Road Safety Barriers and the Safety of Road Users – the Analysis of the Situation in Poland

Road safety barriers are a basic element of the road infrastructure aimed at improving the safety of road users. Design parameters and indications for assembly are strictly regulated by the GDDKiA (General Directorate for National Roads and Motorways) guidelines in accordance with the European standards. In Poland, the most commonly used barriers are thin-walled metal sheet barriers, rope barriers, and concrete ones. The types differ in terms of technical parameters and level of security they provide. One of the purposes of installing road safety barriers is to protect road users from hitting an obstacle in the vicinity of the road, and to protect people around the accident from the effects of an uncontrolled vehicle leaving the road. The effects of a collision caused by hitting a protective road barrier depend mainly on the type of the barrier and the vehicle. The authors made a detailed and interdisciplinary analysis of data on accidents resulting from hitting a road safety barrier, comparing them with information available in the literature, combining the technical aspects of the use of barriers with a medical description of the description of typical injuries

Long-Term Clinical Protection from Falciparum Malaria Is Strongly Associated with IgG3 Antibodies to Merozoite Surface Protein 3

Using data from malaria cases in Senegal, Pierre Druilhe and colleagues found that antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3) were strongly predictive of clinical outcome

T-cell and serological responses to Erp, an exported Mycobacterium tuberculosis protein, in tuberculosis patients and healthy individuals

<p>Abstract</p> <p>Background</p> <p>The identification of antigens able to differentiate tuberculosis (TB) disease from TB infection would be valuable. Cellular and humoral immune responses to Erp (Exported repetitive protein) – a recently identified <it>M. tuberculosis </it>protein – have not yet been investigated in humans and may contribute to this aim.</p> <p>Methods</p> <p>We analyzed the cellular and humoral immune responses to Erp, ESAT-6, Ag85B and PPD in TB patients, in BCG⁺individuals without infection, BCG⁺individuals with latent TB infection (LTBI) and BCG^-controls. We used lymphoproliferation, ELISpot IFN-γ, cytokine production assays and detection of specific human antibodies against recombinant <it>M. tuberculosis </it>proteins.</p> <p>Results</p> <p>We included 22 TB patients, 9 BCG⁺individuals without TB infection, 7 LTBI and 7 BCG^-controls. Erp-specific T cell counts were higher in LTBI than in the other groups. Erp-specific T cell counts were higher in LTBI subjects than TB patients (median positive frequency of 211 SFC/10⁶PBMC (range 118–2000) for LTBI subjects compared to 80 SFC/10⁶PBMC (range 50–191), p = 0.019); responses to PPD and ESAT-6 antigens did not differ between these groups. IFN-γ secretion after Erp stimulation differed between TB patients and LTBI subjects (p = 0.02). Moreover, LTBI subjects but not TB patients or healthy subjects produced IgG3 against Erp.</p> <p>Conclusion</p> <p>The frequencies of IFN-γ-producing specific T cells, the IFN-γ secretion and the production of IgG3 after Erp stimulation are higher in LTBI subjects than in TB patients, whereas PPD and ESAT-6 are not.</p

Longevity and Composition of Cellular Immune Responses Following Experimental Plasmodium falciparum Malaria Infection in Humans

Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n = 5) or multiple (n = 10) experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only ‘adaptive’ but also ‘innate’ lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO+ CD62L- effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ+IL-2+) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field

Differential patterns of IgG subclass responses to <i>Plasmodium falciparum</i> antigens in relation to malaria protection and RTS,S vaccination

Naturally acquired immunity (NAI) to Plasmodium falciparum malaria is mainly mediated by IgG antibodies but the subclasses, epitope targets and effector functions have not been unequivocally defined. Dissecting the type and specificity of antibody responses mediating NAI is a key step toward developing more effective vaccines to control the disease. We investigated the role of IgG subclasses to malaria antigens in protection against disease and the factors that affect their levels, including vaccination with RTS,S/AS01E. We analyzed plasma and serum samples at baseline and 1 month after primary vaccination with RTS,S or comparator in African children and infants participating in a phase 3 trial in two sites of different malaria transmission intensity: Kintampo in Ghana and Manhiça in Mozambique. We used quantitative suspension array technology (qSAT) to measure IgG1-4 responses to 35 P. falciparum pre-erythrocytic and blood stage antigens. Our results show that the pattern of IgG response is predominantly IgG1 or IgG3, with lower levels of IgG2 and IgG4. Age, site and RTS,S vaccination significantly affected antibody subclass levels to different antigens and susceptibility to clinical malaria. Univariable and multivariable analysis showed associations with protection mainly for cytophilic IgG3 levels to selected antigens, followed by IgG1 levels and, unexpectedly, also with IgG4 levels, mainly to antigens that increased upon RTS,S vaccination such as MSP5 and MSP1 block 2, among others. In contrast, IgG2 was associated with malaria risk. Stratified analysis in RTS,S vaccinees pointed to novel associations of IgG4 responses with immunity mainly involving pre-erythrocytic antigens upon RTS,S vaccination. Multi-marker analysis revealed a significant contribution of IgG3 responses to malaria protection and IgG2 responses to malaria risk. We propose that the pattern of cytophilic and non-cytophilic IgG antibodies is antigen-dependent and more complex than initially thought, and that mechanisms of both types of subclasses could be involved in protection. Our data also suggests that RTS,S efficacy is significantly affected by NAI, and indicates that RTS,S vaccination significantly alters NAI

The Other Face of Insulin&mdash;Overdose and Its Effects

Insulin is the most effective glycemic-lowering drug, and for people suffering from type 1 diabetes it is a life-saving drug. Its self-dosing by patients may be associated with a higher risk of overdose, both accidental and deliberate. Insulin-induced hypoglycemia causes up to 100,000 emergency department calls per year. Cases of suicide attempts using insulin have been described in the literature since its introduction into therapy, and one of the important factors in their occurrence is the very fact of chronic disease. Up to 90% of patients who go to toxicology wards overdose insulin consciously. Patients with diabetes are burdened with a 2&ndash;3 times higher risk of developing depression compared to the general population. For this reason, it is necessary to develop an effective system for detecting a predisposition to overdose, including the assessment of the first symptoms of depression in patients with diabetes. A key role is played by a risk-conscious therapeutic team, as well as education. Further post-mortem testing is also needed for material collection and storage, as well as standardization of analytical methods and interpretation of results, which would allow for more effective detection and analysis of intentional overdose&mdash;both by the patient and for criminal purposes

Probable macrophage origin of the lipopolysaccharide-induced cytostatic effect on intra-erythrocytic malarial parasites (plasmodium vinckei).

This study showed that intra-erythrocytic Plasmodium vinckei parasites taken from either normal, irradiated, nude or splenectomized mice 7–8 hr after the injection of a small dose of bacterial lipopolysaccharide (LPS) incorporate hypoxanthine more slowly in an in vitro assay than parasites from saline-treated controls. The incorporation by parasites of isoleucine, which was also measured in some experiments, was similarly affected. However, this cytostatic effect on parasite metabolism was found to be markedly reduced in experiments with mice which had received an intravenous injection of silica dust 28–30 hr before being injected with LPS. These findings indicate that macrophages, being radioresistant and silica-sensitive, are the source of the cytostatic effect. The present results also imply that T cells are not required in the response, and they show that the host cells mediating this response are not restricted to the spleen. It was also shown that an intravenous injection of a small dose of LPS into mice infected with P. vinckei 24 hr previously, could temporarily arrest the rise in parasitaemia in these animals, thereby prolonging their survival. This protection afforded by LPS was also found to be radioresistant and T-independent. It is suggested that the effect on parasitaemia seen in vivo and the cytostatic effect in vitro are both due to the release of a soluble factor from macrophages which is ultimately capable of causing intra-erythrocytic parasite death. P. vinckei-infected mice exhibited symptoms of endotoxaemia following the injection of LPS. However, no clear relationship was noted between the severity of the illness in the host and the cytostatic effect on the parasites