Aims.
We systematically inspected the microlensing data acquired by the KMTNet survey during the previous seasons in order to find anomalous lensing events for which the anomalies in the lensing ...light curves cannot be explained by the usual binary-lens or binary-source interpretations.
Methods.
From the inspection, we find that interpreting the three lensing events OGLE-2018-BLG-0584, KMT-2018-BLG-2119, and KMT-2021-BLG-1122 requires four-body (lens+source) models, in which either both the lens and source are binaries (2L2S event) or the lens is a triple system (3L1S event). Following the analyses of the 2L2S events presented in our previous work, here we present the 3L1S analysis of the KMT-2021-BLG-1122.
Results.
It is found that the lens of the event KMT-2021-BLG-1122 is composed of three masses, in which the projected separations (normalized to the angular Einstein radius) and mass ratios between the lens companions and the primary are (
s
2
,
q
2
)∼(1.4, 0.53) and (
s
3
,
q
3
)∼(1.6, 0.24). By conducting a Bayesian analysis, we estimate that the masses of the individual lens components are (
M
1
,
M
2
,
M
3
)∼(0.47
M
⊙
, 0.24
M
⊙
, 0.11
M
⊙
). The companions are separated in projection from the primary by (
a
⊥, 2
,
a
⊥, 3
)∼(3.5, 4.0) AU. The lens of KMT-2018-BLG-2119 is the first triple stellar system detected via microlensing.
The choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal ...cognitive decline in patients with Parkinson disease (PD).
We retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high-resolution T1-weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV.
CPV negatively correlated with composite scores of the frontal/executive function domain (β = -0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio HR = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015).
Baseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 ...mL/min/1.73 m
and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice.
A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60-89; G3ab, 30-59; G4-5, < 30 mL/min/1.73 m
) and three UACR categories (A1, < 30; A2, 30-300; A3, > 300 mg/g) were used to define CKD status.
Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %). Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m
and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation.
Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.
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•A series of electron-rich and electron-deficient UiO-66s have strong interactions with Xe and Kr atoms.•Xe/Ke selectivity increases with the electron density of the ligands.•Xe/Ke ...selectivity is correlated with the unsymmetrical arrangement of the functional groups of the ligands.•A new MOF, UiO-66-NH2(OMe)2, exhibits the highest Xe/Kr Henry's constant ratios.
A Zr-based metal-organic framework (MOF), UiO-66, is considered to be one of the most stable MOFs and has recently been shown to be a good candidate for adsorptive separation of Xe/Kr mixtures. Since the ability to impart chemical functionalities is an attractive characteristic of MOFs, herein, we prepared a series of functionalized UiO-66 materials (UiO-66-NH2, UiO-66-(OMe)2, UiO-66-NH2(OMe)2, and UiO-66-F4) by incorporating several polar functionalities into UiO-66. We found that series of electron-rich and electron-deficient UiO-66 materials have stronger interactions with Xe and Kr atoms than pristine UiO-66. We also found that Xe/Kr selectivity increases with the electron density of the ligand. Although there was a reduction in surface area, UiO-66-NH2(OMe)2 exhibited the highest Xe/Kr Henry's constant ratio (14.4), possibly due to having the highest electron density as well as an unsymmetrical arrangement of functional groups of the ligands. Furthermore, the breakthrough experiments show that UiO-66-NH2(OMe)2 can effectively separate Xe from Kr under dynamic mixture conditions and can be easily regenerated under a mild regeneration condition.
Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that ...can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti‐inflammatory glycocalyx‐mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD. The anti‐inflammatory GlyNP library was created by attaching bilirubin (BR) to a library of glycopolymers composed of random combinations of the five most naturally abundant sugars. Direct in vivo screening of 31 BR‐attached anti‐inflammatory GlyNPs via oral administration into mice with acute colitis led to identification of a candidate GlyNP capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms. These findings suggest that the BR‐attached GlyNP library can be used as a platform to identify anti‐inflammatory nanomedicines for various inflammatory diseases.
A library of bilirubin‐attached glycocalyx‐mimicking nanoparticles was constructed as a platform enabling identification of an anti‐inflammatory nanomedicine. Direct in vivo screening of the nanoparticle library by oral administration into mice with acute colitis led to identification of a candidate anti‐inflammatory nanomedicine capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms.
Impaired autophagy has been implicated in many neurodegenerative diseases, such as Parkinson’s disease (PD), and might be responsible for deposition of aggregated proteins in neurons. However, little ...is known about how neuronal autophagy and clearance of aggregated proteins are regulated. Here, we show a role for Toll-like receptor 2 (TLR2), a pathogen-recognizing receptor in innate immunity, in regulation of neuronal autophagy and clearance of α-synuclein, a protein aggregated in synucleinopathies, including in PD. Activation of TLR2 resulted in the accumulation of α-synuclein aggregates in neurons as a result of inhibition of autophagic activity through regulation of the AKT/mTOR pathway. In contrast, inactivation of TLR2 resulted in autophagy activation and increased clearance of neuronal α-synuclein, and hence reduced neurodegeneration, in transgenic mice and in in vitro models. These results uncover roles of TLR2 in regulating neuronal autophagy and suggest that the TLR2 pathway may be targeted for autophagy activation strategies in treating neurodegenerative disorders.
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•Activation of Toll-like receptor 2 antagonizes autophagy in neurons•TLR2 regulates neuronal autophagy via the AKT/mTOR pathway•Inhibition of the TLR2 pathway reduces neuronal α-synuclein aggregation•Inhibition of TLR2 rescues Lewy body disease models from neurodegeneration
Impairment of neuronal autophagy is implicated in the pathogenesis of neurodegenerative proteinopathies. However, little is known about the extracellular cues that regulate neuronal autophagy. Kim et al. show that activation of Toll-like receptor 2 negatively regulates neuronal autophagy, and synucleinopathy lesions are rescued by antagonizing TLR2.
Radiographic analysis was performed retrospectively. Outcomes and complications were collected prospectively.
To assess complications after posterior fusion and instrumentation for degenerative ...lumbar scoliosis, to determine risk factors of complications, and to analyze the clinical outcomes of surgery.
The complications after degenerative lumbar scoliosis surgery have reported to be high. Risk factors for developing complications are unknown.
Forty-seven patients (average age, 66.6 years; range, 48-83 years) with degenerative lumbar scoliosis undergoing posterior fusion and instrumentation were analyzed. Seven patients had additional posterior lumbar interbody fusion at the lumbosacral junction. The average number of levels fused was 4.7 +/- 2.2 segments. We evaluated the early perioperative (<3 months after surgery) and late complications.
There were 14 early perioperative complications and 18 late complications. There was 1 case of mortality by pulmonary embolism. Early complications included ileus, urinary tract infection, transient delirium, superficial infection, and neurologic deficit. Late complications included adjacent segment diseases, pseudarthrosis, and loosening of screws. Adjacent segment disease developed at the proximal segment in 10 patients and at the distal segment in 5 patients. Pseudarthrosis was noted at the lumbosacral junction in 2 patients. Revision surgery was performed in 7 patients. Older patients (>65 years) had the tendency to increase early complications without statistical difference (P = 0.053). Excessive intraoperative blood loss was the most significant risk factor for the development of early perioperative complications, and number of levels fused was related to blood loss. Operative time and multiple medical comorbidities were not associated with higher complication rate. There were no specific factors related to the development of late complications.
The complication rate after posterior fusion and instrumentation for degenerative lumbar scoliosis was 68%. Abundant blood loss was a significant risk factor for early perioperative complications. The improvement of Oswestry disability index was less in patients with late complications.
Blood pressure (BP) is directly and causally associated with body size in the general population. Whether muscle mass is an important factor that determines BP remains unclear.
To investigate whether ...sarcopenia is associated with hypertension in older Koreans.
We surveyed 2,099 males and 2,747 females aged 60 years or older.
Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was <1 SD below the gender-specific mean for young adults. Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2). Subjects were divided into four groups based on presence or absence of obesity or sarcopenia. Hypertension was defined as a systolic BP (SBP) ≥ 140 mmHg, a diastolic BP (DBP) ≥ 90 mmHg, or a self-reported current use of antihypertensive medications.
The overall prevalence of hypertension in the four groups was as follows 49.7% for non-obese non-sarcopenia, 60.9% for non-obese sarcopenia, 66.2% for obese non-sarcopenia and 74.7% for obese sarcopenia. After adjustment for age, gender, regular activity, current smoking and alcohol use, the odds ratio (OR) for having hypertension was 1.5 (95% confidence interval (CI) = 1.23-1.84) in subjects in the non-obese sarcopenia group, 2.08 (95% CI = 1.68-2.57) in the obese non-sarcopenia group and 3.0 (95% CI = 2.48-3.63) in the obese sarcopenia group, compared with the non-obese non-sarcopenia group (p for trend <0.001). Controlling further for body weight and waist circumference did not change the association between hypertension and sarcopenia. The association between sarcopenia and hypertension was more robust in the subjects with diabetes mellitus.
Body composition beyond BMI has a considerable impact on hypertension in elderly Koreans. Subjects with sarcopenic obesity appear to have a greater risk of hypertension than simply obese or sarcopenia subjects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend ...discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking.
The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation.
The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation.
https://www.clinicaltrials.gov. Unique identifier: NCT04250116.
Understanding the origin of the phonon modes of highly efficient electro-optic crystals is very important for designing materials and for optimizing their photonic applications. Here we investigate ...the origin of phonon modes in the 0.1–15 THz range of the benchmark electro-optic OH1 (2-(3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene)malononitrile) crystal, which is interesting due to its large electro-optic coefficient and high THz-wave generation efficiency. The phonon modes (and vibrational absorption properties) of OH1 crystals are evaluated theoretically by periodic density functional theory and also experimentally by THz absorption spectroscopy. The theoretical calculations are well-matched with experimental results. The THz absorption properties are highly anisotropic; the amplitude of the vibrational absorption is the largest along the polar c-axis compared to the other two crystallographic axes. For comparison, the vibrational absorption modes of the OH1 molecule in the gas phase are also calculated. The calculated vibrational absorption spectrum of OH1 crystalline powder appears similar to that of the OH1 molecule in the gas phase. However, the molecular vibrational motions in the crystalline state are coupled motions of vibrational motions in the gas phase. Interestingly, the vibrational mode of the torsion of the O–H bond with the largest absorption strength in the gas phase is in the crystal inhibited due to the crystal field effect. The origin of the intense phonon modes of OH1 crystals is mainly related to relatively strong distortions of the push–pull π-conjugated system including electron donor and acceptor groups.
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