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The use of oral nutritional supplements (ONS) in the hospital setting is important to reach individual protein and energy goals in patients at risk for malnutrition. Compliance with ONS can be challenging but may be improved by prescribing ONS in smaller portions with medication rounds (MEDPass). We compared the likelihood of meeting energy and protein requirements in patients receiving ONS with MEDPass versus conventional ONS administration. The MEDPass Trial is a randomized, controlled, open-label superiority trial conducted on medical and geriatric wards in a University Hospital in Switzerland. The MEDPass group was allocated to receive 50 ml of ONS four times per day with the medication rounds. The control group received ONS per conventional care between the meals. The primary outcome was the percentage of energy in relation to the individual requirement. Secondary outcomes included the coverage of protein intake in relation to the individual requirement, the amount of daily consumed ONS, the course of handgrip strength (HGS), body weight appetite and nausea. Furthermore, we compared 30-day mortality and hospital length of stay (LOS) was studied in medical patients. From November 22nd, 2018 until November 30th, 2021, 204 patients were included in the trial (MEDPass group n = 100, control group n = 104). A total of 203 patients at nutritional risk were analyzed in the intention-to-treat analysis (ITT). Regarding the primary endpoint, there was no difference in the coverage of energy requirement between the MEDPass and control group (82 vs. 85% (Δ −3%, 95%CI -11 to 4%), p = 0.38). Similarly, no differences were found for the secondary outcomes including coverage of protein requirement (101 vs. 104% (Δ −3%, 95% CI -12 -7%), p = 0.57, average daily intake of ONS (170 vs 173 ml (Δ – 3 ml, 95% CI -14 to 8 ml), p = 0.58) and 30-day mortality (3 vs. 8 patients, OR 0.4 (95% CI 0.1–1.4), p = 0.15). The course of HGS, body weight, appetite and nausea did not differ between the groups (p = 0.29, p = 0.14, p = 0.65 and p = 0.94, respectively). The per protocol analysis including 178 patients showed similar results. Within this controlled trial setting, we found a high compliance for ONS intake and high coverage of protein requirements but no further improvement when ONS was administered using MEDPass compared to conventional care. MEDPass administration may provide an alternative that is easy to integrate into nursing routines, which may lead to lower workload with cost benefits and reduction of food waste. ClinicalTrials.gov: NCT03761680. [ABSTRACT FROM AUTHOR]

Among complications of malnutrition secondary to anorexia nervosa (AN) or atypical anorexia nervosa (AAN), renal impairment remains poorly elucidated. Evaluating renal function in hospitalized pediatric patients with AN and AAN undergoing refeeding will yield important information to guide clinicians in screening and managing renal dysfunction in this population. This is a secondary analysis of data from the Study of Refeeding to Optimize Inpatient Gains trial, a multicenter randomized clinical trial comparing higher calorie refeeding versus lower calorie refeeding in 120 adolescents and young adults hospitalized with medical instability secondary to AN or AAN. Baseline disease characteristics were obtained. Vital sign measurements, weight, electrolytes, and fluid status were evaluated daily to ascertain medical stability. Renal function on admission and throughout hospitalization was quantified using daily creatinine measurement and calculation of the estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. Regression analysis and mixed linear models were utilized to evaluate factors associated with eGFR. Of the 111 participants who completed treatment protocol, 33% had a baseline eGFR less than 90, suggesting renal impairment. Patients who experienced more rapid weight loss and more severe bradycardia were more likely to have low admission eGFR. While eGFR improved during refeeding, eGFR change by day based on refeeding treatment assignment did not reach statistical significance (95% confidence interval, −1.61, 0.15]; p =.095). Renal impairment is evident on admission in a significant number of adolescents and young adults hospitalized with AN and AAN. We demonstrate that short-term medical refeeding yields improvement in renal function. [ABSTRACT FROM AUTHOR]

Shipping emissions were measured in Dunkirk, France. Elevated aerosol extinction coefficients (AEC), nitrogen dioxide (NO 2) and sulphur dioxide (SO 2) were observed up to 500 m from surface. Formaldehyde (HCHO) did not show an increase every time, which suggests that oxidation of emitted volatile organic compounds (VOCs) took longer than the transport to the observation path and dilution of direct emissions had occurred. Background NO 2, HCHO, and SO 2 levels were higher when the wind came over land or the surrounding industrial area, indicating that land-based sources contribute significantly; however, clear spikes in NO 2 and SO 2 were observed whenever ship plumes were sampled. Observations show that the ship emission contribution to pollution is significant, but land-based sources still dominate. The SO 2 /NO 2 ratio was low throughout the campaign, although varying according to the ship type, confirming that the new fuel content regulations are being followed by most ships in this region. • A month-long campaign shows that ship emissions in the North Sea usually have low sulphur content. • In ship plumes, an increase in aerosol extinction coefficients, NO 2 and SO 2 was measured; HCHO did not increase every time. • Land-based emissions dominate absolute concentrations of pollutants, but ship emissions contribute significantly to them. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to determine whether a provider mobile phone application, used with or without a patient educational tool accessed on a computer tablet, would promote adherence to guidelines for cervical cancer screening and management of abnormal cytology in young women.Methods: The study was conducted as a prospective cohort study in which 14 Family Planning, Access, Care, and Treatment provider clinics were randomized to 1 of 2 arms: (1) provider mobile phone application only or (2) provider mobile phone application plus patient educational tool. The provider mobile phone application gave information to providers regarding cervical cancer screening and management of abnormal cytology. The patient educational tool accessed on a computer tablet was a patient-centered educational tool. Each arm was compared with clinic control groups (no intervention) in a 2:1 ratio (control:intervention). Claims data were used to calculate and compare 18-month cytology (Pap) and colposcopy rates before the intervention and during the 18 months using the Poisson mixed-effect regression model. A sensitivity analysis examined the differences in the rate of change between each arm and controls. The study took place between July 2015 and December 2016, and analysis was performed in 2019.Results: The clinics randomized to the provider mobile phone application plus patient educational tool arm and their control group achieved similar 18-month Pap rates (0.52, 95% CI=0.37, 0.74 and 0.68, 95% CI=0.53, 0.86, respectively) as well as the provider mobile phone application arm and their control group (0.44, 95% CI=0.33, 0.58 and 0.41, 95% CI=0.34, 0.51; p-values >0.1). In the sensitivity analysis, the difference in the rate of change in Pap rates for the provider mobile phone application plus patient educational tool arm and their control group before and during the intervention was -0.22 and -0.09, respectively (p=0.02), but no differences were seen between the provider mobile phone application arm and their control group. No significant changes were observed for colposcopy rates.Conclusions: Providing clinicians and patients with information on guidelines had no demonstrable effect on 18-month Pap and colposcopy rates in the regression model; however, results from the sensitivity analysis for the patient educational tool were encouraging.Trial Registration: This study is registered at www.clinicaltrials.gov NCT02270021. [ABSTRACT FROM AUTHOR]

• The Regional Innovation System (RIS) needs revision to explain innovation in China. • Concept development is approached through qualitative methods to work critically. • In Chongqing, innovation is organised through two different RIS frameworks. • Institutional conditions in China hamper the convergence of the frameworks. • "Two RIS in one region" helps analysing transformation of China's innovation model. The Regional Innovation System (RIS) is a popular concept for approaching research on geographies of innovation. Political research and innovation studies in emerging economies suggest that there are much different institutional preconditions for and far more types of innovation than hitherto considered. It is thus unlikely that the RIS model as derived from "best practice" cases in the Global North has sufficient explanatory power for regional innovation dynamics in less developed regions in China. From an empirical qualitative analysis on Chongqing, China, as a non-"best practice" case, we find that it is more appropriate to consider separate RIS within one region. The analysis shows that different RIS-frameworks matter for different actors, who engage in different types of innovation. These frameworks are exclusive and do not provide their functions equally to all innovation actors in place. The separation of RIS frameworks acknowledges the co-existence of different structures and trajectories, which is explicitly helpful for understanding regional innovation dynamics in China, where the national government currently aims to transform its innovation model from state-control to an open system of innovation. This paper further discusses how the notion of separate RIS is more appropriate for capturing regional innovation dynamics in the Chinese context in contrast to previous concepts of emerging RIS or fragmented regions. [ABSTRACT FROM AUTHOR]

Angiogenesis is a crucial process for the maintenance of normal tissue physiology and it is involved in tissue remodeling and regeneration. This process is essential for adipose tissue maintenance. The adipose tissue is composed by different cell types including stromal vascular cells as well as adipose stem cells (ASCs). In particular, ASCs are multipotent somatic stem cells that are able to differentiate and secrete several growth factors; they are recently emerging as a new cell reservoir for novel therapies and strategies in many diseases. Several studies suggest that ASCs have peculiar properties and participate in different disease-related processes such as angiogenesis. Furthermore, pathological expansion of adipose tissue brings to hypoxia, a major condition of unhealthy angiogenesis. Recent evidences have shown that microRNAs (miRNAs) play a crucial role also on ASCs as they take part in stemness maintenance, proliferation, and differentiation. It has been suggested that some miRNAs (MIR126, MIR31, MIR221 MIR222, MIR17-92 cluster, MIR30, MIR100 and MIR486) are directly involved in the angiogenic process by controlling multiple genes involved in this pathway. With the present review, we aim at providing an updated summary of the importance of adipose tissue under physiological and pathological conditions and of its relationship with neovascularization process. In particular, we report an overview of the most important miRNAs involved in angiogenesis focusing on ASCs. Hopefully the data presented will bring benefit in developing new therapeutic strategies. [ABSTRACT FROM AUTHOR]

The higher concentrations of atmospheric particles, such as black carbon (BC) and organic matter (OM), detected in streets compared to the urban background are predominantly attributed to road traffic. The integration of this source of pollutant in air quality models nevertheless entails a high degree of uncertainty and some other sources may be missing. Through sensitivity scenarios, the impacts on pollutant concentrations of sensitivities related to traffic and road-asphalt emissions are evaluated. The 3D Eulerian model Polair3D and the street network model MUNICH are applied to simulate various scenarios and their impacts at the regional and local scales. They are coupled with the modular box model SSH-aerosol to represent formation and aging of primary and secondary gas and particles. Traffic emissions are calculated with the COPERT methodology. Using recent volatile organic compound speciations for light vehicles with more detailed information pertaining to intermediate, semi- and low-volatile organic compounds (I/S/LVOCs) leads to limited reductions of OM concentrations (10% in streets). Changing the method of estimating I/S/LVOC emissions leads to an average reduction of 60% at emission and a decrease of the OM concentrations of 27% at the local scale. An increase in 219% of BC emissions from tire wear, consistent with the uncertainties found in the literature, doubles the BC concentrations at the local scale, which remain underestimated compared to observations. I/S/LVOC emissions are several orders of magnitude higher when considering emissions from road asphalt due to pavement heating and exposure to sunlight. However, simulated concentrations of PM at the local scale remain within acceptable ranges compared to observations. These results suggest that more information is needed on I/S/LVOCs and non-exhaust sources (tire, brake and road abrasion) that impact the particle concentration. Furthermore, currently unconsidered emission sources such as road asphalt may have non-negligible impacts on pollutant concentrations in streets. • Traffic emission uncertainties have more impact at street scale than city scale. • Organic matter concentrations are reduced with the use of recent VOC speciations. • The COPERT methodology may underestimate tyre-wear emissions. • Road asphalt emission is a missing source for organic matter concentrations. [ABSTRACT FROM AUTHOR]

The atmospheric chemistry of (CH 3 ) 3 CNH 2 ( tert -butylamine, t BA) and (CH 3 ) 2 (CH 2 OH)CNH 2 (2-amino-2-methyl-1-propanol, AMP) has been studied by quantum chemistry methods and in photo-oxidation experiments in the EUPHORE chamber in Valencia (Spain). Aerosol formation and composition has been quantified. Yields of nitramines and other products in the photo-oxidations have been determined and complete photo-oxidation schemes including branching between the major reaction routes have been obtained. [ABSTRACT FROM AUTHOR]

While the problem of Pressure Ulcers (PU) in adults has received a great deal of attention, far less is known about PUs in neonates and children. The overall health status of children is generally better and multi-morbidity is limited to a small percentage of patients, like very low term neonates (born before 32 weeks of gestation age), newborns with congenital abnormalities, genetic disorders, perinatal distress syndrome or children with a limited immunity. Survival rates of both critically and chronically ill neonates, infants and children have improved dramatically in recent years, introducing new challenges for medical and nursing care. Children's skin undergoes several changes throughout the first 18 years of life. The most important function of the skin is to protect against water loss, absorptions of noxious substances, intrusions of microorganisms and physical trauma. Effective PU prevention includes device related under-padding and careful positioning and fixation of such devices. At least regular head-to-toe-skin assessment of neonates and infants at risk of PUs should be performed. [ABSTRACT FROM AUTHOR]

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks. [ABSTRACT FROM AUTHOR]

The arts offer alternative insights into reality, which are explored by science in general, and broadened by the activities conducted by the European Space Agency [4] and other space agencies. Similar to the way the members of ESA are ambassadors for spaceflight and science, artists and cultural professionals are ambassadors for human expression, experimentation, and exploration. In June 2011, the ESA Topical Team Arts and Sciences (ETTAS) held a three-day workshop at the European Astronaut Centre in Cologne, Germany. During this workshop, topics and ideas were discussed to develop initiatives between the arts, sciences and ESA. The aim was to foster and expand the human and cultural aspects of space exploration, and at the same time offer a means of communication that aims to reach audiences beyond the scope of traditional space-related channels. The consensus of the team was that establishing and sustaining a transdisciplinary professional community consisting of ESA representatives, scientists and artists would fuel knowledge transfer, and mutual inspiration. Potential ways to provide a sustainable cooperation within and between the various groups were discussed. We present the preliminary findings including a number of measures and mechanisms to initiate and conduct such an initiative. Plausible organisational measures, procedures and consequences, as well as a proposition on how to proceed are also discussed. Overall, the involvement and cooperation between the arts, space science research and ESA will enhance in the citizens of the ESA member states the sense of public ownership of ESA results, and participation in ESA׳s research. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study examined risk factors associated with recent substance use (SU) among perinatally human immunodeficiency virus (HIV)-infected (PHIV+) and perinatally exposed, uninfected (PHEU) youth and compared SU lifetime prevalence with the general population of United States (U.S.) adolescents. Methods: We conducted cross-sectional and longitudinal analyses of 511 PHIV+ and PHEU youth (mean age at study entry, 13.2 years; 51% female; 69% PHIV+; and 72% African-American) enrolled in a U.S. multisite prospective cohort study between 2007 and 2009. Substance use data were collected by audio computer–assisted self-interview. Youth Risk Behavior Surveillance System and Monitoring the Future data were used to compare SU lifetime prevalence with U.S. samples. Results: Perinatal HIV infection was not a statistically significant risk factor for alcohol or marijuana use. Risk factors for alcohol use among PHIV+ youth included higher severity of emotional and conduct problems and alcohol and marijuana use in the home by the caregiver or others. Risk factors for marijuana use among PHIV+ youth included marijuana use in the home, higher severity of conduct problems, and stressful life events. Similar SU risk factors among PHEU youth included SU in the home and higher severity of conduct and emotional problems. Overall lifetime prevalence of SU by age was similar to that in national surveys. Conclusions: Although SU lifetime prevalence and risk factors for PHIV+ and PHEU adolescents were similar to national norms, the negative consequences are potentially greater for PHIV+ youth. Prevention efforts should begin before SU initiation and address the family and social environment and youth mental health status. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Current recommendations for refeeding in anorexia nervosa (AN) are conservative, beginning around 1,200 calories to avoid refeeding syndrome. We previously showed poor weight gain and long hospital stay using this approach and hypothesized that a higher calorie approach would improve outcomes. Methods: Adolescents hospitalized for malnutrition due to AN were included in this quasi-experimental study comparing lower and higher calories during refeeding. Participants enrolled between 2002 and 2012; higher calories were prescribed starting around 2008. Daily prospective measures included weight, heart rate, temperature, hydration markers and serum phosphorus. Participants received formula only to replace refused food. Percent Median Body Mass Index (%MBMI) was calculated using 50th percentile body mass index for age and sex. Unpaired t-tests compared two groups split at 1,200 calories. Results: Fifty-six adolescents with mean (±SEM) age 16.2 (±.3) years and admit %MBMI 79.2% (±1.5%) were hospitalized for 14.9 (±.9) days. The only significant difference between groups (N = 28 each) at baseline was starting calories (1,764 [±60] vs. 1,093 [±28], p < .001). Participants on higher calories had faster weight gain (.46 [±.04] vs. .26 [±.03] %MBMI/day, p < .001), greater daily calorie advances (122 [±8] vs. 98 [±6], p = .024), shorter hospital stay (11.9 [±1.0] vs. 17.6 [±1.2] days, p < .001), and a greater tendency to receive phosphate supplementation (12 vs. 8 participants, p = .273). Conclusions: Higher calorie diets produced faster weight gain in hospitalized adolescents with AN as compared with the currently recommended lower calorie diets. No cases of the refeeding syndrome were seen using phosphate supplementation. These findings lend further support to the move toward more aggressive refeeding in AN. [Copyright &y& Elsevier]

Abstract: Purpose: Current refeeding recommendations for adolescents hospitalized with anorexia nervosa (AN) are conservative, starting with low calories and advancing slowly to avoid refeeding syndrome. The purpose of this study was to examine weight change and clinical outcomes in hospitalized adolescents with AN on a recommended refeeding protocol. Methods: Adolescents aged 13.1–20.5 years were followed during hospitalization for AN. Weight, vital signs, electrolytes, and 24-hour fluid balance were measured daily. Percent median body mass index (%MBMI) was calculated as 50th percentile BMI for age and gender. Calories were prescribed on admission and were increased every other day. Results: Thirty-five subjects with a mean (SD) age of 16.2 (1.9) years participated over 16.7 (6.4) days. Calories increased from 1,205 (289) to 2,668 (387). No subjects had refeeding syndrome; 20% had low serum phosphorus. Percent MBMI increased from 80.1 (11.5) to 84.5 (9.6); overall gain was 2.10 (1.98) kg. However, 83% of subjects initially lost weight. Mean %MBMI did not increase significantly until day 8. Higher calories prescribed at baseline were significantly associated with faster weight gain (p = .003) and shorter hospital stay (p = .030) in multivariate regression models adjusted for %MBMI and lowest heart rate on admission. Conclusions: Hospitalized adolescents with AN demonstrated initial weight loss and slow weight gain on a recommended refeeding protocol. Higher calorie diets instituted at admission predicted faster weight gain and shorter hospital stay. These findings support the development of more aggressive feeding strategies in adolescents hospitalized with AN. Further research is needed to identify caloric and supplementation regimens to maximize weight gain safely while avoiding refeeding syndrome. [Copyright &y& Elsevier]

Abstract: The atmospheric photo-oxidation of 2-aminoethanol (MEA, NH2CH2CH2OH) was studied at the European Photochemical Reactor, EUPHORE, in Valencia (Spain). The experiments were carried out under different atmospherically relevant NOx conditions. The photo-oxidation was monitored in situ by FT-IR and on-line by PTR-TOF-MS, and samples were collected on various adsorbents for subsequent off-line analysis. The formation of particles was monitored by SMPS and AMS on-line instruments and filter sampling followed by LC/HRMS(TOF) analysis. The obtained results suggest that more than 80% of the reaction between MEA and OH radicals takes place at–CH2–, while less than 10% occurs at–NH2 and at–CH2OH, respectively. The major observed products (>80%) in the photo-oxidation were formamide (NH2CHO) and formaldehyde (CH2O). Minor detected products (<10%) were amino acetaldehyde (NH2CH2CHO) and 2-oxo acetamide (NH2C(O)CHO). 2-nitroamino ethanol, O2NNHCH2CH2OH, was confirmed as product in the experiments. [Copyright &y& Elsevier]

Abstract: Purpose: To examine using functional magnetic resonance imaging whether adolescents with low levels of nicotine exposure (light smokers) display neural activation in areas shown to be involved with addiction in response to smoking-related stimuli. Design/Setting/Participants: A total of 12 adolescent light smokers (aged 13–17, who smoked 1–5 cigarettes per day) and 12 nonsmokers (ages 13–17, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, the adolescents were shown photographic blocks of smoking and control cues. Smoking cues comprised pictures of individuals smoking cigarettes and smoking-related objects such as lighters and ashtrays. Neutral cues comprised images of everyday objects and individuals engaged in daily activities. Findings: For smokers, smoking cues elicited greater activation than neutral cues in the mesolimbic reward circuit (left anterior cingulate: t = 7.04, p < .001; right hippocampus: t = 6.37, p < .001). We found activation from smoking cues versus neutral cues within both the left and right frontal medial orbital regions (t = 5.09, p < .001 and t = 3.94, p = .001, respectively). Nonsmokers showed no significant difference in activation between smoking-related cues and neutral cues. Conclusion: Our finding that smoking cues produced activation in adolescent light smokers in brain regions, similar to that seen in adult and teenage heavy smokers, suggests that adolescents exhibit heightened reactivity to smoking cues even at low levels of smoking. This article adds to the existing published data by suggesting that nicotine dependence may begin with exposure to low levels of nicotine, thus underscoring the need for early intervention among adolescent smokers. [Copyright &y& Elsevier]

Abstract: Purpose: Few studies have examined the relationships between sexual or hygienic behaviors and human papillomavirus (HPV) transmission. Our objectives were to (1) describe HPV concordance between the anogenital, oral, and palmar areas of monogamous heterosexual couples; and (2) determine sexual behaviors, hygienic practices, sexual histories, and subject characteristics associated with HPV anogenital concordance. Methods: Couples were recruited from women who developed an incident HPV infection while being enrolled in a longitudinal HPV natural history study that recruited from two family-planning clinics. Men were their monogamous partners of at least 3 months. Samples were tested for HPV-DNA of 37 high- and low-risk genotypes. Questionnaires completed privately assessed health, sexual, hygienic history, and behaviors. Results: A total of 25 couples enrolled between February 2006 and July 2007; none had received HPV vaccine. The average age was 25 years (SD, 6) for men and 23 years (SD, 3) for women. HPV-84 was the most commonly shared HPV type in the anogenital and palmar areas. HPV-16 was the only shared oral-HPV type. Sixty-eight percent of couples had type-specific anogenital concordance. Receiving finger-anal sex (p = .05), sharing towels (p = .04), longer time since last intercourse (women: p = .03, men: p = .02 men), and men washing their genitals after sex (p = .03) were associated with decreased likelihood of concordance. Persistence of incident HPV types in women was associated with HPV in men (p = .002). Conclusions: Our findings show that certain hygienic and sexual behaviors are associated with anogenital concordance between healthy, monogamous, heterosexual couples. Future studies are needed to see whether these detections reflect contamination, transient, or established infections. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To examine the longitudinal changes in the epithelial topography of the cervix in healthy young women; and to determine the sociodemographic, behavioral, and biological factors associated with the rate of cervical epithelial maturation. Methods: Healthy young women were enrolled from October 2000 to September 2002 as part of a larger study of human papillomavirus (HPV). At interval visits, interviews, infection testing, and colpophotography (3% acetic acid; 10x, 16x magnifications) were performed. Areas of total cervical face and cervical immaturity, defined as columnar and early squamous metaplasia, were quantitatively measured using computerized planimetry. Cervical immaturity was expressed as percentage of total cervical face. This analysis includes the first consecutive 145 women with greater than 10% immaturity at baseline. The rate of cervical maturation was defined as change in percent-immaturity. Predictors included sociodemographics, sexual behaviors, and infections. Data analyses included multivariate generalized linear models with repeated measures. Results: The baseline mean age was 17.8 years. Colpophotographs were available from 815 total visits, representing 2.7 years mean follow-up per woman and 5.9-month mean intervals. Women began the study with a median of 39% immaturity and ended with 8% immaturity. After adjusting for time and baseline percent-immaturity, an increased rate of cervical maturation was associated with oral contraceptive pill use (parameter estimate −.023, p =.04) and smoking (−.039, p =.01). Conclusions: Cervical maturation was documented during relatively short time periods for the vast majority of these women. Oral contraceptive pills and smoking may accelerate the maturational process, representing increased cell proliferation and thus a possible greater vulnerability to HPV. [Copyright &y& Elsevier]

Abstract: Purpose: To investigate whether factors influencing body composition may be unique for male and female adolescents with horizontal transmission of human immunodeficiency virus (HIV). Methods: HIV infected and uninfected youth (aged 13–18 years) participating in the multi-center project REACH (Reaching for Excellence on Adolescent Health Care) had at baseline anthropomorphic measurements including height, weight, bicep, tricep, subscapular and suprailiac skinfold measurements and midarm circumference. Body mass index, muscle mass, fat free body mass, and fat mass were calculated and predictors of these measures were assessed using multiple variable linear regression. Predictors included contraception, HIV status and related variables (CD4 counts, treatment status, and viral load), substance use, androgen levels as well as appetite changes, and bone age. Results: In multiple variable linear regression analysis, female adolescents’ body composition was associated with HIV status, CD4 + T cell counts, and free testosterone levels. HIV status was found associated with higher fat and lean body mass, however lower CD4+T cell counts were associated with lower fat and lean body mass. Higher testosterone levels were associated with higher lean and fat mass. For adolescent males, higher total testosterone levels but not free testosterone levels were associated with lower lean and fat mass. Conclusions: HIV status was not associated with a lower muscle or fat mass. Different factors influenced body composition for females than males. Higher testosterone levels may be protective against loss in lean and fat mass in females. [Copyright &y& Elsevier]

: PurposeTo compare cytology with cervicography in HIV-infected and uninfected adolescent females: MethodsAt the time of analysis, 334 girls aged 13–19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram™ (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams™ were sent to the parent company for diagnosis and were categorized as: “negative” or “positive” (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram™ were calculated compared with repeat Papanicolaou (Pap) smears.: ResultsTwo consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43–59) of the 142 HIV-positive youth and 19% (95% CI, 9–29) of the 58 HIV-negative youth had SIL on at least one Pap smear (p < .001). A positive Cervigram™ was observed in 44% (95% CI, 36–53) of the HIV-infected group and 29% (95% CI, 17–41) of the HIV-uninfected group (p = .06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram™ to detect SIL were 58% (95% CI, 45–71), 69% (95%CI, 57–80), and 64% (95%CI, 52–77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31–89), 80% (95% CI, 65–90), and 44% (95% CI, 19–68), respectively. The combined sensitivity, using both the Pap smear and Cervigram™ result from V1 to detect SIL, was 82% (95% CI, 71–91 for HIV+ and 48–98 for HIV−) in both groups. However, the PPV based the performance of the Cervigram™ in Pap smear-negative women as 33% (95% CI, 17–53) and 15% (95% CI, 2–45) for the HIV-infected and uninfected group, respectively (p = not significant [ns]).: ConclusionAlthough the sensitivity of a single Pap smear increased significantly when the Cervigram™ was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations. [Copyright &y& Elsevier]

: PurposeTo determine the effects of pro- and anti-tobacco advertising on nonsmoking adolescents’ intention to smoke in a single cohort.: MethodsAll ninth graders at seven public high schools were invited to participate in a study on adolescent tobacco use; 59.0% participated (n = 1229; active positive parental consent required). Adolescents who self-identified as never having smoked even a puff of a cigarette (n = 512) completed a self-administered questionnaire that included questions on intention to smoke in the near future and tobacco advertising. Independent variables used to predict intention included exposure to, recognition of, and receptivity and attitudes toward pro-tobacco and anti-tobacco advertising. Potential confounding variables included gender, race/ethnicity, smoking influences (adult household members, siblings, and friends), socioeconomic status, stress, and depression. Data analysis used logistic regression.: ResultsDemographics: 50.5% female, average age 14.9 ± 0.4 years old at baseline, and varied race. Those variables found to be significant predictors of intention to smoke included: (positive, or increased intention) recognition of brand of favorite advertisement, willingness to use or wear tobacco-branded products, stress, and having friends who smoke and (negative, or decreased intention) agreement with anti-tobacco advertising and having a live-in father who smokes.: ConclusionsAlthough anti-tobacco advertising has a protective effect, it was unable to counteract the effects of pro-tobacco advertising in the same cohort. [Copyright &y& Elsevier]

We have carried out a detailed comparison of the motile properties of differentiated HL-60 cells and human peripheral blood neutrophils. We compared the effects of chemotactic stimuli and of inhibitors of signalling proteins on morphology, chemokinesis and chemotaxis of neutrophils and differentiated HL-60 cells using videomicroscopy and a filter assay for chemotaxis. We also assessed expression of signalling and cytoskeletal proteins using Western blotting.Chemotactic peptide induced a front-tail polarity in HL-60 cells comparable to that of neutrophils. Chemokinetic and chemotactic responses to chemotactic peptide were also very similar for both cell types, concerning mean speed of migration, the fraction of migrated cells and the concentration of stimulus optimal for activation. The cytokine interleukin-8 was in contrast clearly less effective in activating motile responses of differentiated HL-60 cells as compared to neutrophils.An important functional role of Rho-activated kinases and phosphatidylinositol 3-kinase in motile responses of HL-60 cells, consistent with their upregulation during differentiation, could be confirmed using inhibitors with specificity for the corresponding enzymes. The only difference observed here between HL-60 cells and neutrophils concerned the differential effects of a protein kinase C inhibitor.In summary, the results presented here show that differentiated HL-60 cells, stimulated with chemotactic peptide, are a valid model system to study molecular mechanisms of neutrophil emigration. [Copyright &y& Elsevier]

• Stem cell therapy success is determined by "cell-quality" of the implanted cells. • The precise gene expression of several mRNAs was found to be indicative of SASCs. • We propose, for the first time, a "cell quality" model of SASCs. • SASCs can be an excellent candidate in transplants and regenerative medicine fields. Adipose stem cells (ASCs) represent a reliable source of stem cells with a widely demonstrated potential in regenerative medicine and tissue engineering applications. New recent insights suggest that three-dimensional (3D) models may closely mimic the native tissue properties; spheroids from adipose derived stem cells (SASCs) exhibit enhanced regenerative abilities compared with those of 2D models. Stem cell therapy success is determined by "cell-quality"; for this reason, the involvement of stress signals and cellular aging need to be further investigated. Here, we performed a comparative analysis of genes connected with stemness, aging, telomeric length and oxidative stress, in 3D and 2D primary cultures. The expression levels of stemness-related markers and anti-aging Sirtuin1 were significantly up-regulated (P < 0.001) in SASCs-3D while gene expression of aging-related p16INK4a was increased in ASCs-2D (P < 0.001). The 3D and 2D cultures also had a different gene expression profile for genes related to telomere maintenance (Shelterin complex, RNA Binding proteins and DNA repair genes) (P < 0.01 and P < 0.001) and oxidative stress (aldehyde dehydrogenase class1 and 3) (P < 0.05, P < 0.01 and P < 0.001) and presented a striking large variation in their cellular redox state. Based on our findings, we propose a "cell quality" model of SASCs, highlighting a precise molecular expression of several genes involved with stemness (SOX2, POU5F1 and NANOG), anti-aging (SIRT1), oxidative stress (ALDH3) and telomeres maintenance. [ABSTRACT FROM AUTHOR]

Nowadays, solid organ transplantation (SOT) is an established treatment for patients with end-organ dysfunction, which dramatically improves the quality-of-life. Vascularized composite allotransplants (VCAs) including hand and face have been reported worldwide over the last 20 years. However, VCAs, differently to SOT, are life-enhancing instead of life-saving and are not routinely performed due to the risk of immune rejection and the adverse effects of immunosuppression. Over the past decade, although considerable improvements in short-term outcomes after allotransplantation have been registered, these results have not been translated into major progress in long-term allograft acceptance and patient survival. Recently active researches in the field of biomarker discovery have been conducted to develop individualized therapies for allograft recipients. MicroRNAs (miRNAs) are a small noncoding RNAs functioning as critical regulators of gene and protein expression by RNA interference. They have been connected in numerous biological processes and diseases. Due to their immunomodulatory functions, miRNAs have been amended as potential diagnostic and prognostic biomarker for the detection of rejection in allotransplantation. Due to their specific circulating expression profile, they could act as noninvasive predictive tools for rejection that may help clinicians in an early adjustment of the immunosuppression protocol during acute rejections episodes. Indeed, specific anti-sense oligonucleotides suppressing miRNAs expressed in rejection could reduce the rejection rate in allografts and decrease the use of immunosuppressants. We present a literature review of the immunomodulatory properties and characteristics of miRNAs. We will summarize the current knowledge on miRNAs as potential biomarkers for allograft rejection and possible application in allotransplantation monitoring. Finally, we will discuss the advances in preclinical miRNA-based therapies for immunosuppression. Unlabelled Image • miRNAs are a potential diagnostic and prognostic biomarker for the detection of rejection in allotransplantation. • Many miRNAs have been identified with the aim to distinguish between tolerant and rejecting allografts. • Anti-sense oligonucleotides suppressing miRNAs could reduce the rejection rate and decrease the use of immunosuppressants. • Circulating miRNAs could predict the allograft status in preclinical miRNA-based therapies for immunosuppression. [ABSTRACT FROM AUTHOR]

Empirical methods applied in Regional Innovation System (RIS) research have two shortcomings. First, they usually have difficulties when it comes to explaining the interplay and relative importance of the elements of a RIS. Second, they are not capable of showing whether specific RIS can indeed be attributed to a pre-defined region. We draw on four contrasting regions in China exhibiting strong disparities with regard to innovation resources to examine how the "Analytic Hierarchy Process" (AHP), a comparative method widely used in business and management studies, can help to address these methodological shortcomings. Results show that in combination with qualitative analyses, the AHP can support empirical RIS research to decide whether or not a particular pre-defined RIS model can adequately describe empirical reality: the AHP evaluates the relative importance of both quantitative and qualitative RIS elements contributing to innovation in a pre-defined area through comparative expert assessments. Also drawing on sensitivity checks, the AHP is capable of providing a critical evaluation of the importance of both factors and spatial delimitations affecting innovation. The method thus informs theoretical development on the elements and spatial boundaries of RIS and helps empirical innovation research to apply the RIS framework in a more fruitful manner. • The Analytic Hierarchy Process improves Regional Innovation System research. • The method examines spatial boundaries of Regional Innovation System models. • The method investigates the relevance of innovation system elements. • The method reduces innovation system complexity for regional comparative studies. [ABSTRACT FROM AUTHOR]

Current methods to induce tolerance following allotransplantation or in autoimmunity carry significant morbidity, and research is very active in investigating alternative methods which could minimize toxicity. Spheroids from adipose stem cells (SASCs) are increasingly gaining interest, they hold a great proliferative and differentiating potential. An immunomodulatory effect has not been investigated on SASCs yet. In this study, we analysed the immunomodulatory properties of SASCs and compared them to ADSCs. Adipose stem cells (SASCs and ADSCs) and peripheral blood mononuclear cells (PBMCs) were collected from healthy individuals. We analysed the cytokine production and proliferation of T cells co-cultured with adipose samples or conditioned medium. SASCs modulated cytokines production and proliferation of heterologous and autologous T cells. In the heterologous assays, we observed a reduction of IFNγ and IL-17 production and an increase of IL-9 in γδ T cells. The soluble factors present in SASCs sovranatants were also able to induce a slight reduction of IFNγ and an increase of IL-9, IL-10 and IL-17 while they could not modulate the proliferative ability of γδ T cells. In the autologous assays, we observed a reduction of the proliferative ability of T cells in co-culture at different ratios with SASCs. Analysis of the SASCs secretome showed an increased IL-5, IL-10, IL-4 and IL-13 production compared to the ADSCs one, demonstrating greater anti-inflammatory properties. Our preliminary results support the idea that SASCs exert more pronounced biological immune modulation compared to the classical adherent ADSCs, especially in heterologous experimental settings. • Research is active in investigating methods which could minimise toxicity in allotransplantation or in autoimmunity. • SASCs hold a great proliferative and differentiating potential. Their immunomodulatory effect has not been investigated yet. • We showed that SASCs modulated cytokines production and proliferation of heterologous and autologous T cells. • Our preliminary results support the idea that SASCs exert more pronounced biological immune modulation compared to the ADSCs. [ABSTRACT FROM AUTHOR]

Abstract: This chapter addresses the natural history of anogenital human papillomavirus (HPV) infection. Cervical infections are the best understood HPV infection. Cervical HPV persistence is the known necessary event for the development of cervical cancer. New infections appearing at any age are benign unless they persist. Several long-term natural history studies have now shed light on the very low risk of cervical intraepithelial neoplasia (CIN) 3+ in women past the peak of HPV acquisition (e.g., 30 or older) who are HPV-negative or clear their HPV. Although data on transmission of HPV are finally emerging, rates of transmission between heterosexual couples vary widely among studies. Factors that affect the calculations of these rates include a) intervals between testing points, b) rates of concordance or discordance at baseline, and c) difficulty in defining established infections versus contamination. Both cervix to anus and anus to cervix autoinoculation in the same woman appears to be quite common. Whether either site serves as a long-term reservoir is unknown. Studies show that anal infections in women and in men who have sex with men are quite common with cumulative rates up to 70–90%. Similarly, clearance of anal HPV is also common, with few individuals showing persistence unless they are human immunodeficiency virus (HIV)-infected. HIV strongly influences the development of anal intraepithelial neoplasia (AIN). The few studies on the natural history of AIN in HIV-infected men suggest that high-grade AIN is a precursor to invasive anal cancer. Although no natural history studies of AIN are available in women, women with other HPV-associated lesions, including CIN3+ and vulvar cancer, have higher rates of anal cancer. Data on the natural history of HPV of the male genitalia are also emerging, although penile intraepithelial neoplasia is poorly understood. Cumulative rates of HPV are extremely high in men and risks are associated with sexual behavior. Unlike women, prevalence rates are steady across all ages, suggesting that men do not develop protection against reinfection. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012. [Copyright &y& Elsevier]

Objective Although HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5 year period after either 3 or 4 doses of QHPV. Design/methods HIV-infected children, ages 7-to-11 years, received 3 doses of QHPV (n = 96) or placebo (n = 30). At 72 weeks QHPV recipients received a fourth dose (n = 84), while placebo recipients began the 3-dose QHPV schedule (n = 27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5 years after the last dose of QHPV in each treatment arm. Results At 4-to-5 years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86–93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1 month after completing vaccination. Conclusions Children with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels. Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556 . [ABSTRACT FROM AUTHOR]