Oxygen-Glucose Deprivation Increases NR4A1 Expression and Promotes Its Extranuclear Translocation in Mouse Astrocytes.

Hypoxic-ischemic brain injury induces metabolic dysfunction that ultimately leads to neuronal cell death. Astrocytes, a type of glial cell, play a key role in brain metabolism; however, their response to hypoxic-ischemic brain injury is not fully understood. Microglia were removed from murine primary mixed glial cultures to enrich astrocytes. Next, we explored genes whose expression is altered following oxygen-glucose deprivation using a microarray. Microarray analysis revealed that the expression of Nr4a1 and Nr4a3 is markedly increased in astrocyte-enriched cultures after 15 h of oxygen-glucose deprivation. The expression of both Nr4a1 and Nr4a3 was regulated by HIF-1α. At the protein level, NR4A1 was translocated from the nucleus to the cytoplasm following oxygen-glucose deprivation and co-localized with mitochondria in apoptotic cells; however, its localization was restored to the nucleus after reoxygenation. Oxygen-glucose deprivation causes an increase in NR4A1 mRNA in astrocytes as well as its nuclear to cytoplasmic transfer. Furthermore, reoxygenation enhances NR4A1 transcription and promotes its nuclear translocation.

Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Fatty Liver-Related Indices in a Japanese Population.

Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. It is uncertain how indices that predict fatty liver are associated with MAFLD in Japanese. Methods: Among subjects who underwent a health examination at our hospital, 1257 (men: 787, women: 474) subjects participated in fatty liver evaluation of the fatty liver index (FLI) and fatty liver predicting index (FLPI) were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using receiver operating characteristic curve analysis. The association between FLI, FLPI, and MAFLD was investigated using multiple logistic regression analysis. Results: FLI and FLPI had good discriminatory ability for identifying MAFLD in both men and women, with specific cutoff values. Both FLI and FLPI were significantly higher in subjects with MAFLD, and the odds of MAFLD were higher among those in the highest tertile relative to the lowest tertile in both men and women. FLI and FLPI were higher in subjects who met the criteria for both MAFLD and metabolic syndrome (MetS) compared to those who had MAFLD or MetS alone, and most of the examined parameters in subjects with both conditions indicated a high metabolic risk profile. Conclusions: The study suggests that FLI and FLPI are valuable tools for predicting MAFLD and are similarly correlated with the disease. Furthermore, the highest values of these indices were observed in subjects who met the criteria for both MAFLD and MetS, emphasizing the importance of considering both conditions when assessing metabolic risk.

Relationship Between Pancreatic Cysts and Cysts in Other Organs in Patients Undergoing Medical Checkup.

OBJECTIVE: We investigated the association between pancreatic cysts and cystic diseases of other organs using abdominal ultrasonography in patients undergoing medical checkup. METHODS: Between April 2021 and March 2022, 4496 patients had a comprehensive medical checkup at our hospital, which included abdominal ultrasonography. RESULTS: Among 4496 patients, 172 (3.8%), 1592 (35.4%), and 1425 (31.7%) had pancreatic, liver, and renal cysts, respectively. Multivariate analysis revealed that the significant factors were female sex and the presence of renal cysts. CONCLUSION: Pancreatic cysts were more common in females. Renal cysts are relatively commonly detected on abdominal ultrasonography. If renal cysts are detected, comorbidities with pancreatic cysts should be considered.

Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Insulin Resistance-Related Indices in the Japanese Population.

Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), which is based on evidence of hepatic steatosis and any of the following three conditions: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation, has been proposed. It is uncertain how indices that predict insulin resistance (IR) are associated with MAFLD. Methods: Among subjects who had undergone health examinations at our hospital, 1,257 (787 men and 474 women) who underwent fatty liver evaluation, were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using a receiver operating characteristic curve analysis. The associations between the homeostasis model assessment-IR (HOMA-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride-glucose (TyG) index, and MAFLD were investigated using multiple logistic regression analysis. Results: The mean age and body mass index of MAFLD subjects were 58.1 years and 26.0 kg/m2 in men and 63.0 years and 26.1 kg/m2 in women, respectively. The cutoff values of HOMA-IR, TG/HDL-C ratio, and TyG index in men and women were 1.40 (area under the curve [AUC]: 0.81) and 1.90 (AUC: 0.88); 1.56 (AUC: 0.75) and 1.06 (AUC: 0.78); and 8.62 (AUC: 0.75) and 8.45 (AUC: 0.80), respectively. All indices were significantly higher in both men and women with MAFLD. In the multivariate models, the odds of MAFLD were higher among both men and women in the highest tertile than those in the lowest tertile. When subjects were divided by sex, presence of MAFLD, and alanine aminotransferase (ALT) values, all indices were significantly higher in both men and women with high ALT levels who were diagnosed with MAFLD. Conclusion: IR strongly correlated with MAFLD, particularly in subjects with high ALT levels.

Lipocalin-2 production by astrocytes in response to high concentrations of glutamate.

AIMS: Glutamate-induced excitotoxicity is mainly mediated by neuronal NMDA receptors; however, it is unclear how astrocytes are involved in this phenomenon. This study aimed to explore the effects of excess glutamate on astrocytes both in vitro and in vivo. METHODS: We used astrocyte-enriched cultures (AECs), in which microglia were removed from mixed glial cultures, to investigate the effects of extracellular glutamate on these cells by microarray, quantitative PCR, ELISA, and immunostaining. We also examined the production of lipocalin-2 (Lcn2) by immunohistochemistry in the brains of mice after status epilepticus induced by pilocarpine and by ELISA in the cerebrospinal fluid (CSF) of patients characterised by status epilepticus. RESULTS: Microarray analysis identified Lcn2 as a factor upregulated in AECs by excess glutamate; glutamate addition increased Lcn2 in the cytoplasm of astrocytes and AECs released Lcn2 in a concentration-dependent manner. Lcn2 production was reduced by chemical inhibition of metabotropic glutamate receptor or siRNA knockdown of metabotropic glutamate receptor 3. Furthermore, Lcn2 was increased in the astrocytes of a status epilepticus mouse model and in the CSF of human patients. CONCLUSION: These results indicate that astrocytes stimulate Lcn2 production via metabotropic glutamate receptor 3 in response to high concentrations of glutamate.

ATP1A3-related early childhood onset developmental and epileptic encephalopathy responding to corpus callosotomy: A case report.

BACKGROUND: VariousATP1A3variant-related diseases have been reported, including alternating hemiplegia of childhood; rapid-onset dystonia-parkinsonism; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. Moreover, a few cases of developmental and epileptic encephalopathy (DEE) with none of these symptoms have been reported. Here, we present a case of DEE with early childhood onset caused by anATP1A3variant that was effectively treated using corpus callosotomy (CC). CASE PRESENTATION: At the age of 3 years, the patient developed epileptic spasms, complicated by generalized and focal aware tonic seizures. Based on the seizure type and electroencephalographic findings showing a generalized spike and waves as well as interictal left frontal-dominant spikes, combined generalized and focal epilepsy was diagnosed. Whole-exome sequencing revealed a de novo missense variant inATP1A3(c.2888G > A, p.Gly963Asp), which was classified as likely pathogenic. At the age of 5 years, CC for generalized tonic seizures resulted in seizure-freedom using two anti-seizure medications. Subsequently, the patient achieved better verbal development. DISCUSSION AND CONCLUSION: Early childhood onset DEE has not been reported in patients with ATP1A3 variants. Moreover, CC was extremely effective in our case. Although more research is needed to determine the etiology of epilepsy caused by theATP1A3 variant, the clinical course of DEE caused by the ATP1A3 variant is diverse and its prognosis may be improved in early childhood onset cases using aggressive control of epilepsy, such as CC.

Association of High-Density Lipoprotein Subclasses Levels with Sleep Duration and Other Lifestyles in Middle-Aged and Elderly Women: Cross-Sectional Study.

Objective: We aimed at investigating the association of high-density lipoprotein subclasses (HDL2-C and HDL3-C) levels with sleep duration, in comparison to other lifestyles in middle-aged and elderly women. Materials and Methods: A total of 69 women aged older than 40 who underwent "Anti-aging Health Checkups" were enrolled in the study. The analyses were conducted for all the subjects using personal data regarding clinical characteristics and lifestyle. Sleep duration was categorized into two groups of less than or more than 6 hrs. First, an analysis was performed to assess the correlation of two major HDL subclasses with various factors. Next, a multiple regression analysis was conducted to identify the association for each HDL2-C and HDL3-C with lifestyles such as sleep duration, daily breakfast, dinner time, habitual exercise, and drinking. Moreover, we examined the associations between HDL2-C and sleep duration combined with other lifestyle factors such as dinner time, daily breakfast, habitual exercise, and drinking. Results: In comparison to lifestyles, sleep duration had a strong association with only HDL2-C after adjustment for confounders. The "less 6 hrs sleep" group in combination with the "no exercise habit" or the "routine drinking habit" significantly decreased HDL2-C levels more than the assumed reference group. Regarding breakfast, there is a significant association between the "less than 6 hrs sleep with no daily breakfast" and the "more than 6 hrs sleep with daily breakfast." Conclusion: The results of this study may suggest that sufficient sleep might be significant for maintaining appropriate HDL2-C levels in middle-aged and elderly women under the condition that lifestyle might change during the ongoing COVID-19 pandemic.

Analysis of Comorbidity for Patients with Pancreatic Cysts in Medical Checkup Screening.

OBJECTIVES: We investigated whether there is a difference in the frequency of comorbidity between patients with pancreatic cysts and those without pancreatic cysts by abdominal ultrasonography in patients undergoing medical checkup screening. METHODS: The subjects were 6,627 patients who underwent abdominal ultrasonography at Tokai University Hachioji Hospital's Health Screening Center between April 2019 and March 2020. RESULTS: Of the total 6,627 patients, 158 (2.4%) were pointed out to have pancreatic cysts. Multivariate analysis revealed that the related factors were female sex, age 60 years or older, diabetes, lung cancer, and uterine/ovarian cancer. CONCLUSION: Unlike pancreatic cancer, pancreatic cysts are more common in women. In addition, it is known that pancreatic cysts have a high complication rate of cancers of other organs; lung cancer and uterine/ovarian cancer were identified as high-risk factors in this study.

Estimated Elovl6 and delta-5 desaturase activities might represent potential markers for insulin resistance in Japanese adults.

Purpose: Results from a recent study indicated that lower stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with metabolically unhealthy obesity. However, this has not been extensively studied in the Japanese population. Methods: We recruited 291 Japanese subjects with serum free fatty acid profiles undergoing health examinations. Whole serum desaturase activity was estimated as the product: precursor ratio -SA/PA ratio for elongation of long-chain fatty acid family member 6 (Elovl6) and AA/DGLA for delta-5 desaturase (D5D). The determinants of Elovl6 and D5D activity were investigated using multiple regression analyses. Results: The Elovl6 and D5D activities exhibited a negative correlation with the logmatic-transformed TG/HDL-C ratio and TyG index. Multiple regression analyses revealed that the TG/HDL-C ratio and TyG index were negatively associated with Elovl6 and D5D activities. Most atherogenic markers were worse in the low Elovl6 or D5D activity group than in the high Elovl6 or D5D activity group. When study subjects were further stratified by TG levels, most atherogenic markers were the worst in the highest TG group in either the lowest Elovl6 or lowest D5D activity groups. Conclusion: The estimated Elovl6 and D5D activities might be useful markers of insulin resistance in Japanese subjects.

Oleic acid to stearic acid ratio might be a potential marker for insulin resistance in non-obese Japanese.

Results from a recent study indicate that a higher level of oleic acid/stearic acid ratio was associated with metabolically unhealthy obesity. This was further validated in cross-sectional and interventional studies; however, this was not extensively studied in a non-obese population. We recruited 260 Japanese subjects with serum free fatty acid profiles undergoing anti-aging health examinations. The determinants for oleic acid/stearic acid ratio were investigated using multiple regression analyses. To compare different markers, the subjects were classified based on oleic acid/stearic acid ratio and the combination of oleic acid/stearic acid ratio and triglyceride levels. The oleic acid/stearic acid ratio exhibited a positive correlation with the logmatic transformed triglyceride/high-density lipoprotein cholesterol ratio and the fasting triglycerides-glucose index, both of which were used as markers for insulin resistance. Multiple regression analyses revealed that the triglyceride/high-density lipoprotein cholesterol ratio and fasting triglyceride-glucose index were positively associated with the oleic acid/stearic acid ratio. Most markers were the worst in the highest triglyceride group in both oleic acid/stearic acid groups. In addition, most markers were worse in high oleic acid/stearic acid ratio group than low group. In conclusion, oleic acid/stearic acid ratio might be a useful marker for insulin resistance in non-obese Japanese subjects.

Evaluation of the Diagnostic Criteria for Anti-NMDA Receptor Encephalitis in Japanese Children.

OBJECTIVE: To evaluate the validity of the 2016 clinical diagnostic criteria proposed for probable anti-NMDA receptor (NMDAR) encephalitis in children, we tested the criteria in a Japanese pediatric cohort. METHODS: We retrospectively reviewed clinical information of patients with neurologic symptoms whose CSF was analyzed for NMDAR antibodies (NMDAR-Abs) in our laboratory from January 1, 2015, to March 31, 2019. RESULTS: Overall, 137 cases were included. Of the 41 cases diagnosed as probable anti-NMDAR encephalitis (criteria-positive) according to the 2016 criteria, 13 were positive and 28 were negative for anti-NMDAR-Abs. Of the 96 criteria-negative cases, 3 were positive and 93 were negative for anti-NMDAR-Abs. The sensitivity of the criteria was 81.2%, specificity was 76.9%, positive predictive value (PPV) was 31.7%, and negative predictive value was 96.9%. Compared with the true-positive group, the false-positive group contained more male than female patients (male:female, 4:9 in the true-positive vs 19:9 in the false-positive group, p = 0.0425). The majority of the cases with false-positive diagnoses were associated with neurologic autoimmunity. CONCLUSION: The clinical diagnostic criteria are reliable for deciding to start immunomodulatory therapy in the criteria-positive cases. Low PPV may be caused by a lower prevalence of NMDAR encephalitis or lower level of suspicion for encephalitis in the pediatric population. Physicians should therefore continue differential diagnosis, focusing especially on other forms of encephalitis. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the proposed diagnostic criteria for anti-NMDAR encephalitis in children has a sensitivity of 81.2% and a specificity of 76.9%.

Usefulness of Triglyceride to High-Density Lipoprotein Ratio and Alanine Aminotransferase for Predicting Insulin Resistance and Metabolic Syndrome in the Japanese Population.

Background: Considering the fact that both alanine aminotransferase (ALT) and the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio are useful markers for cardiovascular disease, insulin resistance (IR), and metabolic syndrome (MetS), the possible association of ALT and TG/HDL-C ratio is conceivable, but the association is not well studied. Moreover, assessment of IR and MetS by a combination lipid and liver biomarkers has rarely been carried out. Methods: A total of 11,808 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between TG/HDL-C ratio and ALT level was investigated using correlation and multiple linear regression analyses. Homeostasis model assessment of insulin resistance (HOMA-IR) and the number of MetS components were evaluated after subjects were stratified by TG/HDL-C ratio and ALT levels. Results: Correlation analysis revealed that ALT levels were positively associated with TG/HDL-C ratio. Moreover, multiple linear regression analysis revealed that TG/HDL-C ratio was positively associated with ALT levels, and the association was attenuated but persisted in both men and women after additional adjustment for visceral adiposity (body mass index, waist circumference, or fatty liver) and IR (HOMA-IR). HOMA-IR and MetS component number increased with either ALT or TG/HDL-C ratio in both men and women. HOMA-IR and MetS component number were particularly high (HOMA-IR: men 2.82, women 3.22, MetS component number: men 2.6, women 2.1) in subjects with highest ALT level and TG/HDL-C ratio. Conclusions: TG/HDL-C ratio showed a positive association with ALT levels in both sexes. Assessments of IR and MetS can become more precise by evaluating TG/HDL-C ratio and ALT, simultaneously.

The Association between the Triglyceride to High-density Lipoprotein Cholesterol Ratio and Low-density Lipoprotein Subclasses.

Objective The triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is related to insulin resistance (IR). However, information about whether or not the TG/HDL-C ratio is associated with low-density lipoprotein (LDL) subclasses in the Japanese population is limited. Methods In total, 1,068 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between the TG/HDL-C ratio and LDL subclasses was investigated using correlation, multiple regression, and receiver operating characteristic analyses. Results A correlation analysis revealed that both malondialdehyde-modified low-density lipoprotein (MDA-LDL) and small dense low-density lipoprotein cholesterol (sdLDL-C) were positively associated with the TG/HDL-C ratio. Furthermore, a multiple linear regression analysis revealed that the TG/HDL-C ratio was positively associated with MDA-LDL and sdLDL-C in both men and women. The multiple logistic regression analysis also revealed that the TG/HDL-C ratio was positively associated with the upper tertile of MDA-LDL and sdLDL-C in men and women. The LDL-C levels increased with the increasing TG/HDL-C ratio. The MDA-LDL and sdLDL-C are known to be positively associated with LDL-C. However, within the same LDL-C range, both MDA-LDL and sdLDL-C levels increased with the TG/HDL-C ratio, except for MDA-LDL levels in the LDL-C <112 mg/dL group in women. These results further supported the notion that the TG/HDL-C ratio was positively associated with the MDA-LDL and sdLDL-C levels, especially in the higher LDL-C range, in both men and women. The optimal cut-off points of the TG/HDL-C ratio for the upper tertile of MDA-LDL and sdLDL-C were 1.85 and 2.03 in men and 0.88 and 1.30 in women, respectively. Conclusion The TG/HDL-C ratio is positively associated with MDA-LDL and sdLDL-C in Japanese subjects. The relationship was particularly notable in subjects with high LDL-C levels.

Associations Between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Metabolic Syndrome, Insulin Resistance, and Lifestyle Habits in Healthy Japanese.

Background: The triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is related to insulin resistance (IR). However, little information is available on whether TG/HDL-C is associated with IR and components of metabolic syndrome (MetS) and how lifestyle habits affect TG/HDL-C in the healthy Japanese population. Methods: In total, 1068 Japanese subjects who had undergone an annual health examination and who were not receiving medication were recruited. Determinants for TG/HDL-C ratio were investigated using multiple regression analyses. The subjects were divided into three groups by lifestyle habits (i.e., smoking, exercise, and physical activity), homeostasis model assessment of IR (HOMA-IR), and fasting plasma glucose, four groups by alcohol intake, and five groups by numbers of MetS components to compare TG/HDL-C values. All analyses were done separately by sex. Results: Multiple regression analyses revealed that waist circumference and smoking were positively associated with TG/HDL-C in both men and women, whereas physical activity was negatively associated with TG/HDL-C ratio in women. TG/HDL-C increased with increasing number of MetS in both men and women. TG/HDL-C increased as HOMA-IR increased in both men and women, when subjects were stratified according to HOMA-IR. TG/HDL-C values were lower in both men and women who exercised regularly, had high physical activity, or were nonsmokers. Independent of exercise and physical activity, TG/HDL-C was higher in smokers than in nonsmokers for both men and women. The relationship between TG/HDL-C and alcohol intake was not statistically significant in both men and women. Conclusions: The TG/HDL-C ratio is associated with IR, components of MetS, exercise, physical activity, and smoking, but not alcohol intake, in healthy Japanese subjects.

Factors associated with sleep duration among pupils.

BACKGROUND: Sleep shortage has been pervasive among pupils. METHODS: Multiple regression analysis was used to analyze 2,722 questionnaires obtained from grade 5 to 12 pupils, to determine factors associated with sleep duration. RESULTS: Significant regression formulae for sleep duration were obtained for all school types: adjusted R2 / P value were 0.14/<0.001 for elementary school; 0.11/<0.001 for junior high school; 0.06/<0.001 for high school. Longer after-school activities (standardized regression coefficient/ P value were -0.22/<0.001 for elementary school; -0.10/<0.01 for junior high school; -0.18/<0.001 for high school) and more sleepiness (-0.09/<0.001 for elementary school; -0.07/<0.05 for junior high school; -0.07/<0.05 for high school) were significantly associated with reduced sleep duration for all school types. In both elementary and junior high schools, the higher grade (-0.53/<0.001 for elementary school; -0.10/<0.01 for junior high school), and longer weekday screen time (-0.15/<0.001 for elementary school; -0.19/<0.001 for junior high school) were also significantly associated with sleep loss. In elementary school, irregular dinner (-0.07/<0.05), breakfast skipping (-0.11/<0.001), longer weekend screen time (-0.09/<0.05) and better self-reported academic performance (0.07/<0.05) also revealed significant associations with sleep loss. In high school, reduction of sleep duration was also significantly associated with higher standardized body mass index (-0.08/<0.05). CONCLUSIONS: Excessive after-school activity might be considered in association with pupils' sleep reduction.

Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor.

The NLRP3 inflammasome is a molecular complex that translates signals from pathogens and tissue damage into inflammatory responses, and plays crucial roles in numerous neurological diseases. Activation of the NLRP3 inflammasome leads to caspase-1 dependent cleavage of pro-IL-1ß to form mature IL-1ß. By acting on the P2X7 purinergic receptor, extracellular ATP is one of the major stimuli that activates the NLRP3 inflammasome. Although microglia express multiple purinergic receptors, their roles in inflammasome-mediated inflammation are largely unknown. We studied the role of the P2Y12 receptor, a metabotropic P2Y receptor enriched in microglia, on inflammation in vitro. Inhibition of the microglial P2Y12 receptor by PSB0739 or siRNA knockdown suppressed IL-1ß release. P2Y12 receptor-deficient microglia displayed markedly attenuated IL-1ß mRNA expression and release. P2Y12 receptor blockade also suppressed IL-6 production. Both IL-1ß and IL-6 responses were augmented by extracellular ADP or ADP-ßS and were abrogated by PSB0739. Mechanistically, ADP-ßS potentiated NF-κB activation. In addition, ADP altered mitochondrial membrane potential in combination with ATP and increased the number of caspase-1 positive cells through the P2Y12 receptor. These results elucidate a novel inflammatory mechanism by which extracellular ADP acts on the P2Y12 receptor to activate NF-κB and the NLRP3 inflammasome to enhance microglial inflammation.

Long-Term Evaluation of Low-Dose Betamethasone for Ataxia Telangiectasia.

BACKGROUND: Ataxia telangiectasia is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Quality of life is severely impaired by neurological symptoms. However, curative options for the neurological symptoms are limited. Recent studies have demonstrated short-term improvement in neurological symptoms with betamethasone therapy. However, the long-term and adverse effects of betamethasone are unclear. The aim of this study was to evaluate the long-term effects, benefits, and adverse effects of low-dose betamethasone in ataxia telangiectasia. METHODS: Six patients with ataxia telangiectasia received betamethasone at 0.02 mg/kg/day for two years. After cessation of betamethasone, the patients were observed for two additional years. Neurological assessments were performed, and adverse effects were monitored every three months throughout the four-year study period. RESULTS: Transient improvement of neurological symptom was observed in five of the six patients. However, after two years betamethasone treatment, only one of the six patients showed a slight improvement in the neurological score, one patient showed no change, and the neurological scores of the remaining four patients deteriorated. After the cessation of betamethasone treatment, neurological symptoms worsened in all patients. As an adverse effect of betamethasone, transient adrenal dysfunction was observed in all cases. CONCLUSIONS: Although these findings are in agreement with previous studies suggesting that short-term betamethasone treatment transiently benefits patients with ataxia telangiectasia, the long-term benefits and risks should be carefully considered.

The Association Between the Serum Uric Acid to Creatinine Ratio and Metabolic Syndrome, Liver Function, and Alcohol Intake in Healthy Japanese Subjects.

Background: In patients with diabetes mellitus, the serum uric acid (UA) to creatinine (Cr) ratio (UA/Cr) has been reported to be associated with a higher risk of metabolic syndrome (MetS). In healthy subjects, however, this relationship and a possible association with pathological conditions remain undetermined. Methods: In total, 9104 Japanese subjects who had undergone an annual health examination and who were not receiving medication were divided into four groups based on UA/Cr values, and various markers were compared. Results: Anthropometric measures, blood pressure, glycemic state, lipids [except high-density lipoprotein cholesterol (HDL-C)], renal function, transaminases, and numbers of MetS components increased, according to UA/Cr quartiles, as the UA/Cr increased. In contrast, HDL-C and Cr decreased as the UA/Cr increased. UA/Cr values increased as the number of MetS increased. When UA/Cr values within each alcohol consumption group were investigated, the overall metabolic profile was the worst in subjects who consumed ≥75 grams ethanol a day with a UA/Cr of ≥6.8, except for fasting immunoreactive insulin (FIRI), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), and HDL-C values. Subjects who did not consume alcohol with a UA/Cr of ≥6.8 showed the highest FIRI, HOMA-IR, and LDL-C values. Conclusions: The UA/Cr was associated with components of MetS, liver function, and alcohol intake in healthy Japanese subjects. The UA/Cr might be a useful marker to distinguish subjects with high IR and dyslipidemia who do not consume alcohol.

Infantile-onset spinocerebellar ataxia type 5 associated with a novel SPTBN2 mutation: A case report.

BACKGROUND: Spinocerebellar ataxia type 5 (SCA5), a dominant spinocerebellar ataxia is caused by spectrin beta nonerythrocytic 2 gene (SPTBN2) mutation. It typically consists of a slow progressive cerebellar ataxia with an onset principally in adulthood. Here, we report on the first Japanese patient with infantile-onset SCA5 associated with a novel heterozygous SPTBN2 mutation. CASE REPORT: The patient, a 6-year-old girl, developed delayed motor development and unsteady arm movement during infancy. She also showed gaze-evoked nystagmus, saccadic eye pursuit, dysarthria, dysmetria, intention tremor and mild intellectual disability. Brain MRI revealed moderate cerebellar atrophy and mild pontine atrophy. Comprehensive target capture sequencing to identify the causative gene identified a novel missense mutation in SPTBN2 (c.1309C