A hyperpigmented rash on face and chest

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Using a Dihydrofolate Reductase-Based Strategy for Producing the Biosimilar Version of Pertuzumab in CHO-S Cells

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Anti-inflammatory activity and gastroprotective effect of Hertia cheirifolia L. roots extract

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Kaouther Majouli, Assia Hamdi, Amal Abdelhamid, Abderrahman Bouraoui, Adberraouf Kenani
Ethnopharmacological relevanceHertia cheirifolia L. is used traditionally to treat rheumatic pains and known as a medicinal plant having several pharmaceutical and biological activities. The present study evaluated in vivo the anti-inflammatory and gastroprotective effects of the methanolic extract from H. cheirifolia L.Materials and methodsReverse phase high-performance liquid chromatography (RP-HPLC) was performed to identify various chemical components of the plant extract. Anti-inflammatory and gastroprotective activities were assessed on carrageenan-induced paw edema and HCl/ethanol-induced gastric lesions in rats, respectively.Results(RP-HPLC) analysis indicated that coumarin is the abundant component in the extract (53.80%). Intraperitoneal administration of the methanolic extract at different doses showed interesting activities in rats in a dose-dependent manner. At 100 mg/kg, this extract showed the highest acute anti-inflammatory activity and an important inhibition of gastric lesions with inhibition percentage of 79.41% and 88.53%, respectively.ConclusionAltogether, the results of this study reveal the anti-inflammatory and gastroprotective effects of H. cheirifolia extract and promote the traditional use of this plant in the treatment of different pain and inflammatory diseases.

Graphical abstract

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Neuroprotective effect of Da Chuanxiong Formula against cognitive and motor deficits in a rat controlled cortical impact model of traumatic brain injury

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Zhi-Ke Liu, Chun-Fai Ng, Hoi-Ting Shiu, Hing-Lok Wong, Wai-Ching Chin, Jin-Fang Zhang, Ping-Kuen Lam, Wai-Sang Poon, Clara Bik-San Lau, Ping-Chung Leung, Chun-Hay Ko
Ethnopharmacological relevanceDa Chuanxiong Formula (DCXF) is one of the famous herb pairs that contains dried rhizomes of Ligusticum chuanxiong Hort. and Gastrodia elata Bl. in the mass ratio of 4:1. This classic representative traditional Chinese medicine has been widely used to treat brain diseases like headache and migraine caused by blood stasis and wind pathogen. However, the therapeutic effect of DCXF on traumatic brain injury (TBI) has not been reported yet.Aim of studyThe present study was performed to investigate the neuroprotective effects of DCXF and its underlying mechanisms in the controlled cortical impact (CCI)-induced TBI rat model.Materials and methodsMale Sprague-Dawley rats were divided into four groups: Sham, TBI control, 1X DCXF (520.6 mg/kg) and 5X DCXF (2603.0 mg/kg). Two treatment groups (1X and 5X DCXF) were intragastrically administered daily for 7 days before CCI-induced TBI and then DCXF treatments were continued post-TBI until the animal behavioral tests, including Morris water maze test, acceleration rotarod motor test and CatWalk quantitative gait analysis test, were done. The brain water content and blood brain barrier (BBB) integrity were measured by wet-dry weight method and Evans blue method, respectively. The number of neuron cells, neural stem cells (NSCs), GFAP positive cells (astrocyte) as well as Iba-1 positive cells (microglia) were determined by histology and immunohistochemistry.ResultsTreatment with DCXF significantly improved the learning ability and memory retention in Morris water maze test, and remarkably enhanced motor performances in acceleration rotarod motor test and catwalk quantitative gait analysis test after TBI. Moreover, DCXF treatment was able to reduce BBB permeability, brain edema, microglia and astrocyte activation, improve the proliferation of NSCs and decrease neurons loss in the brain with TBI.ConclusionsThe present study demonstrated that DCXF treatment could decrease BBB leakage and brain edema, reduce neuron loss, microglia and astrocyte activation, and increase NSCs proliferation, which may contribute to the cognitive and motor protection of DCXF in the TBI rats. It is the first time to provide potentially underlying mechanisms of the neuroprotective effect of DCXF on TBI-induced brain damage and functional outcomes.

Graphical abstract

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Beasley’s 1981 paper: The power of a well-designed cohort study to drive liver cancer research and prevention

Publication date: Available online 13 February 2018
Source:Cancer Epidemiology
Author(s): Jill Koshiol, Zhiwei Liu, Thomas R. O'Brien, Allan Hildesheim
The 1981 Lancet paper by Beasley et al., "Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22707 men in Taiwan" is a seminal publication that clearly demonstrated that chronic infection with hepatitis B virus (HBV), as measured by seropositivity for the hepatitis B surface antigen (HBsAg), preceded the development of hepatocellular carcinoma (HCC). In doing so, this study paved the way for liver cancer prevention efforts through the implementation of hepatitis B vaccination programs. In this commentary, we will describe the discovery of HBV, which led to the study by Beasley et al.; summarize the major findings of the Beasley paper and its implications; discuss the importance of well-designed cohort studies for prevention activities; and consider the ramifications of the Beasley study and the work that has followed since.



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Asymptomatic facial nodules

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Characterization of oily mature skin by biophysical and skin imaging techniques

Abstract

Background

The skin is a complex biological system and may suffer change according to the environmental factors, as higher temperatures can increase sebum excretion, presenting oiliness and acne. These alterations can persist during the aging and provoke more changes in aged skin. In this study we evaluated the mature oily skin characteristics using biophysical and skin imaging techniques.

Material and methods

Sixty healthy female subjects, aged between 39 and 55 years old were recruited and separated into 2 groups according to their skin type: normal/dry and oily skin. The skin was evaluated in terms of stratum corneum water content, transepidermal water loss (TEWL) sebum content, dermis thickness and echogenicity, skin microrelief, and pores content.

Results

The mature oily skin presented no significant differences when compared to the normal/dry skin on the stratum corneum water content and TEWL parameters. The sebum content was significantly higher on the oily skin group. The microrelief analysis showed an increase of skin roughness values in the oily skin and increase of scaliness in the normal/dry skin. The oily skin showed lower dermis echogenicity mainly in the frontal region and higher dermis thickness when compared to normal/dry skin.

Conclusion

The mature oily skin showed different characteristics from normal/dry skin in terms of sebum content, microrelief parameters, and dermis thickness. This way, the characterization of mature oily skin in an objective way is very important to development of dermocosmetic products for more effective treatments focused specially on this type of skin.

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Asymptomatic facial nodules

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Role of solid lipid nanoparticles as photoprotective agents in cosmetics

Summary

Background

Novel drug delivery systems have gained popularity since last two decades because of its advantages over conventional dosage forms. Effect of UV radiation on skin can cause either acute or chronic damage to our skin. Solid lipid nanoparticles (SLNs) were developed as novel carrier over the conventional carrier systems like liposomes and emulsions. The SLNs were selected as a carrier for the formulation because of its ability to protect the labile drug particles, the ability to make the drug release in a controlled manner, and occlusive property of the SLNs.

Objective

The current review is an attempt to focus on the characteristics of solid lipid nanoparticles, methods for the preparations, and their cosmetic applications along with some future perspectives of the nanodrug delivery systems.

Methods

A review of the current literature of solid lipid nanoparticles (SLNs) as novel carrier showed better photoprotection in sunscreens.

Results and conclusions

The disadvantages of conventional sunscreens can be overcome by incorporation of solid lipid nanoparticles. On comparing the lipid nanobased systems with traditional cosmetic products, the occlusion can be achieved without the use of paraffin and other greasy oils. The film formed by lipid nanoparticles will be smooth as compared to the inflexible films formed by the paraffin. Newer approaches may lead to even better results. They also possess excellent UV-blocking activity and showed better photoprotection.

http://ift.tt/2BqOqIu

Role of solid lipid nanoparticles as photoprotective agents in cosmetics

Summary

Background

Novel drug delivery systems have gained popularity since last two decades because of its advantages over conventional dosage forms. Effect of UV radiation on skin can cause either acute or chronic damage to our skin. Solid lipid nanoparticles (SLNs) were developed as novel carrier over the conventional carrier systems like liposomes and emulsions. The SLNs were selected as a carrier for the formulation because of its ability to protect the labile drug particles, the ability to make the drug release in a controlled manner, and occlusive property of the SLNs.

Objective

The current review is an attempt to focus on the characteristics of solid lipid nanoparticles, methods for the preparations, and their cosmetic applications along with some future perspectives of the nanodrug delivery systems.

Methods

A review of the current literature of solid lipid nanoparticles (SLNs) as novel carrier showed better photoprotection in sunscreens.

Results and conclusions

The disadvantages of conventional sunscreens can be overcome by incorporation of solid lipid nanoparticles. On comparing the lipid nanobased systems with traditional cosmetic products, the occlusion can be achieved without the use of paraffin and other greasy oils. The film formed by lipid nanoparticles will be smooth as compared to the inflexible films formed by the paraffin. Newer approaches may lead to even better results. They also possess excellent UV-blocking activity and showed better photoprotection.

http://ift.tt/2BqOqIu

Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Rupsa Basu, Lukai Zhai, Alice Contreras, Ebenezer Tumban
Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241–259, 294–315, 317–327, 346–361, 377–388 and 421–437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection. Nevertheless, the immunogenicity of these epitopes has never been assessed. Here, we displayed these epitopes on highly immunogenic bacteriophage virus-like particles (VLPs; MS2, PP7 and Qβ) platforms and assessed their immunogenicity in mice. Mice immunized with a mixture of VLPs displaying ZIKV envelope B-cell epitopes elicited anti-ZIKV antibodies. Although, immunized mice were not protected against a high challenge dose of ZIKV, sera – albeit at low titers – from immunized mice neutralized (in vitro) a low dose of ZIKV. Taken together, these results show that these epitopes are B-cell epitopes and they are immunogenic when displayed on a Qβ VLP platform. Furthermore, the results also show that immunization with VLPs displaying a single B-cell epitope minimally reduces ZIKV infection whereas immunization with a mixture of VLPs displaying a combination of the B-cell epitopes neutralizes ZIKV infection. Thus, immunization with a mixture of VLPs displaying multiple ZIKV B-cell epitopes is a good strategy to enhance ZIKV neutralization.



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FlaC supplemented with VAA, OmpK or OmpR as bivalent subunit vaccine candidates induce immune responses against Vibrio anguillarum in flounder (Paralichthys olivaceus)

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Jing Xing, Xiujuan Zhou, Xiaoqian Tang, Xiuzhen Sheng, Wenbin Zhan
In our previous study, ten candidate proteins have been identified with immunogenicity and protection against Vibrio anguillarum in flounder (Paralichthys olivaceus). Among them, FlaC is the important outer protein in the flagellum with immunogenicity; VAA, OmpK and OmpR are protection proteins against V. anguillarum. In this paper, FlaC supplemented with VAA, OmpK or OmpR as bivalent subunit vaccine candidates, and their immune response of flounder and protective effects were evaluated, respectively. Recombinant(r) proteins of FlaC were mixed with rVAA, rOmpK and rOmpR, respectively, rVAA + rFlaC (AF), rOmpK + rFlaC (KF) and rOmpR + rFlaC (RF); formalin-killed cells (FKC) or PBS were injected to flounder, respectively. After immunization, the percentages of CD3⁺ T lymphocytes and surface membrane immunoglobulin-positive (sIg⁺) B lymphocytes in peripheral blood lymphocytes (PBLs), total antibodies (TA), specific antibodies against V. anguillarum (VA), specific antibodies against bivalent recombinant proteins (PA), the expression of immune-related genes and relative percent survivals (RPS) were measured, respectively. The results showed that three bivalent vaccines candidates and FKC could induce the proliferation of sIg⁺ B lymphocytes and CD3⁺ T lymphocytes in PBLs. The TA, VA and PA induced in bivalent vaccines candidates and FKC groups were significantly higher than that of the control group. CD3, IgM, CD4-1, CD4-2, CD8α and CD8β genes were up-regulated. After challenge with V. anguillarum, RPS in AF, KF, RF and FKC groups exhibited 62.6 ± 2.33%, 78.95 ± 3.01%, 75.45 ± 0.97%, and 56.71 ± 2.15% respectively. The results revealed that three bivalent vaccines candidates and FKC could induce the immune response in flounder, and have good protection against V. anguillarum, and KF can be an efficient bivalent subunit vaccine candidate.



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Exceptional influenza morbidity in summer season of 2017 in Israel may predict the vaccine efficiency in the coming winter

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Rakefet Pando, Sivan Sharabi, Michal Mandelboim
Influenza infections are the leading cause of respiratory viral infections worldwide, and are mostly common in the winter season. The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Immediately following each winter season the World Health Organization (WHO) announces the vaccine composition for the following winter. Unexpectedly, during the summer of 2017, in Israel, we observed in hospitalized patients, an exceptionally high numbers of Influenza positive cases. The majority of the influenza B infections were caused by influenza B/Yamagata lineage, which did not circulate in Israel in the previous winter, and most of the influenza A infections were caused by influenza A/H3N2, a strain similar to the strain that circulated in Israel in the previous winter. We therefore predict that these two viruses will circulate in the coming winter of 2017/18 and that the trivalent vaccine, which includes antigenically different viruses will be inefficient.



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Turning up the heat: Effect of new vaccine for children’s (VFC) program recommendations for use of temperature monitors upon incorrect product storage adverse event reporting

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Eileen Wilson, Cong Zhu, Susan Galea, Ann Marko, Veronica Victoria Urdaneta, Walter Straus
BackgroundThe Centers for Disease Control and Prevention (CDC) coordinates the Vaccines For Children (VFC) program, which provides free vaccines to qualified children in the US. In 2009, the CDC issued Vaccine Storage Requirements, which were later replaced (2012) with an interim guidance and toolkit for vaccine storage and handling. The guidance called for use of Digital Data Loggers (DDL) to monitor vaccine storage temperatures. We describe a change in frequency of Incorrect Product Storage Reports (IPSRs) following issuance of the 2009 CDC guidance.MethodsMerck & Co., Inc., Kenilworth, NJ, USA, systematically evaluates vaccine safety concerns for all products. The safety database was queried (01-Jan-2004 through 31-December-2016) to identify all IPSRs associated with 10 vaccines. We compared IPSRs received prior to and following the 2009 CDC guidance, comparing reports received from the US with those received from international sources during the same period.ResultsFollowing the release of the DDL guidance, a progressive increase in IPSRs was identified in the US (1 report received in 2004, 12,993 reports in 2016). In contrast, non-US IPSRs – have not had a similar increase: no reports received in 2004, 216 reports received in 2016. US reports of IPSRs 2004 through 2016 account for 96% of reports worldwide. There were no serious reports found in the database in conjunction with IPSRs, nor were there any additional safety findings in any of the reports with additional events reported.ConclusionVFC DDL guidance was followed by an increase in IPSRs. No similar trend was seen outside the US (where no broad change in DDL guidance occurred). Despite the increase in IPSRs, there have been few associated adverse events (AEs) reported; no new safety concerns were identified. These findings suggest that the increase in IPSRs was associated with the introduction of use of DDLs, and suggests the need for further impact assessment.



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The National Vaccine Advisory Committee at 30: Impact and opportunity

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Kimberly M. Thompson, Bruce G. Gellin, Alan R. Hinman, Walter A. Orenstein
Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) "to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines," this review reflects NVAC's role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.



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Cost-effectiveness of vaccination against cytomegalovirus (CMV) in adolescent girls to prevent infections in pregnant women living in France

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): D.S. N'Diaye, O. Launay, O. Picone, V. Tsatsaris, E. Azria, F. Rozenberg, M. Schwarzinger, Y. Yazdanpanah
BackgroundCMV infections are the most frequent congenital infections worldwide.AimAssess the cost-effectiveness of vaccination strategies of adolescent girls vs. current practice (hygiene counseling) to prevent CMV seroconversions during pregnancy in France.MethodA Markov decision-tree model simulated overtime the trajectory of a single fictive cohort of 390,000 adolescent women aged 14 years old, living in France. Impact of vaccination was explored until the end of their reproductive live 40 years later.Strategies compared"S1: No vaccination" (current practice); "S2: Routine vaccination"; "S3: Screening and vaccination of the seronegative".Model parametersSeroconversion rate without vaccination (0.035%/pregnant woman-week); fetal transmission risk (41%). Vaccine vs. no vaccination: a 50% decrease in maternal seroconversions.OutcomesQuality-Adjusted Life-Years (QALYs) of the cohort-born babies; discounted costs; Incremental Cost-Effectiveness Ratio (ICER).ResultsS2 was the most effective strategy (with 35,000 QALYs gained) and the most expensive (€211,533,000); S1 was the least effective and least costly (€75,423,000). ICERs of strategy S3 vs. S1, and S2 vs. S3 were 6,000€/QALY gained (95% uncertainty range [2700–13,300]) and 16,000€/QALY [negative ICER (S3 dominated by S2) – 94,000] gained, respectively; highly cost-effective because ICER < 1∗France's GPD/capita = €30,000.Sensitivity analysisIf the seroprevalence was >62% (vs. 20% in the base case), S3 would become the most efficient strategy.ConclusionIn France, systematic vaccination of adolescent girls was the most efficient strategy to prevent maternal seroconversions. If the population was less than 62% immune, systematic screening and vaccination of susceptibles would become the most cost-effective approach.



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Vaccination timeliness and co-administration among Kenyan children

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Nina B. Masters, Abram L. Wagner, Bradley F. Carlson, Matthew L. Boulton
BackgroundTimely administration of recommended vaccines requires children to have multiple vaccines co-administered in the first year of life. The objectives of this study were to estimate the proportion of timely vaccinations and the proportion of co-administered vaccines, and to assess the relationship between vaccine co-administration and vaccine timeliness in Kenyan children.MethodsUsing the 2014 Kenyan Demographic and Health Survey (DHS), we calculated the proportion of children who received co-administered and timely vaccine doses. Co-administration was defined as doses administered on the same day with dates recorded on vaccination cards. Vaccines were considered timely if given within four days before to four weeks after the recommended interval for administration.Results10,385 children aged 1–4 years in the Kenyan 2014 DHS dataset had vaccination cards which comprised the study sample. Analysis revealed wide a range for receipt of timely doses, from 90.2% for OPV0 to 56.0% for Measles. Co-administration of the 6-week dose was associated with 2.81 times higher odds of a timely Penta dose 1 (95% CI: 2.28, 3.46) and birth-dose co-administration was associated with a substantial increase in timely BCG vaccination: AOR 7.43 (95% CI: 6.31, 8.75).ConclusionsThough vaccine coverage in Kenya was high, timely vaccination was markedly low, with resultant implications for population immunity and potential spread of communicable diseases in unvaccinated infants. Co-administration of vaccines, place of residence, wealth index, and child age were consistently related to the odds of timely vaccine receipt. These relationships reinforce the importance of dedicating resources to programs that educate low socio-economic groups about the importance of vaccine co-administration.



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Editorial Board/Aims and Scope

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11





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Disparities in parental human papillomavirus (HPV) vaccine awareness and uptake among adolescents

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Narissa J. Nonzee, Susie B. Baldwin, Yan Cui, Rita Singhal
Trends in HPV vaccine awareness among parents of adolescent girls and boys (ages 13–17) and HPV vaccine uptake (≥1 dose) among girls (ages 13–17) were evaluated in Los Angeles County, California. Between 2007 and 2011, parental HPV vaccine awareness increased from 72% to 77% overall, with significant increases among mothers, Latinos, and respondents with daughters and Medi-Cal insured children. In 2011, parents who were male, older, less educated, Asian/Pacific Islander, and had sons remained significantly less likely to be aware. HPV vaccine initiation among daughters nearly doubled from 25% in 2007 to 48% in 2011, and girls who were older, uninsured, and had access-related barriers showed the largest improvements. In 2011, daughters who were younger and who had older and African American parents were at risk for low uptake. Thus, initiatives targeting male and younger adolescents, culturally-relevant information, and access to vaccination may help to reduce identified disparities.



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Evaluation on the persistence of anti-HPV immune responses to the quadrivalent HPV vaccine in Chinese females and males: Up to 3.5 years of follow-up

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Teng Huang, Youping Liu, Yanping Li, Yuqin Liao, Qiong Shou, Minghuan Zheng, Xueyan Liao, Rongcheng Li
BackgroundThis was an extension study of a randomized, double-blind, placebo-controlled immunogenicity and safety study of the quadrivalent human papillomavirus (qHPV) (HPV 6, 11, 16, and 18) vaccine conducted in Chinese female subjects aged 9–45 years and male subjects aged 9–15 years. To investigate the persistence of anti-HPV 6, -11, -16, and -18 responses among Chinese subjects, subjects enrolled in the base study were followed up at around month 42 (approximately 3.5 years after vaccination).MethodsAmong 600 subjects enrolled in the base study, a total of 468 subjects consented for participation in the extension study. Anti-HPV 6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA) and total IgG Luminex immunoassay (IgG LIA).ResultsAmong the female subjects who received the qHPV vaccine, the proportions of subjects remained seropositive were high with both the cLIA and IgG LIA for HPV type 6, 11, and 16 through approximately 42 months following the first dose vaccination. For HPV 18, the seropositivity rate remained high as 82.0% with the IgG LIA, while it decreased to 53.6% with the cLIA, which was similar to the findings observed in other studies. The seropositivity rates remained high at month 42 for all qHPV types with both the cLIA and IgG LIA among the male subjects.ConclusionsAdministration of a 3-dose regimen of qHPV vaccine induces durable anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses among Chinese subjects for at least 3.5 years after vaccination.ClinicalTrials.gov registry:NCT01427777



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Influenza vaccine effectiveness in older adults compared with younger adults over five seasons

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Kate Russell, Jessie R. Chung, Arnold S. Monto, Emily T. Martin, Edward A. Belongia, Huong Q. McLean, Manjusha Gaglani, Kempapura Murthy, Richard K. Zimmerman, Mary Patricia Nowalk, Michael L. Jackson, Lisa A. Jackson, Brendan Flannery
BackgroundThere have been inconsistent reports of decreased vaccine effectiveness (VE) against influenza viruses among older adults (aged ≥ 65 years) compared with younger adults in the United States. A direct comparison of VE over multiple seasons is needed to assess the consistency of these observations.MethodsWe performed a pooled analysis of VE over 5 seasons among adults aged ≥ 18 years who were systematically enrolled in the U.S. Flu VE Network. Outpatients with medically-attended acute respiratory illness (cough with illness onset ≤ 7 days prior to enrollment) were tested for influenza by reverse transcription polymerase chain reaction. We compared differences in VE and vaccine failures among older adult age group (65–74, ≥75, and ≥ 65 years) to adults aged 18–49 years by influenza type and subtype using interaction terms to test for statistical significance and stratified by prior season vaccination status.ResultsAnalysis included 20,022 adults aged ≥ 18 years enrolled during the 2011–12 through 2015–16 influenza seasons; 4,785 (24%) tested positive for influenza. VE among patients aged ≥ 65 years was not significantly lower than VE among patients aged 18–49 years against any subtype with no significant interaction of age and vaccination. VE against A(H3N2) viruses was 14% (95% confidence interval [CI] −14% to 36%) for adults ≥ 65 years and 21% (CI 9–32%) for adults 18–49 years. VE against A(H1N1)pdm09 was 49% (95% CI 22–66%) for adults ≥ 65 years and 48% (95% CI 41–54%) for adults 18–49 years and against B viruses was 62% (95% CI 44–74%) for adults ≥ 65 years and 55% (95% CI 45–63%) for adults 18–49 years. There was no significant interaction of age and vaccination for separate strata of prior vaccination status.ConclusionsOver 5 seasons, influenza vaccination provided similar levels of protection among older and younger adults, with lower levels of protection against influenza A(H3N2) in all ages.



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Impact of introduction of the 9-valent human papillomavirus vaccine on vaccination coverage of youth in North Carolina

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Justin G. Trogdon, Paul Shafer, Brianna Lindsay, Tamera Coyne-Beasley
ObjectivesThe objective of this study was to evaluate the impact of introduction of 9vHPV vaccine on HPV vaccination uptake (doses per capita) and initiation (≥1 doses), completion (≥3 doses) and compliance (≥3 doses within 12 months) by adolescents.MethodsWe used a retrospective cohort analysis using North Carolina Immunization Registry (NCIR) data from January 2008 through October 2016. The sample included Vaccines for Children eligible adolescents aged 9 to 17 years in 2016, for whom the NCIR contains complete vaccination history. We applied an interrupted time series design to measure associations between ZIP Code Tabulation Area (ZCTA)-level HPV vaccination outcomes over time with the introduction of 9vHPV in North Carolina (NC) in July 2015.ResultsEach outcome displayed a linear upward trend over time with large seasonal spikes near August of each year, corresponding to the time when adolescents often receive other vaccines required for school entry. After accounting for these underlying trends, introduction of 9vHPV was not associated with a change in publicly funded HPV vaccination rates in NC.ConclusionsOur results indicate that 9vHPV substituted for 4vHPV in the first year after release in NC, but the release of 9vHPV was not associated with an overall change in HPV vaccination.



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Immune parameters to p67C antigen adjuvanted with ISA206VG correlate with protection against East Coast fever

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Anna Lacasta, Stephen Mwalimu, Elisabeth Kibwana, Rosemary Saya, Elias Awino, Thomas Njoroge, Jane Poole, Nicholas Ndiwa, Roger Pelle, Vishvanath Nene, Lucilla Steinaa
East Coast fever (ECF) is a lymphoproliferative disease caused by the tick-transmitted protozoan parasite Theileria parva. ECF is one of the most serious cattle tick-borne diseases in Sub-Saharan Africa. We have previously demonstrated that three doses of the C-terminal part of the sporozoite protein p67 (p67C) adjuvanted with ISA206VG confers partial protection against ECF at a herd level. We have tested the efficacy of two doses of this experimental vaccine, as reducing the vaccination regimen would facilitate its deployment in the field. We reconfirm that three antigen doses gave a significant level of protection to severe disease (46%, ECF score < 6) when compared with the control group, while two doses did not (23%). Animals receiving three doses of p67C developed higher antibody titers and CD4⁺ T-cell proliferation indices, than those which received two doses. A new panel of immune parameters were tested in order to identify factors correlating with protection: CD4⁺ proliferation index, total IgG, IgG1, IgG2 and IgM half maximal titers and neutralization capacity of the sera with and without complement. We show that some of the cellular and humoral immune responses provide preliminary correlates of protection.



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Long-term immunogenicity of an initial booster dose of an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC) and the safety and immunogenicity of a second JE-VC booster dose in children previously vaccinated with an inactivated, mouse brain-derived Japanese encephalitis vaccine

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Ki Wook Yun, Hoan Jong Lee, Ji Young Park, Hye-Kyung Cho, Yae-Jean Kim, Kyung-Hyo Kim, Nam Hee Kim, Young Jin Hong, Dong Ho Kim, Hwang Min Kim, Sung-Ho Cha
BackgroundThis study was performed with the aim of determining the long-term immunogenicity of an inactivated, Vero cell culture-derived Japanese encephalitis (JE) vaccine (JE-VC) and an inactivated, mouse brain-derived JE vaccine (JE-MB) after the 1st booster dose at 2 years of age, as well as the safety and immunogenicity of the 2nd booster dose of JE-VC at 6 years of age, in children primed and given a 1st booster dose of either JE-VC or JE-MB.MethodIn this multicenter, open-label clinical trial, the study population consisted of healthy Korean children (aged 6 years) who participated in the previous JE vaccine trial. All subjects were subcutaneously vaccinated once for the booster immunization with Boryung Cell Culture Japanese Encephalitis Vaccine® (JE-VC).ResultApproximately 4 years after the 1st booster dose of JE-VC, the seroprotection rate (SPR) and geometric mean titer (GMT) of the neutralizing antibody were 100% and 1113.8, respectively. In children primed and given a 1st booster dose of JE-MB, the SPR and GMT were 88.5% and 56.3, respectively. After the 2nd booster dose of JE-VC, all participants primed and given a 1st booster dose of either JE-MB or JE-VC were seroprotective against JE virus. The GMT of the neutralizing antibody was higher in children primed and given a 1st booster dose of JE-VC (8144.1) than in those primed and given a 1st booster dose of JE-MB (942.5) after the vaccination (p < 0.001). In addition, the 2nd booster dose of JE-VC showed a good safety profile with no serious vaccine-related adverse events.ConclusionThe 1st booster dose of JE-VC and JE-MB showed long-term immunogenicity of at least 4 years, and the 2nd booster dose of JE-VC showed a good safety and immunogenicity profile in children primed and given a 1st booster dose of either JE-VC or JE-MB.ClinicalTtrials.gov Identifier: NCT02532569



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Routing dependent immune responses after experimental R848-adjuvated vaccination

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): Susan van Aalst, Manon A.A. Jansen, Irene S. Ludwig, Ruurd van der Zee, Willem van Eden, Femke Broere
Most traditional vaccines are administered via the intramuscular route. Other routes of administration however, can induce equal or improved protective memory responses and might provide practical advantages such as needle-free immunization, dose sparing and induction of tissue-specific (mucosal) immunity. Here we explored the differences in immunological outcome after immunization with model antigens via two promising immunization routes (intradermal and intranasal) with or without the experimental adjuvant and TLR7/8-agonist R848. Because the adaptive immune response is largely determined by the local innate cells at the site of immunization, the effect of R848-adjuvation on local cellular recruitment, antigenic uptake by antigen-presenting cells and the initiation of the adaptive response were analyzed for the two routes of administration. We show a general immune-stimulating effect of R848 irrespective of the route of administration. This includes influx of neutrophils, macrophages and dendritic cells to the respective draining lymph nodes and an increase in antigen-positive antigen-presenting cells which leads for both intradermal and intranasal immunization to a mainly TH1 response. Furthermore, both intranasal and intradermal R848-adjuvated immunization induces a local shift in DC subsets; frequencies of CD11b⁺DC increase whereas CD103⁺DC decrease in relative abundance in the draining lymph node. In spite of these similarities, the outcome of immune responses differs for the respective immunization routes in both magnitude and cytokine profile. Via the intradermal route, the induced T-cell response is higher compared to that after intranasal immunization, which corresponds with the local higher uptake of antigen by antigen-presenting cells after intradermal immunization. Furthermore, R848-adjuvation enhances ex vivo IL-10 and IL-17 production after intranasal, but not intradermal, T-cell activation. Quite the opposite, intradermal immunization leads to a decrease in IL-10 production by the vaccine induced T-cells. This knowledge may lead to a more rational development of novel adjuvanted vaccines administered via non-traditional routes.



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Editorial Board/Aims and Scope

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10





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The role of timeliness in the cost-effectiveness of older adult vaccination: A case study of pneumococcal conjugate vaccine in Australia

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): C. Chen, J.G. Wood, P. Beutels, R. Menzies, C.R. MacIntyre, S. Dirmesropian, J.F. Reyes, P. McIntyre, A.T. Newall
While the impact of the timeliness of vaccine administration has been well-studied for childhood vaccinations, there has been little detailed quantitative analysis on the potential impact of the timeliness of vaccinations in older adults. The aim of this study was to explore the impact of implementing more realistic observed uptake distributions, taking into the account reduced vaccine efficacy but higher pneumococcal disease burden with increasing age beyond 65 years. A multi-cohort Markov model was constructed to evaluate the cost-effectiveness of a pneumococcal (PCV13) immunisation program in Australia, assuming two different uptake modelling approaches. The approach using an estimate of observed uptake was compared with a scenario in which the total cumulative uptake was delivered at the recommended age of vaccination. We found these two approaches produced different results both in terms of cases prevented and cost-effectiveness. The impact of the non-timely uptake in adult programs may sometimes have positive and other times negative effects, depending on several factors including the age-specific disease rates and the duration of vaccine protection. Our study highlights the importance of using realistic assumptions around uptake (including non-timely vaccination) when estimating the impact of vaccination in adults.



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The impact of expanded program on immunization with live attenuated and inactivated Hepatitis A vaccines in China, 2004–2016

Publication date: 28 February 2018
Source:Vaccine, Volume 36, Issue 10
Author(s): Xiaojin Sun, Fuzhen Wang, Hui Zheng, Ning Miao, Qianli Yuan, Fuqiang Cui, Zundong Yin, Guomin Zhang, Hagai Levine
IntroductionSince 2008, two types of hepatitis A (HepA) vaccines were integrated into the expanded program on immunization (EPI) in China. Children were given either one dose of live attenuated HepA (L-HepA) or two doses of inactivated HepA (I-HepA), depending on geographic regions. We sought to evaluate the impact of the EPI on HepA incidence in China.MethodsWe reviewed the epidemiology of HepA during 2004–2016 from National Notifiable Disease Reporting System (NNDRS). We collected data of L-HepA and I-HepA coverage from Children Immunization Information Management System (CIIMS). Based on the regions where two types of HepA vaccines were used, the coverage and incidence of HepA were compared over time.ResultsIn 2008–2016, the HepA vaccine coverage was 98.8% among target children, with 99.6% in I-HepA region and 98.7% in L-HepA region. HepA incidence declined by 78.0% and 82.3% in L-HepA region and I-HepA region, respectively, without significant difference. Dramatic decline were seen in all age groups of both regions.ConclusionThe study suggests that the EPI, with high coverage for both I-HepA and L-HepA, had positive impact on HepA incidence in China.



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Antigen-dependent effects of divergent selective breeding based on natural antibodies on specific humoral immune responses in chickens

Publication date: 7 March 2018
Source:Vaccine, Volume 36, Issue 11
Author(s): T.V.L. Berghof, J.A.J. Arts, H. Bovenhuis, A. Lammers, J.J. van der Poel, H.K. Parmentier
NAb are defined as antigen binding antibodies present without a known previous exposure to this antigen. NAb are suggested to enhance specific antibody (SpAb) responses, but consequences of different NAb levels on immunization are largely unknown. Layer chickens were divergently selected and bred for keyhole limpet hemocyanin (KLH)-binding NAb titers, resulting in a High line and a Low line. In this study, we investigated: (1) the relation of NAb levels with SpAb titers; and (2) the effect of immunization on NAb titers. The 50 highest females of the High line and the 50 lowest females of the Low line of generation 2 were intramuscularly immunized at 33 weeks of age with 1 mL phosphate buffered saline (PBS) containing one of four treatments: (1) negative control (no antigen), (2) 500 µg KLH, (3) 100 µg avian tuberculin purified protein derivative of Mycobacterium avium (PPD), or (4) 250 µg human serum albumin (HuSA). IgM and IgG titers of NAb and SpAb in plasma were determined prior to immunization and weekly for 5 weeks post immunization by indirect ELISA. In addition, antibody affinity was investigated. No differences in SpAb and NAb response against KLH and PPD were observed as a consequence of different NAb titers, but increased and prolonged SpAb and NAb titer responses against HuSA were observed for the High line compared to the Low line. Different natural antibody titers did not impair SpAb dynamics and SpAb affinity. NAb titers were not, or for only short-term, affected by immunization. We show here that NAb may enhance SpAb responses, but that this effect is antigen-dependent. We hypothesize that NAb play a role in general disease resistance through enhancement of the humoral adaptive immune response.



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Prevalence of Fructose Malabsorption in Patients With Irritable Bowel Syndrome After Excluding Small Intestinal Bacterial Overgrowth.

Prevalence of Fructose Malabsorption in Patients With Irritable Bowel Syndrome After Excluding Small Intestinal Bacterial Overgrowth.

J Neurogastroenterol Motil. 2018 Feb 13;:

Authors: Jung KW, Seo M, Cho YH, Park YO, Yoon SY, Lee J, Yang DH, Yoon IJ, Seo SY, Lee HJ, Park SH, Kim KJ, Ye BD, Byeon JS, Jung HY, Yang SK, Kim JH, Myung SJ

Abstract
Background/Aims: Fructose malabsorption (FM) mimics symptoms of irritable bowel syndrome (IBS), and its prevalence has increased. Diagnosing FM in IBS is challenging because of its overlap with small intestinal bacterial overgrowth (SIBO). We assessed the prevalence of FM by comparing patients with IBS with asymptomatic control individuals after excluding SIBO using the glucose hydrogen breath test (HBT).
Methods: Patients diagnosed with IBS and asymptomatic control individuals were prospectively enrolled in the study. Dietary habits were determined using the Food Frequency Questionnaire. After excluding SIBO, participants were tested using both the 15 g and 25 g fructose HBTs.
Results: Thirty-five patients with IBS and 35 age- and sex-matched asymptomatic control individuals were enrolled. The 15 g fructose HBT was positive in 7 of the 35 (20.0%) patients with IBS and in 2 of 35 (5.7%) controls (P = 0.070). The 25 g fructose HBT was positive in 16 of the 35 (45.7%) patients with IBS and in 8 of the 35 (22.9%) controls (P = 0.040). Analysis of the Food Frequency Questionnaire responses showed no significant differences between the 2 groups in dietary intake, although patients with IBS showed a significantly higher mean fiber intake than controls (21.24 ± 11.35 g vs 15.87 ± 7.07 g, respectively, P = 0.040).
Conclusions: The 25 g fructose HBT identified FM in a significantly higher percentage of SIBO-negative patients with IBS than in asymptomatic control individuals, suggesting that FM may correlate with IBS. Education regarding dietary control of foods containing fructose may be useful for the management of patients with IBS.

PMID: 29433301 [PubMed - as supplied by publisher]

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Differential Emotional Processing in Concrete and Abstract Words.

Author: Yao, Bo; Keitel, Anne; Bruce, Gillian; Scott, Graham G.; O'Donnell, Patrick J.; Sereno, Sara C.

DOI: 10.1037/xlm0000464

Publication Date: POST AUTHOR CORRECTIONS, 12 February 2018

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Is Memory Better for Objects Than for Separate Single Features? The Temporal Hypothesis.

Author: Langerock, Naomi; Vergauwe, Evie; Dirix, Nicolas; Barrouillet, Pierre

DOI: 10.1037/xlm0000501

Publication Date: POST AUTHOR CORRECTIONS, 12 February 2018

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Influence of a mixture of metals on PAHs biodegradation processes in soils

Publication date: 1 July 2018
Source:Science of The Total Environment, Volumes 628–629
Author(s): Oriol Baltrons, Montserrat López-Mesas, Mercè Vilaseca, Carmen Gutiérrez-Bouzán, Franck Le Derf, Florence Portet-Koltalo, Cristina Palet
In order to assess the effect of mixed pollutants, the influence of different concentration levels of a mixture of metals (Cr, Co, Pb, Mn, Ni, Cu, Zn) on the biodegradation of some PAHs (phenanthrene, fluoranthene, pyrene, benzo[b]fluoranthene and benzo[a]pyrene) in soil samples was evaluated. To do so, groups of microcosms of a natural soil from the region of Sabadell (Barcelona, Spain) were prepared as a reproduction of the native environment at laboratory scale, under controlled conditions. Mixtures of PAHs and metals were carefully selected, according to soil characterization and microbiological growth preliminary assays, and were added to microcosms. These microcosms were analyzed at various times, along two months, to obtain PAHs dissipation time-courses. A first-order kinetic modelling allowed obtaining different rate constants and DT50 values as a function of the metal levels introduced in microcosms. As a general observation, the higher the concentration of metals, the lower the biodegradation of PAHs of 3–4 rings (phenanthrene, fluoranthene and pyrene). On the other hand, no important effect on the biodegradation of higher molecular weight PAHs (benzo[b]fluoranthene and benzo[a]pyrene) was observed at the different concentration levels of metals tested.

Graphical abstract

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Arbuscular mycorrhizal fungi alleviate the heavy metal toxicity on sunflower (Helianthus annuus L.) plants cultivated on a heavily contaminated field soil at a WEEE-recycling site

Publication date: 1 July 2018
Source:Science of The Total Environment, Volumes 628–629
Author(s): Yu Zhang, Junli Hu, Jianfeng Bai, Junhua Wang, Rui Yin, Jingwei Wang, Xiangui Lin
An 8-week pot experiment was conducted to investigate the growth and responses of sunflower (Helianthus annuus L.) to arbuscular mycorrhizal (AM) fungal inoculations on a heavily heavy metal (HM)-contaminated (H) soil and a lightly HM-enriched (L) soil, both of which were collected from a waste electrical and electronic equipment (WEEE)-recycling site. Compared with the L soil, the H soil induced significantly larger (P<0.05) concentrations of Cd, Cu, Pb, Cr, Zn and Ni in sunflower (except for root Cr and shoot Ni), which impaired the thylakoid lamellar folds in leaves. The biomasses and P concentrations of shoots and roots, as well as the total P acquisitions per pot were all significantly decreased (P<0.05). Both Funneliformis mosseae (Fm) and F. caledonium (Fc) inoculation significantly increased (P<0.05) root mycorrhizal colonization. For the L soil, AM fungal inoculations had no significant effects on the soil-plant system, except for a decrease of soil pH and increases of soil available P and DTPA-extractable Zn concentrations with the Fm-inoculated treatment. For the H soil, however, AM fungal inoculations significantly increased (P<0.05) the biomasses and P concentrations of shoots and roots, as well as the total P acquisitions per pot, and significantly reduced (P<0.05) the concentrations of HMs in shoots (except for Cu and Pb with Fm- and Fc- inoculated treatments, respectively) and alleviated the toxicity symptoms of HMs in thylakoid structure of leaves. AM fungal inoculations in the H soil also significantly increased (P<0.05) the shoot uptake of HMs (except for Cr), and tended to decrease the total concentrations of HMs in soils. This suggests the potential application of AM fungi for both reducing HM stress and promoting phytoextraction of HM-contaminated soils caused by WEEE recycling.

Graphical abstract

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Characterization and source identification of fine particulate matter in urban Beijing during the 2015 Spring Festival

Publication date: 1 July 2018
Source:Science of The Total Environment, Volumes 628–629
Author(s): Dongsheng Ji, Yang Cui, Liang Li, Jun He, Lili Wang, Hongliang Zhang, Wan Wang, Luxi Zhou, Willy Maenhaut, Tianxue Wen, Yuesi Wang
The Spring Festival (SF) is the most important holiday in China for family reunion and tourism. During the 2015 SF an intensive observation campaign of air quality was conducted to study the impact of the anthropogenic activities and the dynamic characteristics of the sources. During the study period, pollution episodes frequently occurred with 12days exceeding the Chinese Ambient Air Quality Standards for 24-h average PM2.5 (75μg/m³), even 8days with exceeding 150μg/m³. The daily maximum PM2.5 concentration reached 350μg/m³ while the hourly minimum visibility was <0.8km. Three pollution episodes were selected for detailed analysis including chemical characterization and diurnal variation of the PM2.5 and its chemical composition, and sources were identified using the Positive Matrix Factorization model. The first episode occurring before the SF was characterized by more formation of SO4²⁻ and NO3⁻ and high crustal enrichment factors for Ag, As, Cd, Cu, Hg, Pb, Se and Zn and seven categories of pollution sources were identified, whereby vehicle emission contributed 38% to the PM2.5. The second episode occurring during the SF was affected heavily by large-scale firework emissions, which led to a significant increase in SO4²⁻, Cl⁻, OC, K and Ba; these emissions were the largest contributor to the PM2.5 accounting for 36%. During the third episode occurring after the SF, SO4²⁻, NO3⁻, NH4⁺ and OC were the major constituents of the PM2.5 and the secondary source was the dominant source with a contribution of 46%. The results provide a detailed understanding on the variation in occurrence, chemical composition and sources of the PM2.5 as well as of the gaseous pollutants affected by the change in anthropogenic activities in Beijing throughout the SF. They highlight the need for limiting the firework emissions during China's most important traditional festival.

Graphical abstract

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Effect of Co doping on the magnetic and DC electrical properties of Mn-Zn nanoferrites

Publication date: 15 June 2018
Source:Journal of Magnetism and Magnetic Materials, Volume 456
Author(s): H. Khandan Fadafan, R. Lotfi Orimi, S. Nezhadeini
In this study, Cobalt-Manganese-Zinc nanoferrites with the formula CoxMn0.5−xZn0.5Fe2O4 with x = 0.0, 0.1, 0.3, and 0.5 prepared by chemical Co-precipitation method. Then the structure and morphology of the synthesized nanoparticles were characterized by X-ray diffraction (XRD) and transmitting electron microscopy (TEM), respectively. The XRD patterns indicated the formation of single-phased cubic structure of spinel ferrite in nanometer size with no minor phase. The TEM image showed the formation of nanoparticles with average size of about 40 nm and normal size distribution. The magnetic measurements of the nanoparticles were done at room temperature using a vibrating sample magnetometer (VSM). Results exhibited a super-paramagnetic like behavior for some of the samples. DC electrical resistivity measurements were carried out by two-probe technique from 25 to 250 °C and showed decreasing of the resistivity with temperature meanwhile passing a transition to form of a peak. The peaks values observed near the Curie temperatures of samples suggest that anomaly behavior can attributed to spin canting associated with the phase transition from para to ferromagnetic state at TC.

Graphical abstract

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The Visible Burrow System: A behavioral paradigm to assess sociability and social withdrawal in BTBR and C57BL/6J mice strains

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Maria Bove, Kevin Ike, Adriaan Eldering, Bauke Buwalda, Sietse F. de Boer, Maria Grazia Morgese, Stefania Schiavone, Vincenzo Cuomo, Luigia Trabace, Martien J.H. Kas
Disrupted sociability and consequent social withdrawal are (early) symptoms of a wide variety of neuropsychiatric diseases, such as schizophrenia, autism spectrum disorders, depressive disorders and Alzheimer's disease. The paucity of objective measures to translationally assess social withdrawal characteristics has been an important limitation to study this behavioral phenotype, both in human and rodents. The aim of the present study was to investigate sociability and social withdrawal in rodents using an ethologically valid behavioral paradigm, the Visible Burrow System (VBS). The VBS mimics a natural environment, with male and female rodents housed together in an enclosure where a large open arena is connected to a continuously dark burrow system that includes 4 nest boxes. In this study, mixed-sex colonies of C57BL/6J and of BTBR mice have been investigated (n = 8 mice per colony). Results showed marked differences between the two strains, in terms of sociability as well as social withdrawal behaviors. In particular, BTBR mice performed less social behaviors and have a preference for non-social behaviors compared to C57BL/6J mice. Neurobiologically, the decreased sociability of BTBR was accompanied by reduced GABA and increased glutamate concentrations in brain prefrontal cortex (PFC) and amygdala regions. In conclusion, our study validated the use of the VBS as an ethologically relevant behavioral paradigm in group-housed mice to investigate individual sociability and social withdrawal features and their underlying neurobiology. This paradigm may provide new insights to develop new therapeutic treatments for behavioral dysfunctions that may be relevant across neuropsychiatric diseases.



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Pharmacological manipulation of GABA activity in nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS) impairs figure-ground discrimination in pigeons

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Martin J. Acerbo, Olga F. Lazareva
Figure-ground segregation is a fundamental visual ability that allows an organism to separate an object from its background. Our earlier research has shown that nucleus rotundus (Rt), a thalamic nucleus processing visual information in pigeons, together with its inhibitory complex, nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS), are critically involved in figure-ground discrimination (Acerbo et al., 2012; Scully et al., 2014). Here, we further investigated the role of SP/IPS by conducting bilateral microinjections of GABAergic receptor antagonist and agonists (bicuculline and muscimol, respectively) and non-NMDA glutamate receptor antagonist (CNQX) after the pigeons mastered figure-ground discrimination task. We used two doses of each drug (bicuculline: 0.1 mM and 0.05 mM; muscimol: 4.4 mM and 8.8 mM; CNQX: 2.15 mM and 4.6 mM) in a within-subject design, and alternated drug injections with baseline (ACSF). The order of injections was randomized across birds to reduce potential carryover effects. We found that a low dose of bicuculline produced a decrement on figure trials but not on background trials, whereas a high dose impaired performance on background trials but not on figure trials. Muscimol produced an equivalent, dose-dependent impairment on both types of trials. Finally, CNQX had no consistent effect at either dose. Together, these results further confirm our earlier hypothesis that inhibitory projections from SP to Rt modulate figure-ground discrimination, and suggest that the Rt and the SP/IPS provide a plausible substrate that could perform figure-ground segregation in avian brain.

Graphical abstract

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Retina dose as a predictor for visual acuity loss in 106Ru eye plaque brachytherapy of uveal melanomas

Publication date: Available online 13 February 2018
Source:Radiotherapy and Oncology
Author(s): Gerd Heilemann, Lukas Fetty, Matthias Blaickner, Nicole Nesvacil, Martin Zehetmayer, Dietmar Georg, Roman Dunavoelgyi
Background and purposeTo evaluate the retina dose as a risk factor associated with loss of visual acuity (VA) in ¹⁰⁶Ru plaque brachytherapy.Material/methods45 patients receiving ¹⁰⁶Ru plaques brachytherapy (median follow-up 29.5 months) were included in this study. An in-house developed treatment planning system with Monte Carlo based dose calculation was used to perform treatment planning and dose calculation. Risk factors associated with loss of VA were evaluated using the Cox proportional hazards models, Kaplan–Meier estimates and Pearson correlation coefficients.ResultsA significant correlation was found between VA loss and mean (r = 0.49, p = 0.001) and near maximum (r = 0.47, p = 0.001) retina dose D2% and tumor basal diameter (r = 0.50, p < 0.001). The Kaplan–Meier and Cox proportional hazards model yielded a significantly higher risk for VA loss (>0.3Snellen) for patients receiving a maximum dose of >500 Gy (p = 0.002). A Cox multivariate analysis including the macula dose (p = 0.237) and basal diameter (p = 0.791) showed that a high maximum retinal dose is the best risk factor (p = 0.013) for VA loss.ConclusionThe study showed that retina dose (D2% and Dmean) is a suitable predictor for VA loss.



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Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma

Publication date: Available online 13 February 2018
Source:Radiotherapy and Oncology
Author(s): Sunita Ghosh, Sarah Baker, Douglas Guedes de Castro, Lucyna Kepka, Narendra Kumar, Valery Sinaika, Juliana Matiello, Darejan Lomidze, Katarzyna Dyttus-Cebulok, Eduardo Rosenblatt, Elena Fidarova, Wilson Roa
Background and purposeShort-course radiotherapy (25 Gy in five fractions) was recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and/or frail patients with glioblastoma multiforme. This study compared the cost-effectiveness of the two regimens.Material and methodsThe direct unit costs of imaging, radiotherapy (RT), and dexamethasone were collected from the five primary contributing countries to the trial, constituting the data of 88% of all patients. Effectiveness was measured by the restricted mean overall survival (RMOS) and progression free survival (RMPFS). The incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were also estimated for comparison.ResultsThe median OSs for the short-course and commonly used RTs were 8.2 (95% confidence interval [CI] 6.1–10.3) and 7.7 (95% CI 5.5–9.9) months, respectively (log rank p = 0.340). Median PFSs were also not different (p = 0.686). The differences in the RMOS and the ICER, however, were +0.11 life-years and -$3062 United States dollars (USD) per life-year gained, respectively. The differences in the RMPFS and the ICER were +0.02 PFS and -$17,693 USD, respectively.ConclusionThe ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen.



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Microembolic Signals Predict Recurrence of Ischemic Events in Symptomatic Patients with Middle Cerebral Artery Stenosis

Publication date: Available online 13 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Xiaomin Chen, Kangding Liu, Xiujuan Wu, Sibo Wang, Ting Li, Yingqi Xing
Middle cerebral artery (MCA) stenosis is a common cause of ischemic stroke in Asian populations. We sought to determine whether microembolic signals (MESs) can predict the occurrence or recurrence of ischemia in symptomatic and asymptomatic patients with MCA stenosis. The symptomatic group had a significantly higher incidence of MES (30% vs. 16.2%, p < 0.05), as well as higher incidences of cerebral infarction and transient ischemic attack (TIA) (infarction, 13.0% vs. 4.4%, OR 3.123 [95% CI, 1.049–9.294], p < 0.05; TIA, 21.0% vs. 2.9%, OR = 7.108 [95% CI, 1.808–27.949], p < 0.001) than the asymptomatic group. After a follow-up period of 0.5–4.5 y, the subgroup of MES-positive (MES+) symptomatic patients had a significantly higher incidence of TIA (36.7% vs. 14.3%, OR = 1.623 [95% CI, 1.166–2.258]; p < 0.001) than the subgroup of MES-negative (MES-) symptomatic patients. The likelihood of the early occurrence of an endpoint event was also higher in the subgroup of MES+ symptomatic patients. In the group of asymptomatic patients with MCA stenosis, no significant differences were identified between the MES+ and MES− subgroups.



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Avoiding the Trap of Misdiagnosis: Valuable Teaching Points Derived from a Case of Longstanding Popliteal Artery Entrapment Syndrome

Popliteal artery entrapment syndrome (PAES), a condition predominantly affecting young individuals, is a rare clinical entity that can result in significant morbidity. The presence of lower limb pain and claudication in young, physically active individuals should prompt consideration for PAES. Early diagnosis and management is crucial to prevent long-term complications; however, diagnosis is fraught with challenges due to the rarity of the disease and its similar clinical presentation with more common conditions. We present a case of a young female with PAES who was misdiagnosed and underwent a tarsal tunnel release for suspected tarsal tunnel syndrome and subsequent fasciotomies for presumed chronic exertional compartment syndrome (CECS) without any relief. We outline the insidious undiagnosed course of her condition over a period of 12 years, discuss teaching points of how to recognize key differences of PAES and associated conditions, and provide recommendations for how to make the right diagnosis.

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[Spino-pelvic sagittal parameters in an asymptomatic population in Argentina].

[Spino-pelvic sagittal parameters in an asymptomatic population in Argentina].

Surg Neurol Int. 2018;9(Suppl 1):S36-S42

Authors: Guiroy A, Gagliardi M, Sícoli A, Masanés NG, Ciancio AM, Jalón P, Mezzadri JJ

Abstract
Objectives: To assess and describe spinal and pelvic sagittal parameters in a series of 100 Argentinian volunteers.
Methods: Lateral full-spine X-rays were obtained prospectively from 100 volunteers (30 males and 70 females), average age 34.1 years. All the volunteers were asymptomatic at the time of the study. Full-length left lateral spine radiographs (36'' cassette) were made using Kodak Elite CR equipment. The authors made determinations for the digital X-rays using Surgimap®, version 2.2.9.9.2. The following parameters were recorded: C7 SVA, C2-C7 CL, TK, LL, TPA, T1SPi, PI, PT, SS, L4-S1 angle, L1-L4 angle, PI-LL mismatch and CTPA. The data were analyzed using Medcalc 11.2 software. Descriptive statistics were calculated for each parameter according to its own measure score and distribution. Estimates of 95% reference and confidence intervals were calculated for each parameter. P = 0.05 was set as the threshold for statistical significance. Volunteers were classified using the Roussouly morphometric classification system.
Results: Respective means for the above-listed variables were: CL -10.04, TK 30.14, T1SPi -6.5, L1-L4 -12.45, L4-S1 -46.16, CTPA 2.5, TPA 4.65, PT 11.22, PI 48.04, LL -59. 10, PI-LL -11.11, C7 SVA mm -23.68. Plus/minus two standard deviations (SD) for the variables were: CL (-33.26, 13.12); TK (17.15, 43.30); T1SPi (-11.78, -1.25), L1-L4 (-25.55, 0.25), L4-S1 (-64.44, -27.55), CTPA (0.33, 4.80), TPA (-8.64, 18.22), PT (-1.99, 24.75), PI (25.23, 71.44), LL (-78.74, -39.89), PI-LL (-29.10, 7.04), and C7 SVA mm (-79.45, 32.08).
Conclusions: In this prospective series of 100 adult volunteers, normal values for spinal and pelvic sagittal parameters were determined in Argentinian adults.

PMID: 29430329 [PubMed]

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[Invasive sinonasal papilloma with intracranial invasion: Case report and bibliographic review].

[Invasive sinonasal papilloma with intracranial invasion: Case report and bibliographic review].

Surg Neurol Int. 2018;9(Suppl 1):S29-S35

Authors: Di Pietrantonio A, Asmus H, Ingratta C, Brennan W, Schulz J, Carballo L

Abstract
Introduction: Inverted papilloma is a locally-aggressive benign neoplasm of the paranasal sinuses with a high potential for recurrence and malignancy. Intracranial extension is infrequent, and dural penetration even more so, typically associated with recurrence of the disease or its degeneration into squamous cell carcinoma.
Clinical Case: A 32-year-old female patient consulted us for an exophytic lesion in her right nostril and exophthalmos, associated with headache, anosmia and dysgeusia. Craniofacial and brain CT and brain MRI demonstrated a lesion in the right nostril, extending into the aerial sinuses, orbital lateral wall and anterior fossa, with osteolysis and intracranial invasion towards the right frontal region. A mass effect and brain compression were noted. A histological diagnosis of inverted papilloma was made initially. Upon later resection of the lesion by double access, with reconstruction of the anterior cranial fossa, a definitive diagnosis was made of inverted papilloma of the Schneiderian type, with areas of atypical transformation in situ. Post-operatively, the patient has had a favorable course, with full upper airway patency and neither complications nor signs of recurrence after four years of follow-up.
Conclusions: Intracranial invasion of this pathology is extremely uncommon. When it exists, the tumor has a high potential for local recurrence. Consequently, complete excision of the lesion determines the patient's prognosis.

PMID: 29430328 [PubMed]

http://ift.tt/2HfuFV0

[Mild head injury].

[Mild head injury].

Surg Neurol Int. 2018;9(Suppl 1):S16-S28

Authors: Ortega Zufiría JM, Prieto NL, Cuba BC, Degenhardt MT, Núñez PP, López Serrano MR, López Raigada AB

Abstract
Introduction: Mild traumatic brain injury (TBI) represents a major health concern, because a sizeable number of patients with mild TBI will develop potentially life-threatening complications. The target of this study was to describe a large series of adult patients suffering from mild TBI, treated at University Hospital of Getafe, between 2010 and 2015 (n = 2480). We examined the patients' epidemiological and baseline clinical profile, diagnosis, treatment and ultimate outcomes, to identify major prognostic factors that influence the final result.
Methods: We retrospectively extracted patient data from medical records and performed both bivariate and multivariate statistics.
Results: In our sample, mild TBI was more common in men, and the most common causative mechanism was a traffic accident. We proposed a model for classifying patients according to risk, dividing them into low, intermediate and high risk, based upon their baseline clinical picture. This classification scheme correlated well with final outcomes. We investigated indications for skull radiography and computed tomography (CT), as well as for hospital admission for clinical observation.
Conclusions: In this study, the presence of a neurological focus on clinical examination, the existence of a fracture on plain radiographs, advanced age and the presence of a coagulation disorder were associated with the increased likelihood of intracranial complications and a poor prognosis. The Glasgow Coma Scale was deficient predicting patient outcomes, because it failed to account for concussion-related symptoms like amnesia and loss of consciousness, both very common in patients with mild TBI.

PMID: 29430327 [PubMed]

http://ift.tt/2GbNhnB

[Adult Grisel Syndrome and Cervical Skull instability. Transnasal endoscopic odontoidectomy and occipito-cervical fusion. Case report and literature review].

[Adult Grisel Syndrome and Cervical Skull instability. Transnasal endoscopic odontoidectomy and occipito-cervical fusion. Case report and literature review].

Surg Neurol Int. 2018;9(Suppl 1):S8-S15

Authors: Herrera R, Rojas H, Estramian A, Gómez J, Ledesma JL, Pablo J, Pastore J

Abstract
Background: Craniocervical junction pathology is infrequent in daily neurosurgical practice. In general, most of these lesions are of traumatic or rheumatic origin. Atlantoaxial instability of inflammatory origin (Grisel syndrome) is a rare entity of which only 16 adult cases have been reported in the literature. This pathology is characterized by the development of an osteolytic lesion at the level of the atlantoaxial joint after an infectious event, usually of the upper airways.
Case Description: We present the case of a 76-year-old patient who attended our office for clinical symptoms of spinal instability secondary to an osteolytic lesion, with involvement of C1 and C2. The symptomatology began after an infectious respiratory process. A posterior cervical occiput fixation and an endoscopic transnasal odontoidectomy with anterior decompression were performed. The patient evolved with complete resolution of symptoms. The cultures were negative, and the pathological anatomy study concluded nonspecific inflammatory changes.
Conclusion: Until a few years ago, the only option to address this pathology was the transoral pathway with microsurgical technique. Nowadays, endoscopy offers many technical advantages. This is an option to be considered when planning approaches to craniocervical junction.

PMID: 29430326 [PubMed]

http://ift.tt/2HendcO

[Minimally invasive extraforaminal lumbar interbody fusion].

[Minimally invasive extraforaminal lumbar interbody fusion].

Surg Neurol Int. 2018;9(Suppl 1):S1-S7

Authors: Landriel F, Hem S, Rasmussen J, Vecchi E, Yampolsky C

Abstract
Objectives: The objective of the present study was to determine the indications, surgical technique, results, and complications of minimally invasive extraforaminal lumbar interbody fusion (ELIF).
Introduction: ELIF is characterized as removal of the superior articular process (SAP) to access the intra-canalicular root and disc through Kambin's triangle.
Methods: A retrospective study was conducted of 40 patients operated upon between 2013 and 2015. Patients with low back pain or root pain due to degenerative disc disease, spondylolisthesis grade 1 and 2, recurrent disc herniation, and recess-foraminal stenosis were included. A visual analogue scale (VAS), the Oswestry index, the Weiner scale and the modified MacNab criteria were used to assess pain, clinical and functional results and patient satisfaction one year after surgery. Complications were documented and rated according to their severity, in four degrees.
Results: We operated on 25 women and 15 men of average age 57 years. Of the forty, 47.5% were treated for spondylolisthesis, 25% by recess foraminal stenosis. In total, 54 interbody cages and 188 percutaneous pedicle screws were placed; and the mean duration of surgery was 245 (±25.4) minutes. The mean hospitalization time was 3.5 (±0.49) days. We observed nine Grade 1 and one Grade 2 complication. The mean preoperative ODI score was 51.9 ± 4.96, which improved to 12.2 ± 3.19 at one year (P < 0.0001). The mean VAS low back pain rating improved from 8.81 ± 0.62 to 2.12 ± 0.89 (P < 0.0001). By one year post-operatively, 77.5% of the patients had fusion (Bridwell grade 1 or 2).
Conclusions: ELIF is a safe and effective surgical approach. Satisfactory clinical outcomes, comparable to traditional techniques, can be achieved with facet resection limited to the superior articular process.

PMID: 29430325 [PubMed]

http://ift.tt/2GbCKZi

Recent findings related to immune responses against leptospirosis and novel strategies to prevent infection

Publication date: Available online 13 February 2018
Source:Microbes and Infection
Author(s): Frédérique Vernel-Pauillac, Catherine Werts
What are the new approaches and emerging ideas to prevent leptospirosis, a neglected bacterial re-emerging zoonotic disease? How do Leptospira interrogans escape the host defenses? We aim here to review and discuss the most recent literature that provides some answers to these questions, in particular data related to a better understanding of adaptive and innate immunity towards leptospires, and design of vaccines. This is an opinion paper, not a comprehensive review. We will try to highlight the new strategies and technologies boosting the search for drugs and vaccines. We will also address the bottlenecks and difficulties impairing the search for efficient vaccines and the many gaps in our knowledge of immunity against leptospirosis. Finally, we aim to delineate how Leptospira spp. escape the innate immune responses of Toll-Like receptors (TLR) and Nod-Like receptors (NLR). The rational use of TLR and NLR agonists as adjuvants could be key to design future vaccines against pathogenic leptospires.



http://ift.tt/2BX0FgZ

Physiologically distinct subpopulations formed in Escherichia coli cultures in response to heat shock

Publication date: Available online 13 February 2018
Source:Microbiological Research
Author(s): Bożena Bruhn-Olszewska, Paweł Szczepaniak, Ewelina Matuszewska, Dorota Kuczyńska-Wiśnik, Karolina Stojowska-Swędrzyńska, María Moruno Algara, Ewa Laskowska
Bacteria can form heterogeneous populations containing phenotypic variants of genetically identical cells. The heterogeneity of populations can be considered a bet-hedging strategy allowing adaptation to unknown environmental changes – at least some individual subpopulations or cells might be able to withstand future adverse conditions. Using Percoll gradient centrifugation, we demonstrated that in an Escherichia coli culture exposed to heat shock at 50 °C, two physiologically distinct subpopulations were formed. A high-density subpopulation (HD50) demonstrated continued growth immediately after its transfer to LB medium, whereas the growth of a low-density subpopulation (LD50) was considerably postponed. The LD50 subpopulation contained mainly viable but non-culturable bacteria and exhibited higher tolerance to sublethal concentrations of antibiotics or H2O2 than HD50 cells. The levels of aggregated proteins and main molecular chaperones were comparable in both subpopulations; however, a decreased number of ribosomes and a significant increase in protein oxidation were observed in the LD50 subpopulation as compared with the HD50 subpopulation. Interestingly, under anaerobic heat stress, the formation of the HD50 subpopulation was decreased and culturability of the LD50 subpopulation was significantly increased. In both subpopulations the level of protein aggregates formed under anaerobic and aerobic heat stress was comparable. We concluded that the formation of protein aggregates was independent of oxidative damage induced by heat stress, and that oxidative stress and not protein aggregation limited growth and caused loss of LD50 culturability. Our results indicate that heat stress induces the formation of distinct subpopulations differing in their ability to grow under standard and stress conditions.



http://ift.tt/2Hfp4xN

Bronchoalveolar Lavage Fluid in Children: Comparative Proteomic Analysis in Infectious and Non-Infectious Lung Disease

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2o3KdCl

Impact of oxytetracycline and bacterial bioaugmentation on the efficiency and microbial community structure of a pesticide-degrading biomixture

Abstract

An experimental study evaluating the effect of bioaugmentation and antibiotic (oxytetracycline) application on pesticide degradation and microbial community structure of a biomixture used in a biopurification system (BPR) was conducted. The bioaugmentation employed a carbofuran-degrading bacterial consortium. The non-bioaugmented biomixture showed excellent performance for removal of atrazine (t_1/2: 9.9 days), carbendazim (t_1/2: 3.0 days), carbofuran (t_1/2: 2.8 days), and metalaxyl (t_1/2: 2.7 days). Neither the addition of oxytetracycline nor bioaugmentation affected the efficiency of pesticide removal or microbial community (bacterial and fungal) structure, as determined by DGGE analysis. Instead, biomixture aging was mainly responsible for microbial population shifts. Even though the bioaugmentation did not enhance the biomixtures′ performance, this matrix showed a high capability to sustain initial stresses related to antibiotic addition; therefore, simultaneous elimination of this particular mixture of pesticides together with oxytetracycline residues is not discouraged.

http://ift.tt/2ECaty5

Halimeda jolyana (Bryopsidales, Chlorophyta) presents higher vulnerability to metal pollution at its lower temperature limits of distribution

Abstract

Seaweeds living at their temperature limits of distribution are naturally exposed to physiological stressors, facing additional stress when exposed to coastal pollution. The physiological responses of seaweeds to environmental conditions combining natural and anthropogenic stressors provide important information on their vulnerability. We assessed the physiological effects and ultrastructural alterations of trace metals enrichment at concentrations observed in polluted regions within the temperature ranges of distribution of the endemic seaweed Halimeda jolyana, an important component of tropical southwestern Atlantic reefs. Biomass yield and photosynthetic performance declined substantially in samples exposed to metal, although photosynthesis recovered partially at the highest temperature when metal enrichment was ceased. Metal enrichment caused substantial ultrastructural alterations to chloroplasts regardless of temperatures. The lack of photosynthetic recovery at the lower temperatures indicates a higher vulnerability of the species at its temperature limits of distribution in the southwestern Atlantic.

http://ift.tt/2Bs6Ad6

Polyphenol extracts from dried sugarcane inhibit inflammatory mediators in an in vitro colon cancer model

Publication date: 15 April 2018
Source:Journal of Proteomics, Volume 177
Author(s): Daniel Bucio-Noble, Liisa Kautto, Christoph Krisp, Malcolm S. Ball, Mark P. Molloy
Sugarcane is an important crop grown in tropical regions for sugar, and for ethanol production. Sugarcane is also a source of phytochemicals but its nutraceutical potential has been under-explored. We show that ethanol extracts of whole dried sugarcane (WDS) recovers a rich content of polyphenols, flavonoids and antioxidant activity that act on inflammatory mediator proteins. To investigate the mechanisms of this activity, we stimulated SW480 colon cancer cells with lipopolysaccharide, exposed cells to WDS and quantitated changes to the proteome and phosphoproteome using label-free mass spectrometry. The grape-derived anti-inflammatory polyphenol, resveratrol (RSV) was used as a control. Using SWATH-MS we quantitated ~3000 proteins showing that WDS significantly altered the expression of the oxidative stress regulator SELH. WDS induced changes in protein expression predicted the involvement of NFκB pathway members. Reduced NFκB phosphorylation and IL-8 secretion confirmed this effect. In contrast, RSV was predicted to act primarily through modulation of the PI3K/AKT pathway. Phosphoproteomics studies indicate that WDS interfered in the phosphorylation of cell stress regulators c-Jun, EGFR, PKA, PKCβ and SIRT1. Confirmed through pharmacological inhibition, kinase enrichment analysis presented C-Raf to modulate WDS activity. These results demonstrate the anti-inflammatory utility of WSD and define aspects of its mechanisms of action.SignificanceDespite the increasing interest of nutraceuticals in health promotion, scientific evidence proving the molecular mechanisms involved is still lacking. This study investigated some of the mechanistic aspects of in vitro use of whole dried sugarcane extracts in the context of regulating cellular inflammation by using proteomics and phosphoproteomics strategies. We determined that WDS extracts regulate key inflammatory pathways including NFκB, while kinase enrichment analysis from phosphoproteomics demonstrated a role for C-Raf in controlling this mechanism. We demonstrated that the mechanism of WDS extracts on controlling inflammation differs from that of the polyphenol, resveratrol. The results presented herein contribute towards unravelling the activity of nutraceuticals extracted from sugarcane.

Graphical abstract

http://ift.tt/2o2CTXu

Proteomic characterization of Withaferin A-targeted protein networks for the treatment of monoclonal myeloma gammopathies

Publication date: Available online 13 February 2018
Source:Journal of Proteomics
Author(s): Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM). By blocking the PSMB10 proteasome subunit, downregulation of ANXA4, potential association with HDAC6 and upregulation of HMOX1, WA puts a massive blockage on both proteotoxic and oxidative stress responses pathways, leaving cancer cells defenseless against WA induced stresses. These results indicate that WA mediated apoptosis is preceded by simultaneous targeting of cellular stress response pathways like proteasome degradation, autophagy and unfolded protein stress response and thus suggests that WA can be used as an effective treatment for MGUS and other closely related disorders.SignificanceMultifunctional antitumor compounds are of great potential since they reduce the risk of multidrug resistance in chemotherapy. Unfortunately, characterization of all protein targets of a multifunctional compound is lacking. Therefore, we optimized an SILAC quantitative chemoproteomics workflow to identify the potential protein targets of Withaferin A (WA), a natural multifunctional compound with promising antitumor properties. To further understand the antitumor mechanisms of WA, we performed a differential protein expression analysis and combined the altered expression data with chemoproteome WA target data in the highly curated Ingenuity Pathway database. We provide a first global overview on how WA kills multiple myeloma cancer cells and serve as a starting point for further in depth experiments. Furthermore, the combined approach can be used for other types of cancer and/or other promising multifunctional compounds, thereby increasing the potential development of new antitumor therapies.

Graphical abstract

http://ift.tt/2nY7aHM

Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth

Publication date: Available online 13 February 2018
Source:Journal of Proteomics
Author(s): Arlene M. D'Silva, Jon A. Hyett, Jens R. Coorssen
Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder.Biological significanceIdentifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare term (≥37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a clinical setting as well as for future investigation of underlying aetiological processes.



http://ift.tt/2o8ihgS

Impact of cephalosporin restriction on incidence of infections with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an endemic setting.

Impact of cephalosporin restriction on incidence of infections with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an endemic setting.

J Chemother. 2018 Feb 12;:1-7

Authors: Nadrah K, Pirs M, Kreft S, Mueller Premru M, Beovic B

Abstract
Decreasing cephalosporin use was described as an effective intervention in decreasing the incidence of infections caused by Klebsiella pneumoniae harbouring extended-spectrum beta-lactamase (ESBLKP). Due to sustained increased levels of infections caused by ESBLKP, a multifaceted antibiotic stewardship intervention aimed to decrease cephalosporin use was carried out at a large medical unit of a teaching hospital. All cephalosporins except the first-generation were restricted and could only be prescribed after authorization by an infectious disease physician. The use of cephalosporins decreased significantly after intervention. The effect was most prominent for the third-generation cephalosporins (7.9-1.5 DDD/100 OBD). There was an increase in the consumption of piperacillin/tazobactam, carbapenems and fluoroquinolones. In contrast to our expectations the ESBLKP incidence increased, but the changes were not statistically significant. The intervention was successful in controlling the prescribing of cephalosporins, but had no impact on incidence of ESBLKP infections.

PMID: 29431031 [PubMed - as supplied by publisher]

http://ift.tt/2stA9rQ

Low Proportion of Dietary Plant Protein among Athletes with Premenstrual Syndrome-Related Performance Impairment.

Low Proportion of Dietary Plant Protein among Athletes with Premenstrual Syndrome-Related Performance Impairment.

Tohoku J Exp Med. 2018;244(2):119-122

Authors: Yamada K, Takeda T

Abstract
Premenstrual syndrome (PMS) is psychosomatic disorder that are limited to the late luteal phase in the menstrual cycle. PMS could impair athletic performance. To investigate associations between proportions of dietary plant and animal protein and PMS-related impairment of athletic performance, we surveyed 135 female athletes aged 18-23 years attending Kindai University. Participants belonged to authorized university clubs, all of which have high rankings in Japanese university sports. Participants completed self-administered questionnaires on diet history, demographics, and PMS-related impairment of athletic performance. Total protein, animal protein, and plant protein intake were examined, and the proportion of dietary plant protein was calculated for each participant. We divided athletes into two groups: those without PMS-related impairment of athletic performance (n = 117) and those with PMS-related performance impairment (n = 18). A t-test was used to compare mean values and multivariable adjusted mean values between groups; adjustment variables were energy intake, body mass index, and daily training duration. Total protein intake was not significantly different between the groups. However, athletes whose performance was affected by PMS reported higher intake of animal protein (mean 50.6 g) than athletes whose performance was unaffected by PMS (mean 34.9 g). Plant protein intake was lower among athletes with PMS-related impairment (mean 25.4 g) than among athletes without impairment (mean 26.9 g). The proportion of dietary plant protein was lower among athletes with PMS-related impairment (39.3%) than those without impairment (45.9%). A low proportion of dietary plant protein may cause PMS-related athletic impairment among athletes.

PMID: 29434077 [PubMed - in process]

http://ift.tt/2nXyXZ8

Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis.

Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis.

Tohoku J Exp Med. 2018;244(2):113-117

Authors: Hamada S, Masamune A, Nabeshima T, Shimosegawa T

Abstract
Host-derived factors alter gut microenvironment, and changes in gut microbiota also affect biological functions of host. Alterations of gut microbiota have been reported in a wide variety of diseases, but the whole picture of alterations in pancreatic diseases remains to be clarified. In particular, the gut microbiota may be affected by malnutrition or impaired exocrine pancreas function that is associated with pancreatic diseases. We here conducted comprehensive analysis of gut microbiota in patients with type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of the systemic IgG4-related disease, and chronic pancreatitis (CP). The two diseases were selected, because altered immune reactions in AIP and/or long-standing malnutrition in CP may influence the gut microbiota. Fecal samples were obtained from 12 patients with AIP before the steroid therapy and 8 patients with CP. Metagenome DNA was extracted, and microbiota was analyzed by next generation sequencing. Gut microbiota profiles were different between patients with AIP and those with CP; namely, the proportions of Bacteroides, Streptococcus and Clostridium species were higher in patients with CP. The reasons for the increased proportion of these bacterial species remain unknown, but may reflect malabsorption and/or decreased pancreatic enzymes, both of which are associated with CP. Incidentally, the identified Streptococcus species are oral cavity inhabitants and also known as pathogens for endocarditis. Despite the small sample size, this study has shown the differences in gut microbiota profiles between AIP and CP. Comprehensive analysis of the gut microbiota may be useful for the differential diagnosis of pancreatic diseases.

PMID: 29434076 [PubMed - in process]

http://ift.tt/2o4w8Vj

A Missense Mutation in GJA8 Encoding Connexin 50 in a Chinese Pedigree with Autosomal Dominant Congenital Cataract.

A Missense Mutation in GJA8 Encoding Connexin 50 in a Chinese Pedigree with Autosomal Dominant Congenital Cataract.

Tohoku J Exp Med. 2018;244(2):105-111

Authors: Zhang L, Liang Y, Zhou Y, Zeng H, Jia S, Shi J

Abstract
Congenital cataract is leading cause of visual impairment and blindness in children worldwide. Approximately one-third of congenital cataract cases are familial, whose genetic etiology can be distinguished by targeted exome sequencing. Here, a three-generation congenital cataract pedigree was recruited, and physical and ophthalmologic examinations were taken. Targeted exome sequencing of 139 cataract-related genes was performed on the proband III:1. Sanger sequencing was used to validate the presence of variation identified via exome sequencing in family members and 200 controls. Conservative and functional prediction was performed with bioinformatic tools. We, thus, found a heterozygous missense mutation c.10T>A (p.W4R) in gap junction protein alpha 8 (GJA8) in the patients. However, this mutation was not present in normal family members and 200 unrelated controls. The GJA8 gene encodes a gap junction protein, connexin 50 (Cx50), in lens fibers that provide channels for exchange of ions and small molecules between adjacent cells. Conservative and functional prediction suggests that the W-to-R substitution at codon 4 may impair the function of the human Cx50 protein. Accordingly, we analyzed the distribution of Flag-tagged mutant Cx50 protein in HeLa cervical cancer cells. Immunofluorescent staining showed that the W-to-R substitution impaired Cx50 trafficking to the plasma membrane to form the gap junction. In conclusion, c.10T>A (p.W4R) in GJA8 is the newly identified genetic cause of familial congenital cataract. The W-to-R substitution near the amino-terminus may alter the localization of mutant Cx50, thereby impairing gap junction formation, which is the molecular pathogenic mechanism of this mutation.

PMID: 29434075 [PubMed - in process]

http://ift.tt/2nYIuiF

Lymphaticovenular anastomosis for breast cancer treatment-related lymphedema: three-line strategy for an optimal outcome

The approach to lymphaticovenular anastomosis (LVA) for breast cancer treatment-related lymphedema should differ from that performed for secondary lower extremity lymphedema (LEL) because upper extremity lymphedema (UEL) and LEL differ in terms of the areas affected, imaging features, and postoperative improvements.

http://ift.tt/2Br3WV0

Aesthetic and functional outcomes of radial forearm flap donor site reconstruction with biosynthetic skin substitutes

The radial forearm fasciocutaneous flap (RFFF) is a workhorse flap in reconstructive microsurgery that is favoured for its thinness, reliable vascularity, consistent anatomy, and ability to be harvested concurrently during oncologic resection (1). Despite its popularity, RFFF elevation may lead to wound healing complications, wrist stiffness, weakened grip, sensory impairment, and a visible, potentially stigmatizing forearm scar (2). Various strategies have been investigated to reduce donor site morbidity, including suprafascial dissection, full thickness skin grafting, primary closure with local flaps, and the use of alternative flaps (3).

http://ift.tt/2BY7Jdy

Orchiectomy and letrozole differentially regulate synaptic plasticity and spatial memory in a manner that is mediated by SRC-1 in the hippocampus of male mice

Publication date: Available online 13 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Jikai Zhao, Chen Bian, Mengying Liu, Yangang Zhao, Tao Sun, Fangzhou Xing, Jiqiang Zhang
Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity. Next, we examined the changes in steroid receptors and steroid receptor coactivator-1 (SRC-1) under these treatments. Finally, we constructed an SRC-1 RNA interference lentivirus and an AROM overexpression lentivirus to explore the roles of SRC-1 under T replacement and AROM overexpression. The results revealed spatial memory impairment only after LET. LET induced more actin depolymerization and greater losses of spines, synapses, and postsynaptic proteins compared with ORX. Moreover, although ERα and ERβ were affected by LET and ORX at similar levels, AR, GPR30, and SRC-1 were dramatically decreased by LET compared with ORX. Finally, the T and AROM overexpression-induced changes in synaptic proteins and actin polymerization were blocked by SRC-1 inhibition. These results demonstrate that testicular androgens play a limited role, whereas local E2 is more important for cognition, which may explain why castrated men such as eunuchs usually do not have cognitive disorders. These results also suggest a pivotal role of SRC-1 in the action of steroids; thus, SRC-1 may serve as a novel therapeutic target for cognitive disorders.

Graphical abstract

http://ift.tt/2F0kNxB

Delayed Sleep Phase Syndrome and Bipolar Disorder: Pathogenesis and Available Common Biomarkers

Circadian rhythm disturbances are common in bipolar affective disorder (BD). Delayed sleep-wake phase syndrome (DSWPD) is the most prevalent circadian rhythm sleep-wake disorder (CRSWDs) and is frequently observed in BD. It is unclear whether DSWPD in BD is an independent process or is a consequence of BD. In this hypothetical review, we discuss the overlap between BD and DSWPD and potential common biomarkers for DSWPD and BD. The review will include a discussion of the genetics of DSWPD and BD.

http://ift.tt/2GbIWjX

Integrating plant and animal biology for the search of novel DNA damage biomarkers

Publication date: January–March 2018
Source:Mutation Research/Reviews in Mutation Research, Volume 775
Author(s): Zacharenia Nikitaki, Marcela Holá, Mattia Donà, Athanasia Pavlopoulou, Ioannis Michalopoulos, Karel J. Angelis, Alexandros G. Georgakilas, Anca Macovei, Alma Balestrazzi
Eukaryotic genome surveillance is dependent on the multiple, highly coordinated network functions of the DNA damage response (DDR). Highlighted conserved features of DDR in plants and animals represent a challenging opportunity to develop novel interdisciplinary investigations aimed at expanding the sets of DNA damage biomarkers currently available for radiation exposure monitoring (REM) in environmental and biomedical applications. In this review, common and divergent features of the most relevant DDR players in animals and plants are described, including the intriguing example of the plant and animal kingdom-specific master regulators SOG1 (suppressor of gamma response) and p53. The potential of chromatin remodelers as novel predictive biomarkers of DNA damage is considered since these highly evolutionarily conserved proteins provide a docking platform for the DNA repair machinery. The constraints of conventional REM biomarkers can be overcome using biomarkers identified with the help of the pool provided by high-throughput techniques. The complexity of radiation-responsive animal and plant transcriptomes and their usefulness as sources of novel REM biomarkers are discussed, focusing on ionizing (IR) and UV-radiation. The possible advantages resulting from the exploitation of plants as sources of novel DNA damage biomarkers for monitoring the response to radiation-mediated genotoxic stress are listed. Plants could represent an ideal system for the functional characterization of knockout mutations in DDR genes which compromise cell survival in animals. However, the pronounced differences between plant and animal cells need to be carefully considered in order to avoid any misleading interpretations. Radioresistant plant-based systems might be useful to explore the molecular bases of LD (low dose)/LDR (low dose rate) responses since nowadays it is extremely difficult to perform an accurate assessment of LD/LDR risk to human health. To overcome these constraints, researchers have started exploring radiotolerant non-human species as potential sources of information on the mechanisms involved in LD/LDR and general radiation responses.



http://ift.tt/2BtVior