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Κυριακή 24 Ιανουαρίου 2016

Extensive juvenile “babysitting” facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats

ABSTRACT

Pregnancy and parturition can dramatically affect female neurobiology and behavior. This is especially true for laboratory-reared rodents, in part, because such rearing prevents a host of developmental experiences that females might undergo in nature, including juvenile alloparenting. We examined the effect of chronic exposure to pups during post-weaning juvenile life (days 22–36) on adult maternal responsiveness, anxiety-related behaviors, and dorsal raphe tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) levels in nulliparous rats. Adult females with juvenile alloparental experience showed significantly faster sensitized maternal responsiveness, less anxiety, and more dorsal raphe TPH2. Juvenile alloparenting did not affect females' later social novelty and preference behaviors toward adults, suggesting their increased interest in pups did not extend to all social partners. In a second experiment, suckling a pregnant dam (achieved by postpartum estrus reinsemination), interacting with her after standard laboratory weaning age, and a 3-day exposure to younger siblings also reduced juvenile females' later anxiety but did not affect maternal responsiveness or TPH2. Thus, extensive juvenile "babysitting" can have long-term effects reminiscent of pregnancy and parturition on maternal responsiveness and anxiety, and these effects may be driven by upregulated serotonin. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1–17, 2016.



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Intra-individual stability and developmental change in hair cortisol among postpartum mothers and infants: Implications for understanding chronic stress

ABSTRACT

The study goal was to determine the intra-individual stability, developmental change, and maternal-reported correlates (socio-demographic, stress experiences, hair characteristics, and care) of hair cortisol in mothers and their infants. To assess cortisol deposition in hair during the periods of 6-to-9 months and 9-to-12 months of age, 3 cm segments of hair samples deemed to represent approximately 3 months of retrospective hair cortisol were sampled longitudinally at 9- and 12-months in 41 mothers and infants. Bivariate correlations and mean level comparisons of log-transformed hair cortisol levels at 9- (T1) and 12-months (T2) in mothers and infants were examined. Hair cortisol values were positively correlated from T1 to T2 for mothers (r = .41, p < .05) and infants (r = .39, p < .05). Hair cortisol values did not significantly differ from T1 to T2 in infants but decreased for mothers (F(1,34) = 9.2, p < .01). Maternal and infant hair cortisol was not associated with each other at either time point. Self-reported measures of stress, and hair characteristics and care were not associated with hair cortisol. This is the first study to obtain hair cortisol from more than one time point within the first year after birth in mothers and infants. The intra-individual stability of hair cortisol suggests that it may be a possible biomarker for detecting change in chronic stress experiences within the first year of life and in the postpartum period. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1–10, 2016.



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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

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Here we describe a procedure allowing a detailed analysis of the phosphorylation-dependent activation of the IRF3 transcription factor. This is achieved through the combination of a high resolution SDS-PAGE and a native-PAGE coupled to immunoblots using multiple phosphospecific antibodies.

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Using Digital Image Correlation to Characterize Local Strains on Vascular Tissue Specimens

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We describe the use of digital image correlation to characterize the local surface strain field on vascular tissue samples subjected to uniaxial tensile testing. These measurements facilitate precise quantification of the sample mechanical response and the generation of constitutive stress-strain relations.

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Brain, calvarium, cladistics: A new approach to an old question, who are modern humans and Neandertals?

Publication date: March 2016
Source:Journal of Human Evolution, Volume 92
Author(s): Aurélien Mounier, Antoine Balzeau, Miguel Caparros, Dominique Grimaud-Hervé
The evolutionary history of the genus Homo is the focus of major research efforts in palaeoanthropology. However, the use of palaeoneurology to infer phylogenies of our genus is rare. Here we use cladistics to test the importance of the brain in differentiating and defining Neandertals and modern humans. The analysis is based on morphological data from the calvarium and endocast of Pleistocene fossils and results in a single most parsimonious cladogram.We demonstrate that the joint use of endocranial and calvarial features with cladistics provides a unique means to understand the evolution of the genus Homo. The main results of this study indicate that: (i) the endocranial features are more phylogenetically informative than the characters from the calvarium; (ii) the specific differentiation of Neandertals and modern humans is mostly supported by well-known calvarial autapomorphies; (iii) the endocranial anatomy of modern humans and Neandertals show strong similarities, which appeared in the fossil record with the last common ancestor of both species; and (iv) apart from encephalisation, human endocranial anatomy changed tremendously during the end of the Middle Pleistocene. This may be linked to major cultural and technological novelties that had happened by the end of the Middle Pleistocene (e.g., expansion of the Middle Stone Age (MSA) in Africa and Mousterian in Europe). The combined study of endocranial and exocranial anatomy offers opportunities to further understand human evolution and the implication for the phylogeny of our genus.



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The short-term impact of each primary dose of pneumococcal conjugate vaccine on nasopharyngeal carriage: Systematic review and meta-analyses of randomised controlled trials

Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Thomas Rodger Nicholls, Amanda Jane Leach, Peter Stanley Morris
BackgroundEarly onset of persistent otitis media is a priority issue for Australian Indigenous populations. The objective is to determine the direct and short-term impact of one, two and three doses of any pneumococcal conjugate vaccine (PCV) formulation on nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi), the otopathogens targeted by current PCVs.MethodsWe searched MEDLINE (PubMed) and CENTRAL (Cochrane Library) to 29 September 2015. We also scanned reference lists of recent reviews and contacted authors. We included randomised controlled trials (RCTs) with a PCV schedule commencing ≤3 months of age that reported controlled non-cumulative group-specific prevalence data for carriage of Spn or NTHi at age<12 months. We performed a standard risk of bias assessment. We estimated the pooled relative risk (RR) and 95% confidence interval (95%CI) for each vaccine dose on NP carriage by meta-analysis.ResultsWe included 16 RCTs involving 14,776 participants. The PCVs were conjugated to diphtheria toxin CRM197, diphtheria toxoid, tetanus toxoid or NTHi protein D and varied in valency (4–13). Controls were non-PCVs, placebo or no vaccine. The earliest carriage outcome was from 2 to 9 months of age. Compared to controls, there were no significant differences between one or two doses of PCV on vaccine-type (VT) pneumococcal carriage at ∼4 and ∼6 months respectively. However, VT carriage was significantly lower at ∼7 months RR 0.67 95%CI 0.56–0.81 from 9 studies and 7613 infants and non-vaccine type (NVT) carriage was higher RR 1.23 95%CI 1.09–1.40 from 8 studies and 5861 infants. No impact on overall pneumococcal or NTHi carriage was found.ConclusionsThe primary PCV schedule had no significant short-term impact on overall pneumococcal or NTHi NP carriage and a limited impact on VT pneumococcal carriage before the third dose.



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A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Jorgen Stassijns, Kaatje Bollaerts, Marc Baay, Thomas Verstraeten
IntroductionNew adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children.MethodsWe carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted.ResultsTwenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75–0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases.ConclusionsOur meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted.



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Beyond efficacy: The full public health impact of vaccines

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Publication date: Available online 23 January 2016
Source:Vaccine
Author(s): Mitra Saadatian-Elahi, Olaf Horstick, Robert F. Breiman, Bradford D. Gessner, Duane J. Gubler, Jacques Louis, Umesh D. Parashar, Roberto Tapia, Valentina Picot, Jean-Antoine Zinsou, Christopher B. Nelson
There is an active discussion in the public health community on how to assess and incorporate, in addition to safety and measures of protective efficacy, the full public health value of preventive vaccines into the evidence-based decision-making process of vaccine licensure and recommendations for public health use. The conference "Beyond efficacy: the full public health impact of vaccines in addition to efficacy measures in trials" held in Annecy, France (June 22–24, 2015) has addressed this issue and provided recommendations on how to better capture the whole public health impact of vaccines.Using key examples, the expert group stressed that we are in the midst of a new paradigm in vaccine evaluation, where all aspects of public health value of vaccines beyond efficacy should be evaluated. To yield a wider scope of vaccine benefits, additional measures such as vaccine preventable disease incidence, overall efficacy and other outcomes such as under-five mortality or non-etiologically confirmed clinical syndromes should be assessed in addition to traditional efficacy or effectiveness measurements. Dynamic modelling and the use of probe studies should also be considered to provide additional insight to the full public health value of a vaccine. The use of burden reduction and conditional licensure of vaccines based on collection of outcome results should be considered by regulatory agencies.



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A highly immunogenic vaccine against A/H7N9 influenza virus

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Weiping Cao, Justine S. Liepkalns, Ahmed O. Hassan, Ram P. Kamal, Amelia R. Hofstetter, Samuel Amoah, Jin Hyang Kim, Adrian J. Reber, James Stevens, Jacqueline M. Katz, Shivaprakash Gangappa, Ian A. York, Suresh K. Mittal, Suryaprakash Sambhara
Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/H7N9 viral challenge suggesting its potential utility as a pandemic vaccine.



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Editorial Board/Aims and Scope

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6





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Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Pierre Van Damme, Paolo Bonanni, F. Xavier Bosch, Elmar Joura, Susanne Krüger Kjaer, Chris J.L.M. Meijer, Karl-Ulrich Petry, Benoit Soubeyrand, Thomas Verstraeten, Margaret Stanley
With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses. Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection.



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General practitioners’ attitudes and behaviors toward HPV vaccination: A French national survey

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Fanny Collange, Lisa Fressard, Céline Pulcini, Rémy Sebbah, Patrick Peretti-Watel, Pierre Verger
ObjectiveGeneral practitioners (GPs) play a crucial role in human papillomavirus (HPV) vaccine acceptance in France. We sought to study: (1) GPs' perceptions of its risks and efficacy and their recommendation behavior; (2) the relative importance of factors associated with the frequency of their recommendations.MethodsCross-sectional observational study in 2014 nested in a national panel of 1712 randomly selected GPs in private practice in France (response rate: 92.4%). We used model averaging to analyze the associations of self-reported frequency of GPs' HPV vaccine recommendations with their perception of its risk-benefit balance and their opinions about the utility of vaccines in general.ResultsOverall, 72% of participants reported frequently recommending HPV vaccination; 60% considered that not enough is known about its risks. The model averaging showed that the factors most associated with infrequent recommendation of this vaccine by GPs were: unfavorable perceptions of its risk-benefit balance (OR=0.13; 95%CI=0.09–0.21; partial R2=0.10), a decision not to vaccinate one's own daughter(s) with this vaccine (OR=0.13; 95%CI=0.07–0.24; partial R2=0.05), and doubts about vaccine utility in general (OR=0.78; 95%CI=0.71–0.86; partial R2=0.03).ConclusionAlthough nearly three-quarters of French GPs frequently recommended the HPV vaccine, our findings indicate that a substantial percentage of them are hesitant about it. Doubts about its risks and efficacy strongly influence their recommendation behavior. More research is warranted to help design and evaluate tailored tools and multicomponent intervention strategies to address physician's hesitancy about this vaccine.



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The effect of pneumococcal conjugate vaccines on the incidence of invasive pneumococcal disease caused by ten non-vaccine serotypes in Denmark

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Hans-Christian Slotved, Tine Dalby, Steen Hoffmann
BackgroundSurveillance data on invasive pneumococcal disease (IPD) in Denmark (1999–2014) was analysed regarding the incidence and age-distribution due to ten selected non-PCV serotypes (10-Non-PCV). The effect of PCV-7 and PCV-13 vaccines on the 10-Non-PCV IPD incidence was examined.MethodsIPD cases caused by serotypes included in PCV-7, the additional six serotypes included in PCV-13 and 10-Non-PCV serotypes were identified (8, 9N, 11A, 12F, 15A, 22F, 24F, 20, 23B, 33F). The IPD incidence was stratified by three age groups: 0–4 years, 5–64 years and 65+ years.ResultsThe predominant IPD cases were caused by serotypes that are not included in PCV-13 (71%), followed by the six additional PCV-13 serotypes. The IPD incidence of serotypes included in the PCV-7 decreased markedly after PCV-7 introduction but are still diagnosed at a low level. The IPD incidence for the 10-Non-PCV serotypes was low for age groups 0–4 years and 5–64 years but high for 65+ years.ConclusionFuture vaccinations of the young age group alone with a vaccine targeting some of the 10-Non-PCV serotypes may not elicit the desired effect on herd protection since these serotypes are primarily causing IPD among the elderly. Future pneumococcal vaccination strategies in Denmark may therefore need carriage studies in order to identify among whom the pneumococcal serotypes causing IPD are carried.



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Provider communication and HPV vaccination: The impact of recommendation quality

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Publication date: Available online 24 January 2016
Source:Vaccine
Author(s): Melissa B. Gilkey, William A. Calo, Jennifer L. Moss, Parth D. Shah, Macary W. Marciniak, Noel T. Brewer
BackgroundReceiving a healthcare provider's recommendation is a strong predictor of HPV vaccination, but little is known empirically about which types of recommendation are most influential. Thus, we sought to investigate the relationship between recommendation quality and HPV vaccination among U.S. adolescents.MethodsIn 2014, we conducted a national, online survey of 1495 parents of 11–17-year-old adolescents. Parents reported whether providers endorsed HPV vaccination strongly, encouraged same-day vaccination, and discussed cancer prevention. Using an index of these quality indicators, we categorized parents as having received no, low-quality, or high-quality recommendations for HPV vaccination. Separate multivariable logistic regression models assessed associations between recommendation quality and HPV vaccine initiation (≥1 dose), follow through (3 doses, among initiators), refusal, and delay.ResultsAlmost half (48%) of parents reported no provider recommendation for HPV vaccination, while 16% received low-quality recommendations and 36% received high-quality recommendations. Compared to no recommendation, high-quality recommendations were associated with over nine times the odds of HPV vaccine initiation (23% vs. 74%, OR=9.31, 95% CI, 7.10–12.22) and over three times the odds of follow through (17% vs. 44%, OR=3.82, 95% CI, 2.39–6.11). Low-quality recommendations were more modestly associated with initiation (OR=4.13, 95% CI, 2.99–5.70), but not follow through. Parents who received high- versus low-quality recommendations less often reported HPV vaccine refusal or delay.ConclusionsHigh-quality recommendations were strongly associated with HPV vaccination behavior, but only about one-third of parents received them. Interventions are needed to improve not only whether, but how providers recommend HPV vaccination for adolescents.



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Humoral immune responses in koalas (Phascolarctos cinereus) either naturally infected with Chlamydia pecorum or following administration of a recombinant chlamydial major outer membrane protein vaccine

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Shahneaz Ali Khan, Adam Polkinghorne, Courtney Waugh, Jon Hanger, Jo Loader, Kenneth Beagley, Peter Timms
The development of a vaccine is a key strategy to combat the widespread and debilitating effects of chlamydial infection in koalas. One such vaccine in development uses recombinant chlamydial major outer membrane protein (rMOMP) as an antigen and has shown promising results in several koala trials. Previous chlamydial vaccine studies, primarily in the mouse model, suggest that both cell-mediated and antibody responses will be required for adequate protection. Recently, the important protective role of antibodies has been highlighted. In our current study, we conducted a detailed analysis of the antibody-mediated immune response in koalas that are either (a) naturally-infected, and/or (b) had received an rMOMP vaccine. Firstly, we observed that naturally-infected koalas had very low levels of Chlamydia pecorum-specific neutralising antibodies. A strong correlation between low IgG total titers/neutralising antibody levels, and higher C. pecorum infection load was also observed in these naturally-infected animals. In vaccinated koalas, we showed that the vaccine was able to boost the humoral immune response by inducing strong levels of C. pecorum-specific neutralising antibodies. A detailed characterisation of the MOMP epitope response was also performed in naturally-infected and vaccinated koalas using a PepScan epitope approach. This analysis identified unique sets of MOMP epitope antibodies between naturally-infected non-protected and diseased koalas, versus vaccinated koalas, with the latter group of animals producing a unique set of specific epitope-directed antibodies that we demonstrated were responsible for the in vitro neutralisation activity. Together, these results show the importance of antibodies in chlamydial infection and immunity following vaccination in the koala.



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The transfer and decay of maternal antibody against Shigella sonnei in a longitudinal cohort of Vietnamese infants

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Corinne N. Thompson, Le Thi Phuong Tu, Katherine L. Anders, Nguyen Trong Hieu, Lu Lan Vi, Nguyen Van Vinh Chau, Vu Thuy Duong, Nguyen Ngoc Minh Chau, Tran Thi Hong Chau, Ha Thanh Tuyen, Tran Vu Thieu Nga, Pham Van Minh, Tran Do Hoang Nhu, Le Thi Quynh Nhi, Allan Saul, Laura B. Martin, Audino Podda, Christiane Gerke, Guy Thwaites, Cameron P. Simmons, Stephen Baker
BackgroundShigella sonnei is an emergent and major diarrheal pathogen for which there is currently no vaccine. We aimed to quantify duration of maternal antibody against S. sonnei and investigate transplacental IgG transfer in a birth cohort in southern Vietnam.Methods and resultsOver 500-paired maternal/infant plasma samples were evaluated for presence of anti-S. sonnei-O IgG and IgM. Longitudinal plasma samples allowed for the estimation of the median half-life of maternal anti-S. sonnei-O IgG, which was 43 days (95% confidence interval: 41–45 days). Additionally, half of infants lacked a detectable titer by 19 weeks of age. Lower cord titers were associated with greater increases in S. sonnei IgG over the first year of life, and the incidence of S. sonnei seroconversion was estimated to be 4/100 infant years. Maternal IgG titer, the ratio of antibody transfer, the season of birth and gestational age were significantly associated with cord titer.ConclusionsMaternal anti-S. sonnei-O IgG is efficiently transferred across the placenta and anti-S. sonnei-O maternal IgG declines rapidly after birth and is undetectable after 5 months in the majority of children. Preterm neonates and children born to mothers with low IgG titers have lower cord titers and therefore may be at greater risk of seroconversion in infancy.



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Nasopharyngeal carriage of Streptococcus pneumoniae among children in an urban setting in Brazil prior to PCV10 introduction

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Ana Paula de O. Menezes, Jailton Azevedo, Mariela C. Leite, Leila C. Campos, Marcelo Cunha, Maria da Gloria S. Carvalho, Mitermayer G. Reis, Albert I. Ko, Daniel M. Weinberger, Guilherme Ribeiro, Joice N. Reis
Information on pneumococcal carriage in the pre-vaccine period is essential to predict and assess the impact of PCV in settings where disease surveillance is particularly difficult. Therefore, we present data on pneumococcal carriage before the introduction of the 10-valent-pneumococcal conjugate vaccine (PCV10) in Brazil. We conducted a prospective study on a cohort of 203 children aged <5 years old, randomly selected in an urban community located in the periphery of the city of Salvador, Brazil and followed them from January/2008 to January/2009. Nasopharyngeal swabs were collected from each child at four times. In total, 721 swabs were collected, yielding a pneumococcal carriage prevalence of 55% (n=398). In multivariate analyses, the variables associated with carriage were having contact with three or more children <2 years old (OR, 2.00; 95% CI 1.33–2.89) and living in a house with an average of 3 residents per room (OR, 1.77; 95% CI 1.05–3.10). Also, white participants were more likely to be protected from colonization (OR, 0.52; 95% CI 0.29–0.93), and prevalence of carriage varied over time, with lower prevalence occurring from February to June (OR, 0.53; 95% CI 0.37–0.78) compared to July to January. Contact with children under 2 years of age and living in crowded housing also were associated with colonization by highly invasive serotypes, although this relationship was not significant. The most prevalent vaccine serotypes were 6A/B (25.4%), 19F (10.1%) and 14 (9.0%), while the most prevalent non-vaccine serotypes were 16F (4.8%), 15B/C (4.5%) and 6C/D (3.5%). Overall, 38.4% (153/398) of the isolates were non-susceptible to penicillin, and of those, 73.8% (113/153) were non-susceptible to trimethoprim/sulfamethoxazole. Colonization rate by PCV10 serotypes was 52.2%. Routine PCV10 vaccination can lead to significant changes in pneumococcal serotypes found in NP colonization, indicating a need for continued monitoring, especially in crowded settings, as occurs in Brazil's slums.



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Inactivation of rabies virus by hydrogen peroxide

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Asmaa A. Abd-Elghaffar, Amal E. Ali, Abeer A. Boseila, Magdy A. Amin
Development of safe and protective vaccines against infectious pathogens remains a challenge. Inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. Beta-propiolactone (βPL); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. This study aimed to investigate the ability of hydrogen peroxide (H2O2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenicity in pursuit of finding safe, effective and inexpensive alternative inactivating agents. H2O2 3% rapidly inactivated a Vero cell adapted fixed rabies virus strain designated as FRV/K within 2h of exposure without affecting its antigenicity or immunogenicity. No residual infectious virus was detected and the H2O2-inactivated vaccine proved to be safe and effective when compared with the same virus harvest inactivated with the classical inactivating agent βPL. Mice immunized with H2O2-inactivated rabies virus produced sufficient level of antibodies and were protected when challenged with lethal CVS virus. These findings reinforce the idea that H2O2 can replace βPL as inactivating agent for rabies virus to reduce time and cost of inactivation process.



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Future pandemics and vaccination: Public opinion and attitudes across three European countries

Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Domino Determann, Esther W. de Bekker-Grob, Jeff French, Helene A. Voeten, Jan Hendrik Richardus, Enny Das, Ida J. Korfage
BackgroundUnderstanding public opinion and attitudes regarding vaccination is crucial for successful outbreak management and effective communication at the European level.MethodsWe explored national differences by conducting focus group discussions in The Netherlands, Poland and Sweden. Discussions were structured using concepts from behavioural models.ResultsThematic analysis revealed that participants would base their vaccination decision on trade-offs between perceived benefits and barriers of the vaccine also taking into account the seriousness of the new outbreak. Except for those having chronic diseases, participants expected a low infection risk, resulting in a low willingness to get vaccinated. Information about the health status of cases was considered important since this might change perceived susceptibility. Participants displayed concerns about vaccine safety due to the limited available time to produce and test vaccines in the acute situation of a new pandemic. Swedish participants mentioned their tendency of doing the right thing and following the rules, as well as to get vaccinated because of solidarity with other citizens and social influences. This appeared much less prominent for the Dutch and Polish participants. However, Swedish participants indicated that their negative experiences during the Influenza A/H1N1 2009 pandemic decreases their acceptance of future vaccinations. Polish participants lacked trust in their national (public) health system and government, and were therefore sceptical about the availability and quality of vaccines in Poland.ConclusionsAlthough participants overall expressed similar considerations, important differences between countries stand out, such as previous vaccination experiences, the degree of adherence to social norms, and the degree of trust in health authorities.



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Efficient generation of vesicular stomatitis virus (VSV)-pseudotypes bearing morbilliviral glycoproteins and their use in quantifying virus neutralising antibodies

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Nicola Logan, Elizabeth McMonagle, Angharad A. Drew, Emi Takahashi, Michael McDonald, Michael D. Baron, Martin Gilbert, Sarah Cleaveland, Daniel T. Haydon, Margaret J. Hosie, Brian J. Willett
Morbillivirus neutralising antibodies are traditionally measured using either plaque reduction neutralisation tests (PRNTs) or live virus microneutralisation tests (micro-NTs). While both test formats provide a reliable assessment of the strength and specificity of the humoral response, they are restricted by the limited number of viral strains that can be studied and often present significant biological safety concerns to the operator. In this study, we describe the adaptation of a replication-defective vesicular stomatitis virus (VSVΔG) based pseudotyping system for the measurement of morbillivirus neutralising antibodies. By expressing the haemagglutinin (H) and fusion (F) proteins of canine distemper virus (CDV) on VSVΔG pseudotypes bearing a luciferase marker gene, neutralising antibody titres could be measured rapidly and with high sensitivity. Further, by exchanging the glycoprotein expression construct, responses against distinct viral strains or species may be measured. Using this technique, we demonstrate cross neutralisation between CDV and peste des petits ruminants virus (PPRV). As an example of the value of the technique, we demonstrate that UK dogs vary in the breadth of immunity induced by CDV vaccination; in some dogs the neutralising response is CDV-specific while, in others, the neutralising response extends to the ruminant morbillivirus PPRV. This technique will facilitate a comprehensive comparison of cross-neutralisation to be conducted across the morbilliviruses.



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Improving the performance of reflex Human Papilloma Virus (HPV) testing in triaging women with atypical squamous cells of undetermined significance (ASCUS): A restrospective study in a tertiary hospital in United Arab Emirates (UAE)

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Marwa Fakhreldin, Karim Elmasry
IntroductionCervical cancer is the second commonest cancer in women worldwide. Infection with oncogenic types of human Papillomavirus (HPV) is the most important risk factor for developing cervical cancer. Reflex High risk HPV (HR-HPV) testing is of significant value in the assessment of Papanicolaou (Pap) smear results where ASCUS are identified.ObjectiveTo improve the performance of reflex HR-HPV testing in triage of ASCUS and analyze the factors impacting it.MethodologyIn this study, we generated a database of 9641 women who had cervical smears collected during the study period from the cytopathology record in a large tertiary hospital in UAE. These included 297 smears with ASCUS diagnosis. All cases were retrospectively followed up with a mean duration of 2.44 years. We analyzed data according to the outcome based on several follow-up Pap smear analysis as the reference assessment.ResultsWe detected HR-HPV infection in 17.9% of cases. 9.1% <25, 28.8% 25–34 and 62.1% ≥35 years old. HR-HPV prevalence was higher among premenopausal women (20.7%) compared to postmenopausal women (9.5%) (P-value=0.044). The rate of progression to high grade lesions was also higher (28.7%) in the premenopausal group compared to (12.8%) in the postmenopausal group. Reflex HPV testing had an overall sensitivity of 41.1%, specificity of 88.2%, positive predictive value (PPV) of 62.1%, and negative predictive value (NPV) of 75.9% in detection of cervical lesions. These figures were higher on combining premenopausal status and complaint of abnormal bleeding or discharge/itching (66.7%, 93.3%, 66.8% and 93.3% respectively).ConclusionsThe sensitivity, specificity and NPV of reflex HPV testing in the triage of ASCUS cases can be more accurate in premenopausal women upon adding age group and presenting complaint as a triage item. This improves the performance of reflex HPV testing and the subsequent selection of high risk patients for colposcopy.



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A behavioral economics intervention to increase pertussis vaccination among infant caregivers: A randomized feasibility trial

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Alison M. Buttenheim, Alexander G. Fiks, Randall C. Burson II, Eileen Wang, Susan E. Coffin, Joshua P. Metlay, Kristen A. Feemster
ObjectivesThe incidence of pertussis has tripled in the past five years. Infants can be protected by "cocooning," or vaccinating household contacts with the Tdap vaccine. However, Tdap coverage for adult caregivers of infants is low. This study evaluated the feasibility and impact of interventions informed by behavioral economics (retail pharmacy vouchers for Tdap vaccines and a celebrity public service announcement) to increase Tdap vaccination among caregivers of young infants.MethodsWe conducted a randomized controlled feasibility trial among adults attending newborn well-child visits at an urban Philadelphia pediatric primary care clinic who were not previously vaccinated with Tdap. Participants were randomized to one of four conditions: ($5-off Tdap voucher vs. free voucher)×(watching a 1min video public service announcement (PSA) about Tdap vaccination vs. no PSA). Tdap vaccination was assessed by tracking voucher redemption and following up with participants by phone.ResultsNinety-five adult caregivers of 74 infants were enrolled in the study (mean age 29.3 years; 61% male; relationship to newborn: 54% father, 33% mother, 13% grandparent or other; caregiver insurance status: 35% Medicaid, 34% private insurance, 32% uninsured). Only 1 subject redeemed the retail pharmacy Tdap voucher. Follow-up interviews suggest that, even with the voucher, significant barriers to vaccination remained including: delaying planned vaccination, perceived inconvenient pharmacy locations, and beliefs about pertussis risk and severity.ConclusionsDespite leveraging existing infrastructure for adult vaccination, results suggest that retail pharmacy vouchers delivered during a newborn visit are not an effective strategy for promoting Tdap. Alternate approaches are needed that prioritize convenience and provide an immediate opportunity to vaccinate when motivation is high.



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Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface

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Publication date: Available online 24 January 2016
Source:Vaccine
Author(s): Melissa Samo, Neelima R. Choudhary, Kristina J. Riebe, Ivo Shterev, Herman F. Staats, Gregory D. Sempowski, Isabelle Leduc
The Ducreyi serum resistance A (DsrA) protein of Haemophilus ducreyi belongs to a large family of multifunctional outer membrane proteins termed trimeric autotransporter adhesins responsible for resistance to the bacterial activity of human complement (serum resistance), agglutination and adhesion. The ability of DsrA to confer serum resistance and bind extracellular matrix proteins lies in its N-terminal passenger domain. We have previously reported that immunization with a recombinant form of the passenger domain of DsrA, rNT-DsrA, in complete/incomplete Freund's adjuvant, protects against a homologous challenge in swine. We present herein the results of an immunogenicity study in mice aimed at investigating the persistence, type of immune response, and the effect of immunization route and adjuvants on surrogates of protection. Our results indicate that a 20μg dose of rNT-DsrA administered with alum elicited antisera with comparable bacterial surface reactivity to that obtained with complete/incomplete Freund's adjuvant. At that dose, high titers and bacterial surface reactivity persisted for 211 days after the first immunization. Administration of rNT-DsrA with CpG or imiquimod as adjuvants elicited a humoral response with similar quantity and quality of antibodies (Abs) as seen with Freund's adjuvant. Furthermore, intramuscular administration of rNT-DsrA elicited high-titer Abs with significantly higher reactivity to the bacterial surface than those obtained with subcutaneous immunization. All rNT-DsrA/adjuvant combinations tested, save CpG, elicited a Th2-type response. Taken together, these findings show that a 20μg dose of rNT-DsrA administered with the adjuvants alum, CpG or imiquimod elicits high-quality Abs with reactivity to the bacterial surface that could protect against an H. ducreyi infection.



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Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection

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Publication date: 3 February 2016
Source:Vaccine, Volume 34, Issue 6
Author(s): Xi Li, Eric Wiesen, Sergey Diorditsa, Kohei Toda, Thi Hong Duong, Lien Huong Nguyen, Van Cuong Nguyen, Tran Hien Nguyen
Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.



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Effect of miR-146a/bFGF/PEG-PEI Nanoparticles on Inflammation Response and Tissue Regeneration of Human Dental Pulp Cells

Introduction. Inflammation in dental pulp cells (DPCs) initiated by Lipopolysaccharide (LPS) results in dental pulp necrosis. So far, whether there is a common system regulating inflammation response and tissue regeneration remains unknown. miR-146a is closely related to inflammation. Basic fibroblast growth factor (bFGF) is an important regulator for differentiation. Methods. To explore the effect of miR-146a/bFGF on inflammation and tissue regeneration, polyethylene glycol-polyethyleneimine (PEG-PEI) was synthesized, and physical characteristics were analyzed by dynamic light scattering and gel retardation analysis. Cell absorption, transfection efficiency, and cytotoxicity were assessed. Alginate gel was combined with miR-146a/PEG-PEI nanoparticles and bFGF. Drug release ratio was measured by ultraviolet spectrophotography. Proliferation and odontogenic differentiation of DPCs with 1 μg/mL LPS treatment were determined. Results. PEG-PEI prepared at N/P 2 showed complete gel retardation and smallest particle size and zeta potential. Transfection efficiency of PEG-PEI was higher than lipo2000. Cell viability decreased as N/P ratio increased. Drug release rate amounted to 70% at the first 12 h and then maintained slow release afterwards. Proliferation and differentiation decreased in DPCs with LPS treatment, whereas they increased in miR-146a/bFGF gel group. Conclusions. PEG-PEI is a promising vector for gene therapy. miR-146a and bFGF play critical roles in inflammation response and tissue regeneration of DPCs.

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Predominance of Abdominal Visceral Adipose Tissue Reflects the Presence of Aortic Valve Calcification

Background. Aortic valve calcification (AVC) is a common feature of aging and is related to coronary artery disease. Although abdominal visceral adipose tissue (VAT) plays fundamental roles in coronary artery disease, the relationship between abdominal VAT and AVC is not fully understood. Methods. We investigated 259 patients who underwent cardiac and abdominal computed tomography (CT). AVC was defined as calcified lesion on the aortic valve by CT. %abdominal VAT was calculated as abdominal VAT area/total adipose tissue area. Results. AVC was detected in 75 patients, and these patients showed higher %abdominal VAT (44% versus 38%, ) compared to those without AVC. When the cutoff value of %abdominal VAT was set at 40.9%, the area under the curve to diagnose AVC was 0.626. Multivariable logistic regression analysis showed that age (OR 1.120, 95% CI 1.078–1.168, ), diabetes (OR 2.587, 95% CI 1.323–5.130, ), and %abdominal VAT (OR 1.032, 95% CI 1.003–1.065, ) were independent risk factors for AVC. The net reclassification improvement value for detecting AVC was increased when %abdominal VAT was added to the model: 0.5093 (95% CI 0.2489–0.7697, ). Conclusion. We determined that predominance of VAT is associated with AVC.

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Use of Modified Polysaccharide 4DryField PH for Adhesion Prevention and Hemostasis in Gynecological Surgery: A Two-Center Observational Study by Second-Look Laparoscopy

Purpose. This study evaluates both scopes of 4DryField PH, certified for adhesion prevention and hemostasis, in patients undergoing surgery for various and severe gynecological disorders. Methods. This is a two-institutional study. Adhesion prevention efficacy was evaluated using video documentation of first-look laparoscopies (FLL) and second-look laparoscopies (SLL); other patient data were analyzed retrospectively. Twenty patients with various disorders were evaluated, 4 assigned to a uterus pathology, 10 to endometriosis, and 6 to an adhesion disease group. Nine patients received 4DryField primarily for hemostasis and 11 solely for adhesion prevention. Nineteen patients had SLL after 5 to 12 weeks and one after 13 months. Results. At FLL with 4DryField, immediate hemostasis could be achieved in diffuse bleeding. At SLL, effective adhesion prevention was observed in 18 of all 20 women, with only 2 revealing major adhesions. In particular, only 1 of the 6 women with adhesion disease as predominant disorder showed major adhesions at SLL. Conclusions. Modified polysaccharide 4DryField is not only effective in diffuse bleeding. In this cohort with extensive surgery for various gynecological pathologies, 4DryField showed effective adhesion prevention as confirmed at SLL, too. Its use as premixed gel is a convenient variant for treatment of large peritoneal wounds.

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Masthead

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized, Placebo-Controlled Study

Publication date: Available online 23 January 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Paul F. Pasquina, Briana N. Perry, Aimee L. Alphonso, Sacha Finn, Kevin F. Fitzpatrick, Jack W. Tsao
ObjectiveTo investigate the use of RimabotulinumtoxinB (BoNT-B, Myobloc) compared to placebo in treating hyperhidrosis in the residual limbs of individuals with amputation.DesignRandomized, double-blind, placebo-controlled pilot study.SettingThe study took place at Walter Reed National Military Medical Center (WRNMMC) in Bethesda, M.D., a military medical center that provides both inpatient and outpatient services.ParticipantsNine male subjects with a total of eleven major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study from September 2010 to November 2012. Participants' lower limbs were randomly assigned to either receive injections of BoNT-B (n=7) or placebo (n=4).InterventionRimabotulinumtoxinB (BoNT-B, Myobloc).Main Outcome MeasuresThe primary efficacy variable was a minimum 50% reduction in sweat production 4 weeks after injection as measured by gravimetric assessment following 10 minutes of physical exertion. Secondary analyses were conducted on prosthetic function and pain.ResultsAll volunteers (100%) in the BoNT-B group achieved at least a 50% reduction in sweat, compared to only 50% of the placebo group. The percent reduction was significantly greater for the BoNT-B group compared to controls (-72.7±15.7% vs. -32.7±39.2%; p<0.05). Although both groups self-reported significant subjective sweat reduction and improved prosthetic functioning (both p<0.05), objective gravimetric sweat measurements significantly decreased only for the BoNT-B group (2.3±2.3 g vs. 0.7±1.1 g; p<0.05). Neither group reported a change in phantom limb pain (PLP) or residual limb pain (RLP) (both p>0.05).ConclusionBoNT-B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. There were no differences found between BoNT-B and placebo groups in perceived effect on prosthetic use.



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Editorial Board

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Correction

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Table of Contents

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Editors' Selections From This Issue: Volume 97 / Number 2 / February 2016

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Measurement Characteristics and Clinical Utility of the International Cooperative Ataxia Rating Scale in Individuals With Hereditary Ataxias

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2
Author(s): Maryleen K. Jones, Stephanie A. Combs-Miller




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Request for Proposals

Publication date: February 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 2





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Method Based on the β-Lactamase PenPC Fluorescent Labeled for β-Lactam Antibiotic Quantification in Human Plasma

Recently, Wong et al. have successfully developed a fluorescent biosensor based on the PenPC β-lactamase which changes its intrinsic fluorescence in presence of β-lactam antibiotics (BLAs). Here, we studied systematically this correlation among the fluorescence change of the biosensor and the concentration of different BLAs aimed at developing a novel method for estimating the concentration of a wide range of BLAs. This method showed high precision and specificity and very low interference from clinically relevant samples. We were able to monitor the pharmacokinetics of meropenem in healthy volunteers as well as in an ill animal model too, indicating that the implemented method could be suitable for clinical practice.

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Wen-Xin Decoction ameliorates vascular endothelium dysfunction via the PI3K/AKT/eNOS pathway in experimental atherosclerosis in rats

Nitric oxide (NO) is the most powerful vasodilator that inhibits leukocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. However, excessive NO can cause lipid peroxidation and ...

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Effect of Tualang honey on the anastomotic wound healing in large bowel anastomosis in rats-A randomized controlled trial

Honey has long been used for the treatment of number of ailments and diseases including surgical wounds. Current study evaluates the effectiveness of Tualang honey (TH) for large bowel anastomotic healing in W...

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The neuritogenic and neuroprotective potential of senegenin against Aβ-induced neurotoxicity in PC 12 cells

Improved therapeutics aimed at ameliorating the devastating effects of neurodegenerative diseases, such as Alzheimer's disease (AD), are pertinent to help attenuate their growing prevalence worldwide. One prom...

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Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance

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Publication date: Available online 23 January 2016
Source:Biological Psychology
Author(s): Cédric T. Albinet, Amira Abou-Dest, Nathalie André, Michel Audiffren
The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (HRV) and psychological variables. Thirty-six sedentary seniors aged 60–75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration.



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Corneal Dendritic Cell Density Is Associated with Subbasal Nerve Plexus Features, Ocular Surface Disease Index, and Serum Vitamin D in Evaporative Dry Eye Disease

Dry eye disease (DED) has evolved into a major public health concern with ocular discomfort and pain being responsible for significant morbidity associated with DED. However, the etiopathological factors contributing to ocular pain associated with DED are not well understood. The current IVCM based study investigated the association between corneal dendritic cell density (DCD), corneal subbasal nerve plexus (SBNP) features, and serum vitamin D and symptoms of evaporative dry eye (EDE). The study included age and sex matched 52 EDE patients and 43 heathy controls. A significant increase in the OSDI scores (discomfort subscale) was observed between EDE (median, 20.8) and control (median, 4.2) cohorts . Similarly, an increase in DCD was observed between EDE (median, 48.1 cells/mm2) patients and controls (median, 5.6 cells/mm2) . A significant decrease in SBNP features (corneal nerve fiber length, fiber density, fiber width, total branch density, nerve branch density, and fiber area) was observed in EDE patients with OSDI score >23 . A positive correlation was observed between DCD and OSDI discomfort subscale (; ) and SBNP features. An inverse correlation was observed between vitamin D and OSDI scores (; ) and DCD with dendritic processes (; ). The findings implicate DCD, SBNP features, and vitamin D with EDE symptoms.

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