Insulin Resistance-Varying Associations of Adiposity Indices with Cerebral Perfusion in Older Adults: A Population-Based Study.

OBJECTIVES: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance. DESIGN: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study. SETTING AND PARTICIPANTS: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans. METHODS: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis. RESULTS: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted ß-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05). CONCLUSION: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.

[Analysis of influencing factors of high-frequency hearing loss among male noise workers in an automobile manufacturing enterprise].

Objective: To analysis of high-frequency hearing loss status and risk factors among male noise workers in an automobile manufacturing enterprise in Guangzhou. Methods: From February 2020, a cluster sampling method was used to select 3486 male workers exposed to noise in an automobile manufacturing enterprise in Guangzhou in 2018. After screening, 2608 were selected as the research objects. Pure tone hearing threshold test, noise exposure level test and questionnaire survey were conducted, and the cumulative noise exposure was calculated. Chi square test and unconditional logistic regression were used to analyze the correlation between various factors and high frequency hearing loss. Results: The detection rate of high-frequency hearing loss in noise exposed workers was 34.20% (892/2608) , there were significant differences in the two groups among age, marital status, years of noise exposure, noise exposure equivalent A sound level, CNE, different working hours and exposure to electromagnetic radiation (P<0.05) . Multiple logistic regression analysis showed that age, CNE and exposure to electromagnetic radiation were independent risk factors for high-frequency hearing loss (P<0.05) , three shifts and two shifts were the protective factors for the occurrence of high-frequency hearing loss (OR=0.523, P<0.01) . Conclusion: Noise exposure is the main influencing factor of high-frequency hearing loss of noise-receiving workers in automobile manufacturing enterprises. Enterprises should strengthen noise control in the workplace, improve the working environment of electromagnetic radiation, and implement a scientific and healthy work shift system.

[Combined effect of noise and hand-transmitted vibration on noise-induced hearing loss in the automobile manufacturing industry].

Objective: To investigate the combined effect of noise and hand-transmitted vibration on noise-induced hearing loss (NIHL) in the automobile manufacturing industry. Methods: From September 2018 to January 2019, cluster sampling was used to select 998 workers in an automobile factory as study subjects, among whom 352 workers exposed to noise alone were enrolled as noise group, 342 workers exposed to noise and hand-transmitted vibration were enrolled as combined effect group, and 304 workers without exposure to occupational hazardous factors were enrolled as control group. A questionnaire survey and pure tone audiometry were performed for all study subjects. An analysis of variance was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a ordinal polytomous logistic regression analysis was used to investigate the influencing factors for NIHL (with 0.05 as the inclusion criteria and 0.10 as the exclusion criteria for independent variables) . Results: There was a significant difference in L(Aeq, 8 h) between groups (P<0.05) ; the noise group and the combined effect group had a significantly higher L(Aeq, 8 h) than the control group (P<0.05) , while there was no significant difference in L(Aeq, 8 h) between the noise group and the combined effect group (P>0.05) . The control group had a significantly lower detection rate of hearing loss than the noise group and the combined effect group (P<0.0125) , and the combined effect group had a significantly higher detection rate of hearing loss than the noise group (P<0.0125) . The ordinal polytomous logistic regression analysis showed that after adjustment for confounding factors such as age, working years, sex, smoking, and drinking, both noise exposure and exposure to both noise and hand-transmitted vibration had an influence on workers' hearing (P<0.05) , and the workers exposed to both noise and hand-transmitted vibration had a higher risk of hearing loss than those exposed to noise alone. Conclusion: There may be a combined effect of noise and hand-transmitted vibration in the automobile manufacturing industry, which can increase the risk of NIHL in workers.

[Analysis of common gynecological diseases in 1142 married female workers].

Objective: To understand the prevalence of gynecologic diseases among married female workers. Methods: The data of married female workers who underwent occupational health examination in a physical examination center from January to December 2017 were collected. The relationship between the detection of common gynecological diseases, age and occupational types examined by gynecological routine, TCT, breast B-mode ultrasound, uterus and appendix B-mode ultrasound were analyzed. Results: Among the 1142 female workers, the total detection rate of reproductive tract infections was 67.25% (768/1142), the total detection rate of breast-related diseases was 75.22% (859/1142) ; the total detection rate of gynecological tumors and benign lesions was 14.71% (168/1142). The detection rate of breast hyperplasia was the highest 67.08% (766/1142), followed by vaginitis 51.66% (590/1142). Among the abnormalities detected in breast-related diseases, gynecological tumors and benign lesions, the highest detection rate was found in public institutions (85.66% and 27.13%), and the lowest was found in factory workers (70.24% and 7.89%). With the increase of age, the detection rate of breastrelated diseases (breast hyperplasia, breast cyst), gynecological tumors, benign lesions (uterine myoma), and Nessler's cyst abnormalities in married female workers increased (χ(2)(trend)=7.647、21.653、107.411、53.802, P<0.05), while the detection rate of columnar epithelium of cervix decreased (χ(2)(trend)=7.404, P<0.05). There was no significant difference in the total detection rate of reproductive tract infectious diseases (vaginitis, cervical polyps, cervical hypertrophy) among married famale workers of different ages (P<0.05) . Conclusion: The common gynecological diseases of married female workers are affected by many factors such as age and occupation. Health examination and health education should be carried out regularly to reduce the incidence of gynecological diseases among female workers according to different ages and occupations.

[Effect of long-term low-concentration mixed benzene exposure on male peripheral blood in an automobile manufacturing enterprise].

Objective: To investigated the effect of long-term low-concentration mixed benzene exposure on peripheral blood of male workers. Methods: A case-control study was conducted to select 452 male workers exposed to mixed benzene (benzene, toluene, xylene) for five consecutive years from January 2012 to December 2016 in an automobile manufacturer as case group, and 438 male administrative and logistic managers who underwent physical examination during the same period as control group. The peripheral blood of the two groups was tested and compared, and the occupational hazards in the workplace were detected. Results: There were low dose exposure to mixed benzene in the enterprise, but the test results met the occupational exposure limit requirements. During the five years from 2010 to 2016, between the two groups of workers, the mean values of WBC, NEUT, RBC and Hb were statistically different (P<0.05). There was no statistical difference (P>0.05) in the mean value of PLT. The abnormal rate of main peripheral blood indexes in the control group was higher than that in the exposed group. There were significant differences in NEUT, RBC and Hb (P< 0.05), but no significant differences in WBC and PLT (P>0.05). Conclusion: It can not be concluded that long-term low-concentration mixed benzene exposure can cause the change of peripheral blood index.

Effects of Shenkangling intervention on the MAPK pathway in rats with doxorubicin-induced nephropathy.

Shenkangling plays a role of Yishenhuoxue effect for the treatment of children with nephrotic syndrome. The aim of this study was to investigate the effects of Shenkangling intervention on the mitogen-activated protein kinase (MAPK) pathway in rats with Adriamycin-induced nephropathy (AN) and its underlying mechanism of action. Nephrosis was induced in healthy Sprague-Dawley rats by doxorubicin and the rats were untreated or treated with prednisone, simvastatin, Shenkangling, or a combination thereof. Using real-time PCR, the mRNA expression levels of Chemokine (C-X-C motif) ligand 16 (CXCL16), A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and ADAM17 in the renal tissues of these rats were found to be decreased by the various treatments compared to those in the untreated doxorubicin-induced nephrosis rats. To quantify the activation of the MAPK pathway, western blotting was used to detect the phosphorylation levels of MAPK pathway-associated proteins (p38, ERK1/2, SAPK/JNK) and nuclear factor (NF)-κB p65, which were reduced by the various treatments compared to those in the untreated doxorubicin-induced rats. Serum levels of transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, quantified by ELISA, were decreased by the various treatments compared to the levels in the untreated doxorubicin-induced nephrosis rats. The rats treated with prednisone, simvastatin, and Shenkangling showed the best outcome. The Chinese medicine Shenkangling that is known for nourishing the kidney and promoting blood circulation reduced urinary protein levels, increased serum albumin levels, and reduced cholesterol levels by reducing the release of CXCL16, ADAM10, ADAM17, TGF-ß1, TNF-α, IL-1ß, IL- 6, and other inflammatory mediators and inhibiting the activation of the MAPK signaling pathway, thereby effectively improving the state of nephropathy in AN rats. These results indicate that Shenkangling can be used clinically to treat nephropathy.

Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study.

AIMS/HYPOTHESIS: Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration. METHODS: A dementia-free cohort (n = 1,248) aged >or=75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and Statistical Manual of Mental Disorders, revised third edition [DSM-III-R] criteria). The Alzheimer's disease diagnoses were subdivided into Alzheimer's disease with stroke and Alzheimer's disease without hypertension, heart disease and stroke. Diabetes was ascertained based on medical history, or hypoglycaemic medication use, or a random blood glucose level >or=11.0 mmol/l, which included undiagnosed diabetes when neither a history of diabetes nor hypoglycaemic drugs use was present. Uncontrolled diabetes was classified as a random blood glucose level >or=11.0 mmol/l in diabetic patients. Borderline diabetes was defined as a random blood glucose level of 7.8-11.0 mmol/l in diabetes-free individuals. Cox models were used to estimate HRs. RESULTS: During the 9 year follow-up, 420 individuals developed dementia, including 47 with VaD and 320 with Alzheimer's disease (of the 320 Alzheimer's disease cases, 78 had previous, temporally unrelated stroke, and 137 had no major vascular comorbidities). Overall diabetes was only related to VaD (HR 3.21, 95% CI 1.20-8.63). Undiagnosed diabetes led to an HR of 3.29 (95% CI 1.20-9.01) for Alzheimer's disease. Diabetic patients with random blood glucose levels <7.8 mmol/l showed no increased dementia risk. Uncontrolled and borderline diabetes were further associated with Alzheimer's disease without vascular comorbidities. CONCLUSIONS/INTERPRETATION: Uncontrolled diabetes increases the risk of Alzheimer's disease and VaD. Our findings suggest a direct link between glucose dysregulation and neurodegeneration.

Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study.

BACKGROUND: Research on diabetes mellitus as a risk factor for dementia and its main subtypes has produced conflicting results. The authors investigated the relationship between diabetes mellitus and risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: A dementia-free cohort of 1,301 community dwellers aged 75 years and older in Stockholm, Sweden, was longitudinally examined twice over 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders-III-R diagnostic criteria). Cox proportional hazards models were used to analyze the data with adjustment for several potential confounders. RESULTS: During the 5,584 person-years of follow-up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p = 0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1) for AD. Patients who were treated with oral antidiabetic medications had HRs of 1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for VaD. There were significant interactions of diabetes with severe systolic hypertension (> or =180 mm Hg) on dementia and its main subtypes, and of diabetes with heart disease on VaD. CONCLUSIONS: Diabetes mellitus increases the risk of dementia, and VaD in particular, in very old people. The risk for dementia and VaD is especially high when diabetes mellitus occurs together with severe systolic hypertension or heart disease.

Integrated self-calibration via electrokinetic solvent proportioning for microfluidic immunoassays.

On-board generation of a set of calibration standards was demonstrated within a microfluidic device designed to perform immunoassay. Electrokinetic flow was used to proportionally mix the antibody (Ab) to bovine serum albumin (BSA) and a diluting buffer, to provide varying Ab concentrations for downstream mixing with fluorescently labeled BSA (BSA*). Mixing ratios were determined from electrical impedance modeling of the fluidic network using P-SPICE software, and peak heights for the labeled species were analyzed relative to the concentration calculated from the model. For dilution and separation of fluorescently labeled amino acids, a linear calibration curve was obtained for mixing ratios of 0.118 to 7.46. A linear calibration curve was obtained for the immunoassay calibration using dilution ratios between 0.197 and 5.077. Deviations were observed at larger extremes, possibly due to leakage effects at intersections. Peak height reproducibility was +/- 3% for the immunoassay, using diluted monoclonal Ab in mouse ascites fluid as the analyte. Recovery for on-chip calibration was 92 +/- 6% versus calibrants prepared off-chip, indicating a small bias.

Neonatal palatal cysts and their morphology in cleft lip and palate.

Palatal cysts (Epstein pearls) are occasionally noticed as white papules on the palatal mucosa of a neonate whilst having its 6-week postnatal check. We describe five cleft patients and the distribution characteristics of their palatal cysts, including the previously unrecorded observation of a submucous cleft palate with a double row of palatal cysts, one row on each side of the zona pellucida. The role of spatial morphology of palatal cysts in interpreting cleft pathogenesis is discussed.

Active transforming growth factor-beta in wound repair: determination using a new assay.

Transforming growth factor (TGF)-beta regulates wound repair and scarring in an isoform-specific fashion. TGF-beta is produced in a latent form, and its activation is a critical regulatory step controlling the bioactivity of this growth factor. To date, it has been impossible to determine latent TGF-beta activation in vivo due to a lack of quantitative assays. We describe here a semiquantitative modification of the plasminogen activator inhibitor-1/luciferase bioassay (PAI/L assay) for TGF-beta, which we used to determine active and latent TGF-beta isoforms in frozen sections of rat wound tissue. We found that significant amounts of latent TGF-beta were rapidly activated upon wounding (38% of the total TGF-beta at 1 hour after wounding). A second peak of active TGF-beta (17% of total) occurred at 5 days after wounding. The predominant isoforms were TGF-beta1 and -2 with only minor amounts of TGF-beta3 present. This is the first TGF-beta bioassay allowing semiquantitative determination of active and latent isoforms present in vivo, and our results document the significance and temporal regulation of latent TGF-beta isoform activation in wound repair.

Elevation of auditory thresholds by spontaneous cochlear oscillations.

The inner ear sometimes acts as a robust sound generator, continuously broadcasting sounds (spontaneous otoacoustic emissions) which can be intense enough to be heard by other individuals standing nearby. Paradoxically, most individuals are unaware of the sounds generated within their ears. Two hypotheses could explain this paradox: (1) the spontaneous emissions may not be transmitted to the central nervous system; or (2) the spontaneous emission produces a continuous, high rate of neural activity, which, like the natural pattern of spontaneous activity, is ignored by the central nervous system. Here we demonstrate that high-intensity spontaneous otoacoustic emission can vigorously activate auditory nerve fibres in mammals (Chinchilla laniger). This 'internal biological noise' creates a 'line busy' signal that significantly degrades a neuron's ability to respond to sound and results in a hearing loss completely different from that caused by damage to sensory cells.

The distribution of PDGFs and PDGF-receptors during murine secondary palate development.

The distribution of the 2 homodimer isoforms of platelet-derived growth factor (PDGF)-AA and -BB, and their receptors (PDGF alpha-receptor and PDGF beta-receptor) were mapped immunocytochemically during the development of the embryonic mouse secondary palate, from embryonic day (E) 12 to E15. The staining patterns of PDGF-AA/alpha-receptor and PDGF-BB/beta-receptor are different. Generally, the former is present and the latter is sparse/absent during the period of palate development. The localisations of PDGF-AA and alpha-receptor are more intensive in the epithelia than in the mesenchyme, and change temporally during palatal shelf elevation, midline epithelial seam formation and disruption. Before the palatal shelf has elevated (E13), PDGF alpha-receptor is present in the palatal mesenchyme, nasal and medial edge epithelia (MEE), whilst PDGF-AA stains lightly in the palatal epithelia. During palatal midline epithelial seam formation and following its degeneration throughout E14, PDGF-AA and PDGF alpha-receptor were intensively colocalised in the nasal and midline seam epithelia. These findings indicate that the interaction between PDGF-AA and its receptor may participate in palate development, particularly in regulating palatal midline epithelial seam formation and degeneration.