Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

Aims: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using¹⁸fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day,n=16) for 12weeks.¹⁸F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%).¹⁸F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of¹⁸F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.     

Effect of total higher-order aberrations on accommodation in pseudophakic eyes

PURPOSE: To analyze the effect of total higher-order aberrations (HOAs) on the range of accommodation in pseudophakic eyes and the size of near-vision optotypes. SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan. METHODS: The study comprised 30 patients (44 eyes) who were diagnosed with cataract at Nara University of Medical Science Hospital and Municipal Oyodo Hospital. Inclusion criteria included no other eye disorder and a best corrected distance acuity of 20/20 or better 1 month after cataract surgery. All patients had small-incision phacoemulsification followed by in-the-bag implantation of a monofocal intraocular lens (SA60AT, Alcon). All incisions were self-sealing. Accommodation in pseudophakic eyes was measured by the lens-loading method in an examination room under constant illumination. Ocular HOAs were measured using the KR-9000PW Hartmann-Shack wavefront analyzer (Topcon). RESULTS: The mean patient age was 75.8 years +/- 5.4 (SD) (range 64 to 83 years). The Pearson correlation coefficient (r) showed a significant positive correlation between the range of accommodation and Z7 (vertical coma) for a 4.0 mm pupil using the 1.0 near-vision optotype. There was a significant negative correlation between the range of accommodation and Z12 (spherical aberration) for a 4.0 mm pupil using the 1.0 near-vision optotype (r = .311, P = .040 for Z7;r = -.365, P = .015 for Z12). No other parameter was significantly correlated with the range of accommodation. CONCLUSIONS: Measurement of accommodation in pseudophakic eyes by the lens-loading method using the 1.0 near-vision optotype showed that eyes with larger vertical coma aberrations achieved a larger range of accommodation. In contrast, eyes with larger spherical aberrations had smaller amounts of accommodation. The size of the near-vision optotype may affect accommodation analysis in pseudophakic eyes.     

Quantitative Assay of Epidermal Growth Factor Receptor in Human Squamous Cell Carcinomas of the Oral Region by an Avidin-Biotin Method

A quantitative assay method for epidermal growth factor receptors (EGFRs) of human tumor tissues was established, based on enzyme-labeled avidin-biotin (LAB) interaction with anti-human EGFR monoclonal antibody 52SIgG. A standard calibration curve for EGFR estimation in human tumor tissues was obtained with A431#8 cells cloned from A431 human epidermoid carcinoma cell line. The coefficient of variance for the standard curve was below 35% in the application to tumor tissues from nude mice implanted with human tumor cell lines. The minimum tissue amount required for the quantitative assay was around 0.1 g (wet weight). Using the LAB method, the correlation between the level of EGFR number and tumor malignancy was examined for 14 human squamous cell carcinomas (SCCs) from the oral region. Seven of the SCCs showed a more than two-fold higher EGFR number compared to normal gingival tissues. Three highly aggressive carcinomas with poor prognosis possessed five to ten times higher levels of EGFR number than normal tissues. The elevated EGFR level in the SCCs seems to correlate to increasing tumor size and the stage of SCCs as clinically classified according to the 1987 UICC TNM system.     

An improved assay of thyrotropin in dried blood samples on filter paper as a screening test for neonatal hypothyroidism.

A method for measuring thyrotropin (TSH) in eluates of dried blood samples on filter paper was evaluated and improved as a screening test for neonatal hypothyroidism. A linear relationship between the volume of eluate and the TSH value and good recoveries of endogenous TSH (104%) and added TSH (89%) were obtained, indicating that TSH in dried blood was extracted well by overnight elution and determined accurately by radioimmunoassay. The TSH content in the central portion of a spot was less (71%) than that in the peripheral portion. The TSH in dried blood samples on filter paper was stable at 4 degrees C, room temperature (about 25 degrees C) or 37 degrees C for 1 month. The TSH values of eluates were correlated with those of whole blood (r = 0.90) and serum (r = 0.81). Cases of primary hypothyroidism cound be readily differentiated from normal subjects by this method, even when eluates of their blood were combined with those of normal blood for assay of TSH.     

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa,Japan

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.     

Measures of Perceived Neighborhood Food Environments and Dietary Habits: A Systematic Review of Methods and Associations

Access to healthy food is a necessity for all people. However, there is still a lack of reviews on the assessment of respondent-based measures of neighborhood food environments (perceived food environments). The aim of this systematic review was to evaluate the measurement tools for perceived food environments by five dimensions of food access and to obtain the overview of their associations with dietary habits among people aged 18 years and older in middle- and high-income countries. Observational studies using perceived food environment measures were identified through a systematic review based on two databases for original studies published from 2010 to 2020. A total of 19 final studies were extracted from totally 2926 studies. Pertaining to the five dimensions of food access, 12 studies dealt with accessibility, 13 with availability, 6 with affordability, 10 with acceptability, 2 with accommodation, and 8 with a combination of two or more dimensions. Perceived healthy food environments were positively associated with healthy dietary habits in 17 studies, but 8 of them indicated statistically insignificant associations. In conclusion, this review found accessibility and availability to be major dimensions of perceived food environments. The relationship between healthy food environments and healthy diets is presumably positive and weak.     

Prevalence and time of appearance of Brugada electrocardiographic pattern in young male adolescents from a three-year follow-up study

The prevalence of Brugada's electrocardiographic (ECG) pattern in 7,022 male adolescents in the seventh grade was determined, and the same subjects were reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7 subjects (0.10%) showed Brugada's ECG pattern by the conventional criterion (J point or ST-segment >/=0.1 mV in leads V(1) to V(3)), and no subjects (0%) and 2 subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >/=0.2 mV) in the seventh and tenth grades, respectively, indicating that Brugada's ECG pattern begins to appear during junior high school and increases until late adulthood.     

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

AIM：To examine the prevalence of gastroesophageal reflux disease （GERD） symptoms in a large unselected general population in Japan.
METHODS： In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged 〉 40 years. A total of 160 983 Japanese （60 774 male, 100 209 female; mean age 61.9 years） who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 （34 275 male, 48 619 female; mean age 62.4 years） to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period.
RESULTS： The respective prevalences of the symptoms in males and females were： heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year agegroup. Dysphagia was also significantly more frequent in female patients.
CONCLUSION： The prevalence of typical GERD symptoms （heartburn） was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group.