European Resuscitation Council COVID-19 guidelines executive summary.

Coronavirus disease 2019 (COVID-19) has had a substantial impact on the incidence of cardiac arrest and survival. The challenge is to find the correct balance between the risk to the rescuer when undertaking cardiopulmonary resuscitation (CPR) on a person with possible COVID-19 and the risk to that person if CPR is delayed. These guidelines focus specifically on patients with suspected or confirmed COVID-19. The guidelines include the delivery of basic and advanced life support in adults and children and recommendations for delivering training during the pandemic. Where uncertainty exists treatment should be informed by a dynamic risk assessment which may consider current COVID-19 prevalence, the person's presentation (e.g. history of COVID-19 contact, COVID-19 symptoms), likelihood that treatment will be effective, availability of personal protective equipment (PPE) and personal risks for those providing treatment. These guidelines will be subject to evolving knowledge and experience of COVID-19. As countries are at different stages of the pandemic, there may some international variation in practice.

[Mechanisms influencing implantation of the embryo--the last-years' news]. / Mechanismy ovliviiující implantaci embrya--co je nového v posledních letech.

OBJECTIVE: To summarize recent knowledge concerning mechanisms which influence the implantation of embryo. DESIGN: Literature-based overview. SETTING: Institute for the Care of Mother and Child, Prague. SUBJECT OF THE STUDY: Factors influencing implantation of embryo in the uterus elicit increased interest due to study of unexplained failures of embryotransfer following the successful in vitro fertilization. Our article points to recent information about physiology and pathology of mechanisms controlling implantation, namely the factors of immunity (antibodies, cells, cytokines and other mediators) whose exact regulation on the feto-maternal interface is a crucial precondition of successful implantation. Also the genetics of early embryo, as well as the possibilities of modern endoscopic techniques offer new insight onto mechanisms of implantation. Recommendations for diagnostics and treatment of implantation failure are given in the end of the article.

Immunological properties of heterozygous nu/+ mice: changes in antibody response and inducibility of tolerance to protein antigens.

Heterozygous nu/+ mice are not fully identical in their immunological properties with the mice of wild +/+ genotype. A colony of nu/nu, nu/+ and +/+ mice from the same breeding nucleus was established and their immune reactivity to human serum albumin, inducibility of adult immune tolerance to hen egg lysozyme (HEL), sensitivity of their lymphoid cells to stimulation by mitogens and ratio of CD3, CD4 and CD8 positive cell populations was studied. Both the numbers of antibody-forming cells in regional lymph nodes and the antibody titres in sera of nu/+ mice were highly variable, between undetectable values of nu/nu and high values of +/+ homozygotes. Intravenous pretreatment with soluble HEL, leading in +/+ mice to a deep hyporeactivity to subsequent immunization with the same antigen, did not decrease the response of nu/+ mice significantly. These results indicate that the immunological alteration of nu/+ mice is not only quantitative and that T cell subpopulations might be differentially modified by the presence of nu allele. The finding of decreased CD4:CD8 ratio in nu/+ mice also supports this idea.

Inhibitory effects of 5-azapyrimidine nucleosides on cellular immunity.

The effect of 5-azacytidine (5-AzCR) and 5-aza-deoxycytidine (5-AzCdR) on the survival of skin grafts in mice and rats, the action of these drugs on regional GVH reaction, as well as the formation of haemopoietic colonies (CFU-5) in the spleen were studied. Both drugs prolonged the life span of skin grafts when administered 24 hr before transplantation, or on the 4th post-transplantation day. However, they were little effective when injected 24 hr after skin grafting, or after induction of the regional GVHR. Following intraperitoneal administration, they inhibited CFU-5 formation. Two-hour incubation in vitro of cells with 5-AzCR significantly reduced their GVH reactivity and capacity to form CFU-5; 5-AzCdR under the same conditions was ineffective.

Correlation of asthenozoospermia with increased antisperm cell-mediated immunity in men from infertile couples.

To investigate whether cell-mediated immunity (CMI) against sperm and/or antisperm circulating antibodies are associated with poor semen quality, a leukocyte migration inhibition factor (LMIF) assay and an enzyme-linked immunosorbent assay (ELISA) were performed in groups of men from infertile couples, men from fertile couples and sperm donors. Twenty-five of 102 men (25%) revealed positive CMI against sperm and 10 (10%) had positive antisperm antibody titers in their sera. Fifteen of 28 asthenozoospermic men (53%) from infertile couples revealed positive antisperm CMI. The incidence of antisperm CMI was significantly increased (P < 0.05) in the infertile men with asthenozoospermia compared with the men from the other two groups (men from fertile couples and sperm donors). No significant differences between migration indices were seen when such a comparison was done for oligoasthenoterato- and teratozoospermics. The results indicate that increased antisperm CMI is associated with asthenozoospermia in a significant number of men from infertile couples. The importance of these findings is discussed.

Immunological unresponsiveness to HSA in chickens.

HSA injected into chickens after hatching induces suppression of anti-HSA antibody formation. Unresponsive chickens react by producing the anti-HSA antibodies earlier and more intensively after BSA challenge than after challenge with HSA. This effect cannot be ascribed to T cells, because they were found to play no substantial role in the unresponsiveness to HSA. Neither was active suppression, which could account for the depressed antibody production, detected. B cell inactivation seems to be the major mechanism involved in this unresponsiveness. However, some additional mechanism must prevent B cells of unresponsive chickens from producing anti-HSA antibodies after HSA challenge, although they are able to form them after immunization with BSA. We suggest that cellular interactions, either between B cells of different specificities or between B cells and macrophages, are responsible for this differential reactivity.

Autoimmune antiovarian antibodies and their impact on the success of an IVF/ET program.

In previous papers, we referred to studies of the influence of antiovarian autoantibodies on menstrual cycle disorders in adolescent girls. We examined autoantibodies against ooplasma, zona pellucida, membrana granulosa, theca folliculi interna, and lutein cells. In infertile women in the IVF/ET program, we studied the positivity of antiovarian antibodies and cytokines, namely, TNF-alpha and IL-1 beta, in follicular fluid correlated with the following subgroups, characterized by the outcome of in vitro fertilization, as follows: G, pregnant; F, fertilized; N, nonfertilized; and O, no oocyte gained. The presence of autoantibodies corresponds to the success or failure of the IVF/ET program. Our results support the hypothesis that antiovarian autoantibodies play an important role in both the endocrine and the reproductive function of the human ovary and that it can influence them negatively.

The effect of thymectomy on immunological tolerance to human serum albumin in chickens.

The effect of thymectomy performed on the day of hatching has been studied in chickens rendered tolerant by 100 mg of HSA injected also on the day of hatching. After challenge at the age of 6 and 9 weeks, no significant difference was observed between the group of tolerant chickens, in which the thymectomy was complete or incomplete, and the non-operated tolerant one. The delayed recovery from tolerance observed in mammals was not seen even in chickens in which thymus was removed completely and no thymic residue remained. The anti-HSA antibodies were even slightly higher in thymectomized birds than in the non-operated ones but the difference was statistically non-significant.

Increase by bacterial lipopolysaccharide of antibody production in mice rendered hyporesponsive to lysozyme.

The effect of bacterial lipopolysaccharide (LPS) on the immune response of adult mice to hen egg lysozyme (HEL) was studied under conditions in which hyporesponsiveness to HEL was induced by: (i) the intravenous injection of syngeneic spleen cells incubated with HEL; (ii) the intravenous administration of soluble HEL, and (iii) the intraperitoneal injection of HEL in IFA. In all cases, mice were immunized by footpad injection of HEL, with or without LPS. The antibody response produced was measured by the number of indirect anti-HEL plaque forming cells (PFC) detected in popliteal lymph nodes. The incorporation of LPS in the immunizing dose of HEL had little effect on the response of controls; however, it resulted in an appreciable increase in the antibody response of all three groups of hyporesponsive mice. Although, after treatment with LPS, the number of PFC detected in mice made tolerant by spleen cell injection approached those of the controls, lower increases in the antibody response were noted for the remaining two groups of hyporesponsive mice.

Corticosterone treatment affects neonatal induction of immunological tolerance to hen egg lysozyme in mice.

Immunological tolerance to hen egg lysozyme (HEL) was induced in mice by one injection of 0.1 mg of HEL intraperitoneally on day 0 (i.e. within the first 24 h after birth). After immunization with the same antigen 8 weeks later, such mice developed markedly lower numbers of specific antibody-forming cells than did the untreated controls. When the tolerized mice were injected with three doses (1 microgram each) of corticosterone (CN) on days 1, 3 and 5, the tolerogenic effect was markedly diminished. However, in adult animals neither the inducibility of tolerance nor the intensity of immune reaction was influenced by the early treatment with CN. No influence of early CN treatment on the in vitro response of spleen cells to T- and B-cell mitogens was found, when tested in adult animals. The results support a view that neonatally induced immunological tolerance to hen egg lysozyme is mediated by a population of antigen-specific regulatory cells, generation of which can be prevented by treatment with CN.

Attempts to characterize cellular mechanisms of immunologic tolerance to HSA in chickens.

Partial suppression of antibody formation in neonatally induced tolerance to HSA as observed during immunization at 6 weeks of age or at a later time, is caused mainly by a rapid escape from tolerance. The following findings support this view: 1. After immunization at 4 weeks of age with a larger dose of HSA, which elicits detectable circulating antibody formation in all control birds, anti-HSA antibodies cannot be demonstrated in a large majority of tolerant chickens. 2. Surgical bursectomy performed in tolerant birds on the day of hatching or 7 or 11 days after hatching increases considerably the degree of suppression of anti-HSA antibody formation and slows down the return of reactivity to HSA. These findings suggest that new immunocompetent cells originating in the bursa are responsible for escape from tolerance in this experimental system. The existence of suppressor cells in birds tolerant to HSA was not demonstrated by the transfers of spleen cell mixtures from immune and tolerant donors to young, irradiated recipients.

Antibody-producing cells in chickens tolerant to human serum albumin.

Cells forming antibodies to HSA were determined by the haemolytic plaque technique in the spleens of chickens in which tolerance to HSA was induced on the day of hatching. After immunization with HSA 2 weeks after hatching, no anti-HSA PFC or their very low numbers were observed in chickens rendered tolerant by the dose of 100 mg HSA. In a considerable proportion of the chickens, in which tolerance was induced by 1 mg or 0.1 mg of HSA, PFC were detected, though in statistically significantly lower numbers than in control birds. In tolerant chickens receiving 100 mg of HSA after hatching, the number of PFC after immunization at 4 weeks of age was statistically significantly and at 6 weeks non-significantly lower than in the controls. After immunization with BSA at 4 weeks of age, chickens injected with 100 mg HSA after hatching had the number of anti-HSA plaque-forming cells higher than the controls, but the difference was not statistically significant.

Termination of tolerance to HSA in chickens.

A major part of chickens made tolerant to HSA at hatching formed anti-HSA antibodies when immunized with cross-reacting antigen, the BSA, at 4 weeks of age, although tolerant birds immunized with HSA produced no detectable antibody levels. Immunization with HSA + BSA did not prevent anti-HSA antibody formation in tolerant chickens, but it seems that the escape from tolerance is more rapid in birds immunized with BSA only than in those immunized with HSA + BSA and/or HSA only.

Chromosomal aberrations in mouse bone marrow cells and antibody production changes induced by long-term exposure to cyclophosphamide and alpha-tocopherol.

The frequency of chromosomal aberrations in bone marrow cells and the primary immne response to sheep erythrocytes were studied at weekly intervals in mice exposed to cyclophosphamide (0.01% or 0.02% concentration in drinking water) and/or alpha-tocopherol(1000 mg/kg intraperitoneally, twice a week) throughout 4 weeks. Both 0.01% and 0.02% CY concentrations induced approximately the same levels of aberrant cells (7.5 and 9.2%, respectively). No significant rise in the frequency of aberrant cells was observed during the four-week course of experiment. The lower (0.01%) concentration of CY significantly increased IgM haemagglutinin titres, while IgG titres decreased rapidly after 3 weeks of exposure; 0.02% CY suppressed almost completely both IgM and IgG antibody levels already after one week of treatment. Simultaneous application of alpha-tocopherol significantly increased the frequency of aberrant cells in 0.01% Cy-treated mice but had no effect on 0.02% CY-treated group. No considerable changes in antibody titres were induced by alpha-tocopherol in both CY-treated and untreated animals.

Persistence of immunological tolerance to HSA in chickens after cell transfer to immunosuppressed hosts.

The nature of immunological tolerance to HSA in chickens was analyzed by means of spleen cell transfers to 3-day-old, cyclophosphamide-treated, syngeneic recipients. The cell donors were 2-week-old tolerant or control chickens. The primary challenge with HSA was done 26 days after cell transfer. Spleen cells from both control and tolerant donors restored the immunoglobulin levels and the ability to produce antibodies to SRBC to normal. While cells from normal donors also reconstituted the ability to form antibodies to HSA, the recipients of cells from tolerant donors either did not form detectable amounts or formed only low titres of these antibodies. The ability of cells from normal donors to respond by anti-HSA antibody formation, when transferred together with cells from tolerant donors, was neither suppressed nor decreased. Thus, tolerance to HSA in chickens was not reversible and the existence of an active immune process, causing its duration, could not be demonstrated.

The effect of bone marrow regulatory peptides on antibody production by hybridoma cells.

Peptides produced by bone marrow cells (myelopeptides) increase antibody production. Since antibody producing cells seemed to be their targets, we tested in these experiments the effect of myelopeptides on antibody production by 2B2 and 2C12 hybridoma cells. Both hybridomas produce anti-SRBC monoclonal antibodies of the IgM class. The 2B2 cells do not produce direct haemolytic plaques and less than 5% of them produce the indirect ones during the 90-min assay period. When they were cultivated with myelopeptides for 15 h, the number of indirect plaques increased two-fold. A slightly lower increase was observed after 24 h of incubation, while the 48-h incubation period did not increase the number of detected plaques. After 6 h of preincubation, only a slight increase in indirect plaque numbers was observed. About 25% of the 2C12 hybridoma cells produce both direct and indirect haemolytic plaques during the assay period. The effect of myelopeptides was studied only on the indirect ones and no clear effect was observed. Only after the 15-h incubation period a slight increase in plaque numbers was observed. Because the myelopeptides affect antibody production of hybridoma cells, antibody producing cells are evidently the targets of these substances. It remains to be established, whether they are the only target cells in the myelopeptide action on the immune response.

Cellular cooperation at the level of antibody-producing cells in chickens.

The effect of in vitro cocultivation of immune and non-immune syngeneic lymphoid cells on the antibody response was studied in chickens. Cocultivation of immune and non-immune spleen cells did not affect significantly the PFC numbers. Substantial increase in PFC was observed in mixed cultures of immune spleen cells with non-immune bone marrow cells. The existence of an enhancing effect of non-immune cells on the antibody-producing cells, which had been earlier described in mice, was observed in a phylogenetically distant species. Therefore it seems probable that it exists in most, if not all, homoiotherm animal species.

Quantitative characteristics of antibody forming cells in partial tolerance.

Direct PFC to SRBC were enumerated simultaneously by the LHL and LHG in the spleens of partially tolerant and control rats. The sensitivity of LHL was higher than that of LHG, but the factor by which the number of PFC was higher in LHL than in LHG was in the two groups similar (1.44 in tolerant and 1.47 in control group). When the plaque size distribution was studied in the LHL, a significant increase in small size plaques was observed in tolerant rats. The findings are discussed and the conclusion is reached that the decrease in AFC number and not in antibody production by individual PFC is the main factor responsible for partial tolerance.