Circulating adiponectin levels are associated with peak oxygen uptake in Japanese

Objective

The aim of this study was to investigate the link between circulating adiponectin levels and peak oxygen uptake and/or physical activity in Japanese.

Methods

A total of 528 subjects (188 men and 340 women) were enrolled in this cross-sectional study. Circulating adiponectin levels, physical activity measured by tri-axial accelerometers, peak oxygen uptake and metabolic risk parameters were evaluated. We also assessed anthropometric factors, blood pressure, blood examinations and energy intake.

Results

Circulating adiponectin levels were 6.7 ± 3.0 μg/mL in men and 11.0 ± 4.9 μg/mL in women. Circulating adiponectin levels were positively correlated with physical fitness after adjusting for age, physical activity evaluated by Σ [metabolic equivalents × h per week (METs h/w)], cigarette smoking habit and energy intake in both sexes. However, these associations were attenuated further after adjusting for body mass index including other confounding factors, especially in men. However, circulating adiponectin levels were not associated with physical activity in either sex.

Conclusion

Circulating adiponectin levels were associated with peak oxygen uptake rather than physical activity.     

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

GeroScience - The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery...     

Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients

Background

Cervical intraepithelial neoplasia grade 3 (CIN3) is a mucosal precancerous lesion caused by high-risk human papillomavirus (HPV). Induction of immunological clearance of CIN3 by targeting HPV antigens is a promising strategy for CIN3 therapy. No successful HPV therapeutic vaccine has been developed.

Methods

We evaluated the safety and clinical efficacy of an attenuated Lactobacillus casei expressing modified full-length HPV16 E7 protein in patients with HPV16-associated CIN3. Ten patients were vaccinated orally during dose optimization studies (1, 2, 4, or 6 capsules/day) at weeks 1, 2, 4, and 8 (Step 1). Seven additional participants were only tested using the optimized vaccine formulation (Step 2), giving a total of 10 patients who received optimized vaccination. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were collected and E7 specific interferon-γ-producing cells were counted (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. All patients were re-evaluated 9 weeks after initial vaccine exposure using cytology and biopsy to assess pathological efficacy.

Results

No patient experienced an adverse event. E7-CMI in both CxLs and PBMCs was negligible at baseline. All patients using 4–6 capsules/day showed increased E7-CMI in CxLs, whereas patients using 1–2 capsules/day did not. No patient demonstrated an increase in E7-CMI in their PBMCs. In comparison between patients of cohorts, E7-CMI at week 9 (9 wk) in patients on 4 capsules/day was significantly higher than those in patients on 1, 2, or 6 capsules/day. Most patients (70%) taking the optimized dose experienced a pathological down-grade to CIN2 at week 9 of treatment. E7-CMI in CxLs correlated directly with the pathological down-grade.

Conclusions

Oral administration of an E7-expressing Lactobacillus-based vaccine can elicit E7-specific mucosal immunity in the uterine cervical lesions. We are the first to report a correlation between mucosal E7-CMI in the cervix and clinical response after immunotherapy in human mucosal neoplasia.     

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

Purpose

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease.

Method

Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake ( \(\dot V\) O_2peak) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of \(\dot V\) O_2peak for sex and decade.

Results

Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and \(\dot V\) O_2peak were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects.

Conclusion

Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.     

Streptococcus gallolyticus subsp. pasteurianus meningitis in an infant

Streptococcus gallolyticus subsp. pasteurianus was formerly classified as S. bovis biotype II/2, which is recognized as a rare cause of neonatal sepsis and meningitis. Since the taxonomy classification change, there have not been many reports of meningitis due to S. gallolyticus subsp. pasteurianus. Moreover, the pathogenesis of late onset S. gallolyticus subsp. pasteurianus meningitis in infants is unclear. Here we report a case of meningitis in a 5‐week‐old infant with preceding diarrhea. S. bovis biotype II/2 was isolated from the blood, cerebrospinal fluid and stool, and then was identified as S. gallolyticus subsp. pasteurianus on 16S rRNA gene sequencing. Isolates from all three sample types had identical profiles on pulsed‐field gel electrophoresis. The intestinal tract was thought to be the source of the infection.     

Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.     

Corrosion Behavior of Ultrafine-Grained CoCrFeMnNi High-Entropy Alloys Fabricated by High-Pressure Torsion

The influence of the nanocrystalline structure produced by severe plastic deformation (SPD) on the corrosion behavior of CoCrFeMnNi alloys with Cr contents ranging from 0 to 20 at.% was investigated in aqueous 0.5 M H₂SO₄ and 3.5% NaCl solutions. The resistance to general corrosion and pitting became higher in both the solutions, with higher passivation capability observed with increasing Cr content, and it is believed that the high corrosion resistance of CoCrFeMnNi alloys can be attributed to the incorporation of the Cr element. However, the impact of the nanocrystalline structure produced by SPD on the corrosion behavior was negligibly small. This is inconsistent with reports on nanocrystalline binary Fe–Cr alloys and stainless steels processed by SPD, where grain refinement by SPD results in higher corrosion resistance. The small change in the corrosion behavior with respect to grain refinement is discussed, based on the passivation process of Fe–Cr alloys and on the influence of the core effects of HEAs on the passivation process.     

Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.