Simple models to include influenza vaccination history when evaluating the effect of influenza vaccination

BackgroundMost reports of influenza vaccine effectiveness consider current-season vaccination only.AimWe evaluated a method to estimate the effect of influenza vaccinations (EIV) considering vaccination history.MethodsWe used a test-negative design with well-documented vaccination history to evaluate the average EIV over eight influenza seasons (2011/12–2018/19; n = 10,356). Modifying effect was considered as difference in effects of vaccination in current and previous seasons and current-season vaccination only. We also explored differences between current-season estimates excluding from the reference category people vaccinated in any of the five previous seasons and estimates without this exclusion or only for one or three previous seasons.ResultsThe EIV was 50%, 45% and 38% in people vaccinated in the current season who had previously received none, one to two and three to five doses, respectively, and it was 30% and 43% for one to two and three to five prior doses only. Vaccination in at least three previous seasons reduced the effect of current-season vaccination by 12 percentage points overall, 31 among outpatients, 22 in 9–65 year-olds, and 23 against influenza B. Including people vaccinated in previous seasons only in the unvaccinated category underestimated EIV by 9 percentage points on average (31% vs 40%). Estimates considering vaccination of three or five previous seasons were similar.ConclusionsVaccine effectiveness studies should consider influenza vaccination in previous seasons, as it can retain effect and is often an effect modifier. Vaccination status in three categories (current season, previous seasons only, unvaccinated) reflects the whole EIV.     

CB(1) cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices

CB(1) cannabinoid receptors located at presynaptic sites suppress synaptic transmission in the rat brain. The aim of this work was to examine by single-unit extracellular techniques the effect of the synthetic cannabinoid receptor agonist WIN 55212-2 on KCl-evoked excitation of locus coeruleus neurons in rat brain slices. Short applications of KCl (30 mM) increased by 9-fold the firing rate of locus coeruleus cells. Perfusion with the GABA(A) receptor antagonist picrotoxin (100 microM) increased KCl-evoked effect, whereas NMDA and non-NMDA glutamate receptor antagonists (D-AP5 100 microM and CNQX 30 microM, respectively) were able to decrease KCl-evoked effect only in the presence of picrotoxin (100 microM). Bath application of WIN 55212-2 (10 microM) inhibited KCl-evoked effect; this inhibition was blocked by the CB(1) receptor antagonist AM 251 (1 microM). However, a lower concentration of WIN 55212-2 (1 microM) did not significantly change KCl effect. In the presence of picrotoxin (100 microM), perfusion with D-AP5 (100 microM) or CNQX (30 microM) blocked WIN 55212-2-induced inhibition, although picrotoxin (100 microM) itself failed to affect cannabinoid effect. In conclusion, GABAergic and glutamatergic components are both involved in KCl-evoked excitation of LC neurons, although CB(1) receptors only seem to inhibit the glutamatergic component of KCl effect in the locus coeruleus.     

Complete T2-Fogging of Pontomedullary Infarction in Locked-In Syndrome

We report a patient who was treated with intravenous thrombolysis, and subsequently developed a Locked-In Syndrome (LIS). After 2 days, magnetic resonance imaging showed a large bilateral pontomedullary infarction. However, in contrast to the patient’s clinical situation, the follow-up T2-weighted MR images up to day 26 did not display the infarction. This phenomenon is known as the so-called fogging effect. An erratum to this article can be found at     

Morphometric analysis of immunoselection against hyperploid cancer cells

An at least transient increase of ploidy, usually by whole genome duplication, is a frequent event in oncogenesis, explaining the cytogenetic features of at least 40% of solid cancers. Here, we show that fibrosarcomas induced by the carcinogen methylcholanthrene (MCA) are distinct with respect to their ploidy status when they arise in immunocompetent wild type versus severely immunodeficient Rag2^−/−γc^−/− mice. MCA-induced fibrosarcomas are particularly hyperploid if they develop in an immunodeficient setting, correlating with higher DNA content, increased nuclear surface, as well as hyperphosphorylation of eukaryotic initiation factor 2` (eIF2`), a biomarker indicating endoplasmic reticulum (ER) stress. Upon transfer of such cells into wild type mice, such hyperploid, ER-stressed cells (that originated in Rag2^−/−γc^−/− mice) fail to proliferate and actually induce a protective anticancer immune response. In contrast, such cells do form tumors in Rag2^−/−γc^−/− recipients (which lack T, B and NK cells) as well as in Rag2^−/− recipients (which only lack T and B lymphocytes) and conserve their hyperploidy as well as eIF2` hyperphosphorylation. To measure these parameters, we developed a morphometric analysis tool that is applicable to immunohistochemistry of formaldehyde-fixed, paraffin-embedded tissues. This software automatically identifies and quantifies the surface of nuclei and determines the intensity of eIF2` phosphorylation within a perinuclear region of interest. Comparative analyses performed on cultured cells and tissue sections validated the accuracy of this method, which can be used to investigate ploidy and ER stress in cancers in situ.     

Gorlin-Goltz syndrome: clinicopathologic aspects

Gorlin-Goltz syndrome, also known as nevoid basal cell carcicoma syndrome, comes into being due to a genetic alteration produced by a mutation in the "Patched" tumour suppressor gene, and it is inherited in a dominant autosomal way, though sporadic cases have been found. This syndrome shows a high penetrance and variable expressiveness. It is about a multisystemic process that is characterised by the presence of multiple pigmented basocellular carcinomas, keratocysts in the jaws, palmar and/or plantar pits and calcification of the falxcerebri. Together with these major features a great number of processes considered as minor features have also been described. The latter include numerous skeletical, dermatology related and neurological anomalies among others. In some occasions, the presence of very aggressive basocellular carcinomas has been described as well as other malignant neoplasias. Due to the importance of oral maxillofacial manifestations of this syndrome, it is fundamental to know its characteristic in order to make a diagnosis, an early preventive treatment and establish right genetic advice. In this work the main clinicopathologic and the therapeutic aspects related to the syndrome under consideration have been revised and updated.