Developing an Intuitive Graph Representation of Knowledge for Nonpharmacological Treatment of Psychotic Symptoms in Dementia.

Applying person-centered, nonpharmacological interventions to manage psychotic symptoms of dementia is promoted for health care professionals, particularly gerontological nurses, who are responsible for care of older adults in nursing homes. A knowledge graph is a graph consisting of a set of concepts that are linked together by their interrelationship and has been widely used as a formal representation of domain knowledge in health. However, there is lack of a knowledge graph for nonpharmacological treatment of psychotic symptoms in dementia. Therefore, we developed a comprehensive, human- and machine-understandable knowledge graph for this domain, named Dementia-Related Psychotic Symptom Nonpharmacological Treatment Ontology (DRPSNPTO). This graph was built by adopting the established NeOn methodology, a knowledge graph engineering method, to meet the quality standards for biomedical knowledge graphs. This intuitive graph representation of the domain knowledge sets a new direction for visualizing and computerizing gerontological knowledge to facilitate human comprehension and build intelligent aged care information systems. [Journal of Gerontological Nursing, 48(4), 49-55.].

Plasmodium falciparum LipB mutants display altered redox and carbon metabolism in asexual stages and cannot complete sporogony in Anopheles mosquitoes.

Malaria is still one of the most important global infectious diseases. Emergence of drug resistance and a shortage of new efficient antimalarials continue to hamper a malaria eradication agenda. Malaria parasites are highly sensitive to changes in the redox environment. Understanding the mechanisms regulating parasite redox could contribute to the design of new drugs. Malaria parasites have a complex network of redox regulatory systems housed in their cytosol, in their mitochondrion and in their plastid (apicoplast). While the roles of enzymes of the thioredoxin and glutathione pathways in parasite survival have been explored, the antioxidant role of α-lipoic acid (LA) produced in the apicoplast has not been tested. To take a first step in teasing a putative role of LA in redox regulation, we analysed a mutant Plasmodium falciparum (3D7 strain) lacking the apicoplast lipoic acid protein ligase B (lipB) known to be depleted of LA. Our results showed a change in expression of redox regulators in the apicoplast and the cytosol. We further detected a change in parasite central carbon metabolism, with lipB deletion resulting in changes to glycolysis and tricarboxylic acid cycle activity. Further, in another Plasmodium cell line (NF54), deletion of lipB impacted development in the mosquito, preventing the detection of infectious sporozoite stages. While it is not clear at this point if the observed phenotypes are linked, these findings flag LA biosynthesis as an important subject for further study in the context of redox regulation in asexual stages, and point to LipB as a potential target for the development of new transmission drugs.

High-Sensitivity Troponin I Assay for DifferentialDiagnosis of New-Onset Myocardial Infarctionin Patients with Acute Decompensated Heart Failure

Purpose@#Acute decompensated heart failure (ADHF) caused by ischemic heart disease is associated with higher mortality and requires immediate diagnosis. Recently, novel methods to diagnose non-ST elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin have been applied. We compared the clinical utility of high-sensitivity troponin I (hS-TnI), delta troponin I, and other traditional methods to diagnose NSTEMI in patients with ADHF. @*Materials and Methods@#This retrospective cross-sectional study was conducted to analyze patients with ADHF who underwent hS-TnI evaluation of 0–2-h protocol in our emergency department. Patients were grouped according to a diagnosis of NSTEMI. @*Results@#A total of 524 ADHF [ADHF with NSTEMI, n=109 (20.8%)] patients were enrolled in this analysis. The mean values of hS-TnI (ng/mL) in the ADHF with and without NSTEMI groups were 2.44±5.60 and 0.25±0.91, respectively. Multivariable analysis revealed that regional wall-motion abnormality, T-wave inversion/hyperacute T wave, and initial and delta hS-TnI were predictive factors for NSTEMI. Laboratory values related to cardiac biomarkers, including hS-TnI [odds ratio (OR) (95% confidence interval, CI): 2.18], and the delta hS-TnI [OR (95% CI): 1.55] were significant predictors of NSTEMI. Moreover, receiver operating characteristic analysis showed that the areas under receiver operating characteristic curves for electrocardiographic abnormalities, initial hS-TnI, and delta hS-TnI were 0.794, 0.802, and 0.773, respectively. @*Conclusion@#For diagnosis of suspected NSTEMI in patients with ADHF, initial hS-TnI assay has similar predictive value as ischemic changes on electrocardiogram and superior predictive value than delta hS-TnI calculated by the 0–2-h protocol.

Validation of a novel diagnostic nomogram for pulmonary thromboembolism in the emergency department

Objective@#Diagnosis of pulmonary thromboembolism (PTE) is essential for preventing serious complications in the emergency department (ED) or intensive care unit. Contrast computed tomography (CT) of the chest is used for confirming pulmonary embolism, but there is a low specificity and radiation- or contrast-related side effects. We developed a novel nomogram to facilitate decision-making for performing contrast CT of the chest in the ED. @*Methods@#A retrospective observational study was conducted to develop a prediction model of PTE. The prediction model was derived from demographic characteristics, clinical history data and results of laboratory tests, ultrasonography and echocardiography. A nomogram was constructed from the variables of the prediction model and validated. @*Results@#A total of 326 patients were analyzed (a training cohort, 260; a validation cohort, 66). Wells’ score, D-dimer level>1,100 ng/dL, positive McConnell’s sign and D-shaped left ventricle were associated with the occurrence of PTE. The overall predictive accuracy of the prediction model was 0.802 (0.748-0.849) (area under the curve with 95% confidence interval). The calibration plots for the probability of PTE showed good agreement between the nomogram prediction and actual probability among cohorts. @*Conclusion@#A novel nomogram using risk stratification, laboratory test and sonographic examination findings is a good screening tool for predicting PTE, and it can be helpful to decide whether an ED physician should perform a contrastenhanced chest CT in the ED.

Developing an ontology for representing the domain knowledge specific to non-pharmacological treatment for agitation in dementia.

INTRODUCTION: A large volume of clinical care data has been generated for managing agitation in dementia. However, the valuable information in these data has not been used effectively to generate insights for improving the quality of care. Application of artificial intelligence technologies offers us enormous opportunities to reuse these data. For health data science to achieve this, this study focuses on using ontology to coding clinical knowledge for non-pharmacological treatment of agitation in a machine-readable format. METHODS: The resultant ontology-Dementia-Related Agitation Non-Pharmacological Treatment Ontology (DRANPTO)-was developed using a method adopted from the NeOn methodology. RESULTS: DRANPTO consisted of 569 concepts and 48 object properties. It meets the standards for biomedical ontology. DISCUSSION: DRANPTO is the first comprehensive semantic representation of non-pharmacological management for agitation in dementia in the long-term care setting. As a knowledge base, it will play a vital role to facilitate the development of intelligent systems for managing agitation in dementia.

Ivermectin for causal malaria prophylaxis: a randomised controlled human infection trial.

OBJECTIVE: Ivermectin is safe and widely used for treating helminth infections. It also kills arthropods feeding on treated subjects, including malaria vectors. Thus, ivermectin mass drug administration as an additional tool for malaria control is being evaluated by WHO. As in vitro data, animal experiments and epidemiological observations suggest that ivermectin has a direct effect on the liver stages of the malaria parasite, this study was designed to assess the prophylactic effect of ivermectin on Plasmodium falciparum controlled human malaria infection. METHODS: A total of 4 volunteers were randomised to placebo, and 8 volunteers were randomised to receive ivermectin 0.4 mg/kg, orally, once 2 h before being experimentally infected intravenously with 3200 P. falciparum sporozoites. The primary endpoint was time to parasitaemia detected by positive thick blood smear; RT-qPCR was performed in parallel. RESULTS: All but one volunteer became thick blood smear positive between day 11 and day 12 after infection, and there was no significant effect of ivermectin on parasitaemia. CONCLUSION: Ivermectin - at the dose used - has no clinically relevant activity against the pre-erythrocytic stages of P. falciparum.

OBJECTIF: L'ivermectine est sûr et largement utilisé pour traiter les helminthiases. Il tue également les arthropodes se nourrissant sur les sujets traités, y compris les vecteurs du paludisme. Ainsi, l'administration en masse d'ivermectine en tant qu'outil supplémentaire de lutte contre le paludisme est actuellement évaluée par l'OMS. Comme les données in vitro, les expériences sur animaux et les observations épidémiologiques suggèrent que l'ivermectine a un effet direct sur les stades hépatiques du parasite du paludisme, cette étude a été conçue pour évaluer l'effet prophylactique de l'ivermectine sur l'infection paludéenne humaine par Plasmodium falciparum contrôlée. MÉTHODES: Quatre volontaires ont été randomisés pour un placebo et 8 volontaires ont été randomisés pour recevoir de l'ivermectine à 0,4 mg/kg en une fois par voie orale, 2 heures avant d'être expérimentalement infectés par voie intraveineuse avec 3.200 sporozoïtes de P. falciparum. Le critère d'évaluation principal était le temps à la parasitémie détectée par un frottis sanguin épais positif. Une RT-qPCR a été réalisée en parallèle. RÉSULTATS: Tous les volontaires sauf un sont devenus positifs pour les frottis sanguins épais entre le jour 11 et le jour 12 après l'infection et il n'y avait aucun effet significatif de l'ivermectine sur la parasitémie. CONCLUSION: L'ivermectine - à la dose utilisée - n'a aucune activité cliniquement pertinente contre les stades pré-érythrocytaires de P. falciparum.

Descriptive analysis of prevalence and medical expenses of cancer, cardio-cerebrovascular disease, psychiatric disease, and musculoskeletal disease in Korean firefighters

Prediction Model for Massive Transfusion in Placenta Previa during Cesarean Section

0.05). The area under the receiver operating characteristics curve (AUC) was 0.922 [95% confidence interval (CI) 0.89–0.95]. In external validation, the discrimination was good, with an AUC value of 0.833 (95% CI 0.70–0.92) for this model. Nomogram calibration plots indicated good agreement between the predicted and observed outcomes, exhibiting close approximation between the predicted and observed probability.CONCLUSION: We constructed a scoring model for predicting massive transfusion during cesarean section in women with placenta previa. This model may help in determining the need to prepare an appropriate amount of blood products and the optimal timing of blood transfusion.

Incidence, Risk Factors, and Prediction of Myocardial Infarction and Stroke in Farmers: A Korean Nationwide Population-based Study / 예방의학회지

Objectives@#This study was conducted to determine the incidence and risk factors of myocardial infarction (MI) and stroke in farmers compared to the general population and to establish 5-year prediction models. @*Methods@#The farmer cohort and the control cohort were generated using the customized database of the National Health Insurance Service of Korea database and the National Sample Cohort, respectively. The participants were followed from the day of the index general health examination until the events of MI, stroke, or death (up to 5 years). @*Results@#In total, 734 744 participants from the farmer cohort and 238 311 from the control cohort aged between 40 and 70 were included. The age-adjusted incidence of MI was 0.766 and 0.585 per 1000 person-years in the farmer and control cohorts, respectively. That of stroke was 0.559 and 0.321 per 1000 person-years in both cohorts, respectively. In farmers, the risk factors for MI included male sex, age, personal history of hypertension, diabetes, current smoking, creatinine, metabolic syndrome components (blood pressure, triglycerides, and high-density lipoprotein cholesterol). Those for stroke included male sex, age, personal history of hypertension, diabetes, current smoking, high γ-glutamyl transferase, and metabolic syndrome components (blood pressure, triglycerides, and high-density lipoprotein cholesterol). The prediction model showed an area under the receiver operating characteristic curve of 0.735 and 0.760 for MI and stroke, respectively, in the farmer cohort. @*Conclusions@#Farmers had a higher age-adjusted incidence of MI and stroke. They also showed distinct patterns in cardiovascular risk factors compared to the general population.

The Trend in Incidence and Case-fatality of Hospitalized Acute Myocardial Infarction Patients in Korea, 2007 to 2016

Descriptive analysis of prevalence and medical expenses of cancer, cardio-cerebrovascular disease, psychiatric disease, and musculoskeletal disease in Korean firefighters

BACKGROUND@#Firefighters are exposed to many dangerous working conditions. Many studies have identified the risk of disease for firefighters, but only a few studies have addressed the medical expenses of firefighters, which represents a concrete scale of disease. Our purpose in this study was to determine the medical expenditures of firefighters to assess the overall scale of disease in Korea. We focused on cancer, mental disorders, cardio-cerebrovascular disease, and musculoskeletal disease, the prevalence of which was expected to be high in firefighters.@*METHODS@#This study utilized National Health Insurance Service data. We targeted firefighters, police officers, and government officials. We classified disease based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. We compared prevalence by the age-standardized prevalence rate, considering standard distribution of the population. Medical expenditure of disease was defined as outpatient fees, hospitalization fees, and drug costs. Total medical expenditures were calculated by the sum of those 3 categories.@*RESULTS@#The age-standardized prevalence of cancer, mental disorders, and cardiovascular disease in firefighters was slightly higher than or similar to that of government officials and police officers (no significant difference). However, medical expenditures for stomach cancer, mental disorders, and most cardio-cerebrovascular diseases were higher in firefighters than in others. In particular, firefighters spent 12 times more money for ischemic heart disease than did government officials. Of musculoskeletal diseases, lumbar disc disorder had the highest expenditures among firefighters.@*CONCLUSIONS@#The age-standardized prevalence of most of diseases of firefighters was not as high as in the other groups, but the medical expenses of firefighters were much higher than those of government officials and police officers.

Descriptive analysis of prevalence and medical expenses of cancer, cardio-cerebrovascular disease, psychiatric disease, and musculoskeletal disease in Korean firefighters

BACKGROUND@#Firefighters are exposed to many dangerous working conditions. Many studies have identified the risk of disease for firefighters, but only a few studies have addressed the medical expenses of firefighters, which represents a concrete scale of disease. Our purpose in this study was to determine the medical expenditures of firefighters to assess the overall scale of disease in Korea. We focused on cancer, mental disorders, cardio-cerebrovascular disease, and musculoskeletal disease, the prevalence of which was expected to be high in firefighters.@*METHODS@#This study utilized National Health Insurance Service data. We targeted firefighters, police officers, and government officials. We classified disease based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. We compared prevalence by the age-standardized prevalence rate, considering standard distribution of the population. Medical expenditure of disease was defined as outpatient fees, hospitalization fees, and drug costs. Total medical expenditures were calculated by the sum of those 3 categories.@*RESULTS@#The age-standardized prevalence of cancer, mental disorders, and cardiovascular disease in firefighters was slightly higher than or similar to that of government officials and police officers (no significant difference). However, medical expenditures for stomach cancer, mental disorders, and most cardio-cerebrovascular diseases were higher in firefighters than in others. In particular, firefighters spent 12 times more money for ischemic heart disease than did government officials. Of musculoskeletal diseases, lumbar disc disorder had the highest expenditures among firefighters.@*CONCLUSIONS@#The age-standardized prevalence of most of diseases of firefighters was not as high as in the other groups, but the medical expenses of firefighters were much higher than those of government officials and police officers.

Prognostic Effect of Guideline-Directed Therapy Is More Noticeable Early in the Course of Heart Failure

BACKGROUND: There have been few studies to evaluate the prognostic implications of guideline-directed therapy according to the temporal course of heart failure. This study assessed the relationship between adherence to guideline-directed therapy at discharge and 60-day clinical outcomes in de novo acute heart failure (AHF) and acute decompensated chronic heart failure (ADCHF) separately. METHODS: Among 5,625 AHF patients who were recruited from a multicenter cohort registry of Korean Acute Heart Failure, 2,769 patients with reduced ejection fraction were analyzed. Guideline-directed therapies were defined as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor II blocker (ARB), β-blocker, and mineralocorticoid receptor antagonist. RESULTS: In de novo AHF, ACEI or ARB reduced re-hospitalization (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34–0.95), mortality (HR, 0.41; 95% CI, 0.24–0.69) and composite endpoint (HR, 0.52; 95% CI, 0.36–0.77) rates. Beta-blockers reduced re-hospitalization (HR, 0.62; 95% CI, 0.41–0.95) and composite endpoint (HR, 0.65; 95% CI, 0.47–0.90) rates. In ADCHF, adherence to ACEI or ARB was associated with only mortality and β-blockers with composite endpoint. CONCLUSION: The prognostic implications of adherence to guideline-directed therapy at discharge were more pronounced in de novo heart failure. We recommend that guideline-directed therapy be started as early as possible in the course of heart failure with reduced ejection fraction.

Traumatic Absence of the Shaft of the Radius in a Child: A 15-Year Follow-up after Reconstruction by a Modified Define's One Bone Forearm Procedure

Traumatic absence of the entire radial shaft in children has not been reported though there are a few reports of adult cases. We report a 5-year-old boy with traumatic absence of the entire right radial shaft. The Define's reconstruction procedure was chosen to localize the surgery only to the distal forearm and avoid further additional damage to the forearm muscles. The child's forearm was successfully reconstructed by the authors' modified Define's procedure, which was followed until his maturity. Hand function was well maintained.

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity.

Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.

Spinal Tuberculosis in Children: Predictable Kyphotic Deformity after Cure of the Tuberculosis / 대한정형외과학회잡지

PURPOSE: To assess the chronological changes of disease-related kyphosis after chemotherapy alone. MATERIALS AND METHODS: A total of 101 children aged 2 to 15 years with spinal tuberculosis, accompanied by various stages of disease processes were enrolled for analysis. By utilizing the images in them, the growth plate condition and chronological changes of kyphosis after chemotherapy were analyzed at two points in time; the first assessment was at post-chemotherapy one-year and second at the final discharge. RESULTS: Complete disc destruction in the cervical, dorsal and lumbosacral spines was observed in 2 out of 40 children (5.0%), 8 out of 30 children (26.7%), and 6 out of 31 children (19.4%), respectively. In those cases, the residual kyphosis inevitably developed. In the remaining children, the discs were intact or partially damaged. Among the 101 children kyphotic deformity was maintained without change in 20 children (19.8%). Kyphosis decreased in 14 children (13.9%), while it increased in 67 children (66.3%) with non-recoverably damaged growth plate. CONCLUSION: Although it is tentatively possible to predict the deformity progress or non-progress and spontaneous correction at the time of the initial treatment, its predictive accuracy is low. Therefore, assessment of the chronological changes should be performed at the end of chemotherapy. In children with progressive curve change, assessment of deformity should be continued until maturity.

Mycobacterium Tuberculosis in Spinal Tuberculosis

Even in an era of remarkable medical advances, there is an issue of why tuberculosis remains in the list of disastrous diseases, afflicting humans and causing suffering. There has not been a plausible answer to this, and it has been suggested that clinicians and medical scientists could presently not win the war against the tubercle bacilli. With regards to this issue, based on the authors' own clinical and research experiences, in this review, the available literature was revisited in order to address the raised questions and to provide recent information on characteristics of tubercle bacilli and possible ways to more effectively treat tuberculosis.

Alagille Syndrome Mimicking Biliary Atresia Confirmed by Jagged1 (JAG1) Gene Analysis in a Newborn: A Case Report

Alagille syndrome is a complex autosomal dominant disorder secondary to defects in the Notch signaling pathway, primarily caused by mutations in the Jagged1 (JAG1) gene. The liver, heart, skeleton, face and eyes are the body parts most commonly involved. Alagille syndrome may mimic other causes of high gamma-glutamyl transferase (GGT)-linked cholestasis, most notably biliary atresia in the neonatal period. Infants with Alagille syndrome are occasionally misdiagnosed as cases with biliary atresia due to variations in clinical features that might be expressed in early infancy. We describe a case of Alagille syndrome mimicking biliary atresia, identified by sequencing analysis of the JAG1 gene in a newborn. During counseling, family members of the patient have also been found to demonstrate various phenotypes and levels of disease severity of Alagille syndrome.

Efficacy of early steroid use in Mycoplasma pneumoniae pneumonia

PURPOSE: The aim of this study was to evaluate whether or not the early use of steroid is useful for treating Mycoplasma pneumoniae pneumonia. METHODS: A prospective study was conducted on 85 patients with M. pneumoniae pneumonia admitted to Gwangju Christian Hospital between September 2015 and April 2016. A total of 85 patients were enrolled. Of these, 33 were treated with steroids (methyl-prednisolone 1 mg/kg/day), while 52 were not; both were treated with macrolides. The overall duration of fever was compared between the 2 groups and findings on chest radiographs were evaluated for their deterioration. RESULTS: The duration of fever after admission (1.36±0.92 days vs. 2.17±1.30 days, P=0.003) and the overall duration of fever (4.42±2.13 days vs. 6.07±2.59 days, P=0.003) were significantly lower in the steroid group. The duration of fever before admission was not different between the steroid and macrolide groups (3.06±1.74 days vs. 3.90±2.21 days, P=0.068). On chest radiographs taken 3 days later, 1 of 33 patients in the steroid group and 5 of 50 patients in the macrolide group worsened, although there was no statistically significant difference between the 2 groups (P=0.395). There was no significant difference in the duration of hospitalization between the 2 groups (6.72±1.54 days vs. 6.92±1.87 days, P=0.618). CONCLUSION: Early administration of steroids on patients with M. pneumoniae pneumonia reduced the duration of fever, but there was no difference in duration of admission and x-ray deterioration.

Seasonal Influenza-Related Neurologic Complications in Children from 2010 to 2015 / 대한소아신경학회지

PURPOSE: Influenza-associated neurologic complications in children are diverse. But there has been little long-term and large-scale research about neurologic complications of seasonal influenza. This study aimed to identify the incidence, characteristics, and risk factors for neurologic complications in children hospitalized with influenza. METHODS: Retrospective analysis was conducted on the clinical data of 940 children hospitalized with confirmed influenza infection from Oct, 2010 to May, 2016 in Kwangju Christian Hospital. RESULTS: A total of 940 children with influenza were hospitalized, of whom 96 (10.2%) had neurologic complications:81 children presented febrile seizures (8.6%) and some included 12 other seizures (1.3%),1 encephalitis (0.1%), 1 Guillain-Barré syndrome (0.1%), 1 aseptic meningitis (0.1%). They had good prognosis except the encephalitis child. The incidence of neurologic complications was significantly higher in influenza A than in influenza B (11.9% vs. 7.0%, P=0.036). The incidence of influenza A was highest in February, while that of influenza B was highest in March and April. The monthly distribution of neurological complications reflected the influenza incidence. The risk factors for influenza-associated neurologic complications were underlying neurologic disease and young age. No significant clinical differences were observed between influenza A and B in febrile seizure. CONCLUSION: Febrile seizures are the most common neurologic complication with good prognosis. Although encephalitis/encephalopathy is rare, it can be severe with sequelae, so prompt diagnosis and treatment should be initiated. And influenza vaccine should be encouraged to children with underlying neurologic disease.