Evaluation of a Machine Learning-Based Decision Support Intervention for Inpatient Falls.

Inpatient falls are frequent adverse events, with various injuries occurring in one-third of falls. International practice guidelines recommend multifaceted risk assessment and risk-targeted interventions through multifactorial activities. However, the effectiveness is mixed for such recommendations implemented using traditional approaches. This study proposed a well-designed systemic and clinical decision support approach using machine learning techniques to leverage the implementation of preventive activities of nursing processes leading to outcome changes.

Evaluation of an approach to clinical decision support for preventing inpatient falls: a pragmatic trial.

Objectives: To assess whether a fall-prevention clinical decision support (CDS) approach using electronic analytics that stimulates risk-targeted interventions is associated with reduced rates of falls and injurious falls. Materials and Methods: The CDS intervention included a machine-learning prediction algorithm, individual risk-factor identification, and guideline-based prevention recommendations. After a 5-month plan-do-study-act quality improvement initiative, the CDS intervention was implemented at an academic tertiary hospital and compared with the usual care using a pretest (lasting 24 months and involving 23 498 patients) and posttest (lasting 13 months and involving 17 341 patients) design in six nursing units. Primary and secondary outcomes were the rates of falls and injurious falls per 1000 hospital days, respectively. Outcome measurements were tested using a priori Poisson regression and adjusted with patient-level covariates. Subgroup analyses were conducted according to age. Results: The age distribution, sex, hospital and unit lengths of stay, number of secondary diagnoses, fall history, condition at admission, and overall fall rate per 1000 hospital days did not differ significantly between the intervention and control periods before (1.88 vs 2.05, respectively, P = .1764) or after adjusting for demographics. The injurious-falls rate per 1000 hospital days decreased significantly before (0.68 vs 0.45, P = .0171) and after (rate difference = -0.64, P = .0212) adjusting for demographics. The differences in injury rates were greater among patients aged at least 65 years. Conclusions: This study suggests that a well-designed CDS intervention employing electronic analytics was associated with a decrease in fall-related injuries. The benefits from this intervention were greater in elderly patients aged at least 65 years. Trial Registration: This study was conducted as part of a more extensive study registered with the Clinical Research Information Service (CRIS) (KCT0005378).

A Novel, Selective c-Abl Inhibitor, Compound 5, Prevents Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. The nonreceptor tyrosine kinase c-Abl has shown a potential role in the progression of PD. As such, c-Abl inhibition is a promising candidate for neuroprotection in PD and α-synucleinopathies. Compound 5 is a newly synthesized blood-brain barrier penetrant c-Abl inhibitor with higher efficacy than existing inhibitors. The objective of the current study was to demonstrate the neuroprotective effects of compound 5 on the α-synuclein preformed fibril (α-syn PFF) mouse model of PD. Compound 5 significantly reduced neurotoxicity, activation of c-Abl, and Lewy body pathology caused by α-syn PFF in cortical neurons. Additionally, compound 5 markedly ameliorated the loss of dopaminergic neurons, c-Abl activation, Lewy body pathology, neuroinflammatory responses, and behavioral deficits induced by α-syn PFF injection in vivo. Taken together, these results suggest that compound 5 could be a pharmaceutical agent to prevent the progression of PD and α-synucleinopathies.

Comparison of Fatigue, Quality of Life, Turnover Intention, and Safety Incident Frequency between 2-Shift and 3-Shift Korean Nurses.

This study aimed to compare the fatigue, quality of life, turnover intention, and safety incident frequency between 2- and 3-shift nurses, and analyze their perceptions of the 2-shift system. Participants were 227 nurses working for one year or more in a tertiary hospital in Seoul, South Korea (113 were 2-shift nurses for two months or longer, and 114 were 3-shift nurses with no experience of 2-shift work). The Occupational Fatigue Exhaustion Recovery Scale (OFER) and Quality of Life Scale were used. Turnover intention, safety incident frequency, and perceptions of the 2-shift system were surveyed by questionnaires developed by the researchers. Results showed that 2-shift nurses had lower chronic fatigue (t = -2.38, p = 0.018) and higher recovery between shifts (t = 3.90, p < 0.001) and quality of life scores than 3-shift nurses (t = 3.69, p < 0.001). There were no significant differences for turnover intention (t = -1.48, p = 0.140), frequency of needlestick accidents (t = 0.30, p = 0.763), medication errors (t = -1.46, p = 0.146), or near-miss medication errors (t = 0.78, p = 0.437). Two-shift nurses found it easier to secure rest and personal leisure time, and their shift system was shown to improve work satisfaction by increasing the continuity of care. Additional research is necessary to examine how nurses' health status and emotional satisfaction vary by shift type.

SB365 induces apoptosis and suppresses proliferation of glioblastoma cells.

CONTEXT: Glioblastoma is a malignant brain tumor with limited treatment modalities due to its nature. SB365, Pulsatilla saponin D, is known to induce apoptosis and inhibit the growth of many cancer cells. AIM: We elucidated the anticancer effects of SB365 in glioblastoma cells. METHODS: We examined the antiproliferative activity of SB365 in human glioblastoma cell lines. Apoptosis was evaluated using the Hoechst assay, TUNEL assay, DAPI nuclear staining, and Western blotting analysis. To test the antimetastatic capacity of SB365, cell migration assay was conducted, and hypoxia-inducible factor-1 alpha (HIF-1α) expression and vascular endothelial growth factor (VEGF) level were determined under hypoxic conditions. STATICAL ANALYSIS: Significance of the results was confirmed by a one-way analysis of variance analysis. RESULTS: SB365 treatment suppressed the growth of glioblastoma cells and resulted in apoptotic morphological features such as nuclear condensation and fragmentation, enhancing the expression of cleaved poly (ADP-ribose) polymerase and caspase-3. It also significantly delayed cell migration and decreased the HIF-1α expression and VEGF secretion. CONCLUSION: Our findings thus demonstrate that SB365 induced apoptosis and delayed the growth and migration of human glioblastoma cells. It is considered that SB365 would be a promising therapeutic option for glioblastoma.

Predictive Factors of Duration of Continuous Renal Replacement Therapy in Acute Kidney Injury Survivors.

The factors influencing continuous renal replacement therapy (CRRT) duration for critically ill patients with acute kidney injury (AKI) are unclear. Therefore, we investigated the clinical factors that could influence the duration of CRRT for AKI survivors. In this retrospective observational study, the medical records of all hospital survivors who required CRRT for AKI in intensive care units were analyzed. The CRRT duration (median, 6 days) was categorized as short-duration CRRT (≤ 6 days, n = 65) and long-duration CRRT (> 6 days, n = 59), according to the median CRRT duration. A urine output of less than 0.5 mL/kg/h (adjusted odds ratio [OR], 3.4; P = 0.010), mechanical ventilation use (adjusted OR, 7.9; P = 0.001), and extracorporeal membrane oxygenation (ECMO) use (adjusted OR, 6.5; P = 0.010) were independent predictors of long-duration CRRT, whereas serum creatinine and neutrophil gelatinase-associated lipocalin were not significant predictors. A clinical model demonstrated a good discriminatory ability to predict long-duration CRRT (area under the curve, 0.84; 95% confidence interval, 0.76-0.90). The urine output immediately before CRRT initiation and factors associated with disease severity significantly affected the duration of CRRT. Simultaneously considering the urine output, mechanical ventilation use, and ECMO use predicted CRRT duration in AKI survivors.

Change in alkaline phosphatase activity associated with intensive care unit and hospital length of stay in patients with septic acute kidney injury on continuous renal replacement therapy.

BACKGROUND: Evidence suggests that alkaline phosphatase attenuates inflammatory response in sepsis by lipopolysaccharide detoxification and adenosine triphosphate dephosphorylation. We sought to determine changes in alkaline phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical parameters associated with AP activity. METHODS: In this retrospective study, we investigated baseline (when initiating CRRT) and follow-up AP activity on day 3, and associated outcomes in patients who underwent continuous renal replacement therapy (CRRT) due to septic AKI. RESULTS: We analyzed the baseline AP activity of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was not associated with renal or inflammatory biomarkers, or outcomes. It did not significantly differ between the 75 survivors and 80 non-survivors (p = 0.155). AP activity was higher on day 3 than at baseline (105 U/L [interquartile range, 79-156] vs 90 U/L [interquartile range, 59-133]). In particular, liver and bone isoforms increased significantly (p < 0.05), but intestine isoforms did not reach statistical significance (p = 0.367). In addition, day 3 AP activity showed a weak correlation with length of ICU stay (r = 0.213, p = 0.018) and length of hospital stay (r = 0.216, p = 0.017), but not with survival (r = - 0.035, p = 0.698). CONCLUSION: Endogenous AP activity significantly increased in patients with septic AKI. However, neither baseline nor follow-up AP activity was associated with survival.

Blood Glucose Control and Related Factors at a Camp for Korean Children and Adolescents with Type 1 Diabetes.

Data about Asian children and adolescents with type 1 diabetes are sparse. This study's objectives were to describe blood glucose (BG) levels and related factors at a camp for Korean children and adolescents with type 1 diabetes. This descriptive study was conducted January 8-10, 2015. The participants, 24 children and adolescents, were recruited for a 3-day residential diabetes camp. Data on 24 campers were analyzed. Their mean age was 13.4 (± 1.7) years; 44.4% were boys, and mean HgbA1c was 8.5% (± 1.4%). Results revealed that BG levels were maintained safely: The mean BG level during the 3-day stay was 171.1 (± 33.3) mg/dl. Multiple regression analysis showed that insulin adjustment for hyperglycemia (standardized ß = .426; t = 2.431; p = .030) and snacks for hypoglycemia (standardized ß = -.719; t = -3.723; p = .003) at the camp were the only independent contributors to mean BG levels during the 3-day study period. No demographic or clinical factor was found to be associated with the mean BG level. This is the first study of its kind to be conducted in an Asian population, presumably because the prevalence of type 1 diabetes in Asia is low and diabetes camps are a novel concept. Further research is recommended to assess the characteristics of campers (e.g., diet, activity levels, and cultural background) and to determine how the health outcomes of children and adolescents with type 1 diabetes are affected by camp programs.

Early continuous renal replacement therapy in septic acute kidney injury could be defined by its initiation within 24 hours of vasopressor infusion.

PURPOSE: The optimal timing for the initiation of early continuous renal replacement therapy (CRRT) is uncertain and requires a practically feasible definition with acceptable evidence. MATERIALS AND METHODS: We investigated the clinical impacts of 3-time interval parameters on the morbidity and mortality of 177 patients with septic shock-induced acute kidney injury: (1) time from vasopressor initiation to CRRT initiation (Tvaso-CRRT), (2) time from intensive care unit (ICU) admission to CRRT initation (TICU-CRRT), and (3) time from endotracheal intubation to CRRT initiation (Tendo-CRRT). RESULTS: The proportion of the patients with Tvaso-CRRT less than 24 h (median, 14 h, interquartile range [IQR], 5-30 h) was significantly higher in the survival group than in the non-survival group (84.3% vs. 58.5%, p < 0.001). Tvaso-CRRT less than 24 h and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. TICU-CRRT (median, 17 h, IQR, 5-72 h) and Tendo-CRRT (median, 13 h, IQR, 4-48 h) were significantly correlated with both the length of ICU stay (p < 0.001) and mechanical ventilation duration (p < 0.001), but not mortality. CONCLUSIONS: Considering the possible therapeutic measurement by physician on the basis of the results in this study, early CRRT could be defined by a Tvaso-CRRT less than 24 h.

Field evaluation of an improved cell line for the detection of human adenoviruses in environmental samples.

Human enteric adenoviruses (HAdVs) are commonly detected in waters contaminated with human fecal material and persistent in the environment. Detecting infectious enteric HAdVs is limited by the difficulty of growing them in cell cultures. Recently, an improved cell line (293 CMV) has been described, which enhanced the propagation of enteric HAdVs (Kim et al., 2010. Appl. Environ. Microbiol. 76, 2509-2516). The present study evaluated the transactivated 293 CMV cell line for detecting enteric HAdVs from field samples, which is an important step in demonstrating the usefulness of the improved cell line for water monitoring programs. Field samples consisted of the following: concentrated sewage samples (from 1L) collected from three different wastewater treatment plants (WWTPs) and concentrated raw source water samples (from 20L) collected from six water treatment plants (WTPs). Infectious HAdVs were detected using a combined cell culture/mRNA RT-PCR assay. Concentrated samples were assayed, in parallel, using the standard (STD) G293 and 293 CMV cell lines. Viral replication was determined by measuring viral mRNA and viral DNA levels during infection. Infectious HAdVs were successfully detected from environmental samples using the new transactivated and standard cell lines. Infectivity assays of concentrated sewage samples demonstrated higher viral mRNA expression (p=0.02) and viral DNA concentrations (p=0.02) in the transactivated 293 CMV than in the G293 cell line. Although not statistically significant, infectious HAdVs were detected in more raw water samples using the 293 CMV cells (8 of 18) than in the STD G293 cells (4 of 18). However, when results of the source water samples were pooled, the number of flasks positive using the 293 CMV cells was significantly greater than those using the G293 cells (p=0.01). Overall, the results of the present study demonstrate the effectiveness of the new transactivated 293 CMV cell line for improved propagation and detection of HAdVs from environmental samples.

Enhancement of enteric adenovirus cultivation in a novel Ras-overexpressing cell line.

Enteric human adenoviruses (HAdVs; serotypes 40 and 41) have been identified as an emerging cause of drinking water contamination. Due to their fastidious characteristics, HAdVs are difficult to cultivate and therefore not detected easily by standard mammalian cell cultivation methods. Here we found that human embryonic kidney 293 cells, transformed transiently with Ras, enhanced HAdV replication by more than threefold. We also constructed a stable cell line overexpressing the Ras protein, 293-Ras, in which the replication of three HAdV strains of serotypes 40 and 41 was increased markedly. However, only HAdV replication was enhanced; infection of 293 and 293-Ras cells with human rhinivorus-6 showed no significant differences in replication rate. Infected 293-Ras cells exhibited an increased level and phosphorylation of extracellular regulated kinase (ERK). In addition, the Ras-mediated increase in HAdV replication was impaired by the mitogen-activated protein kinase/ERK kinase (MEK1) inhibitor U0126, suggesting direct involvement of the MEK1/ERK pathway in enhanced HAdV replication. Based on these results, we suggest that the 293-Ras cell line be used for the efficient detection and cultivation of HAdV strains in both clinical and environmental specimens.

Antibiotic resistance of bacteria isolated from the internal organs of edible snow crabs.

Antibiotic resistance and microbiota within edible snow crabs are important for the Chionoecetes (snow crab) fishing industry. We investigated these parameters using culture methods and antibiotic susceptibility tests with six internal organs from three species of Chionoecetes. Each sample revealed many unexpected microbial species within Chionoecetes internal organs. On the basis of 16S rRNA sequence analysis of 381 isolates, the most abundant genera identified in Chionoecetes opilio were Acinetobacter spp. (24%), Bacillus spp. (4%), Pseudomonas spp. (34%), Stenotrophomonas spp. (28%), and Agreia spp. (11%). In Chionoecetes sp. crabs, Acinetobacter spp. (23%), Bacillus spp. (12%), and Psychrobacter spp. (20%) were most prevalent, while Agreia spp. (11%), Bacillus spp. (31%), Microbacterium spp. (10%), Rhodococcus spp. (12%), and Agrococcus spp. (6%) were most abundant in C. japonicus. Our antibiotic resistance test found resistance to all nine antibiotics tested in 19, 14, and two of the isolates from C. opilio, Chionoecetes sp., and, C. japonicus respectively. Our results are the first to show that microbes with antibiotic resistance are widely distributed throughout the internal organs of natural snow crabs.

Survival of microorganisms on antimicrobial filters and the removal efficiency of bioaerosols in an environmental chamber.

Exposure to bioaerosols causes various adverse health effects including infectious and respiratory diseases, and hypersensitivity. Controlling exposure to bioaerosols is important for disease control and prevention. In this study, we evaluated the efficacies of various functional filters coated with antimicrobial chemicals in deactivating representative microorganisms on filters or as bioaerosols. Tested functional filters were coated with different chemicals that included (i) Ginkgo and sumac, (ii) Ag-apatite and guanidine phosphate, (iii) SiO2, ZnO, and Al2O3, and (iv) zeolite. To evaluate the filters, we used a model ventilation system (1) to evaluate the removal efficiency of bacteria (Escherichia coli and Legionella pneumophila), bacterial spores (Bacillus subtilis spore), and viruses (MS2 bacteriophage) on various functional filters, and (2) to characterize the removal efficiency of these bioaerosols. All experiments were performed at a constant temperature of 25 degrees C and humidity of 50%. Most bacteria (excluding B. subtilis) rapidly decreased on the functional filter. Therefore, we confirmed that functional filters have antimicrobial effects. Additionally, we evaluated the removal efficiency of various bioaerosols by these filters. We used a six-jet collision nebulizer to generate microbial aerosols and introduced it into the environmental chamber. We then measured the removal efficiency of functional filters with and without a medium-efficiency filter. Most bioaerosol concentrations did not significantly decrease by the functional filter only but decreased by a combination of functional and medium-efficiency filter. In conclusion, functional filters could facilitate biological removal of various bioaerosols, but physical removal of these by functional was minimal. Proper use of chemical-coated filter materials could reduce exposure to these agents.

Design and synthesis of novel arylpiperazine derivatives containing the imidazole core targeting 5-HT(2A) receptor and 5-HT transporter.

Serotonin antagonist reuptake inhibitor (SARI) drugs that block both 5-HT(2) receptors and the serotonin transporters have been developed. The human 5-HT(2A/2C) receptor has been implicated in several neurological conditions, and potent selective 5-HT(2A/2C) ligands may have therapeutic potential for treatment of CNS diseases such as depression. An imidazole moiety usually provides good pharmacokinetic properties as a drug substance, and thus considerable efforts have been devoted to develop imidazole derivatives into drug candidates. The imidazole series of compounds was evaluated against 5-HT(2A/2C) and serotonin reuptake inhibition. A few of the compounds in the series showed promising IC(50) values and antidepressant-like effect in in vivo forced swimming test (FST). On the basis of these results, further lead optimization studies resulted in identifying promising compounds potentially for therapeutic use.

Characterization of the autophosphorylating kinase, PkaF, in Streptomyces coelicolor A3(2) M130.

Streptomyces coelicolor, the model species for morphologically complex actinomycete bacteria, has unique characteristics such as morphological and physiological differentiation, which are controlled by various factors and several protein kinases. From the whole genomic sequence of S. coelicolor A3(2), 44 putative serine/threonine (Ser/Thr) protein kinases were identified, and the pkaF gene was chosen as the best-conserved protein for typical Ser/Thr protein kinases. pkaF encodes a 667-amino acid protein with a predicted N-terminal Ser/Thr kinase domain and four repeated C-terminal penicillin-binding domains and Ser/Thr kinase-associated (PASTA) domains. Based on PCR, a pkaF gene was cloned and heterologously expressed. PkaF expressed in Escherichia coli had the bigger molecular size than the expected value (75 kDa) and was further purified by Ni2+-NTA agarose affinity column chromatography to homogeneity. The purified PkaF was autophosphorylated through the transfer of the γ-phosphate group of ATP. The extent of phosphorylation was proportional to the amount of PkaF, and the phospho-PkaF was dephosphorylated by the addition of the cell lysate of S. coelicolor A3(2). Although no change was observed in the pkaF disruptant, overexpression of pkaF induced severe repression of morphogenesis and actinorhodin production, but not undecylprodigiosin production, implying that PkaF specifically regulates morphogenesis and actinorhodin production in S. coelicolor.

Investigation of norovirus occurrence in groundwater in metropolitan Seoul, Korea.

Groundwater is an important source of drinking and household water worldwide. Hence, the quality of groundwater is very important for preventing waterborne disease outbreaks and should be properly monitored. This study investigated the prevalence of waterborne viruses and fecal indicators in groundwater in metropolitan Seoul and Gyeonggi province, South Korea. A total of 116 samples of groundwater were taken using NanoCeram filters during both summer (June to August) and fall-winter seasons (October to December) in 2008. Among 71 sampling sites, 28 (48.3%) and 18 (35.3%) were positive for norovirus (NoV) from the summer and fall-winter season, respectively. The identified genotypes of NoV include GI-1, 4, 8, 9 and GII-4, 10, 11 (or 17), 13, 15 (or 16). None of fecal indicators was significantly correlated with NoV in groundwater. Among the tested fecal indicators, somatic coliphage (95.3%) showed an excellent true-negative rate of NoV occurrence. The combination of chemical, microbial and viral indicators increased the positive predictive value (50-100%). This study demonstrated a high prevalence of NoV in groundwater in metropolitan Seoul areas and characterized the positive and negative predictive values of a fecal indicator for predicting NoV prevalence.

Evaluation of electropositive filtration for recovering norovirus in water.

The virus adsorption-elution (VIRADEL) technique has been widely used in the recovery of various enteric viruses in water, and an electropositive filter such as 1 MDS has been commonly applied. However, effective methods of monitoring waterborne norovirus (NoV) have not yet been well characterized and optimized. Hence, in this study, the VIRADEL technique was evaluated and optimized for effectively detecting NoV in water by two commonly used electropositive filters (1MDS and NanoCeram filter). Various elution and concentration methods were evaluated by using both murine norovirus (MNV) and human NoV. Among the tested elution buffers, the most effective was 1.5% beef extract plus 0.01% Tween 80 for both 1MDS (67.5%) and NanoCeram (85.7%) microfilters. The recovery rate of GII-4 human NoV was higher by organic flocculation (86.6%) than by polyethylene glycol (PEG) precipitations (11.6~73.6%). When both 1MDS and NanoCeram filters were tested to detect NoV in surface and groundwater, the sensitivity of NoV recovered by these filters appeared to depend on the types and conditions of environmental water. The results of this study will help to set a standard of detection method for NoV in water.

Development of a latex agglutination test for norovirus detection.

Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide. Currently, reverse transcription polymerase chain reaction (RT-PCR) is used commonly to detect NoVs in both clinical and environmental samples. However, RT-PCR requires expensive equipment and cannot be performed on site. In this study, a latex agglutination test (LAT) using antibody-labeled latex beads for detecting NoVs was developed. Two kinds of polyclonal antibodies, one generated from synthetic peptides and the other from E. coli-expressed NoV capsid proteins, were used to develop the LAT. Each of these polyclonal antibodies was immobilized on the surface of latex beads and tested for the ability to detect NoVs. Under optimized conditions, our LAT detected GII.4 NoV at concentrations as low as 3.3x10(5) RT-PCR units/ml in stool samples. The detection limit for the LAT was approximately 1.7 103 RT-PCR units. Forty-eight stool samples were tested for NoVs using this LAT. In comparison with an RT-PCR assay, the sensitivity and specificity of the LAT were 35% and 100%, respectively. With further optimization, this LAT used with appropriate antibodies could be applied for convenient detection of NoVs in clinical diagnosis and food monitoring.

Discovery of 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl-1,3,4-thiadiazole (GCC2680) as a potent, selective and orally efficacious cannabinoid-1 receptor antagonist.

Structure-activity relationship studies in a series of diarylpyrazolyl thiadiazoles identified cannabinoid-1 receptor antagonists with excellent potency and selectivity. Based on its exceptional in vivo efficacy in animal models and its favorable pharmacokinetic and toxicological profiles, 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl-1,3,4-thiadiazole (GCC2680) was selected as a preclinical candidate for the treatment of obesity.