Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Ocular Motor Findings Aid in Differentiation of Spinocerebellar Ataxia Type 17 from Huntington's Disease.

Differentiation of spinocerebellar ataxia type 17 (SCA17) from Huntington's disease (HD) is often challenging since they share the clinical features of chorea, parkinsonism, and dystonia. The ocular motor findings remain to be elucidated in SCA17, and may help differentiating SCA17 from HD. We retrospectively compared the ocular motor findings of 11 patients with SCA17 with those of 10 patients with HD. In SCA17, abnormal ocular motor findings included impaired smooth pursuit (9/11, 82%), dysmetric saccades (9/11, 82%), central positional nystagmus (CPN, 7/11, 64%), abnormal head-impulse tests (4/11, 36%), and horizontal gaze-evoked nystagmus (GEN, 3/11, 27%). Among these, CPN was more frequently observed in SCA17 than in HD (7/11 (64%) vs. 0/10 (0%), p = 0.004) while saccadic slowing was more frequently observed in HD than in SCA17 (8/10 (80%) vs. 2/11 (18%), p = 0.009). Of six patients with follow-up evaluation, five later developed bilateral saccadic hypermetria (n = 4), GEN (n = 1), CPN (n = 1), bilaterally abnormal smooth pursuit (n = 1), and hyperactive head-impulse responses (n = 1) along with a clinical decline. Ocular motor abnormalities can be utilized as a diagnostic marker for differentiation of SCA17 from HD as well as a surrogate marker for clinical decline in SCA17.

The associations between changes in hepatic steatosis and heart failure and mortality: a nationwide cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a well-known risk factor for cardiovascular (CV) disease (CVD) and mortality. However, whether the progression or regression of NAFLD can increase or decrease the risk of heart failure (HF) and mortality has not been fully evaluated. We investigated the association between changes in hepatic steatosis and the risks of incident HF (iHF), hospitalization for HF (hHF), and mortality including CV- or liver-related mortality. METHODS: Using a database from the National Health Insurance Service in Korea from January 2009 to December 2012, we analyzed 240,301 individuals who underwent health check-ups at least twice in two years. Hepatic steatosis was assessed using the fatty liver index (FLI), with an FLI ≥ 60 considered to indicate the presence of hepatic steatosis. According to FLI changes, participants were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models. RESULTS: Persistent hepatic steatosis increased the risk of iHF, hHF, and mortality including CV- and liver-related mortality compared with the group that never had steatosis (all P < 0.05). Incident hepatic steatosis was associated with increased risk for iHF and mortality including CV- or liver-related mortality (all P < 0.05). Compared with persistent steatosis, regression of hepatic steatosis was associated with decreased risk for iHF, hHF, and liver-related mortality (iHF, HR [95% CI], 0.800 [0.691-0.925]; hHF, 0.645 [0.514-0.810]; liver-related mortality, 0.434 [0.223-0.846]). CONCLUSIONS: FLI changes were associated with increased or decreased risk of HF outcomes and mortality.

The associations of hepatic steatosis and fibrosis using fatty liver index and BARD score with cardiovascular outcomes and mortality in patients with new-onset type 2 diabetes: a nationwide cohort study.

BACKGROUND: Although both type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are associated with increased risk of cardiovascular disease (CVD), evidence is lacking as to whether the presence of NAFLD confers an additional risk of CVD in patients with T2DM. We investigated the associations between hepatic steatosis and/or fibrosis and risk of myocardial infarction (MI), stroke, heart failure (HF), and mortality in patients with new-onset T2DM. METHODS: Using the Korean National Health Insurance dataset, we included 139,633 patients diagnosed with new-onset T2DM who underwent a national health screening from January 2009 to December 2012. Hepatic steatosis and advanced hepatic fibrosis were determined using cutoff values for fatty liver index (FLI) and BARD score. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models. RESULTS: During the median follow-up of 7.7 years, there were 3,079 (2.2%) cases of MI, 4,238 (3.0%) cases of ischemic stroke, 4,303 (3.1%) cases of HF, and 8,465 (6.1%) all-cause deaths. Hepatic steatosis defined as FLI ≥ 60 was associated with increased risk for MI (HR [95% CI], 1.28 [1.14-1.44]), stroke (1.41 [1.25-1.56]), HF (1.17 [1.07-1.26]), and mortality (1.41 [1.32-1.51]) after adjusting for well-known risk factors. Compared to the group without steatosis, the group with steatosis and without fibrosis (BARD < 2) and the group with both steatosis and fibrosis (BARD ≥ 2) showed gradual increased risk for MI, stroke, HF, and mortality (all p for trends < 0.001). CONCLUSION: Hepatic steatosis and/or advanced fibrosis as assessed by FLI or BARD score were significantly associated with risk of CVD and mortality in new-onset T2DM.

Transient Vestibular Symptoms Preceding Posterior Circulation Stroke: A Prospective Multicenter Study.

BACKGROUND AND PURPOSE: The recognition of clinical features of transient vestibular symptoms (TVSs) preceding posterior circulation stroke (PCOS) would be informative to discriminate dizziness/vertigo due to vertebrobasilar transient ischemic attack from the acute transient vestibular syndrome. We sought to determine the prevalence and characteristics of TVSs preceding PCOS. METHODS: We performed a prospective multicenter observational study that had recruited 447 patients with PCOS from referral-based 4 university hospitals in Korea. We investigated the timing, pattern, frequency, duration, and accompanying neurological symptoms of TVSs during the 3 months preceding PCOS. RESULTS: The prevalence of TVSs preceding PCOS was 12% (55/447) during the previous 3 months. The TVSs preceding PCOS occurred within 1 week (33%), between 1 week and 1 month (16%), or between 1 and 3 months (51%). The TVSs were mostly dizziness/vertigo with (36%) or without (60%) imbalance, while the remaining 4% had an isolated imbalance. The dizziness/vertigo was spinning in 38% and was aggravated during head position in 45%. The duration of TVSs was mostly a few seconds (55%) or minutes (38%). Approximately 72% of the patients with PCOS had TVSs 1 to 5 times, while 16% had >10 times. Accompanying neurological symptoms, including headache, tinnitus, limb weakness, sensory change, dysarthria, visual field defect, and diplopia, were reported in 11%. CONCLUSIONS: Preceding TVSs can occur in 12% of PCOS during the previous 3 months. Isolated dizziness/vertigo of unknown cause needs to be considered as a vertebrobasilar transient ischemic attack symptom, especially in patients with vascular risk factors. The characteristics of isolated vestibular symptom in vertebrobasilar transient ischemic attacks is highly variable and atypical compared with other transient ischemic symptoms.

Early mortality and cardiovascular disease, varied association with body mass index and its changes in insulin-treated diabetes: a nationwide study.

BACKGROUND/OBJECTIVES: We investigated the hazards of cardiovascular diseases (CVDs) and all-cause death during follow-up according to baseline body mass index (BMI) and percent change in BMI among adults with insulin-treated diabetes. SUBJECTS/METHODS: Using the Korean National Health Insurance Service datasets (2002-2017), the hazards of myocardial infarction (MI), stroke, and all-cause mortality during follow-up were analyzed according to baseline BMI and percent change in BMI among adults with insulin-treated diabetes and without baseline CVD and/or malignancy (N = 44,055). RESULTS: At baseline, 67.3% of total subjects were either obese or overweight. During a mean 3.8 years, 1,081 MI and 1,562 stroke cases developed; 2,847 deaths occurred over a mean 3.9 years. Compared with normal weight, overweight and obesity were associated with lower hazards of outcomes [hazard ratio (95% CI): 0.836 (0.712-0.981), 0.794 (0.687-0.917) for MI; 0.829 (0.726-0.946), 0.772 (0.684-0.870) for stroke; 0.740 (0.672-0.816), 0.666 (0.609-0.728) for death, respectively]. Underweight was associated with a higher hazard of all-cause death during follow-up [hazard ratio (95% CI): 2.035 (1.695-2.443)]. When the group with minimum absolute value for percent change in BMI was set as a reference, the relative reduction in BMI was associated with increased hazards of MI, stroke, and all-cause death, and relative increase in BMI was associated with increased hazards of stroke and all-cause death during follow-up. CONCLUSIONS: Among adults with insulin-treated diabetes, a high prevalence of overweight and obesity was observed, and baseline BMI category was inversely associated with CVD incidence and all-cause death during follow-up. Both weight loss and gain were associated with increased CVD incidence and all-cause death during follow-up, showing a U-shaped relationship between weight change and outcome. Stable body weight might be a predictor of a lower risk of CVDs and premature death among individuals with insulin-treated diabetes.

The association of hepatic steatosis and fibrosis with heart failure and mortality.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. METHODS: We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. RESULTS: A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24-1.36), hHF (HR 1.54, 95% CI 1.44-1.66), all-cause mortality (HR 1.62, 95% CI 1.54-1.70), and CV mortality (HR 1.41 95% CI 1.22-1.63) in the general population and hHF (HR 1.26, 95% CI 1.21-1.54) and all-cause mortality (HR 1.54 95% CI 1.24-1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05). CONCLUSION: Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality.

Thermodynamics of Alkanethiol Self-Assembled Monolayer Assembly on Pd Surfaces.

We investigate the structure and binding energy of alkanethiolate self-assembled monolayers (SAMs) on Pd (111), Pd (100), and Pd (110) facets at different coverages. Dispersion-corrected density functional theory calculations are used to correlate the binding energy of alkanethiolates with alkyl chain length and coverage. The equilibrium coverage of thiolate layers strongly prefers 1/3 monolayer (ML) on the Pd (111) surface. The coverage of thiolates varies with chemical potential on Pd (100) and Pd (110), increasing from 1/3 to 1/2 ML on (100) and from 1/4 to 1/2 ML on (110) as the thiol chemical potential is increased. Higher coverages are driven by attractive dispersion interactions between the extended alkyl chains, such that transitions to higher coverages occur at lower thiol chemical potentials for longer chain thiolates. Stronger adsorption to the Pd (100) surface causes the equilibrium Wulff construction of Pd particles to take on a cubic shape upon saturation with thiols. The binding of H, O, and CO adsorbates is weakened as the thiolate coverage is increased, with saturation coverages causing unfavorable binding of O and CO on Pd (100) and weakened binding on other facets. Temperature-dependent CO diffuse reflectance infrared Fourier transform spectroscopy experiments are used to corroborate the weakened binding of CO in the presence of thiolate SAMs of varying surface density. Preliminary results of multiscale modeling efforts on the Pd-thiol system using a reactive force field, ReaxFF, are also discussed.

Efficient Epoxidation of Styrene Derivatives by a Nonheme Iron(IV)-Oxo Complex via Proton-Coupled Electron Transfer with Triflic Acid.

Styrene derivatives are not oxidized by [(N4Py)Fe(IV)(O)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) in acetonitrile at 298 K, whereas epoxidation of styrene derivatives by the iron(IV)-oxo complex occurs efficiently in the presence of triflic acid (HOTf) via proton-coupled electron transfer (PCET) from styrene derivatives to the diprotonated species of [(N4Py)Fe(IV)(O)](2+) with HOTf. Logarithms of the first-order rate constants of HOTf-promoted expoxidation of styrene derivatives with [(N4Py)Fe(IV)(O)](2+) and PCET from electron donors to [(N4Py)Fe(IV)(O)](2+) in the precursor complexes exhibit a remarkably unified correlation with the driving force of PCET in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes are taken into account. The same PCET driving force dependence is obtained for the first-order rate constants of HOTf-promoted oxygen atom transfer from thioanisols to [(N4Py)Fe(IV)(O)](2+) and HOTf-promoted hydrogen atom transfer from toluene derivatives to [(N4Py)Fe(IV)(O)](2+) in the precursor complexes. Thus, HOTf-promoted epoxidation of styrene derivatives by [(N4Py)Fe(IV)(O)](2+) proceeds via the rate-determining electron transfer from styrene derivatives to the diprotonated species of [(N4Py)Fe(IV)(O)](2+), as shown in the reactions of HOTf-promoted oxygen atom transfer from thioanisols to [(N4Py)Fe(IV)(O)](2+) and HOTf-promoted hydrogen atom transfer from toluene derivatives to [(N4Py)Fe(IV)(O)](2+).

Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling.

Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and AKT. MMP-2 activation was also significantly increased. Specific inhibitors of p38 (SB203580) and JNK (SP600125) inhibited tube formation and wound healing, while an ERK inhibitor (PD98059) did not. MMP-2 activation and AKT phosphorylation were also attenuated and associated with the suppression of p38 and JNK phosphorylation, but not with that of ERK. These results indicate that fucoidan, in the presence of FGF-2, induces angiogenesis through AKT/MMP-2 signalling by activating p38 and JNK. These findings provide basic molecular information on the effect of fucoidan on angiogenesis in the presence of FGF-2.

Unified view of oxidative C-H bond cleavage and sulfoxidation by a nonheme iron(IV)-oxo complex via Lewis acid-promoted electron transfer.

Oxidative C-H bond cleavage of toluene derivatives and sulfoxidation of thioanisole derivatives by a nonheme iron(IV)-oxo complex, [(N4Py)Fe(IV)(O)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), were remarkably enhanced by the presence of triflic acid (HOTf) and Sc(OTf)3 in acetonitrile at 298 K. All the logarithms of the observed second-order rate constants of both the oxidative C-H bond cleavage and sulfoxidation reactions exhibit remarkably unified correlations with the driving forces of proton-coupled electron transfer (PCET) and metal ion-coupled electron transfer (MCET) in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes between PCET and MCET were taken into account, respectively. Thus, the mechanisms of both the oxidative C-H bond cleavage of toluene derivatives and sulfoxidation of thioanisole derivatives by [(N4Py)Fe(IV)(O)](2+) in the presence of HOTf and Sc(OTf)3 have been unified as the rate-determining electron transfer, which is coupled with binding of [(N4Py)Fe(IV)(O)](2+) by proton (PCET) and Sc(OTf)3 (MCET). There was no deuterium kinetic isotope effect (KIE) on the oxidative C-H bond cleavage of toluene via the PCET pathway, whereas a large KIE value was observed with Sc(OTf)3, which exhibited no acceleration of the oxidative C-H bond cleavage of toluene. When HOTf was replaced by DOTf, an inverse KIE (0.4) was observed for PCET from both toluene and [Ru(II)(bpy)3](2+) (bpy =2,2'-bipyridine) to [(N4Py)Fe(IV)(O)](2+). The PCET and MCET reactivities of [(N4Py)Fe(IV)(O)](2+) with Brønsted acids and various metal triflates have also been unified as a single correlation with a quantitative measure of the Lewis acidity.

Local Ordering, Distortion, and Redox Activity in (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 Investigated by a Computational Workflow for Compositionally Complex Perovskite Oxides.

Mixing multiple cations can result in a significant configurational entropy, offer a new compositional space with vast tunability, and introduce new computational challenges. For applications such as the two-step solar thermochemical hydrogen (STCH) generation techniques, we demonstrate that using density functional theory (DFT) combined with Metropolis Monte Carlo method (DFT-MC) can efficiently sample the possible cation configurations in compositionally complex perovskite oxide (CCPO) materials, with (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 as an example. In the presence of oxygen vacancies (VO), DFT-MC simulations reveal a significant increase of the local site preference of the cations (short-range ordering), compared to a more random mixing without VO. Co is found to be the redox-active element and the VO is the preferentially generated next to Co due to the stretched Co-O bonds. A clear definition of the vacancy formation energy (Evf) is proposed for CCPO in an ensemble of structures evolved in parallel from independent DFT-MC paths. By combining the distribution of Evf with VO interactions into a statistical model, the oxygen nonstoichiometry (δ), under the STCH thermal reduction and oxidation conditions, is predicted and compared with the experiments. Similar to the experiments, the predicted δ can be used to extract the enthalpy and entropy of reduction using the van't Hoff method, providing direct comparisons with the experimental results. This procedure provides a full predictive workflow for using DFT-MC to obtain possible local ordering or fully random structures, understand the redox activity of each element, and predict the thermodynamic properties of CCPOs, for computational screening and design of these CCPO materials at STCH conditions.

Protein-energy restriction-induced lipid metabolism disruption causes stable-to-progressive disease shift in Mycobacterium avium-infected female mice.

BACKGROUND: Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model. METHODS: We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction. FINDINGS: Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression. INTERPRETATION: Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection. FUNDING: This research was funded by the National Research Foundation of Korea, the Korea Research Institute of Bioscience and Biotechnology, and the Korea National Institute of Health.

Risk of Depression according to Cumulative Exposure to a Low-Household Income Status in Individuals with Type 2 Diabetes Mellitus: A Nationwide Population- Based Study.

BACKGRUOUND: We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). METHODS: For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). RESULTS: During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. CONCLUSION: Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Genetic stability of Mycobacterium abscessus during antibiotic treatment.

OBJECTIVES: Genetic changes in Mycobacterium abscessus during antibiotic treatment are not fully understood. This study aimed to investigate the genetic changes in M. abscessus in patients receiving antibiotic treatment, and their clinical implications. METHODS: Pretreatment and 12-month post-treatment M. abscessus isolates were obtained from patients with M. abscessus pulmonary disease. Isolates from each time point were separated into six groups based on their distinctive morphological characteristics. Twenty-four isolates, comprising 12 from patient A exhibiting progressive disease and 12 from patient B demonstrating stable disease, underwent sequencing. Subsequently, minimal inhibitory concentrations (MICs) for the administered antibiotics were measured. RESULTS: Persistent infection with a single strain was observed in patients A and B. During 12 months of treatment, MICs for administered drugs did not generally change over time in either patient and single nucleotide variations (SNV) associated with antimicrobial resistance (rrl, rrs, erm(41), gyrA, gyrB, whiB7 and hflX) were not mutated. Although not significant, 47 and 52 non-synonymous SNVs occurred in M. abscessus from patients A and B, respectively, and the accumulation of these SNVs differed in patients A and B, except for five SNVs. The most variable positions were within a probable NADH-dependent glutamate synthase gene and a putative YrbE family protein gene in patients A and B, respectively. CONCLUSIONS: Persistent infections by a single strain of M. abscessus were observed in two patients with different clinical courses. Genetic changes in M. abscessus during antibiotic treatment were relatively stable in these patients. CLINICAL TRIALS IDENTIFIER: NCT01616745 (ClinicalTrials.gov ID).

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Brønsted acid-promoted C-H bond cleavage via electron transfer from toluene derivatives to a protonated nonheme iron(IV)-oxo complex with no kinetic isotope effect.

The reactivity of a nonheme iron(IV)-oxo complex, [(N4Py)Fe(IV)(O)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), was markedly enhanced by perchloric acid (70% HClO4) in the oxidation of toluene derivatives. Toluene, which has a high one-electron oxidation potential (Eox = 2.20 V vs SCE), was oxidized by [(N4Py)Fe(IV)(O)](2+) in the presence of HClO4 in acetonitrile (MeCN) to yield a stoichiometric amount of benzyl alcohol, in which [(N4Py)Fe(IV)(O)](2+) was reduced to [(N4Py)Fe(III)(OH2)](3+). The second-order rate constant (kobs) of the oxidation of toluene derivatives by [(N4Py)Fe(IV)(O)](2+) increased with increasing concentration of HClO4, showing the first-order dependence on [HClO4]. A significant kinetic isotope effect (KIE) was observed when mesitylene was replaced by mesitylene-d12 in the oxidation with [(N4Py)Fe(IV)(O)](2+) in the absence of HClO4 in MeCN at 298 K. The KIE value drastically decreased from KIE = 31 in the absence of HClO4 to KIE = 1.0 with increasing concentration of HClO4, accompanied by the large acceleration of the oxidation rate. The absence of KIE suggests that electron transfer from a toluene derivative to the protonated iron(IV)-oxo complex ([(N4Py)Fe(IV)(OH)](3+)) is the rate-determining step in the acid-promoted oxidation reaction. The detailed kinetic analysis in light of the Marcus theory of electron transfer has revealed that the acid-promoted C-H bond cleavage proceeds via the rate-determining electron transfer from toluene derivatives to [(N4Py)Fe(IV)(OH)](3+) through formation of strong precursor complexes between toluene derivatives and [(N4Py)Fe(IV)(OH)](3+).

Unusual aliovalent doping effects on oxygen non-stoichiometry in medium-entropy compositionally complex perovskite oxides.

Aliovalent doping of perovskite oxides can tune the oxygen vacancy formation energy. This work discovers normal vs. abnormal aliovalent doping effects on redox behaviors in medium-entropy compositionally complex perovskite oxides (CCPOs) (La1-xSrx)(Mn1/3Fe1/3Ti1/3)O3-δ (LS_MFT) vs. (La1-xSrx)(Mn1/3Fe1/3Cr1/3)O3-δ (LS_MFC). In the LS_MFC series, the oxygen non-stoichiometry range Δδ (= δred - δox) linearly depends on the Sr molar ratio x, while the LS_MFT series shows a V-shape dependence of Δδ on x. This unusual observation is investigated and explained based on the analysis of the energy loss near edge structure (ELNES) in STEM electron energy loss spectroscopy, along with density functional theory (DFT) calculations. In LS_MFC, Cr-L2,3, Mn-L2,3 and Fe-L2,3 peaks have a similar linear shift to higher energy with increasing x, which indicates higher oxidation states of Cr, Mn, and Fe with lower oxygen vacancy formation energies. In LS_MFT, the V-shape of the Δδ vs. x curve is caused by the stable Ti4+ state and a V-shape Mn/Fe valency dependence on x. This study suggests the possible existence of different (including unexpected) coupled aliovalent doping effects in CCPOs with multiple B-site redox active elements.