Batteryless implantable device with built-in mechanical clock for automated and precisely timed drug administration.

Adherence to medication plays a crucial role in the effective management of chronic diseases. However, patients often miss their scheduled drug administrations, resulting in suboptimal disease control. Therefore, we propose an implantable device enabled with automated and precisely timed drug administration. Our device incorporates a built-in mechanical clock movement to utilize a clockwork mechanism, i.e., a periodic turn of the hour axis, enabling automatic drug infusion at precise 12-h intervals. The actuation principle relies on the sophisticated design of the device, where the rotational movement of the hour axis is converted into potential mechanical energy and is abruptly released at the exact moment for drug administration. The clock movement can be charged either automatically by mechanical agitations or manually by winding the crown, while the device remains implanted, thereby enabling the device to be used permanently without the need for batteries. When tested using metoprolol, an antihypertensive drug, in a spontaneously hypertensive animal model, the implanted device can deliver drug automatically at precise 12-h intervals without the need for further attention, leading to similarly effective blood pressure control and ultimately, prevention of ventricular hypertrophy as compared with scheduled drug administrations. These findings suggest that our device is a promising alternative to conventional methods for complex drug administration.

Mdivi-1: Effective but complex mitochondrial fission inhibitor.

Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.

Ultrafast sequence-based prediction model and nomogram to differentiate additional suspicious lesions on preoperative breast MRI.

OBJECTIVES: To investigate whether ultrafast sequence improves the diagnostic performance of conventional dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiating additional suspicious lesions (ASLs) on preoperative breast MRI. MATERIALS AND METHODS: A retrospective database search identified 668 consecutive patients who underwent preoperative breast DCE-MRI with ultrafast sequence between June 2020 and July 2021. Among these, 107 ASLs from 98 patients with breast cancer (36 multifocal, 42 multicentric, and 29 contralateral) were identified. Clinical, pathological, conventional MRI findings, and ultrafast sequence-derived parameters were collected. A prediction model that adds ultrafast sequence-derived parameters to clinical, pathological, and conventional MRI findings was developed and validated internally. Decision curve analysis and net reclassification index statistics were performed. A nomogram was constructed. RESULTS: The ultrafast model adding time to peak enhancement, time to enhancement, and maximum slope showed a significantly increased area under the receiver operating characteristic curve compared with the conventional model which includes age, human epidermal growth factor receptor 2 expression of index cancer, size of index cancer, lesion type of index cancer, location of ASL, and size of ASL (0.92 vs. 0.82; p = 0.002). The decision curve analysis showed that the ultrafast model had a higher overall net benefit than the conventional model. The net reclassification index of ultrafast model was 23.3% (p = 0.001). CONCLUSION: A combination of ultrafast sequence-derived parameters with clinical, pathological, and conventional MRI findings can aid in the differentiation of ASL on preoperative breast MRI. CLINICAL RELEVANCE STATEMENT: Our prediction model and nomogram that was based on ultrafast sequence-derived parameters could help radiologists differentiate ASLs on preoperative breast MRI. KEY POINTS: Ultrafast MRI can diminish background parenchymal enhancement and possibly improve diagnostic accuracy for additional suspicious lesions (ASLs). Location of ASL, larger size of ASL, and higher maximum slope were associated with malignant ASL. The ultrafast model and nomogram can help preoperatively differentiate additional malignancies.

CRISPR/Cas9-mediated knockout of tnf-α1 in zebrafish reduces disease resistance after Edwardsiella piscicida bacterial infection.

Tumor necrosis factor (TNF) is an important cytokine involved in immune responses to bacterial infections in vertebrates, including fish. Although Tnf-α is a well-studied cytokine, there are contradictory findings about Tnf-α function following bacterial infection. In this study, we analyzed the expression and function of the Tnf-α-type I isoform (Tnf-α1) in zebrafish by knockout experiments using the CRISPR/Cas9 gene-editing tool. The open reading frame of tnf-α1 encodes a 25.82 kDa protein with 234 amino acids (aa). The expression of tnf-α1 in the early stages of zebrafish was observed from the 2-cell stage. Adult zebrafish spleens showed the highest expression of tnf-α1. To evaluate the function of Tnf-α1, an 8 bp deletion in the target region, resulting in a short truncated protein of 55 aa, was used to create the tnf-α1 knockout mutant. The pattern of downstream gene expression in 7-day larvae in wild-type (WT) and tnf-α1 knockout fish was examined. We also verified the fish mortality rate after Edwardsiella piscicida challenge and found that it was much higher in tnf-α1 knockout fish than in WT fish. Additionally, downstream gene expression analyses after E. piscicida exposure revealed a distinct expression pattern in tnf-α1 knockout fish compared to that in WT fish. Overall, our study using tnf-α1 deletion in zebrafish confirmed that Tnf-α1 is critical for immune regulation during bacterial infection.

Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Clinical Impact and Risk Factors of Seizure After Liver Transplantation: A Nested Case-Control Study.

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23 kg/m2, donor age ≥45 years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Impact of Blood Pressure on Allograft Function and Survival in Kidney Transplant Recipients.

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.

CXCL5/CXCL8 induces neutrophilic inflammation in peri-implantitis.

OBJECTIVE AND BACKGROUND: This research aimed to examine the role of C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 8 (CXCL8; also known as IL-8) in neutrophilic inflammation triggered by peri-implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. MATERIALS: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri-implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3' mRNA-Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t-test was employed to conduct statistical analyses. RESULTS: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and CXCL5/CXCL8 was assessed via RT-qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p < .045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p < .008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri-implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning.

Predictors of sleep quality components in patients undergoing transarterial chemoembolisation: a cross-sectional study.

PURPOSE: Patients undergoing transarterial chemoembolisation experience postembolisation symptoms and interferences affecting sleep quality, which require intervention. The study aimed to identify the predictors of sleep quality components in patients undergoing transarterial chemoembolisation. METHODS: This study included two groups of participants: 50 patients undergoing transarterial chemoembolisation and 45 nurses caring for them. Data were collected from September to November 2022 using a structured questionnaire, and analysed using descriptive statistics, the t-test, analysis of variance, Spearman's rank correlation, and multiple regression analysis using the SPSS 27.0 program (IBM Corp., Armonk, NY, USA). RESULTS: The mean sleep quality score was 40.28±14.10. Heat sensation (t=-2.08, p=.043) and fatigue (t=-4.47, p<.001) predicted sleep fragmentation in 38.6% of the patients. Abdominal pain (t=-2.54, p=.014), vomiting (t=-2.21, p=.032), and the expected fatigue by the nurses (t=2.68, p=.014) predicted sleep length in 41.7% of patients. Abdominal pain (t=-2.05, p=.046) explained 42.9% of sleep depth. CONCLUSION: Based on the predictors of sleep quality components obtained in this study, strategies to improve sleep quality tailored to patients undergoing transarterial chemoembolisation should be developed. This study highlighted the need to bridge the gap between patients' and nurses' expected fatigue and its contribution to sleep fragmentation and sleep length. It also highlighted the importance of noncontact temperature measurement, controlling vomiting, and pain relief for improving sleep length in patients undergoing transarterial chemoembolisation.

Overview of regulatory frameworks on the national lot release of plasma-derived medicinal products in Korea.

Plasma-derived medicinal products (PDMPs) are essential in the treatment of acute and chronic life-threatening diseases. The Korea Ministry of Food and Drug Safety has conducted a national lot release (NLR) of PDMPs since 2012 based on a summary protocol review system and lot release testing. However, few studies have investigated the performance or characteristics of the NLR framework. Over the past decade, the NLR of PDMPs was approximately 1000 per year, including mainly albumins, immunoglobulins, fibrin sealant kits, and coagulation factors, among others. The NLR system for PDMPs is similar to that for vaccines, except that PDMPs are manufactured using human plasma, which requires strict safety management. This study describes the status of NLR procedures for PDMPs and outlines the regulatory requirements needed to safely manage plasma for fractionation in Korea. This study can aid national control laboratories and marketing authorization holders in developing regulatory systems that assure the availability of safe and effective PDMPs.

Association between the COVID-19 pandemic and childhood development aged 30 to 36 months in South Korea, based on the National health screening program for infants and children database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on the neurodevelopment of children. However, the precise effects of the virus and the social consequences of the pandemic on pediatric neurodevelopment are not yet fully understood. We aimed to compare the neurodevelopment of children between before and during the COVID-19 pandemic, as well as examine the impact of socioeconomic status (SES) and regional differences on the development. METHODS: The study used the Korean Developmental Screening Test to compare the difference in the risk of neurodevelopmental delay between before and during the COVID-19 pandemic. Multivariable logistic regression analysis was conducted to identify the relationship between experiencing the COVID-19 pandemic and the risk of neurodevelopmental delay. Stratified analyses were performed to determine whether the developmental delays caused by the pandemic's impact varied depending on SES or regional inequality. RESULTS: This study found an association between the experience of COVID-19 and a higher risk of neurodevelopmental delay in communication (adjusted OR [aOR]: 1.21, 95% confidence interval [CI]: 1.19, 1.22; P-value: < 0.0001) and social interaction (aOR: 1.15, 95% CI: 1.13, 1.17; P-value: < 0.0001) domains among children of 30-36 months' ages. Notably, the observed association in the Medicaid group of children indicates a higher risk of neurodevelopmental delay compared to those in the non-Medicaid group. CONCLUSIONS: These findings highlight the need to be concerned about the neurodevelopment of children who experienced the COVID-19 pandemic. The study also calls for increased training and support for Medicaid children, parents, teachers, and healthcare practitioners. Additionally, policy programs focused on groups vulnerable to developmental delays are required.

COVID-19 and Neurodevelopmental Delays in Early Childhood: A Longitudinal Analysis of Developmental Outcomes in Korean Children.

This study employed a longitudinal analysis to evaluate the association between the coronavirus disease 2019 pandemic and neurodevelopment by analyzing over 1.8 million children from the Korean Developmental Screening Test for Infants and Children included in South Korea's National Health Screening Program. We compared the developmental outcomes in five age groups-9-17 months, 18-29 months, 30-41 months, 42-53 months, and 54-65 months-between the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Significant increases in potential developmental delays were observed during the pandemic in communication, cognitive, social interaction, self-care, and fine motor skills across most age groups. All five age groups experienced notable disruptions in communication and fine motor skills. Children from socioeconomically disadvantaged backgrounds faced higher risks across all domains. These findings highlight the need for targeted interventions and continuous monitoring to support the developmental needs of children affected by pandemic-related disruptions.

Universal health coverage saves more lives among severely ill COVID-19 patients: A difference-in-differences analysis of individual patient data in South Korea.

BACKGROUND: Universal health coverage (UHC) ensures affordability of a variety of essential health services for the general population. Although UHC could mitigate the harmful effects of coronavirus disease 2019 (COVID-19) on patients and their socioeconomic position, the debate on UHC's scope and ability to improve health outcomes is ongoing. This study aimed to identify the impact of UHC policy withdrawal on the health outcomes of South Korea's severely ill COVID-19 patients. METHODS: We used a propensity score matching (PSM) and difference-in-differences combined model. This study's subjects were 44,552 hospitalized COVID-19 patients contributing towards health insurance claims data, COVID-19 notifications and vaccination data extracted from the National Health Information Database and the Korea Disease Control and Prevention Agency from 1 December 2020 to 30 April 2022. After PSM, 2460 patients were included. This study's exposures were severity of illness and UHC policy change. The primary outcome was the case fatality rate (CFR) for COVID-19, which was defined as death within 30 days of a COVID-19 diagnosis. There were four secondary outcomes, including time interval between diagnosis and hospitalization (days), length of stay (days), total medical expenses (USD) and the time interval between diagnosis and death (days). RESULTS: After the UHC policy's withdrawal, the severely ill patients' CFR increased to 284 per 1000 patients [95% confidence interval (CI) 229.1-338.4], hospitalization days decreased to 9.61 days (95% CI -11.20 to -8.03) and total medical expenses decreased to 5702.73 USD (95% CI -7128.41 to -4202.01) compared with those who were not severely ill. CONCLUSIONS: During the pandemic, UHC may have saved the lives of severely ill COVID-19 patients; therefore, expanding services and financial coverage could be a crucial strategy during public health crises.

Posttraumatic Basal Ganglia Infarction by Lenticulostriate Artery Injury in Adult Patients: A Review.

Post-traumatic striatocapsular infarction (SCI) due to lenticulostriate artery (LSA) damage is rare. Most cases reported are in children. We discuss the pathogenesis and differential diagnosis of this kind of SCI after trauma in adult patients. The most common etiology of non-traumatic SCI are an embolism from the proximal artery, cardiogenic embolism, and atherosclerotic plaque in the proximal middle cerebral artery (MCA). However, injury of the LSA after trauma may lead to hemorrhagic infarction in the basal ganglia (BG). Post-traumatic SCI due to LSA damage might be associated with hemorrhage in the BG. The main locations of these lesions are the distal perfusion area of the LSA, similar to SCI due to intracranial atherosclerotic disease affecting the MCA. Vessel wall imaging, magnetic resonance angiography, and ultrahigh-resolution computed tomography can be used for differentiating the injury mechanism in SCI following a traumatic event.

A Novel Fabrication of Heterogeneous Saponified Poly(Vinyl Alcohol)/Pullulan Blend Film for Improved Wound Healing Application.

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.

Mechanism Behind the Loss of Fast Charging Capability in Nickel-Rich Cathode Materials.

Fast charging technology for electric vehicles (EVs), offering rapid charging times similar to conventional vehicle refueling, holds promise but faces obstacles owing to kinetic issues within lithium-ion batteries (LIBs). Specifically, the significance of cathode materials in fast charging has grown because Ni-rich cathodes are employed to enhance the energy density of LIBs. Herein, the mechanism behind the loss of fast charging capability of Ni-rich cathodes during extended cycling is investigated through a comparative analysis of Ni-rich cathodes with different microstructures. The results revealed that microcracks and the resultant cathode deterioration significantly compromised the fast charging capability over extended cycling. When thick rocksalt impurity phases form throughout the particles owing to electrolyte infiltration via microcracks, the limited kinetics of Li+ ions create electrochemically unreactive areas under high-current conditions, resulting in the loss of fast charging capability. Hence, preventing microcrack formation by tailoring microstructures is essential to ensure stability in fast charging capability. Understanding the relationship between microcracks and the loss of fast charging capability is essential for developing Ni-rich cathodes that facilitate stable fast charging upon extended cycling, thereby promoting widespread EV adoption.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.

Regulation of sexually dimorphic placental adaptation in LPS exposure-induced intrauterine growth restriction.

BACKGROUND: Sexual dimorphism in placental physiology affects the functionality of placental adaptation during adverse pregnancy. Defects of placental function compromise fetal programming, affecting the offspring's adult life. However, studies focusing on the relationship between sex-specific placental adaptation and consequent fetal maldevelopment under sub-optimal uterus milieu are still elusive. METHODS: Here, we investigated the effects of maternal lipopolysaccharide (LPS) exposure between placental sex. Pregnant ICR mice received intraperitoneal injection of phosphate-buffered saline or 100, 200, and 400 µg/kg LPS on the gestational day (GD) 15.5. To determine whether prenatal maternal LPS exposure resulted in complicated pregnancy outcomes, survival rate of embryos was calculated and the growth of embryos and placentas was examined. To elucidate global transcriptomic changes occurring in the placenta, total RNA-sequencing (RNA-seq) was performed in female and male placentas. RESULTS: LPS administration induced placental inflammation in both sexes at GD 17.5. Prenatal infection resulted in growth retardation in both sexes of embryos, and especially more prevalently in male. Impaired placental development was observed in a sex-specific manner. LPS 400 µg/kg reduced the percentage area of the labyrinth in females and junctional zone in males, respectively. RNA-sequencing revealed widespread sexually dimorphic transcriptional changes in placenta. In particular, representative changes were involved in biological processes such as trophoblast differentiation, nutrient/ion transporter, pregnancy, and immune system. CONCLUSIONS: Our results present the sexually dimorphic responses of placental physiology in intrauterine growth restriction model and provide tentative relationship further to be elucidated between sex-biased placental functional change and long-term effects on the offspring's later life.

Outcomes and Risk Factors for Liver Transplantation Using graft-to-Recipient Weight Ratio Less than 0.8 Graft from Living Donors: Multicentric Cohort Study.

OBJECTIVE: To compare graft survival after LDLT in patients receiving GRWR<0.8 versus GRWR≥0.8 grafts and identify risk factors for graft loss using GRWR<0.8 grafts. SUMMARY BACKGROUND DATA: Favorable outcomes after living donor liver transplantation (LDLT) using graft-to-recipient weight ratio (GRWR)<0.8 grafts were recently reported; however, these results have not been validated using multicenter data. METHODS: This multicentric cohort study included 3450 LDLT patients. Graft survival was compared between 1:3 propensity score-matched groups and evaluated using various Cox models in the entire population. Risk factors for graft loss with GRWR<0.8 versus GRWR≥0.8 grafts were explored within various subgroups using interaction analyses, and outcomes were stratified according to the number of risk factors. RESULTS: In total, 368 patients (10.7%) received GRWR<0.8 grafts (GRWR<0.8 group), whereas 3082 (89.3%) received GRWR≥0.8 grafts (GRWR≥0.8 group). The 5-y graft survival rate was significantly lower with GRWR<0.8 grafts than with GRWR≥0.8 grafts (85.2% vs. 90.1%, P=0.013). Adjusted hazard ratio (HR) for graft loss using GRWR<0.8 grafts in the entire population was 1.66 (95% confidence interval [CI] 1.17-2.35, P=0.004). Risk factors exhibiting significant interactions with GRWR<0.8 for graft survival were age ≥60 y, MELD score ≥15, and male donor. When ≥2 risk factors were present, GRWR<0.8 grafts showed higher risk of graft loss compared to GRWR≥0.8 graft in LDLT (HR 2.98, 95% CI 1.79-4.88, P<0.001). CONCLUSIONS: GRWR<0.8 graft showed inferior graft survival than controls (85.2% vs. 90.1%), especially when ≥2 risk factors for graft loss (among age ≥60 y, MELD score ≥15, or male donor) were present.