKGROUND: We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan. METHODS: Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge. RESULTS: A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001). CONCLUSIONS: Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.

Lytic Bacteriophage as a Biomaterial to Prevent Biofilm Formation and Promote Neural Growth.

BACKGROUND: Although non-lytic filamentous bacteriophages have been made into biomaterial to guide tissue growth, they had limited ability to prevent bacterial infection. In this work a lytic bacteriophage was used to make an antibacterial biomaterial for neural tissue repair. METHODS: Lytic phages were chemically bound to the surface of a chitosan film through glutaraldehyde crosslinking. After the chemical reaction, the contact angle of the sample surface and the remaining lytic potential of the phages were measured. The numbers of bacteria on the samples were measured and examined under scanning electron microscopy. Transmission electron microscopy (TEM) was used to observe the phages and phage-infected bacteria. A neuroblast cell line was cultured on the samples to evaluate the sample's biocompatibility. RESULTS: The phages conjugated to the chitosan film preserved their lytic potential and reduced 68% of bacterial growth on the sample surface at 120 min (p < 0.001). The phage-linked surface had a significantly higher contact angle than that of the control chitosan (p < 0.05). After 120 min a bacterial biofilm appeared on the control chitosan, while the phage-linked sample effectively prevented biofilm formation. The TEM images demonstrated that the phage attached and lysed the bacteria on the phage-linked sample at 120 min. The phage-linked sample significantly promoted the neuroblast cell attachment (p < 0.05) and proliferation (p < 0.01). The neuroblast on the phage-linked sample demonstrated more cell extensions after day 1. CONCLUSION: The purified lytic phages were proven to be a highly bioactive nanomaterial. The phage-chitosan composite material not only promoted neural cell proliferation but also effectively prevent bacterial growth, a major cause of implant failure and removal.

Influence of daptomycin doses on the outcomes of VRE bloodstream infection treated with high-dose daptomycin.

OBJECTIVES: The CLSI recommended high-dose daptomycin (8-12 mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8 mg/kg. METHODS: We conducted a multicentre prospective observational study of patients who received a ≥8 mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28 day mortality. RESULTS: A total of 661 patients were included. The 28 day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8 mg/kg; P < 0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR) = 0.85; 95% CI = 0.73-0.99; P = 0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11 mg/kg dose of daptomycin (P = 0.003). The 8 to <11 and ≥11 mg/kg doses of daptomycin differed in the 28 day mortality in the higher MIC group (≥2 mg/L) (49.4% versus 33.3%; P = 0.004), but not in the lower MIC group (≤1 mg/L) (29.3% versus 29.4%; P = 0.99). A dose of ≥11 mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000 U/L) compared with 1.1% with 8 to <11 mg/kg (P = 0.04). CONCLUSIONS: The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11 mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11 mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.

Glycolytic metabolism and activation of Na+ pumping contribute to extracellular acidification in the central clock of the suprachiasmatic nucleus: Differential glucose sensitivity and utilization between oxidative and non-oxidative glycolytic pathways.

BACKGROUND: The central clock of the suprachiasmatic nucleus (SCN) controls the metabolism of glucose and is sensitive to glucose shortage. However, it is only beginning to be understood how metabolic signals such as glucose availability regulate the SCN physiology. We previously showed that the ATP-sensitive K+ channel plays a glucose-sensing role in regulating SCN neuronal firing at times of glucose shortage. Nevertheless, it is unknown whether the energy-demanding Na+/K+-ATPase (NKA) is also sensitive to glucose availability. Furthermore, we recently showed that the metabolically active SCN constantly extrudes H+ to acidify extracellular pH (pHe). This study investigated whether the standing acidification is associated with Na+ pumping activity, energy metabolism, and glucose utilization, and whether glycolysis- and mitochondria-fueled NKAs may be differentially sensitive to glucose shortage. METHODS: Double-barreled pH-selective microelectrodes were used to determine the pHe in the SCN in hypothalamic slices. RESULTS: NKA inhibition with K+-free (0-K+) solution rapidly and reversibly alkalinized the pHe, an effect abolished by ouabain. Mitochondrial inhibition with cyanide acidified the pHe but did not inhibit 0-K+-induced alkalinization. Glycolytic inhibition with iodoacetate alkalinized the pHe, completely blocked cyanide-induced acidification, and nearly completely blocked 0-K+-induced alkalinization. The results indicate that glycolytic metabolism and activation of Na+ pumping contribute to the standing acidification. Glucoprivation also alkalinized the pHe, nearly completely eliminated cyanide-induced acidification, but only partially reduced 0-K+-induced alkalinization. In contrast, hypoglycemia preferentially and partially blocked cyanide-induced acidification. The result indicates sensitivity to glucose shortage for the mitochondria-associated oxidative glycolytic pathway. CONCLUSION: Glycolytic metabolism and activation of glycolysis-fueled NKA Na+ pumping activity contribute to the standing acidification in the SCN. Furthermore, the oxidative and non-oxidative glycolytic pathways differ in their glucose sensitivity and utilization, with the oxidative glycolytic pathway susceptible to glucose shortage, and the non-oxidative glycolytic pathway able to maintain Na+ pumping even in glucoprivation.

Development of a novel latent electrochemical molecular substrate for the real-time monitoring of the tumor marker aminopeptidase N in live cells, whole blood and urine.

Aminopeptidase N (APN/CD13) plays an important role in the growth and metastasis, of tumor, and is a potential biomarker for the post-treatment surveillance of cancer reoccurrence and progression of various malignancies. Thus, we have designed and prepared a convenient and ultrasensitive APN-targeting activity-based ratiometric electrochemical molecular substrate (Ala-AFC) for direct real-time monitoring of APN activity in biosamples. The APN in our experiment was used to hydrolyze the alanine moiety of the Ala-AFC probe and, as a result of this hydrolysis, realize concomitantly a cascade reaction to unmask the electrochemical reporter N-alkylated amino ferrocene (AAF). The Ala-AFC probe exhibited high sensitivity with a wide detection range of 0.05-110 ng mL-1 and a low limit of detection of 23.18 pg mL-1. The electrochemical signals were found to be distinctly specific for APN and free of interference from other electroactive biological species. Furthermore, the Ala-AFC probe was employed to monitor and quantify, in real-time, the activity of APN in tumor cells, whole blood, and urine. In addition, the results of our direct electrochemical quantifications of the amount of APN in whole blood and urine were found to be consistent with the results of the use of commercially available fluorometric assay kits to sense APN in serum and urine. Thus our approach shows promise as a point-of-care tool for cancer diagnostics and post-treatment surveillance of cancer reoccurrence.

Perceptions of community dementia friendliness: A cross-sectional study of people with dementia, family caregivers, service providers, and the general public in Taiwan.

Promoting dementia-friendly communities is an important strategy for improving quality of life for people with dementia and dementia-family caregivers. The process of building dementia-friendly communities should include all people living in the community. The objective of this study was to compare perceived dementia friendliness in the community among people with dementia, family caregivers, service providers, and the general public. In Taiwan, we surveyed 60 people with dementia, 140 family caregivers, and 200 members of the general public face to face, with 200 service providers surveyed by mail. Participants completed the Perceived Community Dementia Friendliness measure, consisting of seven subscales: care services, community members, community environment, community interactions, transportation, hospitals, and stores and organisations. This measure has acceptable convergent validity, construct validity, and internal consistency reliability for use in Taiwan. Differences in perceived dementia friendliness were examined by chi-square tests/analysis of variance. Among the seven subscales, hospitals were rated with good dementia friendliness by 70% of people with dementia (n = 42); however, care services were rated poor by 23.3% of people with dementia (n = 14). Hospitals were also rated with good dementia friendliness by 39.2% of family caregivers (n = 54). Care services were rated as having good dementia friendliness by 43.5% of service providers (n = 87) and 47% of the general public (n = 86). Furthermore, community interactions were rated as good by small percentages of family caregivers (11.4%, n = 16), service providers (22.2%, n = 44), and the general public (30.9%, n = 58). Family caregivers, service providers, and the general public rated hospitals with the highest mean dementia-friendliness score and community interactions with the lowest. Perceived community-dementia friendliness among participants with dementia differed from that of participants without. People with dementia prioritised improving care services, while people without dementia rated facilitating community interactions as more vital. These differences provide vital insights into understanding the policies and administration of dementia-friendly communities.

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-Fe3O4 Nanotherapy Drugs.

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe3O4 and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe3O4@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe3O4@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRGTM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

Electroencephalogram patterns in patients comorbid with major depressive disorder and anxiety symptoms: Proposing a hypothesis based on hypercortical arousal and not frontal or parietal alpha asymmetry.

BACKGROUND: Major depressive disorder (MDD) is often comorbid with anxiety disorders or symptoms. Brain hyperactivity, frontal alpha asymmetry (FAA), and parietal alpha asymmetry (PAA) have been considered as trait markers in patients with MDD. This study investigated the electroencephalogram (EEG) patterns among patients with MDD comorbid with anxiety symptoms. METHODS: One hundred and thirty-five patients with MDD comorbid with anxiety (MDD group) and 135 healthy controls (HC group) were analyzed. The Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) were completed, and 19 EEG channels were measured during the resting state, depressive recall and recovery tasks, and happiness recall and recovery tasks. FAA and PAA were computed by log (F4 alpha)-log (F3 alpha) and log (P4 alpha)-log (P3 alpha). RESULTS: The FAA and PAA indices between the two groups showed no significant differences; however, compared with the HC group, the MDD group had lower total delta and theta values, and higher total beta, low beta, and high beta values in the resting state. The total beta value positively correlated with the BDI-II and BAI scores in the MDD group. LIMITATIONS: Most patients had anxious MDD and taking prescriptions, antidepressants or benzodiazepine may affect EEG patterns. CONCLUSION: Compared with HCs, patients with MDD comorbid with anxiety had a higher beta activity in the entire brain region, supporting the role of brain hyperactivity, instead of FAA or PAA, as a trait marker in these patients. A neurofeedback protocol could be developed in future based on the brain hyperactivity findings.

Controlled-release of free bacteriophage nanoparticles from 3D-plotted hydrogel fibrous structure as potential antibacterial wound dressing.

To combat the emergence of drug-resistant bacteria, a locally isolated bacteriophage (HZJ) targeting H5α Escherichia coli was used as an antibacterial agent to make wound dressing samples in this study. The phages were physically embedded within an alginate hydrogel sample so that they could later be released with their tails being free during the infection process, which preserves their lytic activity. The HZJ phage isolated in the study have a 20 min latent period and are stable between pH 6 and pH 9 and at temperatures below 45 °C. The addition of phage to an E. coli culture suppressed over 99% of bacterial growth in 2-h (p < 0.001). Phage-embedded hydrogel fibers were used to create porous wound dressing material using three-dimensional (3D) printing. The majority of phage lytic activity (85%-90%) was preserved after encapsulation. After they were embedded in samples, HZJ lysed 57% to 67% of bacteria (p < 0.001) within 2 h and the antibacterial effects lasted at least 24 h. The small amount of phage released in 2 h was able to quickly replicate and effectively lysed the majority of the bacterial hosts. Phage-embedded alginate samples released 10% of its incorporated phage particles in 24 h. The SEM micrographs show that, compared to phage-free samples, fewer E.coli cells were observed on phage-embedded samples 2 h after bacteria were exposed to the samples. The phage-embedded sample was not cytotoxic to L929 cells. The presence of HZJ in alginate hydrogel promoted cell growth (p < 0.01) and adhesion to the samples. Further, the existence of phage did not alter the tensile strength and modulus of samples (p > 0.05). An antibacterial dressing capable of slowly releasing lytic phages and effectively suppressing bacterial growth for up to 24 h was produced in this study. This model represents an attractive means to reduce use of antibiotics and other additives in conventional dressings.

Effects of situational simulation and online first-aid training programs for nurses in general medical wards: A prospective study.

BACKGROUND: To maintain patient safety, effective first-aid skills are necessary during emergencies. It is important to develop in-service education programs to equip clinical nurses with first-aid skills. OBJECTIVES: This study explored the effects of first-aid skills and knowledge between situational simulation training and online teaching. It also examined the different effects of two training programs associated with nurses' baseline first-aid ability. DESIGN: This was a randomized, single-blind controlled study. SETTING: The study was conducted from December 15, 2016 to May 28, 2018, in the nursing department of a medical center in Taiwan. PARTICIPANTS: Participants were 92 general ward nurses. METHODS: Participants were randomly assigned to either a situational simulation training or an online teaching group. We used a first-aid knowledge test (FAKT) and a first-aid skills test (FAST) to measure the participants' learning outcomes after intervention and we did cost comparisons between groups. RESULTS: There were no significant differences in the changes in FAKT and FAST scores after intervention between situational simulation training and online teaching groups (p = 0.76, p = 0.45). All the participants in both training programs showed improvements via increased scores on FAST (M ± SD = 35.27 ± 12.08 for online teaching, M ± SD = 36.08 ± 10.78 for situational simulation training) and FAKT (M ± SD = 21.09 ± 18.59 for online teaching, M ± SD = 23.39 ± 15.36 for situational simulation training). However, for the subgroup of participants who scored <75% on the FAST pretest, better improvements only occurred in the situational simulation training, but the situational simulation training program had higher costs than the online teaching program. CONCLUSIONS: The improvement was greater in the situational simulation training group among nurses who could not exceed scores of 75% for first-aid skills. First-aid skill scores below 75% are likely a sign of nurses who need more assistance, discussion, and debriefing from situational simulation training.

Memory-driven movement model for periodic migrations.

We propose a model for memory-based movement of an individual. The dynamics are modeled by a stochastic differential equation, coupled with an eikonal equation, whose potential depends on the individual's memory and perception. Under a simple periodic environment, we discover that both long and short-term memory with appropriate time scales are essential for producing expected periodic migrations.

Locally Applied Stem Cell Exosome-Scaffold Attenuates Nerve Injury-Induced Pain in Rats.

PURPOSE: Nerve injury-induced pain is difficult to treat. In this study, we developed an alginate scaffold with human umbilical cord mesenchymal stem cell exosomes (EX-SC) to treat nerve injury-induced pain. MATERIALS AND METHODS: The scaffold was prepared and characterized for its physical traits and biocompatibility. In vitro studies of PC12 and HEK293 cells were used to evaluate the neuroprotective and neurotrophic effects of exosomes. Right L5/6 spinal nerve ligation (SNL) was performed in Sprague-Dawley rats to induce mechanical allodynia and thermal hyperalgesia, evaluated by von Frey hair and radiant heat tests. The EX-SC was wrapped around ligated L5/6 spinal nerves for treatment. Western blotting and immunofluorescence staining were used to evaluate neuron/glial activation, cytokines and neurotrophic factor of affected dorsal root ganglion (DRG). RESULTS: In cell culture assay, the exosomes induce neurite outgrowth of PC12 cells and protect PC12 and HEK293 cells against formaldehyde acid treatment. On post-ligation day 21, rats receiving EX-SC had significantly higher median (interquartile range) withdrawal threshold and latency [14.1 (13.7-15.5) g, 14.2 (13.7-15.3) s] than saline-SC-treated rats [2.1 (1.7-3.0) g, 2.0 (1.8-2.4) s, P=0.02 and 0.002]. The EX-SC also attenuated SNL-induced up-regulation of c-Fos, GFAP, Iba1, TNF-α and IL-1ß, while enhancing the level of IL-10 and GDNF, in the ipsilateral L5/6 DRG. After implantation for 21 days, the EX-SC enhanced the expression of myelin basic protein and IL-10 in injured L5/6 axons. CONCLUSION: We demonstrate the EX-SC possesses antinociceptive, anti-inflammation and pro-neurotrophic effects in the SNL pain model. It could be a promising therapeutic alternative for nerve injury-induced pain.