Monocyte to high-density lipoprotein cholesterol ratio is associated with cerebral small vessel diseases.

BACKGROUND: Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. METHODS: This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 103/µL) / HDL cholesterol (mmol/L). RESULTS: In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [ß = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07-1.91], and CMB (aOR = 1.51, 95% CI = 1.03-2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P < 0.001), lacunes (P < 0.001), and CMBs (P < 0.001). CONCLUSIONS: High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs.

Smoking behavior change and risk of cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus.

BACKGROUND: We aimed to examine the association between smoking behavior change and risk of cardiovascular disease (CVD) incidence and mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: This study used nationwide data from the Korean National Health Insurance System and included 349,137 T2DM patients who smoked. Smoking behavior changes were defined with five groups: quitters, reducers I (≥ 50% reduction), reducers II (20-50% reduction), sustainers (± 20%), and increasers (≥ 20% increase) from the number of cigarettes/day at the baseline. RESULTS: During a median follow-up of 5.1 years, 6,514 cases of myocardial infarction (MI) (1.9%), 7,837 cases of ischemic stroke (IS) (2.2%), and 14,932 deaths (4.3%) were identified. Quitters had a significantly decreased risk of MI (adjusted hazard ratio [aHR] 0.80, 95% CI 0.75-0.86) and IS (aHR 0.80, 95% CI 0.75-0.85) compared to sustainers, whereas reducers did not have a significant association with the risk of MI (aHR 1.03, 95% CI 0.94-1.13) and IS (aHR 1.00, 95% CI 0.92-1.08) in reducer I. Quitters also had a lower all-cause and CVD mortality than sustainers. CONCLUSIONS: Smoking cessation was associated with decreased CVD incidence, and all-cause and CVD mortality among T2DM patients. However, smoking reduction was not associated with decreased risks for these.

Clinical significance of D-dimer levels during acute period in ischemic stroke.

BACKGROUND: Initial D-dimer level is a well-known prognostic parameter in patients with acute ischemic stroke (AIS). However, there have been no studies on the clinical significance of follow-up D-dimer levels. In this study, we evaluated the association between initial and follow-up D-dimer levels and early neurological deterioration (END) in patients with AIS. METHODS: We included consecutive patients with AIS who had a positive initial D-dimer test (> 0.55 mg/L) between March 2021 and November 2022. The follow-up D-dimer test was performed on the 7th day after hospitalization and on the day of discharge if discharged earlier. END was defined as an increase of ≥ 2 in the total NIHSS score, or ≥ 1 in the motor NIHSS score within the first 7 days of admission. As medical conditions closely associated with the initial and follow-up D-dimer levels in AIS patients, we also evaluated the history of cancer, active cancer, and venous thromboembolism (VTE) that occurred during hospitalization together. RESULTS: A total of 246 patients with AIS were evaluated (median age: 87 years, male: 56.5%). In multivariable logistic regression analysis, the initial D-dimer level was closely associated with END after adjusting for confounders (adjusted odds ratio [aOR]: 1.48, 95% CI: 1.06-2.05). The follow-up D-dimer level also showed a close correlation with END (aOR: 1.60, 95% CI: 1.16-2.20). Regarding the analysis of the association between D-dimer levels and underlying cancer or VTE, the initial D-dimer level showed a statistically significant positive relationship only with active cancer (P = 0.024). On the other hand, the follow-up D-dimer level was found to be statistically significantly associated with a history of cancer (P = 0.024), active cancer (P = 0.001), and VTE (P = 0.001). CONCLUSIONS: Initial and follow-up D-dimer levels were associated with END in AIS patients. Particularly, the follow-up D-dimer level showed a clear correlation not only with END but also with the underlying cancer or the occurrence of VTE during the acute period.

H3K9me2 genome-wide distribution in the holocentric insect Spodoptera frugiperda (Lepidoptera: Noctuidae).

BACKGROUND: Eukaryotic genomes are packaged by Histone proteins in a structure called chromatin. There are different chromatin types. Euchromatin is typically associated with decondensed, transcriptionally active regions and heterochromatin to more condensed regions of the chromosomes. Methylation of Lysine 9 of Histone H3 (H3K9me) is a conserved biochemical marker of heterochromatin. In many organisms, heterochromatin is usually localized at telomeric as well as pericentromeric regions but can also be found at interstitial chromosomal loci. This distribution may vary in different species depending on their general chromosomal organization. Holocentric species such as Spodoptera frugiperda (Lepidoptera: Noctuidae) possess dispersed centromeres instead of a monocentric one and thus no observable pericentromeric compartment. To identify the localization of heterochromatin in such species we performed ChIP-Seq experiments and analyzed the distribution of the heterochromatin marker H3K9me2 in the Sf9 cell line and whole 4th instar larvae (L4) in relation to RNA-Seq data. RESULTS: In both samples we measured an enrichment of H3K9me2 at the (sub) telomeres, rDNA loci, and satellite DNA sequences, which could represent dispersed centromeric regions. We also observed that density of H3K9me2 is positively correlated with transposable elements and protein-coding genes. But contrary to most model organisms, H3K9me2 density is not correlated with transcriptional repression. CONCLUSION: This is the first genome-wide ChIP-Seq analysis conducted in S. frugiperda for H3K9me2. Compared to model organisms, this mark is found in expected chromosomal compartments such as rDNA and telomeres. However, it is also localized at numerous dispersed regions, instead of the well described large pericentromeric domains, indicating that H3K9me2 might not represent a classical heterochromatin marker in Lepidoptera. (242 words).

Headaches during pregnancy and the risk of subsequent stroke.

BACKGROUND: Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. METHODS: Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. RESULTS: Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30-1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12-2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23-2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19-2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. CONCLUSIONS: We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Association of Change in Alcohol Consumption With Risk of Ischemic Stroke.

BACKGROUND: The effect of serial change in alcohol consumption on stroke risk has been limitedly evaluated. We investigated the association of change in alcohol consumption with risk of stroke. METHODS: This study is a population-based retrospective cohort study from National Health Insurance Service database of all Koreans. Four lakh five hundred thirteen thousand seven hundred forty-six participants aged ≥40 years who underwent 2 subsequent national health examinations in both 2009 and 2011. Alcohol consumption was assessed by average alcohol intake (g/day) based on self-questionnaires and categorized into non-, mild, moderate, and heavy drinking. Change in alcohol consumption was defined by shift of category from baseline. Cox proportional hazards model was used with adjustment for age, sex, smoking status, regular exercise, socioeconomic information, and comorbidities, Charlson Comorbidity Index, systolic blood pressure, and laboratory results. Subgroup analysis among those with the third examination was conducted to reflect further change in alcohol consumption. RESULTS: During 28 424 497 person-years of follow-up, 74 923 ischemic stroke events were identified. Sustained mild drinking was associated with a decreased risk of ischemic stroke (adjusted hazard ratio, 0.88 [95% CI, 0.86-0.90]) compared with sustained nondrinking, whereas sustained heavy drinking was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.06 [95% CI, 1.02-1.10]). Increasing alcohol consumption was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.11 [95% CI, 1.06-1.17] from mild to moderate; adjusted hazard ratio, 1.28 [95% CI, 1.19-1.38] from mild to heavy) compared with sustained mild drinkers. Reduction of alcohol consumption from heavy to mild level was associated with 17% decreased risk of ischemic stroke through 3× of examinations. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic stroke, although it might be not causal and could be impacted by sick people abstaining from drinking. Reduction of alcohol consumption from heavy drinking is associated with a decreased risk of ischemic stroke.

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). METHODS: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). RESULTS: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. DISCUSSION/CONCLUSION: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Smoking cessation, but not reduction, reduces cardiovascular disease incidence.

AIMS: The aim of this study was to assess the association of smoking cessation and reduction with risk of cardiovascular disease (CVD). METHODS AND RESULTS: A total of 897 975 current smokers aged ≥40 years who had undergone two consecutive national health examinations (in 2009 and 2011) were included. Participants were classified as quitters (20.6%), reducers I (≥50% reduction, 7.3%), reducers II (20-50% reduction, 11.6%), sustainers (45.7%), and increasers (≥20% increase, 14.5%). During 5 575 556 person-years (PY) of follow-up, 17 748 stroke (3.2/1000 PY) and 11 271 myocardial infarction (MI) (2.0/1000 PY) events were identified. Quitters had significantly decreased risk of stroke [adjusted hazard ratio (aHR) 0.77 95% confidence interval (CI) 0.74-0.81; absolute risk reduction (ARR) -0.37, 95% CI -0.43 to -0.31] and MI (aHR 0.74, 95% CI 0.70-0.78; ARR -0.27, 95% CI -0.31 to -0.22) compared to sustainers after adjustment for demographic factors, comorbidities, and smoking status. The risk of stroke and MI incidence in reducers I (aHR 1.02, 95% CI 0.97-1.08 and aHR 0.99, 95% CI 0.92-1.06, respectively) and reducers II (aHR 1.00, 95% CI 0.95-1.05 and aHR 0.97, 95% CI 0.92-1.04, respectively) was not significantly different from the risk in sustainers. Further analysis with a subgroup who underwent a third examination (in 2013) showed that those who quit at the second examination but had starting smoking again by the third examination had 42-69% increased risk of CVD compared to sustained quitters. CONCLUSIONS: Smoking cessation, but not reduction, was associated with reduced CVD risk. Our study emphasizes the importance of sustained quitting in terms of CVD risk reduction.

Different Predictive Factors for Early Neurological Deterioration Based on the Location of Single Subcortical Infarction: Early Prognosis in Single Subcortical Infarction.

Background and Purpose: Patients with single subcortical infarctions (SSIs) have relatively a favorable prognosis, but they often experience early neurological deterioration (END). In this study, we compared the predictors for END in patients with SSI according to the location of the lesion. Methods: We included consecutive patients with SSIs within 72 hours of symptom onset presenting between 2010 and 2016. END was defined as an increase of ≥2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 in the motor NIHSS score within the first 72 hours of admission. Along with the analysis of all patients with SSI, we also analyzed the predictors for END in proximal/distal SSI patients and anterior/posterior circulation SSI patients. Results: A total of 438 patients with SSI were evaluated. In multivariable analysis, initial NIHSS score (adjusted odds ratio, 1.36 [95% CI, 1.15­1.60]), pulsatility index (adjusted odds ratio, 1.25 [95% CI, 1.03­1.52]), parent artery disease (adjusted odds ratio, 2.14 [95% CI, 1.06­4.33]), and neutrophil-to-lymphocyte ratio (adjusted odds ratio, 1.24 [95% CI, 1.04­1.49]) were positively associated with END. In patients with proximal SSI, initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio showed positive associations with END. Meanwhile, no variable related to END was found in the distal SSI group. When we compared the predictors for END based on the involved vascular territory, higher initial NIHSS score and neutrophil-to-lymphocyte ratio were significantly associated with END in patients with anterior circulation SSIs. On the contrary, higher pulsatility index values and the presence of parent artery disease were independent predictors for END in patients with SSIs in the posterior circulation. Conclusions: Initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio are associated with END in patients with SSIs. The frequency and predictors for END differ depending on the location of the SSI.

Integrated miRNA and transcriptome profiling to explore the molecular determinism of convergent adaptation to corn in two lepidopteran pests of agriculture.

BACKGROUND: The degree to which adaptation to same environment is determined by similar molecular mechanisms, is a topic of broad interest in evolutionary biology, as an indicator of evolutionary predictability. We wished to address if adaptation to the same host plant in phytophagous insects involved related gene expression patterns. We compared sRNA-Seq and RNA-Seq data between two pairs of taxa of Ostrinia and Spodoptera frugiperda sharing maize as host-plant. For the latter, we had previously carried out a reciprocal transplant experiment by feeding of the larvae of the Corn strain (Sf-C) and the Rice strain (Sf-R) on corn versus rice and characterized the mRNA and miRNA responses. RESULTS: First, we predicted the genes encoding miRNA in Ostrinia nubilalis (On) and O. scapulalis (Os). Respectively 67 and 65 known miRNA genes, as well as 196 and 190 novel ones were predicted with Os genome using sncRNAs extracted from whole larvae feeding on corn or mugwort. In On, a read counts analysis showed that 37 (55.22%) known miRNAs and 19 (9.84%) novel miRNAs were differentially expressed (DE) on mugwort compared to corn (in Os, 25 known miRs (38.46%) and 8 novel ones (4.34%)). Between species on corn, 8 (12.5%) known miRNAs and 8 (6.83%) novel ones were DE while only one novel miRNA showed expression variation between species on mugwort. Gene target prediction led to the identification of 2953 unique target genes in On and 2719 in Os, among which 11.6% (344) were DE when comparing species on corn. 1.8% (54) of On miR targets showed expression variation upon a change of host-plant. We found molecular changes matching convergent phenotype, i.e., a set of nine miRNAs that are regulated either according to the host-plant both in On and Sf-C or between them on the same plant, corn. Among DE miR target genes between taxa, 13.7% shared exactly the same annotation between the two pairs of taxa and had function related to insect host-plant interaction. CONCLUSION: There is some similarity in underlying genetic mechanisms of convergent evolution of two distant Lepidopteran species having adopted corn in their host range, highlighting possible adaptation genes.

A novel reference dated phylogeny for the genus Spodoptera Guenée (Lepidoptera: Noctuidae: Noctuinae): new insights into the evolution of a pest-rich genus.

The noctuid genus Spodoptera currently consists of 31 species with varied host plant breadths, ranging from monophagous and oligophagous non-pest species to polyphagous pests of economic importance. Several of these pest species have become major invaders, colonizing multiple continents outside their native range. Such is the case of the infamous fall armyworm, Spodoptera frugiperda (J.E. Smith), which includes two recognized host strains that have not been treated as separate species. Following its accidental introduction to Africa in 2016, it quickly spread through Africa and Asia to Australia. Given that half the described Spodoptera species cause major crop losses, comparative genomics studies of several Spodoptera species have highlighted major adaptive changes in genetic architecture, possibly relating to their pest status. Several recent population genomics studies conducted on two species enable a more refined understanding of their population structures, migration patterns and invasion processes. Despite growing interest in the genus, the taxonomic status of several Spodoptera species remains unstable and evolutionary studies suffer from the absence of a robust and comprehensive dated phylogenetic framework. We generated mitogenomic data for 14 Spodoptera taxa, which are combined with data from 15 noctuoid outgroups to generate a resolved mitogenomic backbone phylogeny using both concatenation and multi-species coalescent approaches. We combine this backbone with additional mitochondrial and nuclear data to improve our understanding of the evolutionary history of the genus. We also carry out comprehensive dating analyses, which implement three distinct calibration strategies based on either primary or secondary fossil calibrations. Our results provide an updated phylogenetic framework for 28 Spodoptera species, identifying two well-supported ecologically diverse clades that are recovered for the first time. Well-studied larvae in each of these clades are characterized by differences in mandibular shape, with one clade's being more specialized on silica-rich C4 grasses. Interestingly, the inferred timeframe for the genus suggests an earlier origin than previously thought for the genus: about 17-18 million years ago.

Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening.

BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

Quantification of the inflammatory responses to pro-and anti-inflammatory agents in Manila clam, Ruditapes philippinarum.

Inflammation is a form of innate immune response of living organisms to harmful stimuli. In marine bivalves, inflammation is a common defense mechanism. Several studies have investigated the morphological features of inflammation in bivalves, such as hemocyte infiltration. However, the molecular and biochemical responses associated with inflammation in marine bivalves remain unexplored. Here, we investigated changes in nitric oxide (NO) levels, cyclooxygenase 2 (COX-2) activity, and allograft inflammatory factor-1 (AIF-1) gene expression levels in hemolymph samples collected from Manila clam (Ruditapes philippinarum) exposed to pro- and anti-inflammatory substances. These included the pro-inflammatory agent lipopolysaccharide (LPS), and the nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac, all widely used in vertebrates. Our study showed that NO levels, COX-2 activity, and AIF-1 expression increased in response to the treatments with LPS and decreased in response to the treatments with NSAIDs in a concentration-dependent manner. These results suggest that the mechanism of inflammatory responses in bivalves is very similar to that of vertebrates, and we propose that inflammatory responses can be quantified using these techniques and used to determine the physiological status of marine bivalves exposed to biotic or abiotic stresses.

Positive selection alone is sufficient for whole genome differentiation at the early stage of speciation process in the fall armyworm.

BACKGROUND: The process of speciation involves differentiation of whole genome sequences between a pair of diverging taxa. In the absence of a geographic barrier and in the presence of gene flow, genomic differentiation may occur when the homogenizing effect of recombination is overcome across the whole genome. The fall armyworm is observed as two sympatric strains with different host-plant preferences across the entire habitat. These two strains exhibit a very low level of genetic differentiation across the whole genome, suggesting that genomic differentiation occurred at an early stage of speciation. In this study, we aim at identifying critical evolutionary forces responsible for genomic differentiation in the fall armyworm. RESULTS: These two strains exhibit a low level of genomic differentiation (FST = 0.0174), while 99.2% of 200 kb windows have genetically differentiated sequences (FST > 0). We found that the combined effect of mild positive selection and genetic linkage to selectively targeted loci are responsible for the genomic differentiation. However, a single event of very strong positive selection appears not to be responsible for genomic differentiation. The contribution of chromosomal inversions or tight genetic linkage among positively selected loci causing reproductive barriers is not supported by our data. Phylogenetic analysis shows that the genomic differentiation occurred by sub-setting of genetic variants in one strain from the other. CONCLUSIONS: From these results, we concluded that genomic differentiation may occur at the early stage of a speciation process in the fall armyworm and that mild positive selection targeting many loci alone is sufficient evolutionary force for generating the pattern of genomic differentiation. This genomic differentiation may provide a condition for accelerated genomic differentiation by synergistic effects among linkage disequilibrium generated by following events of positive selection. Our study highlights genomic differentiation as a key evolutionary factor connecting positive selection to divergent selection.

Regional Arterial Spin Labeling Perfusion Defect Is Associated With Early Ischemic Recurrence in Patients With a Transient Ischemic Attack.

Background and Purpose- With the lack of confirmatory examinations, the distinction of a transient ischemic attack (TIA) from various TIA-mimicking diseases is difficult, particularly in diffusion-weighted imaging (DWI)-negative TIAs. In this study, we aimed to evaluate the relationship between arterial spin labeling (ASL) perfusion defects and early ischemic recurrence (FU-DWI [+]) in patients with DWI-negative TIAs. Methods- We assessed consecutive patients with a DWI-negative TIA within 24 hours of symptom onset, who underwent both ASL images and follow-up magnetic resonance imaging during the acute period. As markers of the ASL images, we evaluated the ASL perfusion defects in each hemisphere. Arterial transit artifact (ATA) and intraarterial high-intensity signal (IAS) were also rated as markers of collateral status and blood stagnation due to large vessel occlusion, respectively. Results- Among the 136 patients with a DWI-negative TIA, 33 patients had FU-DWI (+) lesions in 36 hemispheres. In the multivariable analysis, ASL defects remained an independent predictor of FU-DWI (+) (adjusted odds ratio, 13.94 [95% CI, 5.77-33.70], P<0.001). In the evaluation of the interactive relationship between ASL defects and ATA/IAS, the (ASL [+] ATA [-]) group showed the highest frequencies of FU-DWI (+) events (55.6%) with the highest adjusted odds ratio values (adjusted odds ratio, 14.86 [95% CI, 5.63-39.24], P<0.001), indicating a negative synergistic effect between the ASL defects and ATA. Meanwhile, the (ASL [+] IAS [+]) group showed higher frequencies of FU-DWI (+) and higher adjusted odds ratio values than those of the (ASL [+] IAS [-]) and (ASL [-] IAS [-]) groups, indicating a positive synergistic effect. Conclusions- We demonstrated that ASL perfusion defects were associated with ipsilateral FU-DWI (+) in patients with a DWI-negative TIA. Furthermore, this association was enhanced with IASs and attenuated with ATAs.

Correction: Obesity without metabolic disorder and silent brain infarcts in a neurologically healthy population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Obesity without metabolic disorder and silent brain infarcts in aneurologically healthy population.

OBJECTIVE: Obesity without metabolic disorder [Ob(+)MD(-)] is a unique subcategory of obesity where individuals are protected from the obesity-related complications. Although conflicting clinical outcomes have been reported, there has been no study of the effects of Ob(+)MD(-) on cerebrovascular disease. In this study, we evaluated the association between the Ob(+)MD(-) phenotype and silent brain infarcts (SBI) in a neurologically healthy population. SUBJECTS/METHODS: We evaluated a consecutive series of healthy volunteers recruited between January 2006 and December 2013. MD(-) status was assessed using five clinical markers: blood pressure, triglycerides, high-density lipoprotein, fasting plasma glucose, and waist circumference. Obesity was defined when body mass index ≥ 25 kg/m2. SBI was defined as asymptomatic, well-defined lesions with a diameter ≥ 3 mm with the same signal characteristics as the cerebrospinal fluid on T1- or T2-weighted images. RESULTS: A total of 3165 subjects were assessed, and 262 (8%) SBI cases were identified. In multivariate analyses, non-obesity with metabolic disorder [Ob(-)MD(+)] (adjusted odds ratio [aOR] = 1.65, 95% confidence interval [CI] = 1.07-2.56, P = 0.025) and obesity with metabolic disorder [Ob(+)MD(+)] (aOR = 1.75, 95% CI = 1.12-2.75, P = 0.014) were closely associated with SBI after adjustment for confounders. Meanwhile, Ob(+)MD(-) did not show any significant association with SBI (aOR = 0.85, 95% CI = 0.20-3.72, P = 0.832). These findings may indicate that metabolic abnormality, irrespective of obesity status, is a main risk factor of SBI. When we compared SBI burdens between the four metabolic phenotypes, the Ob(+)MD(+) and Ob(-)MD(+) groups had higher rates of multiple lesions than the Ob(+)MD(-) and non-obesity without metabolic disorder groups. CONCLUSIONS: The presence of metabolic abnormality, and not obesity per se, is independently associated with the prevalence of SBI in a healthy population.

High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study.

BACKGROUND: The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH). METHODS: We assessed health check-up participants aged 40-79 years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique. RESULTS: A total of 2615 participants were evaluated (median age: 56 years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06-1.81). Further quantitative analyses showed a positive dose-response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (ß = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR. CONCLUSIONS: A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD.

Evidence that the rate of strong selective sweeps increases with population size in the great apes.

Quantifying the number of selective sweeps and their combined effects on genomic diversity in humans and other great apes is notoriously difficult. Here we address the question using a comparative approach to contrast diversity patterns according to the distance from genes in all great ape taxa. The extent of diversity reduction near genes compared with the rest of intergenic sequences is greater in a species with larger effective population size. Also, the maximum distance from genes at which the diversity reduction is observed is larger in species with large effective population size. In Sumatran orangutans, the overall genomic diversity is ∼30% smaller than diversity levels far from genes, whereas this reduction is only 9% in humans. We show by simulation that selection against deleterious mutations in the form of background selection is not expected to cause these differences in diversity among species. Instead, selective sweeps caused by positive selection can reduce diversity level more severely in a large population if there is a higher number of selective sweeps per unit time. We discuss what can cause such a correlation, including the possibility that more frequent sweeps in larger populations are due to a shorter waiting time for the right mutations to arise.

Remote Management of Poststroke Patients With a Smartphone-Based Management System Integrated in Clinical Care: Prospective, Nonrandomized, Interventional Study.

BACKGROUND: Advances in mobile health (mHealth) have enabled systematic and continuous management of patients with chronic diseases. OBJECTIVE: We developed a smartphone-based mHealth system and aimed to evaluate its effects on health behavior management and risk factor control in stroke patients. METHODS: With a multifaceted stroke aftercare management system that included exercise, medication, and educational materials, we performed a 12-week single-arm intervention among eligible poststroke patients in the stroke clinic from September to December 2016. The intervention consisted of (1) regular blood pressure (BP), blood glucose, and physical activity measurements; (2) stroke education; (3) an exercise program; (4) a medication program; and (5) feedback on reviewing of records by clinicians. Clinical assessments consisted of the stroke awareness score, Beck Depression Inventory-II (BDI), EuroQol-5 Dimensions (EQ-5D), and BP at visit 1 (baseline), visit 2 (4 weeks), and visit 3 (12 weeks). Temporal differences in the parameters over 12 weeks were investigated with repeated-measures analysis of variance. Changes in medication adherence at visit 1-2 (from visit 1 to visit 2) and visit 2-3 (from visit 2 to visit 3) were compared. System satisfaction was evaluated with a self-questionnaire using a 5-point Likert scale at visit 3. RESULTS: The study was approved by the Institutional Review Board in September 2016, and participants were enrolled from September to December 2016. Among the 110 patients enrolled for the study, 99 were included in our analyses. The mean stroke awareness score (baseline: 59.6 [SD 18.1]; 4 weeks: 67.6 [SD 16.0], P<.001; 12 weeks: 74.7 [SD 14.0], P<.001) and BDI score (baseline: 12.7 [SD 10.1]; 4 weeks: 11.2 [SD 10.2], P=.01; 12 weeks: 10.7 [SD 10.2], P<.001) showed gradual improvement; however, no significant differences were found in the mean EQ-5D score (baseline: 0.66 [SD 0.33]; 4 weeks: 0.69 [SD 0.34], P=.01; 12 weeks: 0.69 [SD 0.34], P<.001). Twenty-six patients who had uncontrolled BP at baseline had -13.92 mmHg (P=.001) and -6.19 mmHg (P<.001) reductions on average in systolic and diastolic BP, respectively, without any antihypertensive medication change. Medication compliance was better at visit 2-3 (60.9% [SD 37.2%]) than at visit 1-2 (47.8% [SD 38.7%], P<.001). CONCLUSIONS: Awareness of stroke, depression, and BP was enhanced when using the smartphone-based mHealth system. Emerging mHealth techniques have potential as new nonpharmacological secondary prevention methods because of their ubiquitous access, near real-time responsiveness, and comparatively lower cost.