Summary of knowledge gaps related to quality and efficacy of current influenza vaccines

Influenza viruses are a public health threat, as they are pathogenic, highly transmissible and prone to genetic changes. For decades vaccination strategies have been based on trivalent inactivated vaccines, which are regulated by specific guidelines. The progress in scientific knowledge and the lessons learned from the A(H1N1)2009 pandemic have highlighted further the need to improve current guidelines, including the immunogenicity criteria set by the CHMP in 1997, and to promote the discussion on the shortcomings encountered, e.g. the evaluation of vaccine efficacy in the paediatric and elderly populations, the measurement of the naivety of a population, the impact of prior immunity on subsequent vaccinations, and the technical issues with the serological assays for detection of immunity and immunogenicity.     

Meiotic recombination cold spots in chromosomal cohesion sites

Meiotic chromosome architecture called ‘axis–loop structures’ and histone modifications have been shown to regulate the Spo11‐dependent formation of DNA double‐strand breaks (DSBs) that trigger meiotic recombination. Using genome‐wide chromatin immunoprecipitation (ChIP) analyses followed by deep sequencing, we compared the genome‐wide distribution of the axis protein Rec8 (the kleisin subunit of meiotic cohesin) with that of oligomeric DNA covalently bound to Spo11, indicative of DSB sites. The frequency of DSB sites is overall constant between Rec8 binding sites. However, DSB cold spots are observed in regions spanning ±0.8 kb around Rec8 binding sites. The axis‐associated cold spots are not due to the exclusion of Spo11 localization from the axis, because ChIP experiments showed that substantial Spo11 persists at Rec8 binding sites during DSB formation. Spo11 fused with Gal4 DNA binding domain (Gal4BD‐Spo11) tethered in close proximity (≤0.8 kb) to Rec8 binding sites hardly forms meiotic DSBs, in contrast with other regions. In addition, H3K4 trimethylation (H3K4me3) remarkably decreases at Rec8 binding sites. These results suggest that reduced histone H3K4me3 in combination with inactivation of Spo11 activity on the axis discourages DSB hot spot formation.     

The Performance of Graphene-Enhanced THz Grating: Impact of the Gold Layer Imperfectness

We report the performance of a graphene-enhanced THz grating fabricated by depositing a gold layer on the femtosecond micromachined SiO₂ substrate. The morphology of the gold plated patterned substrate was studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM), while the quality of the chemical vapor deposition (CVD) graphene was evaluated by Raman spectroscopy. The electromagnetic (EM) response of the metasurface comprising the graphene sheet and the gold plated substrate was studied by THz time domain spectroscopy in the 100 GHz–1 THz frequency range. We employed the finite elements method (FEM) to model the metasurface EM response by adjusting the ac conductivity of the gold layer covering the patterned SiO₂ substrate to reproduce the measured transmission/reflection spectra. The results of the numerical simulation reveal the impact of the imperfectness of the gold layer on the performance of the THz metasurface. The experimental results are well described in terms of the Drude–Smith model of metal conductivity that takes into account the anisotropic scattering of the carriers in thin metal films.     

Residual Periodontal Ligament in Extracted Teeth – Is It Associated With Indication for Extraction?

BackgroundPeriodontal disease is a major cause of tooth loss. Few studies have evaluated the residual area of the periodontal ligament in extracted teeth and, to the best of our knowledge, none from Latin America have done so regarding indications for extraction. The aim of this study was to evaluate the residual periodontal ligament (RPL) with respect to indication for extraction in a sample of teeth from a Brazilian Public Health Service district.Materials and methodsAll teeth extracted within the Public Health Service district of Santa Maria, Brazil, over a 5-month period were requested for analysis. A total of 414 teeth eligible for measurement were stained and evaluated for RPL using a stereo microscope. Participating Public Health Service dentists completed a questionnaire detailing demographic variables and indication for each extracted tooth. The percentage of RPL was determined for each tooth. Comparisons of RPL between teeth extracted on periodontal versus other indications were made using the Mann-Whitney test.ResultsRPL averaged 34.8% for teeth extracted on periodontal indications versus 79.5% for other teeth (P ≤ 0.001). When considering teeth with an RPL ≥ 30% as possible to maintain, 189 (76%) of the teeth extracted on periodontal indications could have been maintained. When RPL cut-off limits of ≥ 40% or ≥ 50% are applied, 93 (37%) and 43 (17%) teeth, respectively, could have been maintained.ConclusionThis study suggests that strictly based on RPL, a large number of teeth extracted on periodontal indications conceivably could be maintained.Key words: Cross-sectional studies, Prognosis, Tooth extraction, Tooth loss     

Anxiety,depression, and stress in caregivers of children and adolescents with mental disorders in Ghana and implications for medication adherence

ObjectiveThis study assessed levels of anxiety, depression, and stress among family caregivers of children and adolescents with mental disorders in Ghana and the implication on medication adherence.DesignA cross-sectional study.SettingThe study was conducted at the outpatient departments of the three main public psychiatric hospitals in Ghana.ParticipantsTwo hundred and ten non-paid family caregivers of children and adolescents with mental disorders were recruited for this study.Main Outcome MeasureThe study assessed symptoms of anxiety, depression and stress among the caregivers and estimated caregiver-reported medication adherence.ResultsAbout 56.2%, 66.2% and 78% of the caregivers experienced severe anxiety, severe depression and moderate to severe stress symptoms respectively. From the multiple logistic regression model, while anxiety was significantly affected by religion and education, depression was influenced by sex, age, marital status, proximity to facility, and employment status. Female caregivers had about four times higher odds of being depressed compared to male caregivers (aOR: 3.81, 95% CI: 1.66 – 8.75). The caregiver-reported medication adherence was 11.9%. Anxiety was significantly predictive of medication adherence.ConclusionMost family caregivers of children and adolescents with mental disorders experienced symptoms of anxiety, depression and stress with anxiety having implications for medication adherence. The study findings underscore the need to consider psychological characteristics of caregivers and the provision of mental health support for them, as part of the routine health care for children and adolescents with mental disorders.FundingNone indicated     

Anatomical and behavioral impact of a lentiviral tool tapping onto hippocampal serotonin reuptake in rats

We aimed at the further characterization of rats in which SERT gene silencing was achieved by hippocampal injection of a lentiviral vector, carrying three si-RNA to block SERT mRNA at 66% of normal levels. Improved self-control and reduced restlessness were already demonstrated in these rats. Present further studies consisted of male adult rats, bilaterally inoculated within the hippocampus; control rats received lentivirus particles inactivated with heat. Both groups were maintained in isolation for 5 months, starting from inoculation. Neurochemical changes were studied by proton magnetic resonance spectroscopy (1H-MRS): we found increased hippocampal viability and bioenergetic potential; however, rats showed a behaviorally depressive pattern, also characterized by enhanced affiliation. Based on the extent of such effects, the whole lenti-SERT group was divided into two subgroups, termed intermediate- and extreme- phenotype profiles. While all rats had a widespread modification within dorsal/ventral striatum, amygdala, and hypothalamus, only the former subgroup showed an involvement of Raphé medialis, while, for the latter subgroup, an increase of SERT within hippocampus was unexpectedly caused. Within the less-affected “intermediate” rats, hippocampal 5-HT7 receptors were down-modulated, and also similarly within substantia nigra, septum, and neocortex. This picture demonstrates that additional rather than fewer neurobiological changes accompany a lower phenotypic expression. Overall, tapping hippocampal SERT affected the balance between habits versus strategies of coping by promoting morphogenetic processes indicative of a serotonergic fiber plasticity. Supplementary studies about serotonergic dynamics and neurogenesis within fronto-striatal circuits are needed.