Clinical Course of 53 Previously Vaccinated Patients Admitted to the National Hospital in Warsaw, Poland with COVID-19 Between November 2021 and March 2022.

BACKGROUND Current vaccines against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and vaccine booster programs aim to reduce hospitalizations due to severe COVID-19 (coronavirus disease 2019). It is now accepted that vaccination does not completely prevent infection and that breakthrough COVID-19 does occur. This study included 53 vaccinated patients who were hospitalized at a single center in Poland with breakthrough COVID-19 and aimed to evaluate the factors associated with their clinical course. MATERIAL AND METHODS This study covered the period 26 November 2021 to 11 March 2022. All patients had been vaccinated against COVID-19 with one of the following 4 vaccines: the mRNA-1273 (Moderna) mRNA vaccine (Spikevax); the BNT162b2 (Pfizer-BioNTech) mRNA vaccine (nucleoside-modified) (Comirnaty); the Ad26.COV2.S (Janssen/J0ohnson & Johnson) recombinant vaccine (Jcovden); and the AZD1222 (ChAdOx1) (Oxford/AstraZeneca) recombinant vaccine (Vaxzevria). RESULTS The course of COVID-19 in vaccinated patients was relatively similar. The patients vaccinated more than 24 weeks earlier rarely needed a stay in the Intensive Care Unit (ICU) (P=0.021), and the occurrence of deaths was significantly lower in this group (P=0.046). Women remained in hospital considerably longer than men (P=0.011). Age and comorbidities did not affect the course of this infection. CONCLUSIONS Despite the many advantages of the COVID-19 vaccination, our observations indicate a potential risk of infection after vaccination. The assessment of the course of COVID-19 in vaccinated patients gives the possibility to compare different vaccines and indicate factors that can reduce immunity.

The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans.

Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008-7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. KEY POINTS: • The newly thiazoles showed high antifungal activity and some of them - additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties.

Improving the quality of training paramedics by means of cadavers - a pilot study.

BACKGROUND: Paramedics are authorised to perform emergency procedures, including trauma assessment according to global standards. The aim of the study was to answer the question whether the use of cadavers in teaching practical competencies to medical rescue students, in the field of trauma assessment, is necessary as a supplement to learning in simulated conditions with the use of mannequins. METHODS: Research included several stages. The first stage was conduction of classes for 27 students in the field of rapid trauma assessment, in accordance with the guidelines of the International Trauma Life Support. In the second stage, a plan of a test in which students had to perform an analogous procedure of rapid trauma assessment, but with the use of cadavers, human unfixed specimens, was prepared. The Delphi method was used to develop and approve checklists, as well as a scale to assess the global correctness of identification of head, torso and limb injuries by medical rescue students. RESULTS: The identification rate was 76.54% in the head area, 67.90% in the torso area, while in the limb area it equalled 44.45%. A significant difference in scores, compared to the examination performed on a mannequin, was observed (Wilcoxon = 4.541; p = 0.000). The most difficult to make a correct diagnosis were injuries related to a fracture of the proximal end of the femur and a dislocated wrist (only 18.52% of correct answers). The students highly rated the usefulness of the examination, by awarding it an average of 4.76 points (SD ± 0.56) on the Likert scale (0-5). CONCLUSIONS: The study shows that the use of cadavers to teach practical competencies in the field of trauma assessment to medical rescue students can be an effective supplement to simulated learning. Students could feel the difference between the human body and the mannequin. More research is needed to assess whether realistic simulation translates into objective endpoints, such as the effectiveness of diagnosis in the examination of trauma patients. However, it should be remembered that the introduction of this teaching method is expensive and requires adequate base, as well as the compliance with a number of formal requirements.

Norovirus-specific mucosal antibodies correlate to systemic antibodies and block norovirus virus-like particles binding to histo-blood group antigens.

The best acknowledged correlate of protection from norovirus (NoV) infection is the ability of serum antibodies to block binding of NoV virus-like particles (VLPs) to histo-blood group antigens (HBGAs). We investigated mucosal NoV-specific antibody levels in adult volunteers and used saliva from a single donor to determine whether purified saliva antibodies confer blocking. NoV-specific IgG and IgA levels in saliva and plasma samples were measured against four NoV genotype VLPs. NoV-specific IgG and IgA titers in saliva and plasma samples correlated significantly. Antibodies were detected against all VLPs with the highest level of antibodies directed against ancestral GII.4 99 genotype. Affinity chromatography purified salivary IgA and IgG blocked binding of GII.4 99 VLPs to HBGAs. Saliva sampling is a non-invasive alternative to blood drawing and an excellent biological fluid to study NoV-specific immune responses. Mucosal anti-NoV antibodies block binding of NoV VLPs to HBGAs, and may therefore be protective.

Rotavirus vaccination and infection induce VP6-specific IgA responses.

Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) in young children, but RVGE has drastically been reduced with the introduction of live oral RV vaccines into childhood immunization program in many countries. Serum IgA antibody is a marker of clinical protection against severe RVGE after RV infection and vaccination. This study investigated VP6-specificity of anti-RV IgA antibody levels in Finnish children aged 6-23 months before and after introduction of RotaTeq® into national immunization program. Although RV inner capsid protein VP6 is considered as antigenic target in clinical and seroepidemiological studies, at present VP6 protein is not commonly employed as a primary ELISA-antigen. Thus, sera from 20 unvaccinated and 19 vaccinated children were examined in ELISA with recombinant VP6 (rVP6) protein, and the VP6-specific responses were compared to responses observed with human RV Wa and bovine RV WC3 cell culture antigens. Moreover, fecal antibodies were tested with rVP6 and Wa cell culture antigen. Equal levels of serum anti-RV IgA antibodies were detected by the three antigens. Fecal IgA titers against rVP6 and Wa antigen showed a correlation with the corresponding serum levels. The results suggest that the IgA response measured by virus-capture ELISA is mainly directed to VP6 protein, supporting the usage of rVP6 in detection of anti-RV IgA antibodies. Natural RV infections and vaccinations induced similar levels of serum VP6-specific IgA antibodies. Serum IgA antibodies after RotaTeq® vaccination showed sustained levels up to two years of age in line with long term protection. J. Med. Virol. 89:239-245, 2017. © 2016 Wiley Periodicals, Inc.

Induction of homologous and cross-reactive GII.4-specific blocking antibodies in children after GII.4 New Orleans norovirus infection.

Noroviruses (NoVs) are major causative agents of acute gastroenteritis (AGE) in children worldwide and the most common viral cause of AGE in countries where rotavirus incidence has been eliminated by vaccination. Previous infections with the dominant GII.4 NoV genotype confer only partial protection against evolving immune escape variants that emerge every few years. The objective of this work was to investigate GII.4-specific homologous and cross-reactive antibody responses in young children after NoV GII.4-2009 New Orleans (NO) infection. Virus-like particles (VLPs) representing GII.4-1999, GII.4-2009 NO, and GII.4-2012 Sydney genotypes were used in ELISA and histo-blood group antigen blocking assays to examine acute and convalescent sera of five children <2 years of age infected with GII.4-2009 NO. GII.4-2009 NO infection induced IgG seroconversion to all three tested NoV GII.4 variants. Homologous blocking antibodies to GII.4-2009 NO were detected in each convalescent sera. Fourfold increase in cross-blocking antibodies to GII.4-2012 Sydney was observed in 4/5 subjects, but no child developed cross-blocking antibodies to GII.4-1999. In conclusion, antibodies induced in young children after norovirus GII.4 infection are targeted against the causative variant and may cross-protect against strains that are closely related, but not with more distinct and earlier GII.4 genotypes.

Human proT-cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture.

Hematopoietic stem cell transplantation (HSCT) is followed by a period of immune deficiency due to a paucity in T-cell reconstitution. Underlying causes are a severely dysfunctional thymus and an impaired production of thymus-seeding progenitors in the host. Here, we addressed whether in vitro-derived human progenitor T (proT)-cells could not only represent a source of thymus-seeding progenitors, but also able to influence the recovery of the thymic microenvironment. We examined whether co-transplantation of in vitro-derived human proT-cells with hematopoietic stem cells (HSCs) was able to facilitate HSC-derived T-lymphopoiesis posttransplant. A competitive transfer approach was used to define the optimal proT subset capable of reconstituting immunodeficient mice. Although the 2 subsets tested (proT1, CD34(+)CD7(+)CD5(-); proT2, CD34(+)CD7(+)CD5(+)) showed thymus engrafting function, proT2-cells exhibited superior engrafting capacity. Based on this, when proT2-cells were coinjected with HSCs, a significantly improved and accelerated HSC-derived T-lymphopoiesis was observed. Furthermore, we uncovered a potential mechanism by which receptor activator of nuclear factor κb (RANK) ligand-expressing proT2-cells induce changes in both the function and architecture of the thymus microenvironment, which favors the recruitment of bone marrow-derived lymphoid progenitors. Our findings provide further support for the use of Notch-expanded progenitors in cell-based therapies to aid in the recovery of T-cells in patients undergoing HSCT.

Protection against live rotavirus challenge in mice induced by parenteral and mucosal delivery of VP6 subunit rotavirus vaccine.

Live oral rotavirus (RV) vaccines are part of routine childhood immunization but are associated with adverse effects, particularly intussusception. We have developed a non-live combined RV - norovirus (NoV) vaccine candidate consisting of human RV inner-capsid rVP6 protein and NoV virus-like particles. To determine the effect of delivery route on induction of VP6-specific protective immunity, BALB/c mice were administered a vaccine containing RV rVP6 intramuscularly, intranasally or a combination of both, and challenged with murine RV. At least 65 % protection against RV shedding was observed regardless of delivery route. The levels of post-challenge serum VP6-specific IgA titers correlated with protection.

Multiple consecutive norovirus infections in the first 2 years of life.

Studies investigating the magnitude and breath of protective immune responses after primary and subsequent norovirus infections in pediatric populations are limited. We investigated incidence of norovirus infections and serological responses in a child from longitudinal stool and serum samples collected from birth to 2 years of age. Four consecutive infections with distinct genotypes of norovirus were detected. Serum antibodies were genotype-specific offering no protection to reinfection with heterologous virus. CONCLUSION: This study describes norovirus-specific serological responses in a child with four consecutive norovirus infection during the first 2 years of life. The response is type-specific and does not protect from a subsequent infection with a heterologous virus. WHAT IS KNOWN: • Correlates of protection to norovirus infection and disease are not yet determined, and most of the presently available data concern adult population. WHAT IS NEW: • This manuscript describes serological immune responses after primary and subsequent infections in a child during the first 2 years of life.

High serum levels of norovirus genotype-specific blocking antibodies correlate with protection from infection in children.

BACKGROUND: Norovirus is a common cause of acute gastroenteritis in children. Serum immunoglobulin G (IgG) antibodies have been implicated in protection against norovirus-associated gastroenteritis, but the level, specificity, and functionality necessary for protection remain to be elucidated. METHODS: Norovirus-specific IgG antibodies to genogroup II (GII)-4-2010 New Orleans (NO), GII-4-1999, GII-12-1998, GI-1-2001, and GI-3-2002 virus-like particles (VLPs) were determined by enzyme-linked immunosorbent assay in serum samples collected from children who presented to the hospital because of acute norovirus gastroenteritis in 2009-2011. The blocking activity of the antibodies was tested in a surrogate neutralization assay. RESULTS: Most norovirus infections (62.8%) in the study population were caused by a GII-4 NO variant. Children who acquired GII-4 NO infection had a low preexisting type-specific IgG level and blocking activity of the sera, in contrast to children infected with other GII genotypes. Following GII-4 NO infection, genotype-specific seroconversion and a corresponding increase in blocking antibody potential was observed. Although seroconversion to the heterologous GII-4-1999 variant was observed, there was no corresponding increase in the specific blocking antibody titer. There was no concomitant seroconversion against GI VLPs, indicating a highly genogroup-specific antibody response. CONCLUSIONS: High preexisting norovirus genotype-specific serum IgG titers and blocking activity in children indicate protection from norovirus infection in a strain-specific manner.

MiRNA-21-5p as a biomarker in EBV-associated oropharyngeal cancer.

INTRODUCTION AND OBJECTIVE: Epstein-Barr virus (EBV) is associated with cancers of the head and neck, including oropharyngeal cancer, which is increasing in incidence, and biomarker studies have potential in diagnostics and therapy. One of the most commonly deregulated microRNAs in cancers is miR-21-5p. It has been implicated in neoplastic transformation related to EBV infection in several investigations. The aim of this study was to determine the level of miR-21-5p in the serum of EBV (+) and EBV (-) oropharyngeal cancer patients. MATERIAL AND METHODS: The study was carried out on 78 patients with confirmed OPSCC. Statistical analysis was used to investigate the relationship between clinical and demographic characteristics of patients. Enzyme immunoassays were used to determine the levels of miRNA, TLR9 and MMPs and cytokines. Statistical analysis was used to determine the relationship between miR21-5p and TLR9, MMP3, MMP9 levels, and the cytokines studied. RESULTS: Significantly higher values of all tested parameters for miR-21-5p levels and grading as well as TN stage were found in the EBV (+) group. There was no statistically significant correlation between the miR-21-5p level and the levels of TNFα, VEGF, and TGFß. Positive correlations were shown between miR-21-5p and IL-10, MMP-3 and -9. There was a negative correlation between the level of miR-21-5p and TLR9. CONCLUSIONS: The present study showed that in EBV (+) patients the level of miR-21-5p in the serum was significantly higher than in EBV (-) patients. Our study results could influence future strategies for the diagnosis, prevention and treatment of oropharyngeal cancers.

The Cognitive Aspect of Hope in the Semantic Space of Male Patients Dying of Cancer.

The aim of this study is to characterize the cognitive aspect of the semantic space of hope in patients in the terminal stage of cancer. This was confirmed in the research on hope by C. R. Snyder and B. Schrank. Hope is of great importance in all the great world religions and belief systems, both as regards a personal God or impersonal deities. Hoping is a human capacity with varying affective, cognitive and behavioral dimensions. Psychological, pedagogical (particularly in the framework of special needs pedagogy and thanatological pedagogy) and theological reflection on hope can provide support for dying people. In order to conduct the research, the semantic differential research method was selected. The research technique employed was a therapeutic conversation, and the research tool was the B.L. Block's DSN-3 test. The DSN-3 test allows one to assess hope in the semantic space in three aspects: cognitive, emotional and functional. For the purposes of this study, only the cognitive aspect was taken into account. The study was begun on 1 April 2010 and ended in the last days of December 2020. It included 110 male patients in the terminal stage of cancer. The youngest respondent was 19 years old and the oldest was 94 years old. The surveyed men most often perceived hope in the semantic space in the cognitive aspect as more true, wise, meaningful and real than false, stupid, meaningless and deceptive. Their attitude to hope was, therefore, more affirmative than negative. The research did not reveal the importance of the age of the respondents on the degree of affirmation/negation of hope in the cognitive aspect in the semantic space; however, men in the period of late maturity and professional activity expressed the lowest level of the affirmation of hope. It is worthwhile to conduct further research concerning hope in other aspects (especially emotional and functional) in the semantic space in order to use the obtained results to consider what to take into account when providing patients in the terminal stage of cancer with better personalized holistic care than before.

Assessment of Awareness and Knowledge about Osteoporosis in Relation to Health Prevention among Patients Treated in Osteoporosis Clinics.

The increasing incidence of osteoporosis indicates that the disease is a serious public health problem, with about 200 million people being affected worldwide. The aims of this research are to assess the awareness and knowledge about osteoporosis in relation to risk factors, health condition, supplementation used, socio-demographic factors and other variables among osteoporosis patients. The study was conducted in 2016-2018 in osteoporosis clinics in Poland. The study involved 312 patients with a diagnosis of osteoporosis. In the diagnostic survey method, the authors' own questionnaire was used. The results indicate that the more frequent the symptoms associated with the disease, the lower the general self-assessment of the health condition of the respondents (rho = -0.682, p < 0.001). In addition, almost half of the respondents stated that their knowledge of osteoporosis is negligible. Moreover, the use of dietary supplements significantly differentiated respondents in terms of health self-assessed (p < 0.001), and it is noteworthy that users of dietary supplements assessed their health significantly better. We also saw a statistically significant relationship between the self-assessment of knowledge about osteoporosis and the use of dietary supplements (p < 0.001). Accordingly, significantly more respondents rating their knowledge as good or very good used dietary supplements. The conducted study demonstrates the need to educate patients and implement educational programs at central and provincial levels to improve patient knowledge concerning the disease. Supporting adaptation to chronic diseases and appropriate therapeutic management may contribute to improved osteoporosis treatment and enhanced patient quality of life.

Effects of Prenatal Paracetamol Exposure on the Development of Asthma and Wheezing in Childhood: A Systematic Review and Meta-Analysis.

The aim of the report was to evaluate whether in utero exposure to paracetamol is associated with risk towards developing respiratory disorders such as asthma and wheeze after birth. MEDLINE (PubMed), EMBASE and Cochrane Library databases were searched for articles published in English to December 2021. The study involved 330,550 women. We then calculated the summary risk estimates and 95% CIs and plotted forest plots using random effect models (DerSimonian-Laird method) and fixed effect models. We also performed a systematic review of the chosen articles and a meta-analysis of studies based on the guidelines outlined in the PRISMA statement. Accordingly, maternal exposure to paracetamol during pregnancy was associated with a significant increased risk of asthma: crude OR = 1.34, 95% CI: 1.22 to 1.48, p < 0.001; and significant increased risk of wheeze: crude OR = 1.31, 95% CI: 1.12 to 1.54, p < 0.002. Results of our study confirmed that maternal paracetamol use in pregnancy is associated with an enhanced risk of asthma and wheezing in their children. We believe paracetamol should be used with caution by pregnant women, and at the lowest effective dose, and for the shortest duration. Long-term use or the use of high doses should be limited to the indications recommended by a physician and with the mother-to-be under constant supervision.

Antibodies to NCP, RBD and S2 SARS-CoV-2 in Vaccinated and Unvaccinated Healthcare Workers.

In a few months, the SARS-CoV-2 virus caused a worldwide COVID-19 pandemic. In Poland, 6 million cases of the disease and 113,000 deaths from COVID-19 have been reported. Healthcare workers (HCWs) constitute one of the main COVID-19 risk groups. The Microblot-Array COVID-19 IgG assay was used to detect antibodies against three major SARS-CoV-2 antigens: nucleocapsid (NCP), RBD, and Spike 2 (S2). The aim of our study was to determine the seroprevalence and titer of anti-SARS-CoV-2 IgG antibodies-NCP, RBD, and S2-as markers of the humoral response in vaccinated and unvaccinated HCWs. The study included 203 persons who were divided into four groups: "COVID-19 Vaccinated", "COVID-19 Unvaccinated", "Non-COVID-19 Vaccinated", and "Non-COVID-19 Unvaccinated". The obtained results indicate that both seroprevalence and the antibody titer are the highest in the "COVID-19 Vaccinated" group. There is no so-called sterile vaccination, and after 6 months from the second dose of vaccine, most vaccinated people have a fairly high level of antibodies. We suggest that multiple vaccination and continuous testing are necessary. The Microblot-Array assay can distinguish between antibodies acquired after infection and/or vaccination.

Safety and immunogenicity studies in animal models support clinical development of a bivalent norovirus-like particle vaccine produced in plants.

Noroviruses (NoV) are the leading cause of epidemic acute gastroenteritis in humans worldwide. A safe and effective vaccine that prevents NoV infection or minimizes NoV disease burden is needed, especially for children and the elderly who are particularly susceptible to NoV disease. A plant-based expression system (magnICON®) was used to manufacture two different virus-like particle (VLP) immunogens derived from human NoV genogroups I and II, genotype 4 (GI.4 and GII.4), which were subsequently blended 1:1 (w/w) into a bivalent vaccine composition (rNV-2v). Here, we report on the safety and immunogenicity of rNV-2v from one pilot and two GLP-compliant toxicity studies in New Zealand White rabbits administered the vaccine subcutaneously (SC) or intramuscularly (IM). Strong genogroup-specific immune responses were induced by vaccination without adjuvant at various doses (200 to 400 µg VLP/administration) and administration schedules (Days 1 and 7; or Days 1, 15 and 29). The results showed sporadic local irritation at the injection site, which resolved over time, and was non-adverse and consistent with expected reactogenicity. There were no signs of systemic toxicity related to vaccine administration relative to vehicle-treated controls with respect to clinical chemistry, haematology, organ weights, macroscopic examinations, or histopathology. In a 3-administration regimen (n + 1 the clinical regimen), the NOAEL for rNV-2v via the SC or IM route was initially determined to be 200 µg. An improved GI.4 VLP variant mixed 1:1 (w/w) with the wild-type GII.4 VLP was subsequently evaluated via the IM route at a higher dose in the same 3-administration model, and the NOAEL was raised to 300 µg. Serology performed in samples of both toxicity studies showed significant and substantial anti-VLP-specific antibody titers for rNV-2v vaccines administered via the IM or SC route, as well as relevant NoV blocking antibody responses. These results support initiation of clinical development of the plant-made NoV vaccine.

Antigenicity and immunogenicity of HA2 and M2e influenza virus antigens conjugated to norovirus-like, VP1 capsid-based particles by the SpyTag/SpyCatcher technology.

Virus-like particles (VLPs) modified through different molecular technologies are employed as delivery vehicles or platforms for heterologous antigen display. We have recently created a norovirus (NoV) VLP platform, where two influenza antigens, the extracellular domain of matrix protein M2 (M2e) or the stem domain of the major envelope glycoprotein hemagglutinin (HA2) are displayed on the surface of the NoV VLPs by SpyTag/SpyCatcher conjugation. To demonstrate the feasibility of the platform to deliver foreign antigens, this study examined potential interference of the conjugation with induction of antibodies against conjugated M2e peptide, HA2, and NoV VLP carrier. High antibody response was induced by HA2 but not M2e decorated VLPs. Furthermore, HA2-elicited antibodies did not neutralize the homologous influenza virus in vitro. Conjugated NoV VLPs retained intact receptor binding capacity and self-immunogenicity. The results demonstrate that NoV VLPs could be simultaneously used as a platform to deliver foreign antigens and a NoV vaccine.

Antibody Response after SARS-CoV-2 Infection with the Delta and Omicron Variant.

The SARS-CoV-2 virus caused a worldwide COVID-19 pandemic. So far, 6,120,834 confirmed cases of COVID-19 with 116,773 deaths have been reported in Poland. According to WHO, a total of 54,662,485 vaccine doses have been administered. New variants emerge that become dominant. The aim of this study was a comparison of antibody level after infection caused by Delta and Omicron variants. The study included 203 persons who underwent mild COVID-19 despite two doses of vaccine. The obtained results indicate that a significantly lower titer was observed in patients with the Omicron variant infection. Therefore, these patients may be at risk of reinfection with new strains of the Omicron variant. Due to the possibility of reinfection, booster vaccinations are necessary. Further epidemiological and clinical studies are necessary to develop new prevention strategies.

Role of Phytoestrogen-Rich Bioactive Substances (Linum usitatissimum L., Glycine max L., Trifolium pratense L.) in Cardiovascular Disease Prevention in Postmenopausal Women: A Systematic Review and Meta-Analysis.

The aim of this report was to determine the impact of flaxseed, soy and red clover, and their bioactive substances on the lipid profile in postmenopausal women in cardiovascular diseases prevention. We used the following databases: MEDLINE (PubMed), EMBASE and the Cochrane Library. Meta-analysis indicates that the intake of flaxseed by postmenopausal women is associated with a statistically significant reduction in total cholesterol (TC) levels (weighted-mean difference (WMD) = -0.26; 95% confidence interval (95% CI): -0.38 to -0.13; p = 0.0001), low-density lipoprotein cholesterol (LDL-C) levels (WMD = -0.19; 95% CI: -0.30 to -0.08; p = 0.0006), and high-density lipoprotein cholesterol (HDL-C) levels (WMD = -0.06; 95% CI: -0.11 to -0.01; p = 0.0150). The effect of soy protein on the lipid profile showed a significant decrease in TC levels: WMD = -0.15; 95% CI: -0.25-0.05; p = 0.0048, LDL-C levels: WMD = -0.15; 95% CI: -0.25-0.05; p = 0.0067, as well as a significant increase in HDL-C levels: WMD = 0.05; 95% CI: 0.02-0.08; p = 0.0034. Changes in the lipid profile showed a significant reduction in TC levels after the use of red clover (WMD = -0.11; 95% CI: -0.18--0.04; p = 0.0017) and a significant increase in HDL-C levels (WMD = 0.04; 95% CI: 0.01 to 0.07; p = 0.0165). This meta-analysis provides evidence that consuming flaxseed, soy and red clover can have a beneficial effect on lipids in postmenopausal women and suggest a favorable effect in preventing cardiovascular diseases.

Immunization with dendritic cells transfected in vivo with HIV-1 plasmid DNA induces HIV-1-specific immune responses.

We evaluated the importance of dendritic cells (DCs) in the induction of the immune response after immunization of mice with DNA plasmid Auxo-GTU(®)-MultiHIV. First, GTU(®)-encoded protein was shown to be expressed by DCs of the draining lymph nodes (LNs) following intradermal (i.d.) immunization. Next, donor mice were immunized with the MultiHIV DNA plasmid, and DCs were enriched and further used to immunize naïve recipient mice. For the first time, the results show that i.d. immunization with Auxo-GTU(®)-MultiHIV transfects DCs in vivo, enabling them to present antigens and induce HIV-specific immune responses in recipient mice.