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Skin aging is of immense societal and, thus, scientific interest. Because mechanics play a critical role in skin's function, a plethora of studies have investigated age-induced changes in skin mechanics. Nonetheless, much remains to be learned about the mechanics of aging skin. This is especially true when considering sex as a biological variable. In our work, we set out to answer some of these questions using mice as a model system. Specifically, we combined mechanical testing, histology, collagen assays, and two-photon microscopy to identify age- and sex-dependent changes in skin mechanics and to relate them to structural, microstructural, and compositional factors. Our work revealed that skin stiffness, thickness, and collagen content all decreased with age and were sex dependent. Interestingly, sex differences in stiffness were age induced. We hope our findings not only further our fundamental understanding of skin aging but also highlight both age and sex as important variables when conducting studies on skin mechanics. Our work addresses the question, "How do sex and age affect the mechanics of skin?" Answering this question is of both scientific and societal importance. We do so in mice as a model system. Thereby, we hope to add clarity to a body of literature that appears divided on the effect of both factors. Our findings have important implications for those studying age and sex differences, especially in mice as a model system. [Display omitted] [ABSTRACT FROM AUTHOR]

We examined the potential mediating roles of domain-specific physical activities and sedentary behaviors in the relationship between area-level socioeconomic status (SES) and cardiometabolic risk. Data were from the 2011/2012 Australian Diabetes, Obesity and Lifestyle study (n = 3431). The outcome was a clustered cardiometabolic risk (CCR) score, and the exposure was suburb-level SES. Potential mediators were domain-specific physical activities and sedentary behaviors. Multilevel linear regression models examined associations between SES and potential mediators (α) and between mediators and CCR (β). Mediation was assessed using the joint-significance test. Higher SES was associated with a lower CCR score. Lower SES was associated with less frequent walking for transport, lower vigorous-intensity recreational physical activity, and higher TV time, which were associated with higher CCR scores. However, higher SES was associated with longer transport-related sitting time (all modes and in cars), which were associated with higher CCR scores. The SES-cardiometabolic risk relationship may be partially explained by walking for transport, vigorous-intensity recreational physical activity, and TV viewing. These findings, which require corroboration from prospective evidence and clarification of the roles of transport-related sitting and occupational physical activity, can inform initiatives addressing socioeconomic inequalities in cardiometabolic health. • People living in advantaged areas were likely to have lower cardiometabolic risk. • Inequality was mostly explained by vigorous-intensity recreational physical activity. • Inequality was also in part explained by TV viewing and transport-related walking. • The mediation effect for transport-related sitting was contrary to the inequality. [ABSTRACT FROM AUTHOR]

The use of siRNA therapeutics to treat cancer is a very promising approach. However, specific delivery of siRNAs to tumors remains a major challenge. The recent success of siRNA delivery to the liver has incentivized the development of biomaterials for siRNA delivery into tumors. Here, we report a new class of amino acid-modified lipids for siRNA delivery to cancer cells. Eight lipids were developed by headgroup modification with histidine and lysine. The lipids were screened in PC3-luciferase stable cells for gene silencing and cellular cytotoxicity study. The best lipid LHHK shows a pKa of 6.08, which is within the optimal pKa range of lipid nanoparticles (LNPs) for siRNA delivery. The LHHK LNP protects siRNA from serum degradation for up to 24 h and shows higher endosomal release and better cellular uptake compared to other lysine-modified lipids in PC3 cells. The LHHK LNP exhibits significant silencing activity of IKKα and IKBKE in prostate cancer and pancreatic cancer, respectively. Moreover, the LHHK LNP encapsulating IKBKE siRNA inhibits cell proliferation of pancreatic cancer cells and suppresses the tumor progression in a pancreatic cancer mouse model. Lipid nanoparticle (LNP) is a promising platform for siRNA delivery. However, LNP is generally associated with high systemic toxicity. As a result, efficient and biodegradable lipids are highly needed for siRNA-based cancer therapy. Herein, we develop amino acid-modified biodegradable lipids. These lipids show very low cellular toxicity and high transfection efficiency. The best lipid LHHK shows a pKa of 6.08, which is within the optimal pKa range of LNPs for siRNA delivery. The LHHK LNP efficiently silences IKKα and IKBKE in prostate and pancreatic cancer, respectively. Moreover, the LHHK LNP encapsulating IKBKE siRNA inhibits cell proliferation and suppresses tumor growth of pancreatic cancer in vivo. These results suggest that amino acid-modified lipids possess a great potential for siRNA delivery in cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Liver fibrosis is the excessive accumulation of extracellular matrix due to chronic injuries, such as viral infection, alcohol abuse, high-fat diet, and toxins. Liver fibrosis is reversible before it progresses to cirrhosis and hepatocellular carcinoma. Type 2 diabetes significantly increases the risk of developing various complications including liver diseases. Abundant evidence suggests that type 2 diabetes and liver diseases are bidirectionally associated. Patients with type 2 diabetes experience more severe symptoms and accelerated progression of live diseases. Obesity and insulin resistance resulting from hyperlipidemia and hyperglycemia are regarded as the two major risk factors that link type 2 diabetes and liver fibrosis. This review summarizes possible mechanisms of the association between type 2 diabetes and liver fibrosis. The cellular protein markers that can be used for diagnosis and therapy of type 2 diabetes-associated liver fibrosis are discussed. We also highlight the potential therapeutic agents and their delivery systems that have been investigated for type 2 diabetes-associated liver fibrosis. [ABSTRACT FROM AUTHOR]

In vivo tissue deposition of fibrillar protein aggregates is the cause of several degenerative diseases. Evidence suggests that interfering with the pathology-associated amyloid fibrillogenesis by inhibitory molecules is envisaged as the primary therapeutic strategy. Amyloid fibril formation of proteins has been demonstrated to be influenced by nanoparticles/nanomaterials. As compared with their molecular form counterpart, this work examined the effect of sucrose-terminated nanoparticles on the in vitro amyloid fibrillogenesis and structural properties of β-lactoglobulin at pH 2.0 and 80 °C. ThT binding and electron microscopy results demonstrated that sucrose-terminated nanoparticles were able to suppress β-lactoglobulin fibrillogenesis in a concentration-dependent fashion. Importantly, sucrose-terminated nanoparticles showed better β-lactoglobulin fibril-inhibiting ability than sucrose molecules. ANS fluorescence and right-angle light scattering results showed reduced solvent exposure and decreased aggregation, respectively, in the β-lactoglobulin samples upon treatment with sucrose-terminated nanoparticles. Moreover, fluorescence quenching analyses revealed that the static quenching mechanism and formation of a non-fluorescent fluorophore–nanoparticle complex are involved in the nanoparticle-β-lactoglobulin interaction. We believe that the results from this study may suggest that the nanoparticle form of biocompatible sugar-related osmolytes may serve as effective inhibiting/suppressing agents toward protein fibrillogenesis. [ABSTRACT FROM AUTHOR]

Purpose: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC.Methods and Materials: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348).Results: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively.Conclusions: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement. [ABSTRACT FROM AUTHOR]

Background: Environmental lead exposure is a known risk factor of cardiovascular disease (CVD) in animal and human epidemiological studies of adults, but limited research has been conducted in young populations. Moreover, the association between lead level and common carotid artery intima-media thickness (CIMT) has never been documented.Design: and Participants: In this study, 738 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between lead levels in urine and CVD risk factors, metabolic syndrome (MS) and CIMT.Results: The geometric mean of the urine lead level was 1.50 μg/g creatinine. We found a significant positive association between urine lead levels and CVD risk factors, including diastolic blood pressure (DBP), mean arterial pressure (MAP), as well as markers of glucose homeostasis, such as serum glucose, serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), body mass index (BMI) z score, and CIMT. Overall, increased urine lead concentrations were positively correlated with the prevalence of MS, specifically the criteria of waist/BMI and serum HDL-C. The relationship between urine lead levels and CIMT remained unchanged in all subgroups.Conclusion: In this study, we found that increased urinary levels of lead were positively associated with CVD risk factors, CIMT, and MS in this cohort. Future research to explore the pathogenic basis of exposure to lead and risk of CVDs and their risk factors are warranted. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The accumulation of excessive extracellular matrix (ECM) in the liver is a key characteristic of liver fibrosis. Activated hepatic stellate cells (HSCs) are the major producers of ECM and therefore play irreplaceably important roles during the progression of liver fibrosis. Liver fibrogenesis is highly correlated with the activation of HSCs, which is regulated by numerous profibrotic cytokines. Using RNA interference to downregulate these cytokines in activated HSCs is a promising strategy to reverse liver fibrosis. Meanwhile, microRNAs (miRNAs) have also been exploited for the treatment of liver fibrosis. This review focuses on the current siRNA- and miRNA-based liver fibrosis treatment strategies by targeting activated HSCs in the liver. [ABSTRACT FROM AUTHOR]

Residents of lower socioeconomic status (SES) areas are at a higher risk of overweight/obesity than those from higher SES areas. Built environment attributes may mitigate such inequalities. This systematic review synthesised findings of studies examining built environment attributes as potential moderators of the associations between area-level SES and overweight/obesity in adults. From five databases, nine eligible studies were identified. The SES-overweight/obesity relationship was stronger in inner areas and suburbs of large cities, while it was weaker in more rural areas. Two studies examined walkability and reported contrasting findings: no moderation in one and marginally significant moderation (less inequality in higher walkability areas) in the other. No evidence of moderation was found for street connectivity, population density, the food environment, access to physical activity facilities and several perceived environmental attributes. Further research is needed on other built environment attributes (e.g., access to, quantity and quality of green spaces, active transport features), and ideally using prospective study designs and objective makers of adiposity. • We reviewed studies on environmental moderation of area-level SES-obesity association. • Area SES-obesity association was stronger in larger cities and weaker in rural areas. • Findings for the role of walkability were mixed. • No moderation was found for food environment and physical activity facilities. • Studies need to assess potential moderation by greenspace and transport features. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effects of a nurse-led survivorship care program (SCP) on emotional distress, social support, physical health, mental health, and resilience in primary caregivers of patients with advanced head and neck cancer. A randomized controlled trial was conducted. One hundred patient-primary caregiver dyads were randomized into the nurse-led SCP group (experimental) or the usual care group (control). Participants completed a self-reported questionnaire, including measures of emotional distress, social support, physical health, mental health, and resilience. After 6 months, the experimental group reported a significant improvement in emotional distress, social support, physical health, mental health, and resilience. Compared with the control group, measures of emotional distress, physical health, overall resilience, and the resilience aspects of equanimity and perseverance improved in the experimental group. An SCP may feasibly help alleviate emotional distress, improve social support, increase physical and mental health, and strengthen resilience in the primary caregivers of patients with head and neck cancer. Health care providers should encourage primary caregivers to join an SCP. The nurse-led SCP can be applied before patients complete treatment, which may increase the positive effect on physical health and adaptation. [ABSTRACT FROM AUTHOR]

The link between phthalate exposure and the risk of subclinical atherosclerosis in young population remains unclear. This study investigated the association between phthalate exposure and subclinical atherosclerosis, in terms of carotid intima-media thickness (CIMT), in young population. From a nationwide mass urine screening for renal health, conducted in 1992–2000 among school children 6–18 years of age in Taiwan, we recruited 789 subjects to participate in the cardiovascular health examination in 2006–2008. Among them, 787 received measurements of 7 urinary phthalate metabolites and CIMT. Results showed both mean and maximal values of CIMT at all segments of carotid arteries significantly increased with the urinary mono-2-ethylhexyl phthalate (MEHP), ∑ di-(2-ethylhexyl) phthalate (DEHP), and mono-n-butyl phthalate (MnBP) in a dose-response relationship after adjustment for multiple linear regression models. Multivariate logistic regression analysis showed that higher quartiles of urinary concentrations of MEHP, ∑DEHP, and MnBP were associated with a higher risk of thicker CIMT. Compared to subjects with the lowest quartile (Q1) of urinary MEHP, the adjusted odds ratios (95% confidence interval) for thicker CIMT among subjects with higher urinary MEHP were 2.13 (1.18–3.84) at Q2, 4.02 (2.26–7.15) at Q3 and 7.39 (4.16–13.12) at the highest Q4. In conclusion, urinary phthalate metabolites of MEHP, ∑DEHP, and MnBP are strongly associated with CIMT in adolescents and young adults in Taiwan. Image 1 • Demonstrate urinary metabolites of DEHP and DiBP are significantly and positively associated with CIMT in young population. • A dose-response relationship between phthalate exposure and CIMT at all segments of extracranial carotid bed. • Preventing phthalate exposure is important for primary prevention of atherosclerotic disease. Phthalate exposure increased subclinical atherosclerosis in young population indicated the atherogenic potential of DEHP and MnBP. [ABSTRACT FROM AUTHOR]

Abstract In the family of alkylphenolic compounds, 4-tertiary-Octylphenol (4-t-OP) is extensively used in many products. In animal and in vitro studies, 4-t-OP exposure has been linked to cardiovascular disease (CVD) risk factors; however, there are no previous human epidemiological studies. In this study, 886 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between serum levels of 4-t-OP, CVD risk factors, and common carotid artery intima-media thickness (CIMT). The geometric mean (SD) 4-t-OP concentration was 32.52 (1.71) ng/mL. We found that serum levels of 4-t-OP were negatively associated with markers of glucose homeostasis (insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β)), z score of body mass index (BMI z score) and CIMT but were positively associated with lipid profiles (high density lipoprotein cholesterol (HDL-C), Apolipoprotein A1). A one-unit elevation in natural log-transformed 4-t-OP (ng/mL) was negatively correlated with CIMT (mm) (β = −0.029, SE = 0.003, P < 0.001) in multiple linear regression analyses. The relationship between 4-t-OP and CIMT remained the same in all subgroups or if bisphenol A (BPA) was considered a covariate. In this study, we observed that higher levels of 4-t-OP levels were negatively correlated with markers of glucose homeostasis, BMI z score, and CIMT; positively correlated with lipid profiles (HDL-C and apolipoprotein A) in this cohort. Future research on exposure to 4-t-OP and CVD risk factors is warranted. Graphical abstract Image 1 Highlights • The association between serum 4-t-OP concentration, CVD risk factors and CIMT were studied among 886 young persons. • The serum 4-t-OP concentration was associated with CVD risk factors and CIMT. • The association between 4-t-OP and CIMT was remained the same in all subgroups. 4-tertiary-Octylphenol levels were correlated with CVD risk factors and subclinical atherosclerosis in this cohort of adolescents and young adults. [ABSTRACT FROM AUTHOR]

Abstract More than half of the world's population now lives in urban areas. Understanding the spatial distribution of suicide in these settings may inform prevention. Previous analyses of the spatial distribution of suicide in cities have largely been conducted in Western nations. We investigated the spatial pattern of suicide and factors associated with its spatial distribution in Taipei City, Taiwan. We estimated smoothed standardized mortality ratios for overall suicide and suicide by sex/age group across 432 neighborhoods (mean population size: 5500) in Taipei City (2004–2010) using Bayesian hierarchical models. A range of area-level characteristics including socioeconomic deprivation, social fragmentation, income inequality, and linking social capital were investigated for their associations with suicide mortality. Overall suicide rates were below average in the city center, whereas above average rates were found in some suburbs. The cartogram highlighted the concentration of suicide burden in one western area of the city. Male suicides demonstrated generally similar spatial patterning across age groups, while the geographic distribution of female suicides differed by age. After adjusting for other variables, two area characteristics were found to be associated with area suicide rates: the proportion of divorced/separated adults (rate ratio [RR] per one standard deviation increase = 1.08, 95% confidence interval 1.01–1.16), an indicator of social fragmentation; and median household income (RR = 0.80, 0.73–0.86), an indicator of socioeconomic deprivation. There was a 1.8-fold difference in suicide rates between neighborhood quintiles with the lowest and the highest median household income, with middle-aged males showing the largest gradient (3.2-fold difference). The geography of suicide in Taipei City showed spatial patterning and socioeconomic correlates distinct from cities in Western nations. There is a need for future research to better understand the correlates of change in the geographic distribution of suicide throughout the process of urban development. Highlights • Marked variations in suicide were found across neighbourhoods in Taipei City. • Low suicide rates were shown in the city center compared to some suburbs. • Around 60% of the variations could be explained by area characteristics studied. • Income and divorced/separated adults were linked with neighborhood suicide rates. • Socioeconomic inequality in suicide rates was strongest in middle-aged men. [ABSTRACT FROM AUTHOR]

Abstract Purpose The purpose of this study was to identify the characteristics of swallowing ability, depression, and dysphagia-specific health-related quality of life (QOL), and the predictors of dysphagia-specific health-related QOL in oral cavity cancer patients post-treatment. Methods A cross-sectional study of 151 oral cavity cancer patients was performed at a medical center. Patients were assessed for swallowing ability, depression, and dysphagia-specific health-related QOL. Multiple stepwise regression was used to identify factors related to dysphagia-specific health-related QOL. Results Of the 151 patients surveyed, the top swallowing impairments were difficulty swallowing dry foods, difficulty swallowing hard food, and swallowing problems interfering with enjoyment or QOL. Patients with tumors of the tongue had worse functional dysphagia QOL than those with cancers in other locations. Patients with buccal cancer had worse overall dysphagia QOL, functional dysphagia QOL, and physical dysphagia QOL than patients with cancers in other locations. Patients with poor swallowing ability were more likely to have worse global dysphagia QOL. Emotional dysphagia QOL was associated with poor swallowing ability and depression. Poor swallowing ability, higher level of depression, and tumors of the tongue were associated with the worst functional dysphagia QOL. Patients with poor swallowing ability, higher level of depression, and less functional oral intake were more likely to have worse physical dysphagia QOL. Conclusion Swallowing ability and depression were the most important factors associated with dysphagia-specific health-related QOL. Patient-centered swallowing rehabilitation programs are recommended to help cope with swallowing impairment. Highlights • Patients' top swallowing impairments was difficulty swallowing dry foods. • Patients with tumors of the tongue had worse functional dysphagia QOL than those with cancers in other locations. • Swallowing ability and depression were the most important factors associated with dysphagia-specific health-related QOL. [ABSTRACT FROM AUTHOR]

Acrylonitrile is a colorless volatile liquid mostly present in tobacco smoke. Acrylonitrile exposure has shown to increase oxidative stress in animal studies; however, there was no previous research in human epidemiology. In this study, 853 subjects were recruited from a cohort of Taiwanese adolescents and young adults to investigate the association between urinary concentrations of the acrylonitrile metabolite N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA), the oxidative stress product 8-hydroxydeoxyguanosine (8-OHdG) and cardiovascular disease (CVD) risk factors. The geometric mean (SD) of CEMA and 8-OHdG concentrations were 4.67 (8.61) μg/L and 2.97 (2.14) μg/L, respectively. 10% elevated in CEMA (μg/L) was positively correlated with the change of 8-OHdG levels (μg/L) (β = 0.325, SE = 0.105, P  = 0.002) in multiple linear regression analyses. The urinary CEMA was not related to other CVD risk factors. In subpopulation analyses, the association between CEMA and 8-OHdG was evident in all genders, adolescents, homeostasis model assessment of insulin resistance score ≥0.89, and environmental tobacco smokers. In this study, we observed that higher levels of CEMA levels were correlated with increased levels of 8-OHdG in this cohort. Future research on exposure to acrylonitrile and oxidative stress was warranted. [ABSTRACT FROM AUTHOR]