An all-in-one enzymatic DNA network based on catalytic hairpin assembly for label-free and highly sensitive detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), identified as a prospective cancer biomarker, plays a vital role in the occurrence and progression of cancer cell lines and impacts on genome stability. However, conventional approaches typically rely on the interactions between the antigen and antibody, limiting their utility for qualitative assessments of APE1 expression. Herein, an all-in-one enzymatic DNA network (EDN) assay with catalytic hairpin assembly for label-free and ultrasensitive detection of APE1 has been developed. In this work, the blocking strand can inhibit the initiator by obstructing the complementary region, preventing the hairpin from hybridizing in the absence of APE1 targets. While the presence of targets can activate the unlocking of the initiator, which can trigger the catalytic hairpin reaction, and increase the fluorescent signal. Under optimal conditions, the developed sensing method can detect the target APE1 down to 4.78 × 10-6 U mL-1 with a wide linear range from 5 × 10-6 U mL-1 to 30 U mL-1. This strategy has also been successfully applied to the analysis of complicated biological samples compared to ELISA, demonstrating its potential applications in biochemical and molecular biology research as well as clinical diagnostics. Overall, benefiting from the high amplification efficiency, this strategy has successfully and simply detected low-abundance APE1 without additional enzyme isolation steps, presenting great potential for clinical detection applications.

Risk of peripheral facial palsy following parenteral inactivated influenza vaccination in the elderly Chinese population.

Background: Concern about the risk of peripheral facial palsy (PFP) following vaccination is one reason for hesitancy in influenza vaccination. However, the association between the flu vaccine and PFP is still controversial, and further evidence is urgently needed. Methods: This self-controlled case series study evaluated PFP risk following inactivated influenza vaccine in the elderly using a large linked database in Ningbo, China. Relative incidence ratios (RIRs) and 95% confidence intervals (CIs) estimated using conditional Poisson regression were utilized to determine whether the risk of PFP was increased after vaccination. Results: This study included 467 episodes, which occurred in 244 females and 220 males. One hundred twenty-four episodes happened within 1-91 days after vaccination, accounting for 26.7%. The adjusted RIRs within 1-30 days, 31-60 days, 61-91 days, and 1-91 days after influenza vaccination were 0.95 (95% CI 0.69-1.30), 1.08 (95% CI 0.78-1.49), 1.01 (95% CI 0.70-1.45), and 1.00 (95% CI 0.81-1.24), respectively. Similar results were found in subgroup analyses and sensitivity analyses. Conclusions: Influenza vaccination does not increase PFP risk in the elderly population. This finding provides evidence to overcome concerns about facial paralysis after influenza vaccination.

Associations between reading and writing postures and myopia among school students in Ningbo, China.

Background: We conducted this study to investigate the prevalence of myopia among school students in Ningbo and to explore the associations between reading and writing postures and myopia. Methods: A population-based and cross-sectional study was conducted, and 3,256 school students aged 8-19 years were recruited. Each enrolled subject was assessed for uncorrected distance visual acuity (UDVA) using a standard logarithmic visual acuity E-chart and a non-cycloplegic autorefraction examination. Self-administered questionnaires were used to investigate myopia-related reading and writing postures and behavioral habits among school students. Results: The prevalence of myopia among primary school, middle school, and high school students was 61.49, 81.43, and 89.72%, respectively. Regarding the associations between reading and writing postures and myopia, we identified that a reading distance >33 cm is a protective factor for myopia in female students [odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.15-0.64], in both primary school (OR = 0.55, 95% CI = 0.30-0.99) and middle school (OR = 0.37, 95% CI = 0.15-0.90). Conclusions: A reading distance >33 cm can be used as an additional measure to prevent and control myopia. Proper postural measures for reading and writing may have educational and public health benefits.

Downregulation of serum survivin correlates with increased inflammation, enhanced disease severity and worse prognosis in sepsis patients.

This study aimed to determine the role of survivin in sepsis patients.Serum samples of 288 sepsis patients and 290 healthy individuals (as healthy controls) were collected 24 hours within enrollment. Serum survivin and inflammatory cytokines were detected by enzyme-linked immunosorbent assay, and biochemical indexes were recorded. In sepsis patients, acute pathologic and chronic health evaluation II score and sequential organ failure assessment score were evaluated, and 28-day mortality was recorded.Survivin was greatly decreased in sepsis patients compared to healthy controls (P < .001) and it predicted decreased sepsis risk (area under curve (AUC): 0.921, 95% confidence interval (CI): 0.900-0.942). For clinical characteristics of sepsis patients, survivin was negatively correlated with acute pathologic and chronic health evaluation II score (P < .001), score and sequential organ failure assessment score (P < .001), serum creatinine (P < .001), white blood cell (P = .037), C-reactive protein (P < .001), tumor necrosis factor-α (P < .001), interleukin (IL)-1ß (P < .001), IL-6 (P < .001), and IL-8 (P < .001), while positively correlated with albumin (P < .001). For prognosis of sepsis patients, survivin was decreased in deaths compared to survivors (P < .001), and it predicted decreased death risk (AUC: 0.625, 95% CI: 0.558-0.692). Meanwhile, accumulating mortality was decreased in survivin high patients compared to survivin low patients (P = .006). However, multivariate logistic regression revealed survivin was not an independent predictive factor for 28-day mortality, indicating it might interact with other independent factors to affect prognosis of sepsis patients.Survivin was decreased in sepsis patients and predicted decreased sepsis risk. Meanwhile, survivin was correlated with declined inflammation, reduced disease severity, and favorable prognosis in sepsis patients.

Decreased microRNA 103 and microRNA 107 predict increased risks of acute respiratory distress syndrome and 28-day mortality in sepsis patients.

We aimed to investigate the predictive value of microRNA 103 (MIR103) and microRNA 107 (MIR107) for acute respiratory distress syndrome (ARDS) risk, as well as their correlations with overall disease severity and prognosis in sepsis patients.Plasma samples were collected from 196 sepsis patients within 24 hours after enrollment and from 196 healthy individuals (as healthy controls (HCs)) at enrollment. Plasma MIR103 and MIR107 were detected by reverse transcription-quantitative polymerase chain reaction.MIR103 and MIR107 were both decreased in ARDS sepsis patients and non-ARDS sepsis patients compared to HCs, and were reduced in ARDS sepsis patients than non-ARDS sepsis patients. Decreased MIR103 (area under curve (AUC): 0.727, 95% confidence interval (CI): 0.619-0.835) and MIR107 (AUC: 0.694, 95% CI: 0.577-0.811) predicted increased ARDS risk in sepsis patients. Meanwhile, MIR103 and MIR107 were negatively correlated with acute pathologic and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, serum creatinine, C-reactive protein, tumor necrosis factor, interleukin 1ß, interleukin 6 and interleukin 8, while positively correlated with albumin in sepsis patients. For prognosis, 28-day mortality was increased in ARDS sepsis patients compared to non-ARDS sepsis patients. Finally, MIR103 and MIR107 were reduced in deaths than survivors of sepsis patients, and decreased MIR103 (AUC: 0.704, 95% CI: 0.626-0.782) as well as MIR107 (AUC: 0.649, 95% CI: 0.569-0.729) predicted increased 28-day mortality risk in sepsis patients.MiR-103 and MIR107 were predictive biomarkers for risks of ARDS and 28-day mortality in sepsis patients, which might improve the management of sepsis.

Exposure Factor considerations for safety evaluation of modern disposable diapers.

Modern disposable diapers are complex products and ubiquitous globally. A robust safety assessment for disposable diapers include two important exposure parameters, i) frequency of diaper use & ii) constituent transfer from diaper to skin from direct and indirect skin contact materials. This article uses published information and original studies to quantify the exposure parameters for diapers. Using growth tables for the first three years of diapered life, an average body weight of 10-11 kg can be calculated, with a 10th percentile for females (8.5-8.8 kg). Data from surveys and diary studies were conducted to determine the frequency of use of diapers. The overall mean in the US is 4.7 diapers per day with a 75th, 90th, and 95th percentile of 5.0, 6.0, and 7.0 respectively. Using diaper topsheet-lotion transfer as a model, direct transfer to skin from the topsheet was 3.0-4.3% of the starting amount of lotion. Indirect transfer of diaper core materials as a measure of re-wetting of the skin via urine resurfacing back to the topsheet under pressure was estimated at a range of 0.32-0.66% averaging 0.46%. As described, a thorough data-based understanding of exposure is critical for a robust exposure based safety assessment of disposable diapers.

Probabilistic Monte Carlo estimation for quantitative exposure assessment of lotion transfer via baby wipes usage.

Unique aspects of childhood exposure to products need childs specific exposure data. This study developed a probabilistic exposure model for lotion transfer to diapered skin through normal use of baby wipes in children up to 48 months of age. Monte Carlo simulations used baby wipe diary data from the US, Germany and the UK, body weight data from the US, and lotion transfer data from single and multiple wipes adjusting for separate diaper changes. The models predicted a declining number of wipes used/day with a reduction in lotion transfer as age and body weight increased. Experimental testing on multiple sequential wipes used on an overlapping area showed a reduction in lotion deposition by 23.9% after the first wipe. Overall, the weighted population average over the approximate diapering period of 0-36 months across the three geographies at 50th, 90th, & 95th percentiles, were between 130, 230, 260 mg/kg/day, respectively, and 150, 270, 310 mg/kg/day depending on whether a reduction due to overlap is implemented. The statistical model represents an effective strategy to determine exposure to baby wipes lotion for exposure based risk assessment.

Assessing the dermal compatibility of a new female incontinence product line.

CONTEXT: We have developed a line of products designed to better meet the overall needs of women suffering from urinary incontinence. The products are more discrete and contain a unique odor neutralizing technology (ONT). OBJECTIVE: This paper describes the overall skin compatibility program for this product line in which the new products were compared to negative controls and/or commercially marketed reference products with an established history of safe use. MATERIALS AND METHODS: Test products consisted of several product forms (light pads/pantiliners, moderate pads, briefs and taped diapers) with ONT and having various degrees of protection. Studies were conducted using standard protocols for 4-day and 21-day cumulative irritation, the Human Repeat Insult Patch Test (HRIPT), and the Behind-the-Knee (BTK) test for mechanical and chemical irritation. In one 4-day irritation study and one HRIPT, test subjects consisted of individuals with self-assessed sensitive skin. In addition, one 4-day study was conducted using normal skin sites, and sites compromised by tape stripping. Nonirritant controls were physiologic saline and/or current, commercially marketed incontinence products. All responses were evaluated by visual scoring of erythema. In addition, in the BTK, transepidermal water loss (TEWL) and adverse sensory effects collected from panelists' daily diaries were also evaluated. RESULTS AND DISCUSSION: Two 4-day cumulative irritation studies and one 21-day study demonstrated that a wide range of product forms (liners, light and moderate pads, briefs and adult diapers) produced skin reactions similar to the nonirritant controls. The 4-day study conducted using sensitive skin subjects showed good skin compatibility, and the test products were comparable to the nonirritant controls. In the 4-day study with both normal and compromised skin sites, test products produced mean erythema scores similar to the nonirritant controls. Three HRIPT separate studies confirm that the products do not induce contact sensitization, including one study conducted on individuals with self-assessed sensitive skin. In the BTK, test and control products produced similar irritation, as assessed by erythema, TEWL and sensory effects. CONCLUSION: The results from the patch tests and mechanical irritation test demonstrate good skin compatibility of the new line of products with the unique ONT. In addition, the forms of the product (i.e. liner, pad or brief), were equally compatible with skin.

Safety, immunization coverage and determinants of a new kind of Hepatitis B vaccine firstly applied in Ningbo, China.

Evaluate safety and immunization coverage of a new kind of recombinant Hepatitis B vaccine (HepB) in Ningbo city, China. Two groups were carried out in 2 of 11 randomly selected countries in Ningbo in 2009. All of the infants born from July 1 to December 31, 2009 were enrolled as subjects and received 3 doses of HepB at 0, 1, 6 month. Control group (N = 3452) received current HepB derived from Saccharomyces Cerevisiae Yeast (HepB made by recombinant DNA techniques in Saccharomyces Cerevisiae Yeast, HepB-SCY; 5 µg/0.5 ml per dose) and experimental group (N = 5104) received the new kind of HepB derived from Hansenula polymorpha Yeast (HepB made by recombinant DNA techniques in Hansenula polymorpha Yeast, HepB-HPY; 10 µg/0.5 ml per dose). 3-dose and timely birth dose (TBD) coverage were available and compared between 2 groups. Standard structured questionnaires were applied to record information from parents and hospitals for selecting determinants of coverage. The data were analyzed using stepwise multiple logistic regression models. After each dose, HepB-related adverse events (AEs) and recta-temperature were recorded for 7 days. 3-dose coverage in control group (89.98%) was higher than that in experimental group (χ2 = 575.1173, P < 0.0001). TBD coverage in control and experimental group were 98.41% and 98.53%, respectively. No statistically significant difference in TBD coverage was found between 2 groups (χ2 = 0.0623, P = 0.8029). A total of 9 local AEs were reported, 4 for control group and 5 for experimental group. The percentages of subjects reporting AEs were similar across the 2 vaccination groups. No serious or immediate reactions were found in this study. From logistic models, receiving 10 µg vaccine (odds ratio [OR]:0.38; 95% confidence interval [95%CI]: 0.34-0.44) and mother migrating from other cities (OR: 0.45; 95%CI: 0.42-0.47) were the determinants for non-acceptance of 3 doses of HepB; infants born from low grade hospitals and native mothers contributed to administrate the TBD.

An in vitro skin penetration model for compromised skin: estimating penetration of polyethylene glycol [¹4C]-PEG-7 phosphate.

BACKGROUND/AIMS: Establishing dermal penetration rates is important to better understand the safety of topically applied materials, especially for premature infant skin with compromised skin barrier function. Skin prematurity involves thinner stratum corneum and underdeveloped epidermis/dermis resulting in decreased barrier function, higher transepidermal water loss and greater chemical penetration, when compared to healthy full-term neonate/adult skin. METHODS: We developed an in vitro skin penetration model using human ex vivo skin to estimate penetration for premature/compromised skin barrier conditions by tape stripping. Skin barrier deficiency was characterized by transepidermal water loss. Baby wipe lotion containing 5 mg/cm(2) [(14)C]-PEG-7 phosphate was applied 5 times to human skin samples of intact, moderately or highly compromised skin barrier and once at 25 mg/cm(2) over 24 h. RESULTS: Overall penetration of [(14)C]-PEG-7 phosphate was low (<5%) even for highly compromised skin. The absorption rate was higher (p < 0.001) for compromised skin versus intact skin. No significant difference was seen between moderately and highly compromised skin by repeated dosing. Under single-dose conditions, penetration through highly compromised skin was significantly higher compared to intact skin (p = 0.001). CONCLUSION: Our model demonstrates that even under highly compromised skin conditions, penetration of [(14)C]-PEG-7 phosphate is low (<5%) and only 4-6 times higher compared to mature/intact skin and does not approach 100%. Penetration was unaffected by single or multiple dosing conditions.

Safety of Disposable Diaper Materials: Extensive Evaluations Validate Use.

Disposable diapers are primarily composed of polymers, such as cellulose, polypropylene, polyester, and polyethylene, which are biologically inert and not bioavailable. They are used in clothes, fabrics, personal hygiene products, and other materials that are commonly in contact with the skin. Each component used throughout the production process must undergo rigorous safety evaluations and assessments and are proven to be well tolerated and safe for their intended uses. No materials are incorporated into a diaper until their safety is confirmed through robust assessments, and additional factors are integrated into the process to compensate for the uncertainty associated with extrapolating toxicity data. After a thorough assessment of the materials and final product, extensive skin compatibility evaluations are conducted as appropriate. This rigorous safety process provides reassurance that consumers can rely on the safety of these diapers.

[Use of threshold of toxicological concern for chemical substances safety assessment].

The threshold of toxicological concern (TTC) approach is a risk assessment tool of toxicology. When the exposure dose of human body is below the TTC of chemicals, the likelihood of that chemical causing negative influence on the human health is very low. Earliest, TTC approach was used in the risk assessment of in the respect of the food packing materials. Currently, TTC approach is used for safety assessment in the fields of food packing material, flavoring agents, medicine, industry chemicals, cosmetics, and etc. TTC approach provides useful assessment tool for the safety evaluation for the chemical substances.

Long-term clinical observation of the immunogenicity of inactivated hepatitis A vaccine in children.

110 children who were given the complete course of the inactivated hepatitis A vaccine (Havrix) were followed up 10 years later. Age-matched healthy children who were not inoculated served as controls. One month after two primary injections, all children were positive for serum antibody. After 10 years, 99.09% of inoculated children remained positive for serum anti-HAV antibody, with a geometric mean concentration (GMC) of 61.59mIU/mL. GMC values following a secondary immunization in children with antibody levels <20mIU/mL were significantly elevated (567.9mIU/mL), compared with the primary injection alone. Havrix appears to induce persistent immunity and potent immune memory.

[Levels of transition on maternal transferred measles antibody in infants in 3 cities in China].

OBJECTIVE: To understand the epidemiological characteristics of age distribution of measles and related policies on measles vaccines (live; MV) in infants through analyzing the antibody levels of comparison in maternal-infant pairs. Transition of immunity in infants was also studied to provide theoretic basis for measles immunization strategy and to reduce the incidence of month-old infants. METHODS: In cities of Ningbo, Harbin, and Jinan from Zhejiang, Heilongjiang and Shandong provinces, data was collected from 2004 to 2007 and analyzed regarding the epidemic situation of measles. Studies on maternal-transferred measles antibody were carried our sero-epidemiologically. RESULTS: Most of the measles cases were found among babies younger than 12 months, and the incidence of < 1 year olds had been increasing. The distribution was dominated by 5 - 8 month olds in infant measles cases. The positive rate and GRMT of measles antibody in newborns were 89.3 percent and 738.93. The positive rate of the measles antibody and GMRT of the 6-month infant were 6.9% and 6.89, while 6.7% and 3.69 in 8-month infant. There was a declining trend of the positive rate of the measles antibody during the newborns to 8-month infant. The positive rate and GRMT of measles antibody in mothers were 84.3 percent and 516.94. Mother's measles antibodies mainly to be at low and moderate level, which accounted for 50.4 percent and 30.3 percent respectively, the correlation coefficient between mother and infant was 0.840. CONCLUSION: Maternal-transferred measles antibody decreased as the growth of infants. The positive rates of measles antibody were quite low in 6-month and 8-month olds which were the age range that needs most attention.