The potential for drug incompatibility and its drivers - A hospital wide retrospective descriptive study.

OBJECTIVE: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data. METHODS: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission. RESULTS: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs. CONCLUSIONS: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings.

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Deep learning for predicting rehospitalization in acute heart failure: Model foundation and external validation.

AIMS: Assessing the risk for HF rehospitalization is important for managing and treating patients with HF. To address this need, various risk prediction models have been developed. However, none of them used deep learning methods with real-world data. This study aimed to develop a deep learning-based prediction model for HF rehospitalization within 30, 90, and 365 days after acute HF (AHF) discharge. METHODS AND RESULTS: We analysed the data of patients admitted due to AHF between January 2014 and January 2019 in a tertiary hospital. In performing deep learning-based predictive algorithms for HF rehospitalization, we use hyperbolic tangent activation layers followed by recurrent layers with gated recurrent units. To assess the readmission prediction, we used the AUC, precision, recall, specificity, and F1 measure. We applied the Shapley value to identify which features contributed to HF readmission. Twenty-two prognostic features exhibiting statistically significant associations with HF rehospitalization were identified, consisting of 6 time-independent and 16 time-dependent features. The AUC value shows moderate discrimination for predicting readmission within 30, 90, and 365 days of follow-up (FU) (AUC:0.63, 0.74, and 0.76, respectively). The features during the FU have a relatively higher contribution to HF rehospitalization than features from other time points. CONCLUSIONS: Our deep learning-based model using real-world data could provide valid predictions of HF rehospitalization in 1 year follow-up. It can be easily utilized to guide appropriate interventions or care strategies for patients with HF. The closed monitoring and blood test in daily clinics are important for assessing the risk of HF rehospitalization.

Triglyceride-Related Parameters and Symptomatic Atherosclerotic Lesions in Patients With Ischemic Stroke.

Objective: Recently, evidence has suggested that the pathophysiology and risk factors of intracranial atherosclerosis (ICAS) differs from those of extracranial atherosclerosis (ECAS). In addition, novel parameters reflecting metabolic conditions, such as insulin resistance or atherogenic dyslipidemia, based on triglycerides (TG) and other biomarkers, have emerged. In this study, we evaluated the association between TG-related parameters and symptomatic cerebral atherosclerosis in patients with acute ischemic stroke resulting from large artery atherosclerosis (LAA). Methods: We assessed consecutive acute LAA-stroke patients between January 2010 and December 2020. Based on the radiological findings, we classified the relevant symptomatic arteries that caused the index stroke into LAA-ICAS and LAA-ECAS. As TG-related parameters, the atherogenic index of plasma (AIP) and TG-glucose (TyG) index were calculated according to the following formulas: AIP = log10 (TG Level/High-density Lipoprotein Cholesterol Level), TyG Index = Ln (TG Level × Glucose Level/2). Results: A total of 519 patients with LAA-stroke were evaluated. In multivariable logistic regression analysis to identify predictors of LAA-ICAS, AIP was significantly associated with LAA-ICAS (adjusted odds ratio [aOR], 3.60; 95% confidence interval [CI], 1.60-8.06). TyG index also showed a statistically significant relationship with LAA-ICAS (aOR, 1.60; 95% CI, 1.11-2.32). However, TG per se did not show a statistical association with LAA-ECAS. Conclusion: TG-related parameters were more closely associated with stroke by ICAS than by ECAS. The metabolic conditions reflected by the AIP or TyG index, rather than hypertriglyceridemia itself, may play a greater role in determining the relevant vessel causally involved in a stroke.

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

Transcriptome sequencing of the endangered land snail Karaftohelix adamsi from the Island Ulleung: De novo assembly, annotation, valuation of fitness genes and SSR markers.

BACKGROUND: The Bradybaenidae snail Karaftohelix adamsi is endemic to Korea, with the species tracked from Island Ulleung in North Gyeongsang Province of South Korea. K. adamsi has been classified under the Endangered Wildlife Class II species of Korea and poses a severe risk of extinction following habitat disturbances. With no available information at the DNA (genome) or mRNA (transcriptome) level for the species, conservation by utilizing informed molecular resources seems difficult. OBJECTIVE: In this study, we used the Illumina short-read sequencing and Trinity de novo assembly to draft the reference transcriptome of K. adamsi. RESULTS: After assembly, 13,753 unigenes were obtained of which 10,511 were annotated to public databases (a maximum of 10,165 unigenes found homologs in PANM DB). A total of 6,351, 3,535, 358, and 3,407 unigenes were ascribed to the functional categories under KOG, GO, KEGG, and IPS, respectively. The transcripts such as the HSP 70, aquaporin, TLR, and MAPK, among others, were screened as putative functional resources for adaptation. DNA transposons were found to be thickly populated in comparison to retrotransposons in the assembled unigenes. Further, 2,164 SSRs were screened with the promiscuous presence of dinucleotide repeats such as AC/GT and AG/CT. CONCLUSION: The transcriptome-guided discovery of molecular resources in K. adamsi will not only serve as a basis for functional genomics studies but also provide sustainable tools to be utilized for the protection of the species in the wild. Moreover, the development of polymorphic SSRs is valuable for the identification of species from newer habitats and cross-species genotyping.

Severity of sleep apnea as a prognostic factor for mortality in patients with multiple system atrophy.

BACKGROUND: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis. RESULTS: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069). CONCLUSION: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor.

In silico identification and expression analysis of superoxide dismutases in Tenebrio molitor.

BACKGROUND: Insects encounter various environmental stresses, in response to which they generate reactive oxygen species (ROS). Superoxide dismutase (SOD) is an antioxidant metalloenzyme that scavenges superoxide radicals to prevent oxidative damage. OBJECTIVE: To investigate expressions of SODs under oxidative stress in Tenebrio molitor. METHODS: Here, we investigated the transcriptional expression of SODs by pesticide and heavy metals in Tenebrio moltior. First, we searched an RNA-Seq database for T. molitor SOD (TmSOD) genes and identified two SOD isoforms (TmSOD1-iso1 and iso2). We examined their activities under developmental stage, tissue-specific, and various types (pesticide and heavy metal) of oxidative stress by using qPCR. RESULTS: Our results revealed two novel forms of TmSODs. These TmSODs had a copper/zinc superoxide dismutase domain, active site, Cu2+ binding site, Zn2+ binding site, E-class dimer interface, and P-class dimer interface. TmSODs (TmSOD1-iso1 and iso2) were expressed in diverse developmental phases and tissues. Pesticides and heavy metals caused an upregulation of these TmSODs. CONCLUSION: Our findings suggest that the two TmSODs have different functions in T. molitor, providing insights into the detoxification ability of T. molitor.

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation.

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78-0.95), ischemic stroke (aHR 0.89; 95% CI 0.81-0.99), major bleeding (aHR 0.78; 95% CI 0.68-0.89), and all-cause death (aHR 0.87; 95% CI 0.81-0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.

Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.

In silico identification and expression analyses of peroxidases in Tenebrio molitor.

Human advancements in agriculture, urbanization, and industrialization have led to various forms of environmental pollution, including heavy metal pollution. Insects, as highly adaptable organisms, can survive under various environmental stresses, which induce oxidative damage and impair antioxidant systems. To investigate the peroxidase (POX) family in Tenebrio molitor, we characterized two POXs, namely TmPOX-iso1 and TmPOX-iso2. The full-length cDNA sequences of TmPox-iso1 and TmPox-iso2 respectively consisted of an open reading frame of 1815 bp encoding 605 amino acids and an open reading frame of 2229 bp encoding 743 amino acids. TmPOX-iso1 and TmPOX-iso2 homologs were found in five distinct insect orders. In the phylogenetic tree analysis, TmPOX-iso1 was clustered with the predicted POX protein of T. castaneum, and TmPOX-iso2 was clustered with the POX precursor protein of T. castaneum. During development, the highest expression level of TmPox-iso1 was observed in the pre-pupal stage, while that of TmPox-iso2 expression were observed in the pre-pupal and 4-day pupal stages. TmPox-iso1 was primarily expressed in the early and late larval gut, while TmPox-iso2 mRNA expression was higher in the fat bodies and Malpighian tubules. In response to cadmium chloride treatment, TmPox-iso1 expression increased at 3 hours and then declined until 24 hours, while in the zinc chloride-treated group, TmPox-iso1 expression peaked 24 hours after the treatment. Both treated groups showed increases in TmPox-iso2 expression 24 hours after the treatments.

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study.

BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

Gene expression and characterization of 2-keto-3-deoxy-gluconate kinase, a key enzyme in the modified Entner-Doudoroff pathway of Serratia marcescens KCTC 2172

We cloned 2-keto-3-deoxy-gluconate kinase (KDGK), which catalyzes the phosphorylation of 2-keto-3-deoxygluconate (KDG) to 2-keto-3-deoxy-6-phophogluconate (KDPG) from Serratia marcescens KCTC 2172. The nucleotide sequence revealed a single open reading frame containing 1,208 bp and encoding for 309 amino acids, with a molecular weight of 33,993 Da. The enzyme was purified via GST affinity chromatography. The putative KdgT binding site was detected upstream of the initial codon. The KDG kinase utilized 2-ketogluconate (KG) and KDG as substrates. The optimal temperature and pH for KDGK activity were 50ºC and 8.0, respectively.

Solubilization of insoluble inorganic phosphate by Burkholderia cepacia DA23 isolated from cultivated soil

A mineral phosphate solubilizing bacterium, Burkholderia cepacia DA23 has been isolated from cultivated soils. Phosphate-solubilizing activities of the strain against three types of insoluble phosphate were quantitatively determined. When 3 percent of glucose concentration was used for carbon source, the strain had a marked mineral phosphate-solubilizing activity. Mineral phosphate solubilization was directly related to the pH drop by the strain. Analysis of the culture medium by high pressure liquid chromatography identified gluconic acid as the main organic acid released by Burkholderia cepacia DA23. Gluconic acid production was apparently the result of the glucose dehydrogenase activity and glucose dehydrogenase was affected by phosphate regulation.

Uma bactéria capaz de solubilizar fosfato mineral, Burkholderia cepacea DA23, foi isolada de solo cultivado. A capacidade dessa bactéria solubilizar o fosfato de três tipos de fosfato insolúvel foi quantificada. Quando foi utilizada glicose a 3 por cento como fonte de carbono, a bactéria apresentou uma intensa atividade solubilizante de fosfato, sendo a solubilização diretamente relacionada com a queda de pH causada pela bactéria. A análise do meio de cultura por cromatografia líquida de alta pressão indicou o ácido glicônico como principal ácido produzido por Burkholderia cepacea DA23. Aparentemente, a produção de ácido glicônico foi causada pela atividade da glicose desidrogenase. A enzima foi afetada pela regulação do fosfato.