Flagellin is a Th1 polarizing factor for human CD4+ T cells and induces protection in a murine neonatal vaccination model of rotavirus infection

Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4⁺ T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4⁺ and CD8⁺ T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4⁺ T cells were activated in the presence of flagellin, there was high level of expression of IFN-γ in both neonates and adults. Furthermore, flagellin induced IFN-γ production in Th1 cells obtained from adult donors; in the Th2 population, it inhibited IL-4 cytokine production. Flagellin also promoted expression of the IFN-γ receptor in naive CD4⁺ T cells from neonates and adults. To test the adjuvant capacity of flagellin in vivo, we used a murine neonate vaccination model for infection with rotavirus, a pathogen responsible for severe diarrhea in young infants. Using the conserved VP6 antigen, we observed an 80% protection against rotavirus infection in the presence of flagellin, but only in those mice previously primed in the neonatal period. Our data suggest that flagellin could be an attractive adjuvant for achieving a Th1 response.     

Effect of 2-year treatment with low-dose rosuvastatin on intima-media thickness in hypercholesterolemic subjects with asymptomatic carotid artery disease

Objectives: Recent evidence indicates that rosuvastatin 40 mg may exert a beneficial effect in both carotid and coronary atherosclerosis progression. In particular, 2-year rosuvastatin treatment reduced the progression of carotid intima-media thickness (cIMT) in patients with low cardiovascular risk. However, despite the fact that in clinical practice lower doses of rosuvastatin are usually administered at this time, there are no clear data about its effect on cIMT. Thus, the aim of this study was to evaluate the effect of rosuvastatin 10 mg/day on cIMT over a 2-year follow-up.

Methods: Forty-five patients with hypercholesterolemia and asymptomatic carotid atherosclerosis on baseline carotid ultrasound investigation were treated with rosuvastatin 10 mg/day for 24 months. cIMT and lipid profile were assessed after 12 months and at the end of the study (24 months).

Results: After 24 months, the treatment showed a 35.67% reduction in low-density lipoprotein cholesterol concentration (171 vs 110 mg/dl; p < 0.001), a 32.27% reduction in total cholesterol (251 vs 170 mg/dl; p < 0.001), a 19.67% increase in high-density lipoprotein cholesterol concentration (49 vs 61 mg/dl; p < 0.001), and a 10% reduction in triglycerides (120 vs 108 mg/dl; p < 0.01). Rosuvastatin treatment was associated with a 26.6% reduction in left cIMT (1.20 vs 0.90 mm; p < 0.001) and a 22.2% reduction in right cIMT (1.22 vs 0.95 mm; p < 0.001).

Conclusion: Two-year treatment with rosuvastatin 10 mg/day in hypercholesterolemic adults with evidence of subclinical atherosclerosis establishes a significant reduction in cIMT and improves lipid and lipoprotein levels, with a good tolerability profile.     

Readiness of nursing students to screen women for domestic violence

BackgroundAlthough domestic violence against women is common in Israel and elsewhere, and though medical staff in Israel have a universal obligation to screen women for domestic violence, actual screening rates remain low.ObjectivesTo examine which variables affect nursing students' intention to screen women for domestic violence when providing treatment, and whether the Theory of Planned Behavior (TPB) developed by Ajzen (1991) predicts this intention.DesignThis study is a quantitative cross sectional study.SettingsA large academic nursing school in central Israel.ParticipantsA convenience sample of 200 nursing students who had completed at least one year of studies took part in the study.MethodsStudents completed a questionnaire based on the TPB.ResultsNursing students showed high intention to screen women for domestic violence when providing treatment. Normative beliefs, subjective norms, behavioral beliefs, perceived control, and knowledge were found to affect students' intention to screen women for domestic violence. The opinion of the clinical instructor was most significant for students.ConclusionsThe theoretical model predicted 32% of students' intention to screen women for domestic violence, with normative beliefs being the most significant variable.     

Assessment of poliovirus antibody seroprevalence in polio high risk areas of West Africa

We conducted a serological survey of anti-polio antibodies in polio high-risk areas of Mali, Guinea and Cote d’Ivoire to assess risk of future poliovirus outbreaks.Random community sampling of children 6–11 and 36–48 months-old was conducted; neutralizing antibodies against poliovirus were detected using microneutralization assay.We analysed 1059/1064 (99.5%) of enrolled children. Seroprevalence to poliovirus type 1 (PV1) across all age groups and locations ranged between 92 and 100%, for PV2 it was 77–100%, and 89–95% for PV3. PV2 seroprevalence in the younger age group in Guinea and Cote d’Ivoire was <80%. History of <4 polio vaccine doses and acute malnutrition were associated with seronegativity (OR = 2.1 CI95% = 1.5–3.1, OR = 1.8 CI95% = 1.1–3.3 respectively).The risk of poliovirus outbreak following importation is low because of high population immunity to PV1, however, due to large cohort of PV2 seronegative children any future detection of vaccine-derived poliovirus type 2 requires urgent response to arrest rapid spread.     

Global polio eradication: Where are we in Europe and what next?

The world was never so close to reach the polio eradication: only 37 cases notified in 2016 in only three countries, but the game is not yet at the end. The risk of polio outbreaks in the EU is smaller than it has ever been in the past, but it is not so small that we can ignore it. The EU MS must remain alert and plan and prepare for managing polio events or outbreaks because of the possible dire consequences. The IPV only vaccination schedule universally applied in EU has achieved satisfactory coverage, but constantly leaving small accumulating pockets of susceptible individuals. Moreover the IPV only schedule is not an absolute barrier against poliovirus silent transmission as demonstrated in the recent Israel outbreak. The availability of annually revised S.O.P. from WHO GPEI on the identification and response of a polio event, without local poliovirus transmission or a polio outbreak with sustained transmission, helps and challenge EU countries to update their polio national preparedness plans. The EU/EEA area, in fact, is a peculiar area regarding the polio risk both for its vaccination policy, the large polio vaccines manufactures and the constant immigration from areas at polio high risk, but also EU include cultural and financial potentials crucial to sustain the polio end game strategy and reach the benefit of a world without polio risk. Poliovirus eradication will continue to be challenged as long as there is the worldwide presence of polioviruses in laboratories and vaccine production plants. Most of the world’s OPV vaccines are produced in the EU and many laboratories and research centers store and handle polio viruses. EU Member States are engaged actively in implementing the poliovirus biocontainment plans that are part of the polio eradication strategy and to certify the destruction of poliovirus strains and potentially contaminated biological materials.     

Global economic evaluations of rotavirus vaccines: A systematic review

Introduction: World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted.Methods: We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs.Results: 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings.Conclusion: Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides supporting information to health policy-makers and health professionals when considering rotavirus vaccination as a national program.     

Image guided radiotherapy: Current status of soft tissue imaging

Image guided radiotherapy has evolved from two dimensional (2D) megavoltage imaging, which allowed verification with respect to bony anatomy, to three dimensional (3D) kilovoltage imaging which enables soft tissue structures to be used for verification. Alongside the technological developments, treatment delivery techniques have become more sophisticated and the potential to adapt treatment delivery to changes in tumour and/or organs at risk is increasing. This review explores the current status of soft tissue imaging techniques in conjunction with the potential clinical impact. The common tumour sites where the new treatment techniques are being investigated are identified and it is seen that to support the implementation of these techniques, investment in capital equipment and staff training is essential.