Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila.

All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. Among resident gut microbiota, uracil production is absent in symbionts, allowing harmonious colonization without DUOX activation, whereas uracil release from opportunistic pathobionts provokes chronic inflammation. These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions.

Statistical considerations for some issues in clinical bridging studies evaluating companion diagnostic devices.

An in vitro diagnostic device (IVD) that is essential for the safe and effective use of a corresponding therapeutic product is commonly referred to as companion diagnostic device. Clinical trials using companion diagnostic devices (tests) together with therapies can yield the information necessary to address whether both products are safe and effective. A clinical trial ideally assesses safety and effectiveness of a therapy, where the clinical trial enrolls subjects based on the final market ready companion diagnostic test (CDx). However, such a requirement may be difficult to accomplish or impractical to achieve at the time of the clinical trial enrollment, due to unavailability of the CDx. Instead, clinical trial assay(s) (CTA), which are not the final marketable product, are often used in enrollment of patients in a clinical trial. When CTA is used for subject enrollment, a clinical bridging study provides a mechanism to bridge the clinical efficacy of the therapeutic product from CTA to CDx. This manuscript reviews some issues and challenges commonly associated with clinical bridging studies, including missing data, use of local tests for enrollment, prescreening before enrollment, and evaluation of CDx for low positive rate biomarkers, with particular focus on clinical trials using a binary endpoint and provide alternative statistical methodologies to assess effectiveness of CDx.

Anti-Inflammatory Effect of Chamaecyparis obtusa (Siebold & Zucc.) Endl. Leaf Essential Oil.

Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) belongs to the Cupressaceae family and is native to East Asian regions. Essential oils extracted from the leaves, bark, branches, and roots of C. obtusa have both aesthetic and medicinal properties and are thus widely used. However, detailed analyses of the active ingredients of C. obtusa extract are lacking. In this study, the sabinene content in the hydro-distillation of C. obtusa leaf essential oil (COD) was analyzed using GC-MS, and the anti-inflammatory effect of COD was compared with that of pure sabinene. Cell viability was evaluated by MTT assay, and nitric oxide (NO) production was measured using Griess reagent. Relative mRNA and protein levels were analyzed using RT-qPCR and western blot, and secreted cytokines were analyzed using a cytokine array kit. The results showed that both COD and sabinene inhibited the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 in lipopolysaccharide (LPS)-induced RAW 264.7 cells. COD and sabinene also reduced the production of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-27, IL-1 receptor antagonist (IL-1ra), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The anti-inflammatory mechanisms of COD and sabinene partially overlap, as COD was shown to inhibit MAPKs and the JAK/STAT axis, and sabinene inhibited MAPKs, thereby preventing LPS-induced macrophage activation.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Impact of personal protective equipment attached powered air-purifying respirator on nursing-skill performance and psychosocial stress of intensive care unit COVID-19 nurses: A cross-sectional study.

AIM: To investigate how personal protective equipment with an attached powered air-purifying respirator worn by intensive care unit nurses caring for COVID-19 patients in Korea impacts nursing-skill performance and psychosocial stress. DESIGN: A cross-sectional descriptive study was designed using purposive sampling. REVIEW METHODS: Online data collection was conducted from 3 March 2021-20 March 2021on 181 nurses who had worked for more than 1 month in COVID-19 critical care settings wearing personal protective equipment with a powered air-purifying respirator. A structured questionnaire was used to gather data on sociodemographic characteristics, attitude toward personal protective equipment, nursing-skill performance wearing personal protective equipment and psychosocial stress. DATA SOURCES: Data was sourced from structured questionnaire responses. RESULTS: Nursing skill performance decreased to 63.4%, compared with normal performance. Subjects' perceptions and attitudes related to PPE scored 3.56 out of 5; 44.7% of subjects reported severe psychosocial stress, which was significantly affected by attitude toward personal protective equipment usage, nursing performance, experience caring for COVID-19 patients and length of personal protective equipment usage per shift. CONCLUSION: Greater negative attitude toward usage of personal protective equipment with a powered air-purifying respirator, results in lower nursing-skill performance and higher the psychosocial stress of nurses responding to COVID-19 outbreaks. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: High negative attitude toward PPE and low nursing-skill performance due to PPE with an attached PAPR results in significant and debilitating psychosocial stress in ICU nurses responding to COVID-19 outbreaks. To respond effectively to future infectious disease outbreaks and improve nursing performance, minimising the inconvenience and restrictions experienced by nurses wearing personal protective equipment is critical. REPORTING METHOD: We adhered to relevant EQUATOR guidelines to report. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The relationship between psychological distress, depressive symptoms, emotional eating behaviors and the health-related quality of life of middle-aged korean females: a serial mediation model.

BACKGROUND: This study aimed to examine the effects of psychological distress, depressive symptoms, and emotional eating behaviors on the health-related quality of life of middle-aged Korean females. This study provides primary data for developing an intervention program to improve the health-related quality of life of middle-aged females. METHODS: Middle-aged females between 35 and 64 years old, from July 22 to August 10, 2021, were included in this study. The mediating effects of depressive symptoms and emotional eating behaviors on the relationship between psychological distress and health-related quality of life were investigated. A cross-sectional survey was conducted on 325 subjects. Researchers conducted questionnaires measuring psychological distress, depressive symptoms, emotional eating behavior, and health-related quality of life. RESULTS: The findings of this study demonstrated a correlation between the severity of a female's depressive symptoms and the degree of their psychological distress, indicating that severe depressive symptoms were associated with negative emotions, which increased emotional eating behaviors. Additionally, more severe depressive symptoms indicated a lower health-related quality of life. Higher psychological distress was associated with increased emotional eating behaviors and lower health-related quality of life. The total and direct effects of psychological distress on the health-related quality of life were statistically significant. CONCLUSIONS: In this study, psychological distress, depressive symptoms, and emotional eating behaviors affected the health-related quality of life of middle-aged Korean females. This study also confirmed that psychological distress had a direct effect on health-related quality of life. These findings serve as primary data for evidence-based intervention programs that alleviate emotional health problems, such as psychological distress and depressive symptoms in middle-aged females. Moreover, nurses can help develop effective treatment strategies to improve health-related quality of life by identifying and assessing potential symptoms of psychological distress, depressive symptoms, and emotional eating behaviors.

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN: Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS: The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION: Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

The relationship between changes in the korean fertility rate and policies to encourage fertility.

BACKGROUND: Korean government has established various policies to counter the low fertility rate since the mid-2000s, but it still has the lowest fertility rate among OECD member countries. This study investigated the relationship between changes in the Korean fertility rate and policies to encourage fertility. METHODS: This study utilized data of the total fertility rate of 250 local governments between 2014 and 2018, and a casebook of local government birth promotion policies. The dependent variable was fertility rate, and the independent variable was fertility promotion policy. Using SPSS 25.0 and M-plus 8.0 programs, descriptive statistical analysis and latent growth modeling were conducted. An unconditional quadratic function change model was selected as a final model of this study. RESULTS: The average of the initial fertility rate and the linear rate of change in the Korean fertility rate, and the rate of change of the quadratic function were all statistically significant, meaning that the fertility rate of decline increases over time. Also, the linear rate of change and the quadratic function change rate were significant, showing significant differences in the initial level and rate of change of the fertility rate between local governments. Among fertility policies, only the in-kind policy had a significant effect on the initial value of the fertility rate, meaning that the higher the number of in-kind policies, the higher the fertility rate. CONCLUSION: This study is crucial as it examined the changes in the fertility rate of Korean local governments as well as the policy factors affecting the fertility rate at a quantitative level.

How do ethically competent nurses behave in clinical nursing practice? A qualitative study.

AIM: This study explored how ethically competent nurses behave in clinical nursing practice. BACKGROUND: Nurses' ethical competency is crucial in nursing practice as it promotes patients' safety and quality of care. METHODS: Using a purposive sampling technique, 20 clinical nurses in South Korea were interviewed via an online video platform. The data were analysed using a thematic analysis based on phenomenological approach. RESULTS: The main theme found among the participating nurses' ethical competency was caring beyond egocentrism, with two subthemes: (1) patient-centred care based on compassion and (2) responsible behaviour based on nursing professionalism. Factors that enabled this included (1) reasonable work conditions, (2) interpersonal relationships, and (3) nurses' rich personal experiences. CONCLUSIONS: Nurses' ethical competency depends on how far they can move away from their own egocentrism and act for their clients' benefit, wherein an appropriate workload and warm human relationships with one's colleagues are essential. Nurses should thus receive education on ethics and professionalism and participate in volunteer and leisure activities that cultivate their degree of empathy. IMPLICATION FOR NURSING MANAGEMENT: Nursing leaders and managers should understand nurses' ethical competency and its enabling factors to devise effective strategies to promote it.

Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in drosophila gut.

All metazoan guts are in permanent contact with the microbial realm. However, understanding of the exact mechanisms by which the strength of gut immune responses is regulated to achieve gut-microbe mutualism is far from complete. Here we identify a signaling network composed of complex positive and negative mechanisms that controlled the expression and activity of dual oxidase (DUOX), which 'fine tuned' the production of microbicidal reactive oxygen species depending on whether the gut encountered infectious or commensal microbes. Genetic analyses demonstrated that negative and positive regulation of DUOX was required for normal host survival in response to colonization with commensal and infectious microbes, respectively. Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes.

Enhanced interfacial reaction of silicon carbide fillers onto the metal substrate in carbon nanotube paste for reliable field electron emitters.

Adhesion of carbon nanotube (CNT) onto a cathode substrate is very crucial for field electron emitters that are operating under high electric fields. As a supporting precursor of CNT field emitters, we adopted silicon carbide (SiC) nano-particle fillers with Ni particles and then enhanced interfacial reactions onto Kovar-alloy substrates through the optimized wet pulverization process of SiC aggregates for reliable field electron emitters. As-purchased SiC aggregates were efficiently pulverized from 20 to less than 1 micro-meter in a median value (D50). CNT pastes for field emitters were distinctively formulated by a mixing process of the pulverized SiC aggregates and pre-dispersed CNTs. X-ray photoelectron spectroscopy studies showed that the optimally pulverized SiC-CNT paste-emitter had a stronger Si 2p3/2 signal in the Ni2Si phase than the as-purchased one. The Si 2p3/2 signal would represent interfacial reaction of the SiC nano-particle onto Ni from the CNT paste and the Kovar substrate, forming the supporting layer for CNT emitters. The optimal paste-emitter even in a vacuum-sealed tube exhibited a highly reliable field emission current with a high current density of 100 mA cm-2 for over 50 h along with good reproducibility. The enhanced interfacial reaction of SiC filler onto the metal substrates could lead to highly reliable field electron emitters for vacuum electronic devices.

Cholesterol Granuloma of the Maxillary Sinus Misdiagnosed as Nasal Polyp or Mucocele: Four Cases.

ABSTRACT: Cholesterol granuloma is commonly found in the mastoid air cells but is rare in the paranasal sinuses. The most commonly affected sinuses are the frontal sinus, followed by the maxillary sinus. Cholesterol granuloma can be difficult to diagnose because clinical manifestations and radiologic findings are similar to those of other sinonasal disorders. The authors observed 4 cases of cholesterol granuloma that were preoperatively suspected to be nasal polyps or mucoceles. Here, the authors report on their clinical presentation and their successful treatment using the endoscopic sinus approach. These cases expand the current literature on cholesterol granuloma in the paranasal sinuses.

Discontinuation rates of warfarin versus direct acting oral anticoagulants in US clinical practice: Results from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II).

While oral anticoagulation is a cornerstone of stroke prevention therapy in atrial fibrillation (AF), few studies have evaluated comparative discontinuation rates in clinical practice. The objective of this study is to evaluate discontinuation rates among patients on warfarin and direct oral anticoagulants (DOACs) in clinical practice. METHODS: The ORBIT-AF II Registry enrolled 10,005 total AF patients with a CHA2DS2VASc score of ≥2 on warfarin or DOACs from 235 clinical practices across the US from February 13, 2013 and July 12, 2017. Descriptive statistics and multivariable Cox regression modeling were used to describe baseline characteristics and predictors of discontinuation. Unadjusted and adjusted discontinuation rates and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and propensity score adjustment, respectively. RESULTS: At baseline, 16.4% (N = 1642/10,005) were treated with warfarin, 83.6% (N = 8363/10,005) with DOACs and 1498/10,005 patients (15.0%) discontinued therapy [warfarin = 236/1642 (14.4%) vs DOACs = 1262/8363 (15.1%)]. At 6 and 12 months respectively, among 7049 patients with a new diagnosis of AF within 6 months, adjusted discontinuation rates for warfarin versus DOACs were as follows: [6 months: 7.9%, 95%CI (6.8%-9.0%) vs 9.6% (8.4%-10.7%), P = .16]; [12 months: 12.7% (11.0%-14.3%) vs 15.3% (13.6%-16.9%), P = .02)]. Patients who discontinued therapy with warfarin or DOACs had higher risk of adverse clinical outcomes including: all-cause mortality and cardiovascular death (CV) than those who continued treatment. CONCLUSION: In a community based AF cohort, adjusted rates of discontinuation at 12-months were higher in DOAC-treated versus VKA-treated patients. Discontinuation of oral anticoagulation was associated with increased absolute risk of all-cause mortality and CV death. CLINICAL TRIAL REGISTRATION: URL:https://clinicaltrials.gov. Unique Identifier: NCT01701817.

Kß X-ray Emission Spectroscopy as a Probe of Cu(I) Sites: Application to the Cu(I) Site in Preprocessed Galactose Oxidase.

Cu(I) active sites in metalloproteins are involved in O2 activation, but their O2 reactivity is difficult to study due to the Cu(I) d10 closed shell which precludes the use of conventional spectroscopic methods. Kß X-ray emission spectroscopy (XES) is a promising technique for investigating Cu(I) sites as it detects photons emitted by electronic transitions from occupied orbitals. Here, we demonstrate the utility of Kß XES in probing Cu(I) sites in model complexes and a metalloprotein. Using Cu(I)Cl, emission features from double-ionization (DI) states are identified using varying incident X-ray photon energies, and a reasonable method to correct the data to remove DI contributions is presented. Kß XES spectra of Cu(I) model complexes, having biologically relevant N/S ligands and different coordination numbers, are compared and analyzed, with the aid of density functional theory (DFT) calculations, to evaluate the sensitivity of the spectral features to the ligand environment. While the low-energy Kß2,5 emission feature reflects the ionization energy of ligand np valence orbitals, the high-energy Kß2,5 emission feature corresponds to transitions from molecular orbitals (MOs) having mainly Cu 3d character with the intensities determined by ligand-mediated d-p mixing. A Kß XES spectrum of the Cu(I) site in preprocessed galactose oxidase (GOpre) supports the 1Tyr/2His structural model that was determined by our previous X-ray absorption spectroscopy and DFT study. The high-energy Kß2,5 emission feature in the Cu(I)-GOpre data has information about the MO containing mostly Cu 3dx2-y2 character that is the frontier molecular orbital (FMO) for O2 activation, which shows the potential of Kß XES in probing the Cu(I) FMO associated with small-molecule activation in metalloproteins.

Lower Glucose Level Associated With Increased Risk for Post-Dural Puncture Headache.

OBJECTIVE AND BACKGROUND: Post-dural puncture headache is the most common significant adverse event following lumbar puncture. In this study, we investigated the possible systemic factors associated with risk for post-dural puncture headache (PDPH). METHODS: We performed a retrospective cohort study in 969 patients who underwent diagnostic lumbar puncture following a standardized protocol. We compared the clinical and laboratory profiles of the post-dural puncture headache group and non-headache group. We also identified independent factors associated with the incidence of post-dural puncture headache. RESULTS: A total of 48 patients (5%) reported headache; 12 of these patients (25%) received a therapeutic epidural blood patch and the remaining 36 patients improved with conservative treatment. After adjusting for other variables that could be related to PDPH, we found that the development of post lumbar puncture headache was independently associated with age (OR: 0.97, 95% CI: 0.95-0.99, P = .001) and serum glucose levels (OR: 0.98, 95% CI: 0.97-0.99, P = .008).When the patients were classified by age, serum glucose levels were persistently lower in patients with PDPH vs those patients without PDPH in all age groups, with more clearly significant differences observed in the elderly (age <30 years, 103.4 mg/dL vs 106.3 mg/dL, P = .716; >60 years, 111.8 mg/dL vs 137.3 mg/dL, P = .023). CONCLUSIONS: Low glucose levels were inversely associated with risk for post-dural puncture headache. Patients with low serum glucose should be carefully monitored for headache after lumbar puncture.

Delayed Traumatic Pseudoaneurysm of the Dorsal Nasal Artery.

A pseudoaneurysm is an uncommon pathology arising from any artery in the human body. It typically presents as a pulsatile swelling in contact with a blood vessel. Of pseudoaneurysms of the head and neck region, the most common site is the superficial temporal artery while that of the dorsal nasal artery is extremely rare. A pseudoaneurysm can be routinely diagnosed by its clinical features and confirmed by radiologic evaluation. The authors report a case of pseudoaneurysm of the dorsal nasal artery, which was misdiagnosed as a hematoma owing to its non-pulsatile nature during initial presentation.

Comparing the learning effects of debriefing modalities for the care of premature infants.

The aim of this study was to compare the learning effects of debriefing methods used in the simulation of prematurity care by measuring: (i) academic self-efficacy; (ii) confidence in performance; (iii) self-assessed communication skills; and (iv) satisfaction. We employed a quasi-experimental design with three experimental groups that experienced instructor-directed, self-directed, and video-assisted, self-directed debriefing, respectively. Participants were 146 senior nursing students from three nursing schools. To compare learning effects, the same developed scenario for prematurity care was applied to all three groups. Significant differences were observed in the mean scores for the study variables among the three groups. The post-hoc analysis showed that the video-assisted, self-directed debriefing group obtained the highest mean score difference for confidence in performance, self-assessed communication skills, and satisfaction with the debriefing method. Thus, video-assisted, self-directed debriefing could be the most effective debriefing method for students.

Perverted Downward Corrective Saccades During Horizontal Head Impulses in Chiari Malformation.

The mechanism of perverted vertical responses during horizontal head impulse tests (HITs) requires further elucidation. A 47-year-old woman with a Chiari malformation showed alternating skew deviation, downbeat nystagmus with an increasing slow phase velocity, impaired smooth pursuit, and upward ocular deviation during horizontal HITs and corrective downward saccades in the presence of normal bithermal caloric tests and intact tilt suppressions of the post-rotatory nystagmus. These findings suggest dysfunction of the inferior cerebellum including the tonsil, nodulus, and uvula. We propose that disruption of signals from the medial part of the vestibulocerebellum, which normally inhibits the lateral and anterior canal pathways, may elicit an upward misdirection of the eye velocity during rapid horizontal head rotation. Otherwise, the Chiari malformation may have directly affected the brainstem structures involved in the direction matrix of the vestibulo-ocular reflex.

Cognitive impairment is associated with elevated serum homocysteine levels among older adults.

PURPOSE: The aim of this study was to examine the associations between the risk of cognitive impairment and the serum levels of folate, vitamin B12, and homocysteine (Hcy). METHODS: Subjects were persons aged 60-79 years who participated in the Yangpyeong Cohort study between 2011 and 2012. Cognitive impairment and normal subjects consisted of 100 pairs of old adults matched by age, sex, and education levels. Cognitive function was evaluated with the Korean version of the Mini-Mental State Examination for Dementia Screening (MMSE-DS). Pearson's partial correlation coefficients and conditional multiple logistic regression analysis were applied to determine the associations between cognitive function and the serum levels of folate, vitamin B12, and Hcy. RESULTS: Compared with the matched normal group, the cognitive impairment group had higher proportions of folate deficiency (< 3 ng/mL) and hyperhomocysteinemia (≥ 15 µmol/L). Serum Hcy concentrations were inversely associated with serum folate (r = - 0.234, p = 0.001) and MMSE-DS score (r = - 0.150, p = 0.037) after adjusting for age, sex, and education. The high Hcy group showed a higher prevalence of cognitive impairment (4th vs. 1st quartile, OR 3.30, 95% CI 1.12-9.72, p for trend = 0.014) after adjusting for exercise. CONCLUSIONS: The present findings suggest a putative protective role of high serum folate and normal Hcy against cognitive impairment among older adults.