A comparison of perceived uselessness between centenarians and non-centenarians in China

Abstract Background Self-perceived uselessness is associated with poorer health in older adults. However, it is unclear whether there is a difference in self-perceived uselessness between centenarians and non-centenarians, and if so, which factors contributed to the difference. Methods We used four waves of a nationwide longitudinal dataset from 2005 to 2014 in China to investigate these research goals. We first performed multinomial logit regression models to examine the risk of the high or moderate frequency of self-perceived uselessness relative to the low frequency among centenarians (5778 persons) in comparison with non-centenarians aged 65–99 (20,846 persons). We then conducted a cohort analysis for those born in 1906–1913, examining differences in self-perceived uselessness between those centenarians and those died between ages 91 and 99 during 2005–2014. Results Compared to persons aged 65–79, centenarians had 84% (relative risk ratio (RRR) = 1.84, 95% CI:1.69–2.01) and 35% (RRR = 1.35, 95% CI: 1.25–1.46) higher risk to have the high frequency and the moderate frequency of feeling useless versus low frequency, respectively, when only demographic factors were controlled for. However, centenarians had 31% (RRR = 0.69, 95% CI: 0.54–0.88), 43% (RRR = 0.57, 95% CI: 0.49–0.68), and 25% (RRR = 0.75, 95% CI: 0.67–0.83) lower risk, respectively, to have the high frequency of self-perceived uselessness relative to the low frequency when a wide set of study covariates were controlled for. In the case of the moderate versus the low frequency of self-perceived uselessness, the corresponding figures were 18% (RRR = 0.82, 95% CI: 0.66–1.02), 22% (RRR = 0.78, 95%CI: 0.67–0.90), and 13% (RRR = 0.87, 95% CI: 0.79–0.96), respectively. The cohort analysis further indicates that those who became centenarians were 36–39% less likely than those died at ages 91–94 to report the high and the moderate frequencies of self-perceived uselessness versus the low frequency; no difference was found between centenarians and those died at ages 95–99. In both period and cohort analyses, behavioral and health-related factors affected the perception substantially. Conclusions Overall, centenarians were less likely to perceive themselves as useless compared to non-centenarians of younger birth cohorts when a wide set of covariates were considered and non-centenarians of the same birth cohort. How centenarians manage to do so remains an open question. Our findings may help improve our understanding about the longevity secrets of centenarians

Dual hydrophobic modifications toward anion exchange membranes with both high ion conductivity and excellent dimensional stability

Abstract(#br)Anion exchange membrane (AEMs) as a kind of important functional material are widely used in many fields including fuel cell, electrodialysis and water treatment. However, synthetic AEMs generally suffer a pernicious trade-off: high ion-conductive AEMs lack dimensional stability and vice versa. Herein we demonstrate a versatile strategy to prepare the AEMs with both high ion conductivity and excellent dimensional stability ( i.e. , low swelling ratio) via hydrophobic crosslinking and introducing hydrophobic chains. The hydrophobic length of crosslinkers has great influence on construction of highly efficient ion channels in the AEMs. Amazingly, the hydrophilic poly (phenylene oxide) (PPO) AEM crosslinked by 1,8-diaminooctane has the highest hydroxide conductivity that is further improved to 157.2 mS cm −1 (10% increases) with a low swelling ratio of 12.9% at 80 °C by introducing hydrophobic PPO backbone. This AEM not only overcomes the trade-off between the ion conductivity and the dimensional stability of crosslinked AEMs, but also breaks the upper bound between the ion conductivity and the water uptake. The newly developed strategy of hydrophobic dual-modifications promises to be an effective approach to develop the high-performance AEMs

Link between insulin resistance and hypertension: What is the evidence from evolutionary biology?

Insulin resistance and hypertension are considered as prototypical “diseases of civilization” that are manifested in the modern environment as plentiful food and sedentary life. The human propensity for insulin resistance and hypertension is a product, at least in part, of our evolutionary history. Adaptation to ancient lifestyle characterized by a low sodium, low-calorie food supply and physical stress to injury response has driven our evolution to shape and preserve a thrifty genotype, which is favorite with energy-saving and sodium conservation. As our civilization evolved, a sedentary lifestyle and sodium- and energy-rich diet, the thrifty genotype is no longer advantageous, and may be maladaptive to disease phenotype, such as hypertension, obesity and insulin resistance syndrome. This article reviews human evolution and the impact of the modern environment on hypertension and insulin resistance

Aggregation, Sedimentation and Dissolution of Cu(OH)2-Nanorods-Based Nanopesticide in Soil Solutions

Along with the development of nanotechnology, nanomaterials have been gradually applied to agriculture in recent years, such as Cu(OH)2-nanorods-based nanopesticide, an antibacterial agrochemical with a high efficacy. Nevertheless, knowledge about physical stability of Cu(OH)2 nanopesticide in soil solutions is currently scarce, restricting comprehensive understanding of the fate and risk of Cu(OH)2 nanopesticide in the soil environment. Herein we investigated aggregation, sedimentation and dissolution of Cu(OH)2 nanopesticide in soil solutions extracted from three different soil samples, wherein commercial Cu(OH)2 nanopesticide formulation (NPF), as well as its active ingredient (AI) and laboratory-prepared Cu(OH)2 nanorods (NR) with similar morphology as AI, were used as model Cu(OH)2 nanopesticides. We found that NPF compared to AI showed less extents of aggregation in ultrapure water due to the presence of dispersing agent in NPF. Yet, moderated aggregation and sedimentation were observed for Cu(OH)2 nanopesticide irrespective of NPF, AI or NR when soil solutions were used instead of ultrapure water. The sedimentation rate constants of AI and NPF were 0.023 min−1 and 0.010 min−1 in the ultrapure water, whereas the rate constants of 0.003–0.021 min−1 and 0.002–0.007 min−1 were observed for AI and NPF in soil solutions, respectively. Besides aggregation and sedimentation, dissolution of Cu(OH)2 nanopesticide in soil solutions was highly dependent on soil type, wherein pH and organic matter played important roles in dissolution. Although the final concentrations of dissolved copper (1.08–1.37 mg/L) were comparable among different soil solutions incubating 48 mg/L of AI, NPF or NR for 96 h, a gradual increase followed by an equilibrium was only observed in the soil solution from acidic soil (pH 5.16) with the low content of organic matter (1.20 g/kg). This work would shed light on the fate of Cu(OH)2 nanopesticide in the soil environment, which is necessary for risk assessment of the nanomaterials-based agrochemical

The relevance of ototoxicity induced by radiotherapy

Abstract Background The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity. Methods A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model. Results Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47–0.60; P = 0.73; I2 = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00–2.07; P = 0.69; I2 = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment. Conclusion Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy

GW24-e0756 Nicotine exacerbates atherosclerosis by upregulation and activation of CD36 in macrophage

Objectives CD36, a class B scavenger receptor expressed on macrophages mediates uptake of oxLDL and contributes to foam cell formation, a hallmark of early atherosclerosis. Tobacco smoking is a major risk factor for atherosclerosis. We investigated a role for the CD36 pathway in nicotine-induced activation of macrophages and foam cell formation in vitro and in ApoE-/- mice in vivo. Methods Human THP1-differentiated macrophages were incubated with or without nicotine, the protein and mRNA expression of CD36 or proinflammatory cytokines TNFa, MCP1, IL6 and CXCL9 were determined by real-time PCR or Western blot, respectively, nicotine-induced production of reactive oxygen species were determined by DCFDA assay and lucigenin chemiluminescence. In some experiments, the macrophages were transfected with CD36 siRNA to knockdown CD36. Macrophage uptake of lipoprotein was determined by using 125I-oxLDL lipoprotein cellular degradation assay. Foam cell formation was determined by Oil O Red staining. For in vivo experiments, apoE-/- and CD36-/-/apoE-/- double knockout mice were used and treated with normal mice diet, high fat high cholesterol diet (HF) and HF with nicotine for 15 weeks. CD11b+/Ly-6Chi inflammatory monocyte population in peripheral blood mononuclear cells were determined by fluorescence-activated cell sorting analysis. Atheorgenic lesion area in aorta was determined. Results Nicotine at “physiological” concentrations (100 nmol/L) found in smokers’ serum increased mRNA and protein expression of the B scavenger receptor CD36 by 116 ± 19% without affecting the expression of proinflammatory cytokines. These effects of nicotine were mediated by a common signalling pathway dependent on reactive oxygen species, PKCd phosphorylation and PPARg. Antioxidants as well as non-cholinergic nicotinic blockers prevented nicotine-induced CD36 upregulation. OxLDL increased expression of CD36 and proinflammatory cytokines including TNF-a, MCP-1, IL6, and CXCL9, by 2-4 fold (all p < 0.05); the combination of nicotine with OxLDL increased expression of CD36 and inflammatory cytokines by 3-7 fold (all p < 0.05). siRNA knockdown of CD36 significantly reduced mRNA expression of CD36 and the expression of inflammatory genes. Nicotine dose-dependently increased OxLDL uptake (25%) and intracellular cholesterol accumulation in macrophage, which was prevented by CD36 siRNA. Incubation of macrophages with OxLDL for 72 hours resulted in foam cell formation that was exacerbatedby pre-incubation with nicotine in a CD36-dependent manner. Treatment of ApoE-/- mice with physiological concentrations of nicotine markedly enhanced population of peripheral blood inflammatory monocytes (CD11b+/Ly-6Chi population) and aorta atherosclerotic plaque coverage, effects that were not seen in double knockout ApoE-/-/CD36-/- mice. Conclusions Our results show for the first time that physiological levels of nicotine increase the expression of CD36 and downstream atherogenic pathways in macrophages. The results with transgenic double knockout ApoE-/-CD36-/- mice suggest that macrophahge CD36 is a main signaling pathway in responsible for the pro-inflammatory and pro-atherogenic properties of nicotine. These studies identify nicotine as a critical new cardiovascular risk factor of cigarette smoking and caution against the chronic nicotine delivery programs for smoking cessation

Obesity has an interactive effect with genetic variation in the activating transcription factor 6 gene on the risk of pre-diabetes in individuals of Chinese Han descent.

Endoplasmic reticulum (ER) stress is one of the contributing factors to the development of β-cell failure in type 2 diabetes. ER stress response through ATF6 has been shown to play an important role in insulin resistance and pancreatic β-cell function. We investigated whether genetic polymorphisms in ATF6 were associated with the risk of pre-diabetes in a Chinese Han population, and whether they had a synergistic effect with obesity. Our samples included 828 individuals who were diagnosed as pre-diabetic, and 620 controls. The minor allele A at rs2340721 was associated with increased risk for pre-diabetes(p = 0.013), and this association was still significant after adjusting for gender, age, body mass index (BMI), and waist-hip ratio(p' = 0.011). BMI, treated as a continuous variable, and rs2340721 had an interactive effect on pre-diabetic risk(p for interaction = 0.003, β = 0.106). Carriers of GG at rs7522210 were also at a higher risk compared to non-carriers (OR = 1.390, 95%CI:1.206-1.818, p = 0.013, adjusted OR' = 1.516, 95%CI:1.101-2.006, p' = 0.006). GG homozygotes had increased fasting blood glucose (FBG) levels(GG vs CX: 5.6 ± 0.52 vs 5.5 ± 0.57 mmol/L, p = 0.016), lower insulin levels (0,30,120 minutes after glucose load) (p < 0.05), and reduced areas under the insulin curve than non-carriers(GG vs CX:67.3(44.2-102.3) vs 73.1(49.4-111.4), p = 0.014). rs10918270 was associated with FBG, and rs4657103 with 2 hour glucose levels after a 75 g glucose load. We also identified a haplotype of TTAG composed of rs4657103, rs2134697, rs2340721, and rs12079579, which was associated with pre-diabetes. The genetic variation in ATF6 is associated with pre-diabetes and has interactive effects with BMI on pre-diabetes in the Chinese Han population

The Expression of Proinflammatory Genes in Epidermal Keratinocytes Is Regulated by Hydration Status

Mucosal wounds heal more rapidly, exhibit less inflammation, and are associated with minimal scarring when compared with equivalent cutaneous wounds. We previously demonstrated that cutaneous epithelium exhibits an exaggerated response to injury compared with mucosal epithelium. We hypothesized that treatment of injured skin with a semiocclusive dressing preserves the hydration of the skin and results in a wound healing phenotype that more closely resembles that of mucosa. Here we explored whether changes in hydration status alter epidermal gene expression patterns in rabbit partial-thickness incisional wounds. Using microarray studies on injured epidermis, we showed that global gene expression patterns in highly occluded versus non-occluded wounds are distinct. Many genes including IL-1β, IL-8, TNF-α (tumor necrosis factor-α), and COX-2 (cyclooxygenase 2) are upregulated in non-occluded wounds compared with highly occluded wounds. In addition, decreased levels of hydration resulted in an increased expression of proinflammatory genes in human ex vivo skin culture (HESC) and stratified keratinocytes. Hierarchical analysis of genes using RNA interference showed that both TNF-α and IL-1β regulate the expression of IL-8 through independent pathways in response to reduced hydration. Furthermore, both gene knockdown and pharmacological inhibition studies showed that COX-2 mediates the TNF-α/IL-8 pathway by increasing the production of prostaglandin E2 (PGE2). IL-8 in turn controls the production of matrix metalloproteinase-9 in keratinocytes. Our data show that hydration status directly affects the expression of inflammatory signaling in the epidermis. The identification of genes involved in the epithelial hydration pathway provides an opportunity to develop strategies to reduce scarring and optimize wound healing