PINK1 siRNA-loaded poly(lactic-co-glycolic acid) nanoparticles provide neuroprotection in a mouse model of photothrombosis-induced ischemic stroke.

PTEN-induced kinase 1 (PINK1) is a well-known critical marker in the pathway for mitophagy regulation as well as mitochondrial dysfunction. Evidence suggests that mitochondrial dynamics and mitophagy flux play an important role in the development of brain damage from stroke pathogenesis. In this study, we propose a treatment strategy using nanoparticles that can control PINK1. We used a murine photothrombotic ischemic stroke (PTS) model in which clogging of blood vessels is induced with Rose Bengal (RB) to cause brain damage. We targeted PINK1 with poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles loaded with PINK1 siRNA (PINK1 NPs). After characterizing siRNA loading in the nanoparticles, we assessed the efficacy of PINK1 NPs in mice with PTS using immunohistochemistry, 1% 2,3,5-triphenyltetrazolium chloride staining, measurement of motor dysfunction, and Western blot. PINK1 was highly expressed in microglia 24 h after PTS induction. PINK1 siRNA treatment increased phagocytic activity, migration, and expression of an anti-inflammatory state in microglia. In addition, the PLGA nanoparticles were selectively taken up by microglia and specifically regulated PINK1 expression in those cells. Treatment with PINK1 NPs prior to stroke induction reduced expression of mitophagy-inducing factors, infarct volume, and motor dysfunction in mice with photothrombotic ischemia. Experiments with PINK1-knockout mice and microglia depletion with PLX3397 confirmed a decrease in stroke-induced infarct volume and behavioral dysfunction. Application of nanoparticles for PINK1 inhibition attenuates RB-induced photothrombotic ischemic injury by inhibiting microglia responses, suggesting that a nanomedical approach targeting the PINK1 pathway may provide a therapeutic avenue for stroke treatment.

Perampanel Reduces Brain Damage via Induction of M2 Microglia in a Neonatal Rat Stroke Model.

Purpose: Ischemic stroke is a leading cause of death and disability worldwide. Additionally, neonatal ischemia is a common cause of neonatal brain injury, resulting in cerebral palsy with subsequent learning disabilities and epilepsy. However, there is currently a lack of effective treatments available for patients with perinatal ischemic stroke. In this study, we investigated the effect of perampanel (PER)-loaded poly lactic-co-glycolic acid (PLGA) by targeting microglia in perinatal stroke. Methods: After formation of focal ischemic stroke by photothrombosis in P7 rats, PER-loaded PLGA was injected intrathecally. Proinflammatory markers (TNF-α, IL-1ß, IL-6, COX2, and iNOS) and M2 polarization markers (Ym1 and Arg1) were evaluated. We investigated whether PER increased M2 microglial polarization in vitro. Results: PER-loaded PLGA nanoparticles decreased the pro-inflammatory cytokines compared to the control group. Furthermore, they increased M2 polarization. Conclusion: PER-loaded PLGA nanoparticles decreased the size of the infarct and increased motor function in a perinatal ischemic stroke rat model. Pro-inflammatory cytokines were also reduced compared to the control group. Finally, this development of a drug delivery system targeting microglia confirms the potential to develop new therapeutic agents for perinatal ischemic stroke.

Clinical Safety of Expanded Hemodialysis Compared with Hemodialysis Using High-Flux Dialyzer during a Three-Year Cohort.

Expanded hemodialysis (HD) equipped with a medium cut-off (MCO) membrane provides superior removal of larger middle molecules. However, there is still little research on the long-term benefits of expanded HD. Over a three-year period, this observational study evaluated the efficacy and safety profile of expanded HD for inflammatory cytokines, including IL-6. We conducted a prospective cohort study to investigate the inflammatory cytokine changes and a retrospective observational cohort study to investigate long-term clinical efficacy and safety over a three-year period. We categorized the patients according to dialyzer used: MCO and high-flux (HF) dialyzer. The inflammatory cytokines, including IFN-γ, IL-1ß, IL-6, and TNF-α, were measured annually. The concentrations and changes of the four cytokines over time did not differ between the HF group (n = 15) and MCO group (n = 27). In both prospective and retrospective (HF group, n = 38; MCO group, n = 76) cohorts, there were no significant differences in either death, cardiovascular events, infections, or hospitalizations. Furthermore, the temporal changes in laboratory values, including serum albumin and erythropoietin prescriptions, did not differ significantly between the two groups in either the prospective or retrospective cohorts. In conclusion, clinical efficacy and safety outcomes, as well as inflammatory cytokines, did not differ with expanded HD compared with HF dialysis during a three-year treatment course, although the level of inflammatory cytokine was stable.

Psychological distress of patients with end-stage kidney disease undergoing dialysis during the 2019 coronavirus disease pandemic: A cross-sectional study in a University Hospital.

INTRODUCTION: Previous studies have revealed that the COVID-19 pandemic can cause psychological distress such as depression and anxiety. Patients with chronic kidney disease (CKD) might be more vulnerable to psychological distress due to the COVID-19 pandemic. Its impact could be different according to dialysis modality. The aim of this study was to investigate COVID-19-related psychological stress experienced by end-stage kidney disease (ESKD) patients and identify differences in concerns about COVID-19 between hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: This cross-sectional study included 148 dialysis patients at Soonchunhyang University Cheonan Hospital from August 2020 to September 2020. These patients responded to a questionnaire covering mental health status and COVID-19 related concerns. Symptoms of depression, anxiety, stress, and insomnia were measured using a 9-item Patient Health Questionnaire (PHQ-9), a 7-item Generalized Anxiety Disorder (GAD-7) scale, a 22-item Impact of Event Scale-Revised (IES-R), and a 7-item Insomnia severity Index (ISI), respectively. Outcomes of HD and PD patients were compared by propensity score matching analysis. RESULTS: Dialysis patients reported psychological distress including symptoms of depression, anxiety, stress, and insomnia. HD patients showed higher scores for depression (p = 0.018), anxiety(p = 0.005), stress(p<0.001), and insomnia(p = 0.006) than the PD patients. After propensity score matching, HD was associated with depression(p = 0.0131), anxiety(p = 0.0143), and stress(p = 0.000415). CONCLUSION: Dialysis patients showed psychological distress during the COVID-19 pandemic period, with HD patients having more severe symptoms than PD patients.

Influence of anxiety and resilience on depression among hospital nurses: A comparison of nurses working with confirmed and suspected patients in the COVID-19 and non-COVID-19 units.

AIMS AND OBJECTIVES: This study aimed to compare anxiety, resilience, and depression between COVID-19 unit (confirmed patients and suspected patients) and non-COVID-19 unit nurses and assess their effects on depression. BACKGROUND: Nurses working during the global pandemic are known to be physically and psychologically exhausted, and experience severe anxiety and depression. However, there is a lack of studies comparing anxiety and depression between COVID-19 and non-COVID-19 unit nurses. DESIGN: Descriptive research study. METHODS: This study was conducted on 64 nurses who directly worked for more than a month in a COVID-19 unit of a general hospital with nationally designated negative-pressure isolation beds and 64 nurses working in a non-COVID-19 unit. Data were collected through questionnaires and were analysed using SPSS 25.0. Reporting of this research adheres to the STROBE guidelines. RESULTS: Anxiety and depression were significantly higher in nurses working with patients suspected to have COVID-19 rather than nurses working with confirmed COVID-19 patients and non-COVID-19 patients. Resilience was significantly lower in suspected patient unit nurses than in COVID-19 unit nurses. Anxiety was the major factor predicting depression in both COVID-19 unit (confirmed patients and suspected patients) and non-COVID-19 unit nurses with 76.6%, 80.7%, and 63.6% explanatory power, respectively. CONCLUSIONS: Among nurses working in COVID-19 units, suspected patients unit nurses had higher depression than confirmed patients unit nurses due to an unsafe facility environment, insufficient personal protective equipment, and unknown conditions of the patients. Thus, interventions which have a high impact on depression need to be provided to relieve anxiety. RELEVANCE TO CLINICAL PRACTICE: The nursing organisation must provide comprehensive support including coordinated shifts, internal motivation, incentives, up-to-date information, and clear infection prevention guidelines to relieve anxiety caused by exhaustive workload, uncertainty of infectious diseases, and lack of human and material resources.

Efficacy of 3 fine-needle biopsy techniques for suspected pancreatic malignancies in the absence of an on-site cytopathologist.

BACKGROUND AND AIMS: EUS-guided fine-needle aspiration/biopsy (EUS-FNA/B) has a high diagnostic accuracy for pancreatic tumors. Most reports have focused on the diagnostic yield of cytology or histology; the ability of various FNA/B techniques to obtain an adequate mass of cells or tissue has rarely been investigated. METHODS: Patients with suspected pancreatic malignancy underwent EUS-FNB using a 22-gauge ProCore needle by either the stylet slow-pull-back technique (group A), conventional negative suction after stylet removal (group B), or non-suction after stylet removal (group C) in the absence of an on-site cytopathologist. The adequacy of the 3 techniques based on the diagnostic yield, cellularity, blood contamination, and core-tissue acquisition was evaluated. RESULTS: A total of 50 patients (27 males) were analyzed. The mean tumor size was 21 to 40 mm in 54%. The rate of a good or excellent proportion of cellularity was highest in group A compared with groups B and C (72% vs 60% vs 50%, P = .049). A >25% rate of blood contamination was more prevalent in group B (30% vs 42% vs 10%, P = .009). The rate of adequate core-tissue acquisition was not different (52% vs 34% vs 50%, P = .140). Based on the multivariate generalized estimation equation, the stylet slow-pull-back technique and a tumor size >40 mm were favorable factors for diagnostic adequacy. CONCLUSIONS: The stylet slow-pull-back technique might enable acquisition of tissue and assessment of cellularity for the diagnosis of pancreatic tumors suspected to be malignant. (Clinical trial registration number: KCT0002190.).

Correction: The Effect of Lifestyle Changes on Blood Pressure Control among Hypertensive Patients.

[This corrects the article on p. 173 in vol. 38, PMID: 28775806.].

The Effect of Lifestyle Changes on Blood Pressure Control among Hypertensive Patients.

BACKGROUND: Hypertension is highly prevalent among patients who visit primary care clinics. Various factors and lifestyle behaviors are associated with effective blood pressure control. We aimed to identify factors and lifestyle modifications associated with blood pressure control among patients prescribed antihypertensive agents. METHODS: This survey was conducted at 15 hospital-based family practices in Korea from July 2008 to June 2010. We prospectively recruited and retrospectively assessed 1,453 patients prescribed candesartan. An initial evaluation of patients' lifestyles was performed using individual questions. Follow-up questionnaires were administered at 4, 8, and 12 weeks. We defined successful blood pressure control as blood pressure <140 mm Hg systolic and <90 mm Hg diastolic. RESULTS: Of the 1,453 patients, 1,139 patients with available data for initial and final blood pressures were included. In the univariate analysis of the change in performance index, weight gain (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.52 to 3.11; P<0.001), physical inactivity (OR, 1.195; 95% CI, 1.175 to 3.387; P=0.011), and increased salt intake (OR, 1.461; 95% CI, 1.029 to 2.075; P=0.034) were related to inadequate blood pressure control. Salt intake also showed a significant association. Multivariate ORs were calculated for age, sex, body mass index, education, income, alcohol consumption, smoking status, salt intake, comorbidity, and family history of hypertension. In the multivariate analysis, sex (OR, 3.55; 95% CI, 2.02 to 6.26; P<0.001), salt intake (OR, 0.64; 95% CI 0.43 to 0.97; P=0.034), and comorbidity (OR, 1.82; 95% CI, 1.23 to 2.69; P=0.003) were associated with successful blood pressure control. CONCLUSION: Weight gain, physical inactivity, and high salt intake were associated with inadequate blood pressure control.

Cardiac rehabilitation in an adolescent with DiGeorge Syndrome.

BACKGROUND: DiGeorge Syndrome is a rare disease that has variable clinical symptoms resulting from 22q11 deletions, included cardiac abnormality, abnormal face and thymic aplasia, and cognitive impairment. There was a no reports regarding the efficiency of cardiac rehabilitation (CR) in patients with DiGeorge Syndrome with tetralogy of Fallot. CASE REPORT: A 15-year-old girl with DGS visited our CR center. The patient carried out the exercise training 3 times a week for 6 weeks, using a treadmill with electrocardiogram monitoring. Exercise tolerance testing and Quality of life assessment were performed before and after 6 weeks of training. Improvement of aerobic capacity was not represented, but by her own estimation, her performance ability of daily activities was better than before. CLINICAL REHABILITATION IMPACT: Even though adolescents with congenital heart disease often limit themselves, or are restricted by others, from physical activity, CR should be recommended as a comprehensive health promotion strategy.

Physiological Responses During the Lower Body Positive Pressure Supported Treadmill Test.

OBJECTIVE: To quantify changes in cardiopulmonary function using a lower body positive pressure supported (LBPPS) treadmill during the exercise tolerance test (ETT) in healthy subjects before applying the LBPPS treadmill in patients with gait problems. METHODS: We evaluated 30 healthy subjects who were able to walk independently. The ETT was performed using the Modified Bruce Protocol (stages 1-5) at four levels (0%, 40%, 60%, and 80%) of LBPPS. The time interval at each level of the LBPPS treadmill test was 20 minutes to recover to baseline status. We measured systolic blood pressure, diastolic blood pressure, peak heart rate (PHR), rating of perceived exertion (RPE), metabolic equivalents (METs), and oxygen consumption rate (VO2) during each LBPPS condition. RESULTS: Systolic blood pressure increased as the LBPPS level was increased (40% to 80%). PHR, RPE, METs, and VO2 were negatively associated with the LBPPS condition, although they were not always significant different among the LBPPS levels. The equation from a random effect linear regression model was as follows: VO2 (mL/kg/min)=(2.75×stage)+(-0.14×LBPPS level)+11.9 (r2=0.69). CONCLUSION: Detection of the changes in physiological parameters during a submaximal ETT using the LBPPS system may be helpful for applying the LBPPS treadmill in patients who cannot perform the ETT due to gait problems, even at submaximal intensity.

Successful Treatment of Phantom Limb Pain by 1 Hz Repetitive Transcranial Magnetic Stimulation Over Affected Supplementary Motor Complex: A Case Report.

A 37-year-old man with a right transfemoral amputation suffered from severe phantom limb pain (PLP). After targeting the affected supplementary motor complex (SMC) or primary motor cortex (PMC) using a neuro-navigation system with 800 stimuli of 1 Hz repetitive transcranial magnetic stimulation (rTMS) at 85% of resting motor threshold, the 1 Hz rTMS over SMC dramatically reduced his visual analog scale (VAS) of PLP from 7 to 0. However, the 1 Hz rTMS over PMC failed to reduce pain. To our knowledge, this is the first case report of a successfully treated severe PLP with a low frequency rTMS over SMC in affected hemisphere.

The association between a low urine pH and the components of metabolic syndrome in the Korean population: Findings based on the 2010 Korea National health and nutrition examination survey.

BACKGROUND: Low urine pH is related to obesity and insulin resistance, which are components of metabolic syndrome (MS). The aim of this study was to identify the relation between a low urine pH and MS after controlled for other covariates including demographic and lifestyle factors in adult Korean population. MATERIALS AND METHODS: We analyzed data from the 2010 Korea National Health and Nutrition Examination Survey, a cross-sectional and nationally representative survey and 1960 men and 2702 women were included in this study. Study subjects were divided into the group with urine pH <5.5 and the group with urine pH ≥5.5 refer to literature. We then evaluated the association between low urine pH and MS. RESULTS: After adjusting for age, sex, smoking status, drinking status, regular exercise, and blood urea nitrogen level, the odds ratio (OR) for the presence of MS in the group with urine pH <5.5 was 1.350 (95% confidence interval [95% CI]: 1.158-1.573) using the American Heart Association/National Heart, Lung, and Blood Institute criteria or 1.304 (95% CI: 1.082-1.572) using the International Diabetes Federation criteria. Among MS components, elevated fasting glucose (OR: 1.231, 95% CI: 1.058-1.433, P = 0.007) and elevated triglyceride (TG) (OR: 1.389, 95% CI: 1.189-1.623, P < 0.001) showed a significantly high OR. CONCLUSION: The findings confirmed that low urine pH is associated with MS in the Korean population. Among MS components, elevated fasting glucose and elevated TG showed a significantly high OR.

Sequence discrimination of heterogeneous crossing of seal impression and ink-printed text using adhesive tapes.

This paper presents a technique to discriminate the sequence of stamped seal impression and ink-printed text in a document to detect falsely signed documents. In many Asian countries where a seal is widely used to endorse documents, a possibly forged document involves a seal impressed before the text is printed. The proposed method uses adhesive tapes with peel adhesion strength of approximately 25 oz/in. to exfoliate the top layer of the overlapping region of seal impression and ink-printed text in the document. A pair of digital images of the overlapping region, captured using an infinite focus microscope, is compared for color changes before and after the exfoliation with adhesive tapes. The proposed sequence discrimination index (SDI) measures the amount of color changes before and after the exfoliation to determine the sequence of seal impression and printed text. Experiment results show that the SDI successfully discriminates the sequence of seal impression and printed text for different types of ink cartridges and seal inkpads under various storage conditions, enabling forensic investigation of falsely signed documents with a seal.

In-gel expression and in situ immobilization of proteins for generation of three dimensional protein arrays in a hydrogel matrix.

A method has been developed for the direct conversion of DNA arrays into three dimensional protein arrays on a hydrogel matrix. An agarose gel embedded with bacterial protein synthesis machinery was used as the DNA-programmable expression gel matrix for the in situ translation of genes on a DNA array. Upon incubation of the expression gel matrix cast on a DNA array, protein synthesis took place at the interface of the two surfaces and the cell-free synthesized proteins were deposited on the gel matrix surrounding the corresponding DNA spots. Diffusional dilution of the expressed proteins was minimized by modifying the agarose with Ni-NTA moieties. This procedure resulted in the generation of localized protein spots with confined radii. The developed approach not only simplifies the procedures typically used for the preparation of protein arrays but it also provides conditions for the loading of higher amounts of proteins on the array while retaining their structural integrity and functionality over extended time periods.

Flexible programming of cell-free protein synthesis using magnetic bead-immobilized plasmids.

The use of magnetic bead-immobilized DNA as movable template for cell-free protein synthesis has been investigated. Magnetic microbeads containing chemically conjugated plasmids were used to direct cell-free protein synthesis, so that protein generation could be readily programmed, reset and reprogrammed. Protein synthesis by using this approach could be ON/OFF-controlled through repeated addition and removal of the microbead-conjugated DNA and employed in sequential expression of different genes in a same reaction mixture. Since the incubation periods of individual template plasmids are freely controllable, relative expression levels of multiple proteins can be tuned to desired levels. We expect that the presented results will find wide application to the flexible design and execution of synthetic pathways in cell-free chassis.

On-bead expression of recombinant proteins in an agarose gel matrix coated on a glass slide.

A system for expression and in situ display of recombinant proteins on a microbead surface is described. Biotinylated PCR products were immobilized on microbead surfaces, which were then embedded in a gel matrix and supplied with translation machinery and substrates. Upon the incubation of the gel matrix, target proteins encoded on the bead-immobilized DNA were expressed and captured on the same bead, thus allowing bead-mediated linkage of DNA and encoded proteins. The new method combines the simplicity and convenience of solid-phase separation of genetic information with the benefits of cell-free protein synthesis, such as instant translation of genetic information, unrestricted substrate accessibility and flexible assay configuration design.

Factors Associated with Depressive Symptom in Chronic Obstructive Pulmonary Disease Based on the Third (2005) and Fourth (2008) Korea National Health and Nutritional Examination Survey (KNHANES III, IV).

BACKGROUND: Depressive symptoms accompanied by chronic obstructive pulmonary disease (COPD) can be influenced by socioeconomic status, associated chronic diseases and the current smoking status. This study was conducted to assess factors that are associated with depressive symptoms accompanied by COPD, using the data obtained from the Korea National Health and Nutritional Survey (KNHANES) conducted in 2005 and 2008. METHODS: From the third (2005) and the fourth (2008) KNHANES, 407 (0.9%) with physician-diagnosed COPD were selected. Of the 407 subjects, only 180 (0.4%) who reported having depressive symptoms were included in this study. The associations of depressive symptoms with socioeconomic status, associated chronic diseases and smoking status were investigated. RESULTS: Of the total 180 subjects, 45 (25%) had depressive symptoms. There were 102 males (55%) and 78 females (45%) with a slight predilection for males. In multivariate analysis, significant predictors of depressive symptoms were dependent activities of daily living (odds ratio [OR], 2.42; 95% confidence interval [CI], 2.06 to 2.84) and association with number of chronic diseases (OR of one, two, and three, 1.40, 1.72, 2.60; 95% CI of one, two, and three, 1.20 to 1.63,1.41 to 2.10,1.99 to 3.39). CONCLUSION: This study provides the basis for managing COPD patients in a clinical setting by understanding the number and characteristics of COPD patients with depressive symptoms. The results of this study suggest that primary physicians should manage COPD patients with consideration of risk factors for depressive symptom.

The use of PTC and RFA as treatment alternatives with low procedural morbidity in non-small cell lung cancer.

Minimally invasive percutaneous ablative therapies for treating lung cancers are currently being studied as treatment alternatives. This present study investigated the efficacies of percutaneous thoracic cryotherapy (PTC) and radiofrequency ablation (RFA) on clinical courses of pulmonary malignant tumours, especially in the setting of non-surgical candidates. Sixty-five patients with lung malignancy underwent sixty-seven sessions of RFA and nine sessions of PTC. We evaluated the results of RFA and PTC including efficacies, local progression rate, survival rate, and complications. Twenty-nine patients (43.3%) treated with RFA and six patients (66.7%) with PTC attained complete ablation. In small-sized lung mass (3 cm), complete ablation rate of RFA and PTC was increased to 76.2% and 85.7%, respectively. Additionally, we have found that the complete ablation group had significantly higher survival duration and progression free survival duration compared with the partial ablation group. Moreover, the complication profile was acceptable and the pain associated with the procedures disappeared within 1 day; 42 patients (62.7%) after RFA and all patients after PTC. This study provides evidence for the use of PTC and RFA as treatment alternatives with low procedural morbidity in the management of inoperable pulmonary malignant tumours, although the current study is limited by the small sample size and the short follow-up period.

Extra-axial chordoma presenting as a lung mass.

Chordomas are slow-growing, malignant tumors of bone that are thought to be derived from the primitive notochord and occur almost exclusively in the axial skeleton. The so-called extra-axial chordoma has been shown to demonstrate identical features to the classic chordoma, except that it is found outside the axial skeleton. Only six cases of extra-axial chordoma have been reported in the literature to date. In this report, we present another case of extra-axial chordoma for the first time originating from the lung parenchyma. A 79-year-old man presented a 7.3-cm-sized cavitary lung mass. Pathologic examination, including immunohistochemical studies, revealed that the mass was a chordoma. We report an extra-axial chordoma for the first time presenting as a lung mass.