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1.
Biomed Pharmacother ; 176: 116849, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823275

ABSTRACT

Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.

2.
PLoS One ; 19(4): e0299605, 2024.
Article in English | MEDLINE | ID: mdl-38626061

ABSTRACT

BACKGROUND: The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). METHODS: We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. RESULTS: In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. CONCLUSIONS: This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.


Subject(s)
Dyslipidemias , Renal Insufficiency, Chronic , Humans , Genetic Risk Score , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , Triglycerides , Cholesterol, HDL , Dyslipidemias/complications , Dyslipidemias/genetics , Genetic Predisposition to Disease , Risk Factors
3.
Kidney Int ; 105(6): 1239-1253, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38431216

ABSTRACT

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.


Subject(s)
Acute Kidney Injury , Anti-Bacterial Agents , Disease Models, Animal , Gastrointestinal Microbiome , Methylamines , NADPH Oxidase 2 , Oxidative Stress , Renal Insufficiency, Chronic , Acute Kidney Injury/chemically induced , Acute Kidney Injury/microbiology , Acute Kidney Injury/prevention & control , Acute Kidney Injury/pathology , Acute Kidney Injury/drug therapy , Methylamines/blood , Methylamines/metabolism , Animals , NADPH Oxidase 2/antagonists & inhibitors , NADPH Oxidase 2/metabolism , Humans , Male , Gastrointestinal Microbiome/drug effects , Renal Insufficiency, Chronic/microbiology , Renal Insufficiency, Chronic/complications , Middle Aged , Mice , Oxidative Stress/drug effects , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Mice, Inbred C57BL , Female , Reperfusion Injury/prevention & control , Aged , Apoptosis/drug effects , Disease Progression
4.
Sci Rep ; 14(1): 6621, 2024 03 19.
Article in English | MEDLINE | ID: mdl-38503784

ABSTRACT

Anemia is a common complication of chronic kidney disease (CKD), impacting long-term outcomes such as mortality and morbidity. Analyzing NHANES data from 1999 through 2016 for adults aged ≥ 20 years, we assessed the mediating effects of anemia biomarkers (hemoglobin, hematocrit, red cell distribution width [RDW], and mean corpuscular hemoglobin concentration [MCHC]) on CKD-related outcomes by using hazard ratios from a biomarker-adjusted model. Of 44,099 participants, 7463 experienced all-cause death. Cox proportional hazard models revealed a higher all-cause mortality risk in the > 45 years and CKD groups than in the early CKD group. Hemoglobin, hematocrit and MCHC were inversely related to all-cause mortality; RDW was related to mortality. Single mediation analysis showed greater mediating effects of anemia indicators on CKD and mortality in the elderly (> 65 years) population than those in the general population. In the multimediation analysis, the combined mediating effect of anemia was higher in the CKD population than in the general population. This study showed a proportional increase in the mediating effect of anemia with CKD stage, suggesting potential therapeutic avenues. However, further exploration of other mediating factors on kidney outcomes is necessary.


Subject(s)
Anemia , Renal Insufficiency, Chronic , Adult , Aged , Humans , Nutrition Surveys , Anemia/epidemiology , Anemia/etiology , Kidney , Biomarkers , Renal Insufficiency, Chronic/diagnosis , Hemoglobins , Risk Factors
5.
Heliyon ; 10(3): e25222, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38322898

ABSTRACT

Health risks due to climate change are emerging, particularly from high-temperature exposure. The perceived temperature is an equivalent temperature based on the complete heat budget model of the human body. Therefore, we aimed to analyze the effect of perceived temperature on overall mortality among patients with chronic kidney disease. In total, 32,870 patients with chronic kidney disease in Seoul participated in this retrospective study (2001-2018) at three medical centers. The perceived temperature during the summer season was calculated using meteorological factors, including the air temperature near the automated weather station, dew point temperature, wind velocity, and total cloud amount. We assessed the association between perceived temperature using Kriging spatial interpolation and mortality in patients with CKD in the time-varying Cox proportional hazards model that was adjusted for sex, age, body mass index, hypertension, diabetes mellitus, estimated glomerular filtration rate, smoking, alcohol consumption, and educational level. During the 6.14 ± 3.96 years of follow-up, 3863 deaths were recorded. In multivariable analysis, the average level of perceived temperature and maximum level of perceived temperature demonstrated an increased risk of overall mortality among patients with chronic kidney disease. The concordance index for mortality of perceived temperature was higher than temperature, discomfort index, and heat index. When stratified by age, diabetes mellitus, and estimated glomerular filtration rate, patients with chronic kidney disease with young age (age <65 years) showed higher hazard ratio for mortality (interaction P = 0.049). Moreover, the risk of death in the winter and spring seasons was more significant compared to that of the summer and autumn seasons. Therefore, long-term exposure to high perceived temperature during summer increases the risk of mortality among patients with chronic kidney disease.

6.
Nano Converg ; 11(1): 5, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38285077

ABSTRACT

The concept of three-dimensional stacking of device layers has attracted significant attention with the increasing difficulty in scaling down devices. Monolithic 3D (M3D) integration provides a notable benefit in achieving a higher connection density between upper and lower device layers than through-via-silicon. Nevertheless, the practical implementation of M3D integration into commercial production faces several technological challenges. Developing an upper active channel layer for device fabrication is the primary challenge in M3D integration. The difficulty arises from the thermal budget limitation for the upper channel process because a high thermal budget process may degrade the device layers below. This paper provides an overview of the potential technologies for forming active channel layers in the upper device layers of M3D integration, particularly for complementary metal-oxide-semiconductor devices and digital circuits. Techniques are for polysilicon, single crystal silicon, and alternative channels, which can solve the temperature issue for the top layer process.

7.
Adv Sci (Weinh) ; 11(11): e2309016, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38233207

ABSTRACT

A novel class of o-carboranyl luminophores, 2CB-BuDABNA (1) and 3CB-BuDABNA (2) is reported, in which o-carborane moieties are incorporated at the periphery of the B,N-doped multi-resonance thermally activated delayed fluorescence (MR-TADF) core. Both compounds maintain the inherent local emission characteristics of their MR-emitting core, exhibiting intense MR-TADF with high photoluminescence quantum yields in toluene and rigid states. In contrast, the presence of the dark lowest-energy charge transfer state, induced by cage rotation in THF, is suggested to be responsible for emission quenching in a polar solvent. Despite the different arrangement of the cage on the DABNA core, both 1 and 2 show red-shifted emissions compared to the parent compound BuDABNA (3). By utilizing 1 as the emitter, high-efficiency blue organic light-emitting diodes (OLEDs) are achieved with a remarkable maximum external quantum efficiency of 25%, representing the highest reported efficiency for OLEDs employing an o-carboranyl luminophore as the emitter.

8.
Exp Mol Med ; 56(2): 355-369, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38297163

ABSTRACT

Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6-methyladenosine (m6A) RNA methylation is associated with organ fibrosis. We investigated m6A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-ß-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6A levels. In the UUO model, METTL3 expression and m6A levels were significantly increased. Transcriptomic and m6A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m6A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-ß-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.


Subject(s)
Kidney , Methyltransferases , Renal Insufficiency, Chronic , Animals , Humans , Mice , Kidney/pathology , Methyltransferases/genetics , Renal Insufficiency, Chronic/genetics , RNA, Small Interfering , Transforming Growth Factor beta , Fibrosis
9.
Adv Mater ; 36(4): e2309416, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37856894

ABSTRACT

A multichannel/multicolor visible light communication (VLC) system using entirely organic components, including organic light emitting diodes (OLEDs) and organic photodiodes (OPDs), is developed to demonstrate indoor lighting applications where the integration of OLEDs and OPDs has significant potential. To achieve this, tricolor (Red/Green/Blue(R/G/B))-selective OPD arrays for the receiver and tricolor OLED arrays for the emitter are developed. For (R/G/B)-selective OPDs, a Fabry-Pérot electrode to enhance color selectivity and a thick junction structure to effectively accommodate a wide range of driving voltages are introduced. For tricolor OLEDs, fluorescent-emitting materials are used to enhance the operating frequency in addition to introducing a cavity structure to achieve narrow emission. Utilizing these spectrally refined tricolor OPDs/OLEDs, a VLC system is designed for indoor lighting applications, and a systematic analysis of their signal-to-interference ratio dependence on the distance or angle between the transmitter and receiver is performed. The study's findings indicate the importance of emission angle-dependent wavelength shift of the OLED and the luminosity function, which varies with wavelength, in the R/G/B mixed-white-light-based VLC systems. Finally, the feasibility of VLC using tricolor OPDs/OLEDs in the real-life context of indoor white-color lighting is demonstrated, showing that the transmitted data patterns well-matched the received data patterns.

10.
Exp Neurobiol ; 32(5): 362-369, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37927134

ABSTRACT

This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.

11.
Biomed Pharmacother ; 168: 115811, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37922652

ABSTRACT

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent.


Subject(s)
Antineoplastic Agents , Isoflavones , Neoplasms , Humans , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Signal Transduction , Cell Proliferation , Isoflavones/pharmacology , Isoflavones/therapeutic use , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy
12.
Sci Rep ; 13(1): 16717, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37794030

ABSTRACT

Decreased total CO2 (tCO2) is significantly associated with all-cause mortality in critically ill patients. Because of a lack of data to evaluate the impact of tCO2 in patients with COVID-19, we assessed the impact of tCO2 on all-cause mortality in this study. We retrospectively reviewed the data of hospitalized patients with COVID-19 in two Korean referral hospitals between February 2020 and September 2021. The primary outcome was in-hospital mortality. We assessed the impact of tCO2 as a continuous variable on mortality using the Cox-proportional hazard model. In addition, we evaluated the relative factors associated with tCO2 ≤ 22 mmol/L using logistic regression analysis. In 4,423 patients included, the mean tCO2 was 24.8 ± 3.0 mmol/L, and 17.9% of patients with tCO2 ≤ 22 mmol/L. An increase in mmol/L of tCO2 decreased the risk of all-cause mortality by 4.8% after adjustment for age, sex, comorbidities, and laboratory values. Based on 22 mmol/L of tCO2, the risk of mortality was 1.7 times higher than that in patients with lower tCO2. This result was maintained in the analysis using a cutoff value of tCO2 24 mmol/L. Higher white blood cell count; lower hemoglobin, serum calcium, and eGFR; and higher uric acid, and aspartate aminotransferase were significantly associated with a tCO2 value ≤ 22 mmol/L. Decreased tCO2 significantly increased the risk of all-cause mortality in patients with COVID-19. Monitoring of tCO2 could be a good indicator to predict prognosis and it needs to be appropriately managed in patients with specific conditions.


Subject(s)
COVID-19 , Carbon Dioxide , Humans , Retrospective Studies , Hospital Mortality , Proportional Hazards Models
13.
Sci Rep ; 13(1): 17599, 2023 10 16.
Article in English | MEDLINE | ID: mdl-37845302

ABSTRACT

Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN. The urinary concentrations of POSTN and TNC increased according to the severity of DN in human samples. Streptozotocin (STZ) was administered after unilateral nephrectomy (UNXSTZ) to induce DN in wild-type and Postn-null mice. Four experimental groups were generated: wild-typeham (WT Sham), wild-type UNXSTZ (WT STZ), Postn-null Sham (KO Sham), and Postn-null UNXSTZ (KO STZ). After 20 weeks, the KO STZ group had lower levels of urine albumin excretion, glomerular sclerosis, and interstitial fibrosis than those of the WT STZ group. Additionally, the KO STZ group had lower expression of fibrosis markers, including TNC. The KO STZ group showed better glucose regulation than the WT STZ model. Furthermore, the KO STZ group exhibited significantly preserved pancreatic islet integrity and insulin expression. HK-2 cells were used to observe the aggravation of fibrosis caused by POSTN under TGF-ß conditions. We stimulated INS-1 cells with streptozotocin and evaluated the viability of these cells. The anti-POSTN antibody treatment of INS-1 cells with streptozotocin resulted in higher cell viability than that with treatment with streptozotocin alone. The absence of POSTN in DN contributes to renal fibrosis alleviation by improving pancreatic ß-cell function. Additionally, there is an association between POSTN and TNC.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Animals , Humans , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Fibrosis , Kidney/metabolism , Mice, Knockout , Streptozocin
14.
Micromachines (Basel) ; 14(10)2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37893386

ABSTRACT

The process of the aqueous synthesis of nanomaterials has gained considerable interest due to its ability to eliminate the need for complex organic solvents, which aligns with the principles of green chemistry. Fabricating nanostructures in aqueous solutions has gained recognition for its potential to develop ultrasensitive, low-energy, and ultrafast optoelectronic devices. This study focuses on synthesizing lead iodide (PbI2) nanoplates (NPs) using a water-based solution technique and fabricating a planar photodetector. The planar photodetectors (ITO/PbI2 NPs/Au) demonstrated a remarkable photosensitivity of 3.9 × 103 and photoresponsivity of 0.51 mA/W at a wavelength of 405 nm. Further, we have carried-out analytical calculations for key performance parameters including open-circuit voltage (Voc), short-circuit current (Isc), on-off ratio, responsivity (R), and specific detectivity (D*) at zero applied bias, while photodetector operating in self-powered mode. These values are as follows: Voc = 0.103 V, Isc = 1.93 × 10-8, on-off ratio = 103, R = 4.0 mA/W, and D* = 3.3 × 1011 Jones. Particularly, the asymmetrical output properties of ITO/PbI2 NPs/Au detector provided additional evidence of the effective creation of a Schottky contact. Therefore, the photodetector exhibited a photo-response even at 0 V bias (rise/decay time ~1 s), leading to the realization of self-powered photodetectors. Additionally, the device exhibited a rapid photo-response of 0.23/0.38 s (-5 V) in the visible range. This study expands the scope of aqueous-phase synthesis of PbI2 nanostructures, enabling the large-area fabrication of high-performance photodetectors.

15.
IEEE Sens J ; 23(3): 3079-3089, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37649489

ABSTRACT

Early detection of Alzheimer's Disease and Related Disorders (ADRD) has been a focus of research with the hope that early intervention may improve clinical outcomes. The manifestation of motor impairment in early stages of ADRD has led to the inclusion of gait assessments including spatiotemporal parameters in clinical evaluations. This study aims to determine the effect of adding kinetic and kinematic gait features to classification of different levels of cognitive load in healthy individuals. A dual-task paradigm was used to simulate cognitive impairment in 40 healthy adults, with single-task walking trials representing normal, healthy gait. The Paced Auditory Serial Addition Task was administered at two different inter-stimulus intervals representing two levels of cognitive load in dual-task gait. We predicted that a richer dataset would improve classification accuracy relative to spatiotemporal parameters. Repeated Measures ANOVA showed significant changes in 15 different gait features across all three levels of cognitive load. We used three supervised machine learning algorithms to classify data points using a series of different gait feature sets with performance based on the area under the curve (AUC). Classification yielded 0.778 AUC across all three conditions (0.889 AUC Single vs. Dual) using kinematic and spatiotemporal features compared to 0.724 AUC using spatiotemporal features only (0.792 AUC Single vs. Dual). These data suggest that additional kinematic parameters improve classification performance. However, the benefit of measuring a wider set of parameters compared to their cost needs consideration. Further work will lead to a clinically viable ADRD detection classifier.

16.
Radiat Oncol J ; 41(2): 89-97, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37403351

ABSTRACT

PURPOSE: We aimed to determine whether low-dose radiotherapy (LDRT) is effective in patients with Alzheimer disease (AD). MATERIALS AND METHODS: We included patients according to the following criteria: probable Alzheimer's dementia according to the New Diagnostic Criteria for Alzheimer's Disease; confirmation of amyloid plaque deposits on baseline amyloid positron emission tomography (PET); a Korean Mini-Mental State Examination 2nd edition (K-MMSE-2) score of 13-26; and a Global Clinical Dementia Rating (CDR) score of 0.5-2 points. LDRT was performed six times at 0.5 Gy each. Post-treatment cognitive function tests and PET-CT examinations were performed to evaluate efficacy. The medication for AD treatment was maintained throughout the study period. RESULTS: At 6 months after LDRT, neurological improvement was seen in 20% of patients. Patient #2 showed improvement in all domains of the Seoul Neuropsychological Screening Battery II (SNSB-II). Moreover, the K-MMSE-2 and Geriatric Depression Score-Short Form scores improved from 20 to 23 and from 8 to 2, respectively. For patient #3, the CDR score (sum of box score) improved from 1 (4.0) to 1 (3.5) at 3 months follow-up. Moreover, the Z scores for language and related functions, memory, and frontal executive function improved to -2.56, -1.86, and -1.32, respectively at the 6-month follow-up. Two patients complained of mild nausea and mild hair loss during LDRT, which improved after treatment. CONCLUSION: One of the five patients with AD treated with LDRT experienced a temporary improvement in SNSB-II. LDRT is tolerable in patients with AD. We are currently under follow-up and will conduct cognitive function tests after 12 months after LDRT. A large-scale randomized controlled trial with a longer follow-up period is warranted to determine the effect of LDRT on patients with AD.

17.
Angew Chem Int Ed Engl ; 62(32): e202306879, 2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37321976

ABSTRACT

Designing multi-resonance (MR) emitters that can simultaneously achieve narrowband emission and suppressed intermolecular interactions is challenging for realizing high color purity and stable blue organic light-emitting diodes (OLEDs). Herein, a sterically shielded yet extremely rigid emitter based on a triptycene-fused B,N core (Tp-DABNA) is proposed to address the issue. Tp-DABNA exhibits intense deep blue emissions with a narrow full width at half maximum (FWHM) and a high horizontal transition dipole ratio, superior to the well-known bulky emitter, t-DABNA. The rigid MR skeleton of Tp-DABNA suppresses structural relaxation in the excited state, with reduced contributions from the medium- and high-frequency vibrational modes to spectral broadening. The hyperfluorescence (HF) film composed of a sensitizer and Tp-DABNA shows reduced Dexter energy transfer compared to those of t-DABNA and DABNA-1. Notably, deep blue TADF-OLEDs with the Tp-DABNA emitter display higher external quantum efficiencies (EQEmax =24.8 %) and narrower FWHMs (≤26 nm) than t-DABNA-based OLEDs (EQEmax =19.8 %). The HF-OLEDs based on the Tp-DABNA emitter further demonstrate improved performance with an EQEmax of 28.7 % and mitigated efficiency roll-offs.

18.
Ann Biomed Eng ; 51(9): 1965-1974, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37133540

ABSTRACT

Wearable assistive technology for the lower extremities has shown great promise towards improving gait function in people with neuromuscular injuries. But common secondary impairments, such as hypersensitive stretch reflexes or hyperreflexia, have been often neglected. Incorporation of biomechanics into the control loop could improve individualization and avoid hyperreflexia. However, adding hyperreflexia prediction to the control loop would require expensive or complex measurement of muscle fiber characteristics. In this study, we explore a clinically accessible biomechanical predictor set that can accurately predict rectus femoris (RF) reaction after knee flexion assistance in pre-swing by a powered orthosis. We examined a total of 14 gait parameters based on gait kinematic, kinetic, and simulated muscle-tendon states from 8 post-stroke individuals with Stiff-Knee gait (SKG) wearing a knee exoskeleton robot. We independently performed both parametric and non-parametric variable selection approaches using machine learning regression techniques. Both models revealed the same four kinematic variables relevant to knee and hip joint motions were sufficient to effectively predict RF hyperreflexia. These results suggest that control of knee and hip kinematics may be a more practical method of incorporating quadriceps hyperreflexia into the exoskeleton control loop than the more complex acquisition of muscle fiber properties.


Subject(s)
Gait Disorders, Neurologic , Stroke , Humans , Quadriceps Muscle , Biomechanical Phenomena , Reflex, Abnormal , Gait/physiology , Knee Joint/physiology , Stroke/complications , Hip Joint/physiology , Range of Motion, Articular/physiology
19.
Environ Res ; 231(Pt 3): 116234, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37236389

ABSTRACT

Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.


Subject(s)
Environmental Pollutants , Hypertension , Phthalic Acids , Prehypertension , Adult , Humans , Female , Young Adult , Middle Aged , Lead/toxicity , Creatinine , Cadmium , Prehypertension/chemically induced , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Phthalic Acids/toxicity , Hypertension/chemically induced , Hypertension/epidemiology , Albumins
20.
Medicine (Baltimore) ; 102(19): e33695, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37171361

ABSTRACT

BACKGROUND: Patients with kidney failure must make complicated decisions about the dialysis modalities used either at home or in-hospital. Different options have varying levels of impact on patients' physical and psychological conditions and their social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision making (SDM) in patients' options for dialysis. METHODS: SDM was performed after consent was written for stage 5 chronic kidney disease patients before dialysis, and 435 cases were performed in 408 patients from December 16, 2019 to June 30, 2021. Among these, 101 patients were compared by SDM measurement scale, patient satisfaction, disease recognition scale survey, and dialysis method. RESULTS: The average age of participants was 56 years, with a gender composition of 55 males (54.5%) and 46 females (45.5%). Following SDM, the final dialysis methods decided upon by patients and clinicians were peritoneal dialysis (67 patients, 66.3%), hemodialysis (22 patients, 21.8%), and kidney transplantation (1 patient, 1.0%). CONCLUSIONS: Among participating patients, SDM was effective when used to decide on dialysis treatment, and patients were satisfied with the dialysis method decision process. On the disease awareness scale, those who participated in this project had relatively high positive and low negative perceptions, so it can be concluded that SDM was relatively effective. The implementation of SDM was helpful in selecting patients' best dialysis methods, and SDM scale results were higher in the peritoneal dialysis group than in the hemodialysis group.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Male , Female , Humans , Middle Aged , Renal Dialysis/methods , Decision Making, Shared , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/psychology , Surveys and Questionnaires , Decision Making , Patient Participation/methods
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