The association between polycystic ovary syndrome, obesity, and the serum concentration of adipokines

Abstract

Purpose

This study aimed to investigate the interactive effect of polycystic ovary syndrome (PCOS) status and obesity status on the serum levels of adipokines.

Methods

In this comparative case–control cross-sectional study, 58 women with PCOS and 104 eumenorrheic non-hirsute women as the control group were recruited. They were further divided into two subgroups of overweight/obese and normal weight. The interactive effect of the PCOS status and obesity status on the circulating levels of adipokines was assessed using general linear model with the adjustment of age.

Results

A statistically significant negative interaction was reported between obesity status and PCOS status in the determination of serum adiponectin and resistin concentrations (effect size = −0.14, interaction P = 0.001, effect size = −0.15, P = 0.016). It indicated that adiponectin and resistin were significantly decreased in overweight/obese patients with PCOS compared with other subgroups. Statistically significant positive interactive effects were found between PCOS status obesity status and leptin (effect size = 0.321, interaction P = 0.036), indicating that the overweight/obese women with PCOS had the higher levels of leptin compared with the control group. Also, no interaction was reported between PCOS status and obesity status with regard to the serum levels of other adipokines.

Conclusions

While no sufficient evidence is available with regard to the causal association between adipokines and PCOS, they may contribute to the development of PCOS and regarded as the novel biomarkers of PCOS.

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Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab

Abstract

Purpose

Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab.

Methods

35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39).

Results

In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = −0.39, P = 0.02; r = −0.49, P = 0.01, respectively).

Conclusions

Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

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Sport and male sexuality

Abstract

The relationships between sport and sexuality in males are of great social and clinical interest, because of sports and motor activities that highly promote social and sexual relationships. Even if few literature exist, two main questions should be taken into account: whether and how physical exercise and sport positively or negatively influence sexual health and behavior and/or whether and how sexual behavior may affect a sub-sequent sport performance. Physical exercise and sport per se can influence, positively or negatively, the hypothalamic-pituitary-testicular axis function and, consequently, the individual's reproductive and/or sexual health. This depends on individual factors such as genetic and epigenetic ones and on different variables involved in the practice of sport activities (type of sport, intensity and duration of training, doping and drug use and abuse, nutrition, supplements, psychological stress, allostatic load, etc.). If well conducted, motor and sport activities could have beneficial effects on sexual health in males. Among different lifestyle changes, influencing sexual health, regular physical activity is fundamental to antagonize the onset of erectile dysfunction (ED). However, competitive sport can lead both reproductive and/or sexual tract damages and dysfunctions, transient (genital pain, hypoesthesia of the genitalia, hypogonadism, DE, altered sexual drive, etc.) or permanent (hypogonadism, DE, etc.), by acting directly (traumas of the external genitalia, saddle-related disorders in cyclists, etc.) or indirectly (exercise-related hypogonadism, drug abuse, doping, stress, etc.). Sexual activities shortly performed before a sport competition could differently influence sport performance. Due to the few existing data, it is advisable to avoid an absolute pre-competition sexual abstinence.

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One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival

Abstract

Purpose

We evaluated ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin.

Methods

We retrospectively reviewed 30 patients who were treated with EVL for metastatic RCC between May 2010 and March 2015, by evaluating their FDG PET/CT result before and 1 month after starting EVL treatment. We examined the relationships between each patient's maximum standardized uptake value (max SUVmax) assessed by FDG PET/CT on progression-free survival (PFS) and overall survival (OS).

Results

Median PFS for all 30 patients was 3.77 months (range 0.72–24.56 months) and median OS after EVL treatment of all 30 patients was 11.67 months (range 1.0–62.98 months). Enrolled patients were divided into two groups by max SUVmax prior to EVL (median = 7.6) and at 1 month after EVL treatment (median = 5.7). PFS were significantly shorter in higher max SUVmax prior to EVL (<7.6, PFS 7.8 vs 3.5 months, log-rank P = 0.017) and at 1 month after EVL (<5.7, PFS 10.6 vs 2.7 months, log-rank P = 0.002) than lower max SUVmax. OS were also significantly shorter in higher max SUVmax prior to EVL (<7.6, OS 18.1 vs 7.5 months, log-rank P = 0.010) and at 1 month after EVL (<5.7, OS 17.2 vs 7.5 months, log-rank P = 0.009) than lower max SUVmax. Multivariate Cox hazard regression analysis indicated that max SUVmax at 1 month after EVL is an independent predictor of both PFS and OS in patients treated with EVL although univariate regression analysis showed max SUVmax before EVL is a possible predictor.

Conclusions

Max SUVmax assessed by FDG PET/CT prior to EVL and at 1 month after EVL treatment can accurately predict PFS and can guide decisions on whether to continue or change treatments for patients with EVL-treated RCC who suffer from adverse events.

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Automatic Evaluation of Scan Adequacy and Dysplasia Metrics in 2-D Ultrasound Images of the Neonatal Hip

Publication date: Available online 22 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Niamul Quader, Antony J. Hodgson, Kishore Mulpuri, Emily Schaeffer, Rafeef Abugharbieh
Ultrasound (US) imaging of an infant's hip joint is widely used for early detection of developmental dysplasia of the hip. In current US-based diagnosis of developmental dysplasia of the hip, trained clinicians acquire US images and, if they judge them to be adequate (i.e., to contain relevant hip joint structures), analyze them manually to extract clinically useful dysplasia metrics. However, both the scan adequacy classification and dysplasia metrics extraction steps exhibit significant variability within and between both clinicians and institutions, which can result in significant over- and undertreatment rates. To reduce the subjectivity resulting from this variability, we propose a computational image analysis technique that automatically identifies adequate images and subsequently extracts dysplasia metrics from these 2-D US images. Our automatic method uses local phase symmetry-based image measures to robustly identify intensity-invariant geometric features of bone/cartilage boundaries from the US images. Using the extracted geometric features, we trained a random forest classifier to classify images as adequate or inadequate, and in the adequate images we used a subset of the geometric features to calculate key dysplasia metrics. We validated our method on a data set of 693 US scans collected from 35 infants. Our approach produces excellent agreement with clinician adequacy classifications (area under the receiver operating characteristic curve = 0.985) and in reducing variability in the measured developmental dysplasia of the hip metrics (p < 0.05). The automatically computed dysplasia metrics appear to be slightly biased toward higher Graf categories than the manually estimated metrics, which could potentially reduce missed early diagnoses.



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Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging

Publication date: Available online 22 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Manish Dhyani, Joseph R. Grajo, Atul K. Bhan, Kathleen Corey, Raymond Chung, Anthony E. Samir
The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0–F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p < 0.001). A cut-off value of 7.29 kPa yielded sensitivity of 95.4% and specificity of 50.5% for the diagnosis of METAVIR stage ≥F2 liver fibrosis in patients with liver disease using the SuperSonic Imagine Aixplorer SWE system.



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Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma

Abstract

Objective

We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data.

Design and Patients

This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumor using quantitative and qualitative analyses of preoperative PET/CT data. Clinicopathological data included the primary tumor size, subtype, capsular invasion, extrathyroid extension, multifocality, BRAF V600E mutation status, lymph node metastasis, and distant metastasis.

Results

The SUVmax of the primary tumor was significantly higher in patients with a primary tumor >1 cm, extrathyroid extension, or the BRAF V600E mutation than in patients without these features (P<0.001, 0.049, and <0.001). Univariate analyses showed that primary tumor size, extrathyroid extension, and BRAF V600E mutation status were associated with the SUVmax of the PTC. Multivariate analysis indicated that primary tumor size and the BRAF V600E mutation were associated with the SUVmax of the PTC. In a visual assessment, the primary tumor size was larger in FDG-avid than in non-FDG-avid PTCs (P<0.001). There was no significant difference in the presence of multifocality, thyroid capsular invasion, extrathyroid extension, BRAF V600E mutation, lymph node metastasis, or distant metastasis between FDG-avid and non-FDG-avid PTCs.

Conclusions

Primary tumor size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC.

This article is protected by copyright. All rights reserved.

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Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery

Abstract

Objective

To determine if an overnight metyrapone test (OMT) within the first week post pituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months.

Design

Prospective study measuring morning cortisol levels on day 3 and 4 post-operatively, OMT day 5-7 and week 6, 250μg short Synacthen test (SST) week 6 and insulin tolerance test (ITT) week 7.

Patients and Measurements

Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) and were followed for at least 6 months. 46% had pre-operative adrenal insufficiency.

Primary outcome: Week 1 OMT compared to glucocorticoid requirement at 6 months. Secondary outcomes: the performance of ITT as a "definitive" test and all tests compared to glucocorticoid requirement at 6 months.

Results

Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels. 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80-85%.

Conclusions

OMT within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus definitive testing should be delayed until 6 weeks post-operatively.

This article is protected by copyright. All rights reserved.

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Inherited mutations in DNA repair genes and cancer risk

Publication date: Available online 22 March 2017
Source:Current Problems in Cancer
Author(s): Nuria Romero, Elena Castro
Although most cancer cases are due to somatic mutations, up to 10% of cases are attributable to germline mutations. This inherited cancer predisposition is mostly due to the loss of function of suppressor genes rather than the activation of oncogenes. Defects in DNA repair genes are the genetic events most commonly involved in hereditary cancers. The implementation of high-throughput sequencing in diagnostic testing has uncovered new predisposition genes. Furthermore, for some tumour types these sequencing techniques have also unveiled a prevalence of germline mutations significantly higher than previous estimations. The clinical implications of many of these repair defects are yet to be defined. Further studies will need to be conducted in order to establish the most appropriated management of unaffected carriers that are likely to grow in numbers. On the other hand, the presence of DNA repair defects provides a unique opportunity for the development of treatments that take advantage of a tumour feature.In this review article, we summarize not only the most common syndromes linked to DNA repair defects but also less known entities. We address the underlying genetics and the clinical implications of each DNA repair defect as well as the current recommendations for cancer surveillance.



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Recombinant Newcastle disease virus expressing the infectious bronchitis virus S1 gene protects chickens against Newcastle disease virus and infectious bronchitis virus challenge

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Ran Zhao, Junfeng Sun, Tianming Qi, Wen Zhao, Zongxi Han, Xiaopu Yang, Shengwang Liu
The recombinant LaSota strain expressing a chimeric IBV S1 gene (rLaSota-S1) was constructed with the S1 gene of the LX4 type IBV ck/CH/LDL/091022. The expression of the S1 protein was detected by an indirect immunofluorescence assay and Western blotting. The rLaSota-S1 strain was slightly attenuated, and its growth dynamics were similar to that of the parental LaSota strain. Vaccination of specific pathogen-free chickens with the rLaSota-S1 strain induced NDV hemagglutination inhibition antibodies, and it protected chickens from challenge with virulent NDV. In addition, vaccination with the rLaSota-S1 strain induced IBV-specific IgG antibodies and cellular immunity; however, a single vaccination provided partial protection with reduced virus shedding. Better protection efficiency was observed after a booster vaccination, which resulted in higher antibody titers, significantly fewer disease symptoms, and reduced virus replication and shedding. Our results suggest that the rLaSota-S1 strain is a bivalent vaccine candidate against both NDV and IBV.



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Generation, characterization and immunogenicity of a novel chimeric recombinant protein based on Plasmodium vivax AMA-1 and MSP119

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Mariana Vilela Rocha, Kátia Sanches Françoso, Luciana Chagas Lima, Tarsila Mendes Camargo, Ricardo L.D. Machado, Fabio T.M. Costa, Laurent Rénia, Francois Nosten, Bruce Russell, Mauricio M. Rodrigues, Irene S. Soares
Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119). The recombinant PvAMA166-MSP119 was successfully expressed in Pichia pastoris and used to immunize two different mouse strains (BALB/c and C57BL/6) in the presence of the Poly (I:C) as an adjuvant. Immunization with the chimeric protein induced high antibody titers against both proteins in both strains of mice as detected by ELISA. Antisera also recognized the native proteins expressed on the merozoites of mature P. vivax schizonts. Moreover, this antigen was able to induce IFN-gamma-secreting cells in C57BL/6 mice. These findings indicate that this novel yeast recombinant protein containing PvAMA166 and PvMSP119 is advantageous, because of improved antibody titers and cellular immune response. Therefore, this formulation should be further developed for pre-clinical trials in non-human primates as a potential candidate for a P. vivax vaccine.



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Measuring maternal Tdap and influenza vaccination rates: Comparison of two population-based methods

Publication date: Available online 21 March 2017
Source:Vaccine
Author(s): Ruth Koepke, Stephanie L. Schauer, Jeffrey P. Davis
Pregnant women are routinely recommended to receive Tdap and influenza vaccines to prevent disease and complications among mothers and newborns. Monitoring population trends in maternal vaccination is important in order to evaluate the implementation of these recommendations and to identify pockets of need. We present two methods for measuring maternal vaccination among a state population and discuss the strengths and drawbacks of each method. First, we matched maternal information from records of Wisconsin births during 2013–2015 with maternal vaccination records in the Wisconsin Immunization Registry. Second, we used an all-payer health insurance claims database to identify Wisconsin women with deliveries during 2013–2015 and vaccinations received during pregnancy. Both methods produced similar trends and indicated a substantial increase in the percentage of women receiving Tdap during pregnancy, and lower vaccination rates among women who were Medicaid-insured. When available and timely, both methods are useful for monitoring maternal vaccination.



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Dynamics of African horse sickness virus nucleic acid and antibody in horses following immunization with a commercial polyvalent live attenuated vaccine

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): C.T. Weyer, J.D. Grewar, P. Burger, C. Joone, C. Lourens, N.J. MacLachlan, A.J. Guthrie
African horse sickness (AHS) is a fatal disease of equids relevant to the global equine industry. Detection of AHS virus (AHSV) during outbreaks has become more rapid and efficient with the advent of group specific reverse transcriptase quantitative polymerase chain reaction (GS RT-qPCR) assays to detect AHSV nucleic acid. Use of GS RT-qPCR together with recently described type specific (TS RT-qPCR) assays cannot only expedite diagnosis of AHS but also facilitate further evaluation of the dynamics of AHSV infection in the equine host. A potential limitation to the application of these assays is that they detect viral nucleic acid originating from any AHS live attenuated vaccine (LAV), which is the vaccine type routinely administered to horses in South Africa. The aim of this study was to contrast the dynamics and duration of the RNAaemia to the serological responses of horses following immunization with a commercial polyvalent AHSV-LAV using GS and TS RT-qPCR assays and serum neutralisation tests. The results of the study showed extended RNAemia in vaccinated horses, and that more horses tested positive on GS RT-qPCR with lower Cq values after receiving the AHSV-LAV containing types 1, 3 and 4 prior to the vaccine containing types 2, 6, 7 and 8, rather than when the vaccine combinations were reversed. Furthermore, lower Cq values were obtained when vaccines were administered 4weeks apart as compared with a longer interval or 12weeks apart. These findings are of particular relevance in regions where AHSV-LAVs are used as the use of these vaccines may complicate the accurate interpretation of diagnostic testing results.



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Stabilization study of inactivated foot and mouth disease virus vaccine by size-exclusion HPLC and differential scanning calorimetry

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Yanli Yang, Qizu Zhao, Zhengjun Li, Lijing Sun, Guanghui Ma, Songping Zhang, Zhiguo Su
The inactivated foot and mouth disease virus (FMDV), which has a sedimentation coefficient of 146S, is crucial to the efficacy of vaccine preparations, but extremely unstable in vitro. It is prone to dissociate into smaller particles referred to as 12S with a concomitant decrease in immunogenicity; therefore, it is of great importance to find the best condition for stabilizing the FMDV. In the present work, the effects of solution pH and temperature on the dissociation of 146S was investigated and potential stabilizers were screened, with aid of high-performance size-exclusion chromatography (HPSEC) for rapid and quantitative determination of 146S, together with differential scanning calorimetry (DSC) technology for thermal stability analysis. The most stable pH was found between 7.5 and 8.0. Among excipients tested, sucrose and glycerol provided the best protection, such that the half-life of 146S in solution at 45°C could be prolonged from less than 30min to more than 3days by adding 20% sucrose. The stabilization mechanism was confirmed using DSC analysis, which showed that the transition temperature related to 146S dissociation was increased by 5.4°C in the presence of 20% sucrose. The physical stabilization effects afforded by these stabilizers would allow for the retaining of effective 146S antigens during transportation and storage under relative harsh condition.



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Fewer out-of-sequence vaccinations and reduction of child mortality in Northern Ghana

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Paul Welaga, Abraham Oduro, Cornelius Debpuur, Peter Aaby, Henrik Ravn, Andreas Andersen, Fred Binka, Abraham Hodgson
BackgroundStudies suggest that diphtheria-tetanus-pertussis (DTP) vaccine administered simultaneously with measles vaccine (MV) or DTP administered after MV are associated with higher child mortality than having MV-after-DTP3 as most recent vaccination. We tested this in Northern Ghana where the prevalence of such out-of-sequence vaccinations has declined.MethodsUsing annual cohort data of children aged 12–23months from 1996 to 2012 and Cox proportional hazards models, we assessed survival in relation to the most recent vaccination status within the next 12months and until five years of age. We assessed whether mortality in children aged 12–59months was higher when the most recent vaccine was non-live (DTP) rather than live (MV or OPV).ResultsOut-of-sequence vaccinations with DTP-containing vaccines and MV declined from 86% in 1989 to 24% in 1996 and 0.7% in 2012. Between 1996 and 2012, 38 070 children had their vaccinations status assessed: the adjusted hazard ratio (HR) for out-of-sequence vaccinations (DTP>=MV) compared with the recommended sequence of MV-after-DTP3 was 1.42(1.06–1.90) during the first 12months after assessment of vaccination status and 1.29(1.03–1.60) with follow-up to five years of age; the HR was 2.58(1.14–5.84) before OPV or MV campaigns and 1.37(1.02–1.85) after the campaigns.ConclusionOut-of-sequence vaccinations with DTP and MV are associated with higher mortality than MV as most recent vaccination; the effect is unlikely to be due to confounding. Hence, the reduction in out-of-sequence vaccinations may have lowered child mortality. It is recommended not to give DTP with MV or DTP after MV.



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Off-label use of vaccines

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Pieter Neels, James Southern, Jon Abramson, Philippe Duclos, Joachim Hombach, Melanie Marti, Alanna Fitzgerald-Husek, Jacqueline Fournier-Caruana, Germaine Hanquet
This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as approved by the regulatory authorities (or "label"1 Label: The term "label" means a display of written, printed, or graphic matter upon the immediate container of any article. This includes the Summary of the approved Product Characteristics (SmPC) and Package Insert.¹), and the recommendations for use issued by public health advisory bodies at national and international levels. Differences between public health recommendations and the product label regarding the vaccine use can lead to confusion at the level of vaccinators and vaccinees and possibly result in lower compliance with national vaccination schedules. In particular, in many countries, the label may contain regulatory restrictions and warnings against vaccination of specific population groups (e.g. pregnant women) due to a lack of evidence of safety from controlled trials at the time of initial licensure of the vaccine, while public health authorities may recommend the same vaccine for that group, based on additional post-marketing data and benefit risk analyses.We provide an overview of the different responsibilities between regulatory authorities and public health advisory bodies, and the rationale for off-label use2 Off-label use: Any use of an authorised product not covered by the terms of its marketing authorisation and therefore not in accordance with the SmPC, labelling.² of vaccines, the challenges involved based on the impact of off-label use in real-life. We propose to reduce off-label use of vaccines by requiring the manufacturer to regularly adapt the label as much as possible to the public health needs as supported by new evidence. This would require manufacturers to collect and report post-marketing data, communicate them to all stakeholders and regulators to extrapolate existing evidence (when acceptable) to other groups or to other brands of a vaccine (class effect3 Class effect: An effect for a group of drugs with similar chemical structure and/or drugs with similar mechanism of action and/or drugs with similar pharmacological effects.³). Regulatory authorities have a key role to play by requesting additional post-marketing data, e.g. in specific target groups. When public health recommendations for vaccine use that are outside labelled indications are considered necessary, good communication between regulatory bodies, public health authorities, companies and health care providers or vaccinators is crucial. Recommendations as well as labels and label changes should be evidence-based. The rationale for the discrepancy and the recommended off-label use of a vaccine should be communicated to providers.



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The herd effects of infant PCV7/PCV13 sequential implementation on adult invasive pneumococcal disease, six years post implementation; a nationwide study in Israel

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Gili Regev-Yochay, Michal Katzir, Jacob Strahilevitz, Galia Rahav, Talya Finn, Dan Miron, Yasmin Maor, Bibiana Chazan, Yehudith Schindler, Ron Dagan
BackgroundIntroduction of pneumococcal conjugate vaccine (PCV) has nearly eliminated vaccine-type (VT) invasive pneumococcal disease (IPD) in children, yet the reported resulting reduction of adult IPD is variable. We present the indirect impact of sequential PCV7/PCV13 implementation in Israel on adult IPD.MethodsAn ongoing nationwide active surveillance was initiated on July 2009 when PCV7 was implemented (with Catch-up). PCV7 was gradually replaced by PCV13 since November 2010. Comorbidity and outcome data were collected from medical files. Incidence rates were calculated for overall and vaccine-type IPD.ResultsA total of 2579 IPD cases were diagnosed among a population of 5.0–5.5 million adults >18y (2009–2015). Incidence rates were 9.15/100,000 and 10.16/100,000 in the first and second study years, respectively. However, after PCV13 implementation, the rates decreased to 7.19 within four years, and remained stable in the two following years. Within 6years, PCV7-VT-IPD incidence decreased from 2.52 to 0.52 (79%) and PCV13-VT-IPD from 6.15 to 1.81 (71%). Concurrently, non-VT13 incidence increased from 2.99 to 5.25.Approximately 50% of all patients were adults ≥65y, in whom the decrease in PCV13-VT-IPD incidence was smaller and slower (65% vs. >80% decrease in adults <50y).ConclusionsDespite continued reduction in PCV13-VT-IPD, overall IPD was stable during the last two years due to serotype replacement. Yet, the significant decrease in adult IPD, six years post-PCV7/13 implementation emphasizes the importance of indirect protection in achieving overall population impact and should be considered when discussing the potential additional benefits of direct adult PCV vaccination.



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A fast and efficient purification platform for cell-based influenza viruses by flow-through chromatography

Publication date: Available online 22 March 2017
Source:Vaccine
Author(s): Yu-Fen Tseng, Tsai-Chuan Weng, Chia-Chun Lai, Po-Ling Chen, Min-Shi Lee, Alan Yung-Chih Hu
Since newly emerging influenza viruses with pandemic potentials occurred in recent years, the demand for producing pandemic influenza vaccines for human use is high. For the development of a quick and efficient vaccine production, we proposed an efficient purification platform from the harvest to the purified bulk for the cell-based influenza vaccine production. This platform based on flow-through chromatography and filtration steps and the process only involves a few purification steps, including depth filtration, inactivation by formaldehyde, microfiltration, ultrafiltration, anion-exchange and ligand-core chromatography and sterile filtration. In addition, in the proposed chromatography steps, no virus capture steps were employed, and the purification results were not affected by the virus strain variation, host cells and culturing systems. The results from different virus strains which produced by Vero or MDCK cells in different culturing systems also obtained 33–46% HA recovery yields by this platform. The overall removal rates of the protein and DNA concentration in the purified bulk were over 96.1% and 99.7%, respectively. The low residual cellular DNA concentrations were obtained ranged from 30 to 130pg per human dose (15µg/dose). All influenza H5N1 purified bulks met the regulatory requirements for human vaccine use.



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Microbial interference mitigates Meloidogyne incognita mediated oxidative stress and augments bacoside content in Bacopa monnieri L.

Publication date: Available online 21 March 2017
Source:Microbiological Research
Author(s): Rupali Gupta, Akanksha Singh, P.V Ajayakumar, Rakesh Pandey
Microbial interference plays an imperative role in plant development and response to various stresses. However, its involvement in mitigation of oxidative stress generated by plant parasitic nematode in plants remains elusive. In the present investigation, the efficacy of microbe's viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 single and in combinations was examined to mitigate oxidative stress generated by M. incognita in medicinal plant, Bacopa monnieri. Microbial combination with and without pathogen also enhanced the growth parameters along with secondary metabolites (bacoside) of B. monnieri than the pathogen inoculated control. The study showed that initially the production of hydrogen peroxide (H2O2) was higher in dual microbes infected with pathogen which further declined over M. incognita inoculated control plants. Superoxide dismutase and free radical scavenging activity were also highest in the same treatment which was linearly related with least lipid peroxidation and root gall formation in B. monnieri under the biotic stress. Microscopic visualization of total reactive oxygen species (ROS), H2O2, superoxide radical and programmed cell death in host plant further extended our knowledge and corroborated well with the above findings. Furthermore, scanning electron microscopy confirmed good microbial colonization on the host root surface around nematode penetration sites in plants treated with dual microbes under pathogenic stress. The findings offer novel insight into the mechanism adopted by the synergistic microbial strains in mitigating oxidative stress and simultaneously stimulating bacoside production under pathogenic stress.



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Fengycin produced by Bacillus subtilis 9407 plays a major role in the biocontrol of apple ring rot disease

Publication date: Available online 21 March 2017
Source:Microbiological Research
Author(s): Haiyan Fan, Jinjiang Ru, Yuanyuan Zhang, Qi Wang, Yan Li
Apple ring rot, caused by Botryosphaeria dothidea, is a serious apple disease in China. Bacillus subtilis 9407 was isolated from healthy apples and showed strong antifungal activity against B. dothidea. To identify the primary antifungal compound of B. subtilis 9407 and determine its role in controlling apple ring rot, a transposon mutant library was constructed using TnYLB-1, and a mutant completely defective in antifungal activity was obtained. The gene inactivated in the antifungal activity mutant had 98.5% similarity to ppsB in B. subtilis subsp. subtilis str.168, which encodes one of the five synthetases responsible for synthesizing fengycin. A markerless ppsB deletion mutant was constructed. Compared with the wild-type strain, lipopeptide crude extracts from ΔppsB showed almost no inhibition of B. dothidea mycelial growth. Furthermore, fengycin-like lipopeptides (retention factor 0.1 to 0.2) that exhibited antifungal activity against B. dothidea were observed in the wild-type strain by thin-layer chromatography (TLC)-bioautography analysis, but not in ΔppsB. Semipreparative reverse-phase high performance liquid chromatography (RP-HPLC) detection revealed that ΔppsB lost the ability to synthesize fengycin. These results suggest that ppsB is responsible for synthesizing fengycin and that fengycin is the major antifungal compound produced by B. subtilis 9407 against B. dothidea. Moreover, a biocontrol assay showed that the control efficacy of ΔppsB was reduced by half compared with the wild-type strain, indicating that fengycin plays a major role in controlling apple ring rot disease. This is the first report on the use of a B. subtilis strain as a potential biological control agent to control apple ring rot disease by the production of fengycin.



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