Prosocial polio vaccination in Israel.

Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel's having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children-who had only received the inactivated polio vaccine-with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual's comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.

Overcoming the effect of pandemic fatigue on vaccine hesitancy-Will belief in science triumph?

PURPOSE: The study aims to examine the factors that impact vaccination uptake and additional protective behavior during the fourth wave of the pandemic in Israel, whereas the "pandemic fatigue" phenomenon has been identified as a hurdle to adherence to protective health behaviors against coronavirus disease 2019 (COVID-19). DESIGN: A cross-sectional, structured questionnaire was utilized for this investigation in September 2021, during the fourth wave of the pandemic. METHODS: A sample of the adult (18+) Israeli population was employed for the study. Recruiting participants for the study was conducted through an online internet panel company that consists of over 100,000 members, representing all geographic and demographic sectors of the Israeli population. RESULTS: Our findings indicate that pandemic fatigue has begun to have cascading effects on vaccination efforts. In particular, this study found that at this stage of the COVID-19 pandemic, trust in authorities, and even threat perception components, such as concern and fear of contracting the disease, are incapable of predicting vaccination uptake. Instead, perception of the importance of the vaccine and its effectiveness are predictive of vaccination uptake. CONCLUSION: The findings indicate that at this stage of the pandemic, focusing on the robustness of the science behind the vaccine is more important than trying to regain public trust. The findings also suggest that risk communication employing fear tactics is losing its capacity to generate motivation for vaccination. CLINICAL RELEVANCE: The findings of this study reveal lessons learned from the COVID-19 global pandemic. Specifically, the study reveals how in times of prolonged crisis, we can currently and, in the future, prepare improved strategies for public communication in order to promote uptake of protective health behavior, such as vaccination.

Polarization in public attitudes toward end-of-life decisions in Israel - A cross-sectional study.

OBJECTIVES: End-of-life (EoL) processes are a complex socio-normative and ethical phenomenon. This study aimed to generate a database of public opinion in Israel concerning EoL processes and decisions and to identify differences in attitudes across subgroups in the population, particularly based on experience as a family caregiver of a dying patient. METHODS: This cross-sectional study was performed in late March 2022. The study utilized an online sample of 605 adults over the age of 50 including those who accompanied a loved one to their death in the last 3 years. Participants were requested to provide their opinions and attitudes on several aspects of EoL decisions, including truth-telling, medically assisted dying, EoL procedures, pre-death actions, and family caregivers' engagement. RESULTS: While only 27% and ∼30% of participants support artificial respiration or feeding (respectively) of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. The data show an association between religiosity and agreement with life-extending procedures. For example, while 83% of seculars support medically assisted dying, only 59% and 26% of traditional and religious respondents support it. However, no statistically significant differences were observed in support of family involvement in EoL process in any sociodemographic variable. SIGNIFICANCE OF RESULTS: The results of this study suggest that the Israeli public is relatively polarized on several issues about EoL processes, specifically patient autonomy and medically assisted dying. Yet, at the same time, there is a consensus among the Israeli public about certain EoL elements, particularly the importance of family caregivers in the EoL decision-making process.

Agencies Displayed by Patients, Medical Teams, and Caregivers at the End of Life from the Perspectives of Family Members - A Qualitative Study.

Background: End-of-life (EoL) Care is challenging for terminally-ill patients and their caregivers. This research is aimed to examine the relational agencies of the patients, the caregivers, and the medical teams in the context of EoL care, with a particular emphasis on the caregivers. Methods: This study is based on the qualitative analysis of interviews with 12 individuals who were closely supported a loved one to their death from a terminal illness. Results: Information collected revealed several agency-related themes. Family caregivers are significant entities in managing the 'case' of a seriously ill individual. At the final or more advanced stages of the EoL process, caregivers gradually shift from a supportive role to being active agents, but not always backed by the necessary experience, knowledge, or the requisite emotional resilience. Conclusions: Based on recognizing their agentic proactivity, a clear and elaborate articulation of the family caregivers' roles is needed.

Truth-telling and doctor-assisted death as perceived by Israeli physicians.

BACKGROUND: Medicine has undergone substantial changes in the way medical dilemmas are being dealt with. Here we explore the attitude of Israeli physicians to two debatable dilemmas: disclosing the full truth to patients about a poor medical prognosis, and assisting terminally ill patients in ending their lives. METHODS: Attitudes towards medico-ethical dilemmas were examined through a nationwide online survey conducted among members of the Israeli Medical Association, yielding 2926 responses. RESULTS: Close to 60% of the respondents supported doctor-assisted death, while one third rejected it. Half of the respondents opposed disclosure of the full truth about a poor medical prognosis, and the others supported it. Support for truth-telling was higher among younger physicians, and support for doctor-assisted death was higher among females and among physicians practicing in hospitals. One quarter of respondents supported both truth-telling and assisted death, thereby exhibiting respect for patients' autonomy. This approach characterizes younger doctors and is less frequent among general practitioners. Another quarter of the respondents rejected truth-telling, yet supported assisted death, thereby manifesting compassionate pragmatism. This was associated with medical education, being more frequent among doctors educated in Israel, than those educated abroad. All this suggests that both personal attributes and professional experience affect attitudes of physicians to ethical questions. CONCLUSIONS: Examination of attitudes to two debatable medical dilemmas allowed portrayal of the multi-faceted medico-ethical scene in Israel. Moreover, this study, demonstrates that one can probe the ethical atmosphere of a given medical community, at various time points by using a few carefully selected questions.

The association of medical, social, and normative factors with the implementation of end-of-life care practices.

BACKGROUND: End-of-life (EoL) care practices (EoLCP) are procedures carried out at the EoL and bear directly on this stage in the patient's life. Public support of these practices in Israel is far from uniform. Previous studies show that while ∼30% of participants support artificial respiration or feeding of terminally ill patients, 66% support analgesic treatment, even at the risk of shortening life. This study aimed to create a typology of six end-of-life care practices in Israel and assess the association of medical, social, and normative factors with the implementation of those practices. These practices included mechanical ventilation, artificial feeding, deep sedation, providing information to the patient and family caregivers, including family caregivers in EoL decision-making, and opting for death at home. METHODS: This cross-sectional study was performed as an online survey of 605 adults aged 50 or more in Israel, of which ~ 50% (n = 297) reported supporting a dying terminally ill relative in the last 3 years. Participants were requested to provide their account of the EoL process of their relative dying from a terminal illness in several aspects, as well as the EoL care practices utilized by them. RESULTS: The accounts of the 297 interviewees who supported a dying relative reveal a varied EoL typology. The utilization of end-of-life care practices was associated with the socio-normative beliefs of family caregivers but not with their socioeconomic status. Strong correlations were found between family caregiver support for three key practices (mechanical ventilation, artificial feeding, and family involvement in EoL) and the actual utilization of these practices in the care of dying patients. CONCLUSIONS: The findings portray an important image of equity in the utilization of EoLCP in Israel, as the use of these practices was not associated with socioeconomic status. At the same time, the study found substantial diversity in family caregivers' preferences regarding EoL care practices use not related to socioeconomic status. We believe that differences in preferences that do not lead to problems with equity or other important societal values should be respected. Accordingly, policymakers and health system leaders should resist calls for legislation that would impose uniform EoL practices for all Israelis. Instead, they should take concrete steps to preserve and enhance the widespread current practice of practitioners to adapt EoL care to the varied needs and preferences of Israeli families and cultural, social, and religious subgroups. These steps should include providing frameworks and tools for family caregivers to support their loved ones close to their deaths, such as educational programs, seminars, supportive care before and during the end of life of their loved ones, etc.

The Effects of Sociocultural Transitioning on Accessibility to Healthcare: The Case of Haredi Jews Who Leave Their Communities.

Minority groups and immigrants encounter complex issues when attempting to access healthcare. This study examines factors affecting access to healthcare by a group of individuals in Israel who decided to leave their Haredi Jewish communities. We conducted 23 semi-structured interviews with individuals disaffiliating from Haredi communities in Israel in order to identify hurdles encountered during the process of seeking healthcare. We focused on specific steps in this process, including recognizing the need for help, deciding to actually turn to the health system, interaction with the system, and behavior after referring to the health system. We identified approximately 20 factors which can be either barriers or catalysts affecting healthcare access at the various stages. These were then traced to religious upbringing, hurdles of sociocultural transition, and unique characteristics of individuals reshaping their lives. The findings can be instrumental in designing culturally adapted health programs for individuals leaving the Haredi community. Moreover, the methodology that we are proposing can serve other investigations studying access to healthcare among various groups undergoing sociocultural transitions.

Disaffiliation from Jewish Ultra-Orthodox Communities: Life Trajectories Shaped by the Axes of Rigidity-Fluidity and Alterity-Inclusion.

Increasing numbers of young Israelis annually leave the enclave of the ultra-Orthodox Jewish community. Relying on 16 in-depth interviews, we examine the effects of this disaffiliation on life trajectories and identity reconstruction of individuals who left their society of origin two decades ago. This unveiled a multistep longitudinal process, characterized by moving in and out of various structural stages, coupled with disaffiliates' agency to highlight specific sociocultural characteristics or the more universal nature of the human condition. The life course of disaffiliates begins with a phase of early struggle with the immediate tolls of disaffiliation, followed by a formative period marked by two steps: military service and acquisition of higher education. Here disaffiliates practice adoption of increasingly inclusive identities, in which the past and present are enmeshed. The formative period is followed by three alternative trajectories: (a) adherence to restrictive Israeli conformity, (b) ongoing search for singularity, and (c) integration of ultra-Orthodox heritage with contemporary Israeli realities. The disaffiliation trajectory from the ultra-Orthodox society is embedded in particular sociocultural, political, and historical contexts. However, narratives of disaffiliates adhere to frameworks of cultural Jewish-Israeli particularism, as much as to those of human universalism, plugging in to certain universal themes of the human condition, namely rigidity, fluidity, alterity, and inclusion.

Acceptance on the move: public reaction to shifting vaccination realities.

This review examines four events related to vaccination that have occurred in recent years: (a) the ongoing recovery from the MMR/Autism scare in the UK, (b) the upgrading of the Varicella vaccine to a universal childhood vaccine, (c) the major effort of authorities to provide a vaccine for A/H1N1 influenza and its rejection by the public, and, d) the current attempts to change the HPV vaccine target from girls only to boys and girls. All of these changes have been met with shifts in the public acceptance of the relevant vaccine. These shifts are characterized not only by the number of people willing to be vaccinated, but also by the attitudes and the motives related to acceptance. Examination of the interrelationship between changes in vaccination realities, and changes in acceptance patterns suggests that today, the public has a better understanding of vaccination, is acting in a more reflexive way, and is capable of changing attitudes and behavior. All together, changes in vaccination enhance debates and dialogues about vaccines, and lead to higher awareness and more conscious acceptance.

Interrelationship between dendritic cell trafficking and Francisella tularensis dissemination following airway infection.

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11b(high)/CD11c(med)/autofluorescence(low) DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria ( approximately 75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment.

Assisted life termination and truth telling to terminally ill patients - a cross-sectional study of public opinions in Israel.

BACKGROUND: End-of-life decisions are highly complex socio-normative and ethical phenomena. The goal of this study was to provide an assessment of public opinions in Israel concerning aspects of end-of-life decisions. METHODS: An online cross sectional study was performed in February 2020. The primary tool including items pertaining to death assistance and truth telling to patients. A sample of 515 participants representative of the adult Israeli population was obtained. RESULTS: The majority of participants (71%) supports telling the entire truth to patients even in harsh conditions. Support for truth telling decreases with affiliation to religion, with as little as 40% support among ultra-orthodox. People with vocational education are the least supportive of truth telling. Concerning doctor assisted death, almost half (49%) of the sample were supportive. Opposition is positively associated with religiosity, with 90% of ultra-orthodox and 58% of religious participants opposing doctor-assisted death, compared to only 18% among seculars. Non-Jews were 3.35 times (95%CI: 1.90, 5.91) more likely to oppose doctor assisted death than Jews (p < .0001). An Interrelationship analysis crossing between attitudes revealed that the largest group (39%) was comprised of participants who support both ("autonomists"). CONCLUSIONS: Israelis are overwhelmingly supportive of truth telling to patients. In contrast, Israeli public opinions on doctor assisted death are divided. For both attitudes, religiousness plays a crucial role as a catalyst for conservatism and opposition to change. Almost a half of the public is also supportive of an autonomist approach that would allow patients to decide on ending their own lives.

Flexibility versus "rigidity" of the functional architecture of AChE active center.

Functional architecture of the AChE active center appears to be characterized by both structural "rigidity", necessary to stabilize the catalytic triad as well as by flexibility in accommodating the different, high affinity AChE ligands. These seemingly conflicting structural properties of the active center are demonstrated through combination of structural methods with kinetic studies of the enzyme and its mutant derivatives with plethora of structurally diverse ligands and in particular with series of stereoselective covalent and noncovalent AChE ligands. Thus, steric perturbation of the acyl pocket precipitates in a pronounced stereoselectivity toward methylphosphonates by disrupting the stabilizing environment of the catalytic histidine rather than through steric exclusion demonstrating the functional importance of the "rigid" environment of the catalytic machinery. The acyl pocket, the cation-binding subsite (Trp86) and the peripheral anionic subsite were also found to be directly involved in HuAChE stereoselectivity toward charged chiral phosphonates, operating through differential positioning of the ligand cationic moiety within the active center. Residue Trp86 is also a part of the "hydrophobic patch" which seems flexible enough to accommodate the structurally diverse ligands like tacrine, galanthamine and the two diastereomers of huperzine A. Also, we have recently discovered further aspects of the role of both the unique structure and the flexibility of the "hydrophobic patch" in determining the reactivity and stereoselectivity of HuAChE toward certain carbamates including analogs of physostigmine. In these cases the ligands are accommodated mostly through hydrophobic interactions and their stereoselectivity delineates precisely the steric limits of the pocket. Hence, the HuAChE stereoselectivity provides a sensitive tool in the in depth exploration of the functional architecture of the active center. These studies suggest that the combination of "rigidity" and flexibility within the HuAChE gorge are an essential element of its molecular design.

Disparity between Yersinia pestis and Yersinia enterocolitica O:8 in YopJ/YopP-dependent functions.

YopP in Y. enterocolitica and YopJ in Y. pseudotuberculosis, have been shown to exert a variety of adverse effects on cell signaling leading to suppression of cytokine expression and induction of programmed cell death. A comparative in vitro study with Y. pestis and Y. enterocolitica O:8 virulent strains shows some critical disparity in YopJ/YopP-related effects on immune cells. Involvement of yopJ in virulence was evaluated in mouse model of bubonic plague.

On the implications of desexualizing vaccines against sexually transmitted diseases: health policy challenges in a multicultural society.

Two vaccines against sexually transmitted infections are included in many national vaccination programs: Hepatitis B Virus (HBV) vaccine and Human Papilloma Virus (HPV) vaccine. The trajectories of the implementation of these two programs were marked by differences in the way the sexual context of risk was communicated to the public. These trajectories fluctuated between full accounts of the sexual nature of the infection and attempts to desexualize the vaccines. Vaccine desexualization can be achieved by withholding information of sexual context, blurring information, and distancing the age of vaccination from the age of sexual debut. Desexualization may be advantageous in promoting public health and personal health of people who believe that HPV vaccination leads to increased promiscuity, people who believe that protection against STD is not relevant to their children, and people who are not comfortable discussing the sexuality of their children. On the other hand, desexualizing may be disadvantageous for children to parents who tend to express passiveness towards vaccination, parents who attribute importance to sex education, and teenagers with homosexual orientations. The ethical analysis of vaccine desexualization reveals a complex interplay of considerations related to utility, causation of harm, duty of transparency, right to know, and right not to know. This analysis suggests that the moral merits of applying desexualization are questionable. Lastly, a sociopolitical consideration of the matter, suggests that decisions on vaccine desexualization can have implications on the interrelationships between various social groups and subgroups composing a certain population, and may highlight intercultural schisms. All this indicates that shaping the sexual framework of vaccination programs bears implications far beyond the practical considerations of vaccine promotion.

Vaccine hesitancy as self-determination: an Israeli perspective.

Vaccine hesitancy can be portrayed as a broad spectrum of phenomena, ranging from a genuine call for help to complete defiance of authorities. The emphasis here is made on mid-spectrum hesitancy; hesitancy as an act of personal exploration and deliberation whether to get vaccinated or not. This form of vaccine hesitancy can be identified in the attitude of the Israeli public towards routine childhood vaccination programs, seasonal flu vaccination, newly introduced vaccines, such as human papilloma virus vaccine, as well as towards the emergency vaccination programs against poliovirus and H1N1 pandemic influenza. Vaccine hesitancy in Israel appears to be a process where individuals exercise self-determination and self-empowerment and make their own decisions based on assessment, reflection, choosing between various options and dealing with considerable complexities. Addressing this form of vaccine hesitancy could be challenging, but ultimately fruitful. This would require change of attitudes on the part of policymakers. The first steps should involve the realization that deliberative hesitancy is here to stay, and that hesitant individuals should be respected. This could pave the way for designing appropriate intervention strategies for convincing the hesitant public about the advantages of vaccination.

Using the social structure of markets as a framework for analyzing vaccination debates: The case of emergency polio vaccination.

The framework of the social structure of markets was used to analyze an online debate revolving around an emergency poliovirus vaccination campaign in Israel. Examination of a representative sample of 200 discussions revealed the activity of three parties: authoritative agents promoting vaccinations, alternative agents promoting anti-vaccination, both representing sellers, and the impartial agents, representing the customers-the general public deliberating whether to comply with vaccination or not. Both sellers interacted with consumers using mechanisms of luring and convincing. The authoritative agents conveyed their message by exhibiting professionalism, building trust and offering to share information. The alternative agents spread doubts and evoked negative emotions of distrust and fear. Among themselves, the alternative agents strived to discredit the authoritative agents, while the latter preferred to ignore the former. Content analysis of discussions conducted by the general public reveal reiteration of the messages conveyed by the sellers, implying that the transaction of pro and anti-vaccination ideas indeed took place. We suggest that the framework of the market as a social structure can be applied to the analysis of other vaccination debates, and thereby provide additional insights into vaccination polemics.

Host-regulated disposition of mammalian AChEs.

Primates are characterized by a paucity of soluble acetylcholinesterase (AChE) in the circulation at the adult stage, where the predominant circulating cholinesterase is butyrylcholinesterase. In recent years, we subjected recombinant human and bovine acetylcholinesterase to extensive pharmacokinetic studies in mice, an animal system which also displays very low levels of circulating AChE. In this system, a post-translation-related hierarchical pattern governing circulatory residence through AChE sialylation, subunit tetramerization and glycan loading was elucidated. Based on these studies, coordinated modulation of the sialic acid contents, state of subunit assembly and number of glycans allowed us to generate human or bovine AChE forms which reside in the circulation of mice for long periods of time, mimicking the pharmacokinetic behavior of native serum-derived cholinesterases. However, extension of the pharmacokinetic studies to primates, revealed an additional element, which affects circulatory residence of AChEs in this animal system. Unlike in the case of bovine AChE, optimization of subunit assembly and glycan loading of the primate versions of AChE (human or rhesus) did not increase their circulatory lifetime in rhesus macaques. This differential pharmacokinetic behavior of bovine and primate AChEs in macaques appears to be related to the 35 diverging bovine/primate AChE amino acids which are clustered within three defined domains at the enzyme surface, and thereby may facilitate the specific removal of "self" or "self-like" cholinesterases from the circulation of monkeys and thus provide an explanation for the absence of soluble AChE in the circulation of primates.

Lessons from functional analysis of AChE covalent and noncovalent inhibitors for design of AD therapeutic agents.

Determination of the 3D-structure of acetylcholinesterase (AChE) of Torpedo californica over a decade ago, and more recently that of human enzyme together with extensive targeted mutagenesis of the mammalian AChEs led to a fine mapping of the multiple functional domains within the active center of the enzyme. Many of the contributions of this active center architecture to accommodation of noncovalent ligands could be deduced from the X-ray structures of the corresponding HuAChE complexes. Yet, Michaelis complexes leading to transient covalent adducts are not amenable to structural analysis. Since the rates of formation of the covalent adducts depend predominantly on the stabilities of the corresponding Michaelis complexes, it is essential to characterize the specific interactions contributing to stabilization of these complexes. Functional analysis of interactions with HuAChE enzymes allows for such characterization for carbamates, like pyridostigmine or rivastigmine, much in the same way as that for the noncovalent therapeutic ligands nivalin or aricept. In fact, the observed differences between the affinities toward carbamates and the noncovalent ligands seem to result from specific structural characteristics of the inhibitors rather than from the decomposition path of the particular complex. Replacements at the cation binding site (Trp86), hydrogen bond network (Glu202, Tyr133, Glu450), and hydrophobic pocket result in similar effects for the covalent as well as for the noncovalent inhibitors. Also, while the effects of perturbing the aromatic trapping of the catalytic His447 for pyridostigmine and nivalin were analogous to those for the substrate, the corresponding effects for rivastigmine and aricept were quite different. Thus, elucidation of the functional architecture of the HuAChE active center is bound to be of considerable utility in the current effort to design novel covalent AChE inhibitors as therapeutics for Alzheimer's disease (AD).