Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

Hepatocellular carcinoma with Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with long-term follow-up: a case report

Membranous obstruction of the inferior vena cava (MOVC) is a rare subset of Budd-Chiari syndrome (BCS) with a subacute onset that is often complicated by cirrhosis and hepatocellular carcinoma (HCC). Here we report a case of recurrent HCC in a patient with cirrhosis and BCS that was treated with several episodes of transarterial chemoembolization followed by surgical tumorectomy, whereas the MOVC was successfully treated with balloon angioplasty followed by endovascular stenting. The patient was followed up for 9.9 years without anticoagulation and experienced no stent thrombosis. After the tumorectomy, the patient was HCC-free for 4.4 years of follow-up

The Effect of Regimen Frequency Simplification on Provider Order Generation: A Quasi-Experimental Study in a Korean Hospital

The multiplicity of dosing frequencies that are attached to medication orders poses a challenge to patients regarding adhering to their medication regimens and healthcare professionals in maximizing the efficiencies of health care service delivery. A multidisciplinary team project was performed to simplify medication regimens to improve the computerized physician order entry (CPOE) system to reduce the dosing frequencies for patients who were discharged from the hospital. A 36-month pre-test–post-test study was performed, including 12-month pre-intervention, 12-month intervention, and 12-month post-intervention periods. Two-pronged strategies, including regimen standardization and prioritization, were devised to evaluate the dosing frequencies and prescribing efficiency. The results showed that the standardized menu reduced the dosing frequencies from 4.3 ± 2.2 per day in the pre-intervention period to 3.5 ± 1.8 per day in the post-intervention period (p < 0.001). In addition, the proportion of patients taking medications five or more times per day decreased from 40.8% to 20.7% (p < 0.001). After prioritizing the CPOE dosing regimen, the number of pull-down options that were available reflected an improvement in the prescribing efficiency. Our findings indicate that concerted efforts in improving even a simple change on the CPOE screen via standardization and prioritization simplified the dosing frequencies for patients and improved the physicians’ prescribing process

Healthcare Quality Improvement Analytics: An Example Using Computerized Provider Order Entry

Evaluation of sustainability after quality improvement (QI) projects in healthcare settings is an essential part of monitoring and future QI planning. With limitations in adopting quasi-experimental study design in real-world practice, healthcare professionals find it challenging to present the sustained effect of QI changes effectively. To provide quantitative methodological approaches for demonstrating the sustainability of QI projects for healthcare professionals, we conducted data analyses based on a QI project to improve the computerized provider order entry system to reduce patients’ dosing frequencies in Korea. Data were collected for 5 years: 24-month pre-intervention, 12-month intervention, and 24-month post-intervention. Then, analytic approaches including control chart, Analysis of Variance (ANOVA), and segmented regression were performed. The control chart intuitively displayed how the outcomes changed over the entire period, and ANOVA was used to test whether the outcomes differed between groups. Last, segmented regression analysis was conducted to evaluate longitudinal effects of interventions over time. We found that the impact of QI projects in healthcare settings should be initiated following the Plan–Do–Study–Act cycle and evaluated long-term effects while widening the scope of QI evaluation with sustainability. This study can serve as a guide for healthcare professionals to use a number of statistical methodologies in their QI evaluations

Outbreak of carbapenem-resistant Enterobacterales at a long-term care facility in Seoul, Korea: surveillance and intervention mitigation strategies

OBJECTIVES Because effective decolonization options are not available, and treatment options are limited, carbapenem-resistant Enterobacterales (CRE) constitute increasingly threatening nosocomial pathogens. To prevent CRE-associated transmission and ensure patient safety, healthcare personnel and everyone in contact with CRE-infected patients must implement stringent infection control practices. This report describes a CRE outbreak, possibly related to a caregiver at a long-term care facility (LTCF), and presents a new surveillance model to improve the infection control of CRE in Seoul, Korea. METHODS The Seoul Metropolitan Government surveillance system identified an outbreak of CRE in an LTCF in 2022. We obtained data on the demographic characteristics and contact histories of the inpatients, medical staff, and caregivers. To isolate the inpatients and employees exposed to CRE, we used rectal swab samples and environmental sampling during the study period (May-December 2022). RESULTS We identified 18 cluster cases (1 caregiver and 17 inpatients) and 12 sporadic cases with CRE, and conducted a complete 197-day follow-up of all cases in the LTCF’s isolation wards. CONCLUSIONS This investigation demonstrated that our surveillance model and targeted intervention, based on the cooperation of the municipal government, public health center, and infection control advisory committee, effectively contained the epidemic at the LTCF. Measures to improve the compliance of all employees in LTCFs with infection control guidelines should also be adopted

Methanol Extract of Aerial Parts of Pavetta indica L. Enhances the Cytotoxic Effect of Doxorubicin and Induces Radiation Sensitization in MDA-MB-231 Triple-Negative Breast Cancer Cells

Pavetta indica L. is used in traditional medicine for the treatment of various diseases including hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, no study has evaluated the anticancer effect of P. indica L. In this study, we found that a methanol extract of the leaves and branches of P. indica L. (MEPI) caused cell-cycle arrest at the sub-G1 phase and induced apoptosis, as indicated by the activation of caspase-8, -3, -7, and c-PARP. Western blotting revealed that MEPI significantly reduced the levels of markers of the epithelial-mesenchymal transition, such as Vimentin, Snail, Slug, and matrix metallopeptidase 9. Notably, the expression of multidrug resistance-associated protein 1 in triple negative breast cancer (TNBC) was significantly decreased by MEPI. Moreover, the co-treatment with MEPI and doxorubicin resulted in a synergistic reduction in cell viability. MEPI also induced radiation sensitization of TNBC cells. Gas chromatography-mass spectrometry analysis revealed that 5,6-dehydrokawain (DK) is the major constituent of MEPI. Interestingly, DK exerted significant anti-invasive and anti-metastatic effects. Our results provide a strong rationale for investigating the molecular mechanisms of action of MEPI in TNBC