To investigate the topographic changes of white matter (WM) integrity and cortical thickness related to gait disturbances and determine whether these neural correlates mediate the association between ...cerebral small vessel disease (CSVD) and gait disturbances.
A total of 129 patients with subcortical vascular cognitive impairment were included. CSVD severity was quantified as global and regional WM hyperintensities (WMH) volume and lacune and microbleed numbers. Amyloid burdens were assessed using Pittsburgh compound B (PiB)-PET scanning. Gait score was measured using a standardized scale. WM integrity was assessed by applying tract-based spatial statistics. Cortical thickness was measured using surface-based methods. Path analysis for gait score was performed using regional CSVD markers as predictors and fractional anisotropy (FA) and cortical thickness as mediators.
Periventricular WMH (PWMH) volume was associated with gait score, regardless of other CSVD. PiB retention ratio was not associated with gait score. Gait score was correlated with FA in the frontal and parietal WM and bilateral corpus callosum and with cortical thinning in the bilateral frontal and lateral temporo-parieto-occipital regions. Path analysis for gait score showed that PWMH contributed to gait disturbances with the mediation of mean FA or cortical thickness.
Our findings suggest that WMH-related cortical thinning as well as disrupted integrity of periventricular WM is linked to gait disturbances.
Roll‐to‐roll (R2R) fabrication of high‐performance perovskite solar cells (PSCs) remains challenging for PSC commercialization. Herein, the R2R‐suitable electron transfer layer (ETL) SnO2 ink system ...for flexible PSCs is investigated. Water‐dispersed SnO2 inks, commonly used for flexible PSCs, form dewetting pinholes during R2R slot‐die coating owing to slower evaporation compared to spin coating. To prevent the dewetting of the pinhole, a low surface tension solvent (isopropyl alcohol, IPA) is added to the SnO2 ink. The IPA addition reduced surface tension, enhancing wetting behavior, but increased SnO2 nanoparticles (NPs) aggregation. Interestingly, the fabricated ETL films with highly aggregated SnO2 NPs are smooth, in contrast to the rough layers obtained via the spin‐coating process, owing to the high shear rate. Herein, NP aggregation and surface morphology are explored using Brownian dynamics simulations under shear conditions. Consequently, when the particles are agglomerated, the PSCs with slot‐die coating exhibit higher power conversion efficiency compared to ETL spin‐coated PSCs. Therefore, IPA addition to SnO2 ink is preferred for the R2R slot‐die process by improving the wetting properties and forming smooth films. In this study, a framework is provided for obtaining high‐quality films using the slot‐die coating of ETL and promotes the commercialization of PSCs.
WSnO2 ink is studied as an electron transport material suitable for the roll‐to‐roll (R2R) perovskite solar cell (PSC) manufacturing system. By adding isopropyl alcohol to the SnO2 ink, the wetting property is improved but the SnO2 particles are aggregated. However, found out that the highly aggregated particles can form smooth films and highly efficient PSCs, unlike spin coating.
Ir is one of the most efficient oxygen evolution reaction (OER) catalysts; however, it is also one of the rarest and most expensive elements. Therefore, it is highly desirable to develop Ir catalysts ...with nanostructures that reduce Ir consumption by maximizing the surface‐to‐volume ratio without limiting the mass transport of reactants and products of reactions. Ir OER catalysts on a template that consisted of porous nanotubes (PNTs) based on Ni are fabricated. The Ir/Ni PNTs offer multiple benefits, including high catalytic performance (potential of 1.500 V vs. reversible hydrogen electrode (RHE) at an operating current density of 10 mA cm−2 and Tafel slope of 44.34 mV decade−1), minimal use of Ir (mass activity of 3273 A g−1 at 1.53 V vs RHE), and facile mass transport through the NT‐sidewall pores (stable operation for more than 10 h). The Ir/Ni PNTs are also applied to a tandem device, consisting of a Cu(In,Ga)Se2‐based photocathode and halide perovskite photovoltaic cell, for unassisted water splitting. A solar‐to‐hydrogen conversion efficiency that exceeded 10% is also demonstrated, which is nearly 1% point greater than when a planar Ir film is used as the anode instead of Ir/Ni PNTs.
A highly efficient oxygen evolution reaction catalyst consisting of a small amount of Ir decorated on a vertically aligned Ni porous nanotube template is presented. Thanks to its structural advantages, a potential of 1.500 V versus reversible hydrogen electrode (RHE) at 10 mA cm−2 and an ultrahigh mass activity of 3273 A g−1 at 1.53 V versus RHE are achieved.
Body decomposition is influenced by various factors, including temperature, rainfall, body mass, and the activities of insects and carnivores in areas where carcasses are abandoned. However, the ...specific impact of carcass mass on the decomposition rate remains unclear. Therefore, this study aimed to compare the effects of carcass mass on decomposition rate with controlled domestic environmental conditions. Carcasses were categorized as small and large. Decomposition patterns were evaluated using a visual scatterplot to illustrate the relationship between total body scores and log accumulated degree days (ADD). To quantitatively compare decomposition rates, a linear regression model was employed to analyze differences between the two carcass groups. Regardless of carcass mass, a similar oviposition period for flies (Diptera) was observed, and the external appearance of the carcass remained relatively stable until 1.8 logADD, marking the emergence of maggots. However, decomposition dramatically accelerated after reaching 1.8 logADD, coinciding with maggots hatching from eggs and their commencement of scavenging. In contrast to larger ones, the hastened decomposition of small carcasses can be attributed to the relatively substantial volume of Diptera larvae within the small carcasses, expediting colonization and utilization. Therefore, carcass mass should factor into postmortem interval estimation based on the degree of body decomposition.
The clinical utility of a type 2 diabetes mellitus (T2DM) polygenic risk score (PRS) in the East Asian population remains underexplored. We aimed to examine the potential prognostic value of a T2DM ...PRS and assess its viability as a clinical instrument. We first established a T2DM PRS for 5490 Korean individuals using East Asian Biobank data (269,487 samples). Subsequently, we assessed the predictive capability of this T2DM PRS in a prospective longitudinal study with baseline data and data from seven additional follow-ups. Our analysis showed that the T2DM PRS could predict the transition of glucose tolerance stages from normal glucose tolerance to prediabetes and from prediabetes to T2DM. Moreover, T2DM patients in the top-decile PRS group were more likely to be treated with insulin (hazard ratio = 1.69, p value = 2.31E-02) than were those in the remaining PRS groups. T2DM PRS values were significantly high in the severe diabetes subgroup, characterized by insulin resistance and
-cell dysfunction (p value = 0.0012). The prediction models with the T2DM PRS had significantly greater Harrel's C-indices than did corresponding models without it. By utilizing prospective longitudinal study data and extensive clinical risk factor information, our analysis provides valuable insights into the multifaceted clinical utility of the T2DM PRS.
Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of ...FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient.
This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD.
Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment.
A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI.
These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.
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•The symptoms of functional dyspepsia (FD) are chronic and prone to relapse.•Indigestion symptoms can coexist with anxiety and depression symptoms.•Herbal medicine is an alternative treatment for dyspepsia.•Siho-sogan-san improves discomforts and pain in upper abdomen in patients with FD.•Siho-sogan-san plus Western medicine increases motilin levels in patients with FD.
Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and ...non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population.
One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired CU, 330 with amnestic mild cognitive impairment aMCI, and 477 with AD dementia ADD) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs.
In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10
). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain.
The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.
Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. ...We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner.
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the
gene. Due to the disruption of bile acid synthesis leading to cholesterol and ...cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age.
A 60-year-old woman presented with behavioral and personality changes. She showed disinhibition, such as hoarding and becoming aggressive over trifles; compulsive behavior, such as closing doors; apathy; and dietary change. The patient showed a progressive cognitive decline and relatively sparing memory and visuospatial function. She had hyperlipidemia but no family history of neurodegenerative disorders. Initial fluid-attenuated inversion recovery (FLAIR) images showed a high signal in the periventricular area, and brain spectroscopy showed hypoperfusion in the frontal and temporal lobes, mimicking bvFTD. However, on physical examination, xanthomas were found on both the dorsum of the hands and the Achilles tendons. Hyperactive deep tendon reflexes in the bilateral biceps, brachioradialis, and knee and positive Chaddock signs on both sides were observed. Four years later, FLAIR images showed symmetrical high signals in the bilateral dentate nuclei of the cerebellum. Her serum cholestanol (12.4 mg/L; normal value ≤6.0) and 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) levels were elevated. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) of the
gene were found in trans-location. The patient was diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/day).
This report discusses the case of a middle-aged CTX patient with an unusual phenotype of bvFTD. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) was identified in the
gene. Early diagnosis is important because supplying chenodeoxycholic acid can prevent CTX progression.
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