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The cellular composition of the granulocytic series in normal human bone marrow was studied in aspirates of different volume. An increase in the proportion of polymorphonuclears was observed in samples of more than 1 ml, thus indicating a dilution of bone marrow by peripheral blood. Certain data from the literature, referring to the differential count in the bone marrow granulocytic series, are discussed. The differences between these data can be explained by the dilution of bone marrow cells by mature granulocytes in blood. [ABSTRACT FROM PUBLISHER]

Background: Allergic diseases are among the most common chronic diseases in childhood. Early childhood allergy prevention (ECAP) behaviors of those caring for the infant during pregnancy and the first months of life may influence the risk of allergy development over the life course. Motivation and intention to use appropriate primary ECAP measures are thus of critical importance., Aims: To characterize parental ECAP motivation, (a) valid indicators will be developed and (b) typical parental characteristics will be identified. (c) According to socio-cognitive models, the predictive value of parental risk perception, control belief and self-efficacy for parental ECAP motivation shall be determined., Method: A sample of N = 343 (expectant) mothers of infants completed a questionnaire on self-reported ECAP motivation, risk perception, control belief, and self-efficacy. The cross-sectional data were analyzed using latent class analysis and structural equation modelling including nominal regression models., Results: Four typical maternal response profiles (motivated to a customary degree, 70%; motivated to use primary preventive measures, 17.8%; reluctant towards new prevention measures, 6.4%; highly motivated to apply preventive measures in case of an existing allergy, 5.8%) could be identified for the items on ECAP motivation. After splitting the model variables "risk perception" (allergy vs. allergy-associated general health problems) and "self-efficacy" (trust vs. insecurity) a satisfactory model-fit was achieved (CFI = .939; RMSEA = .064). Particularly, increased "risk perception-allergy" (OR = 1.655) and "self-efficacy-insecurity" (OR = 2.013) as well as lower "risk perception-general health" (OR = 0.555) and "control belief" (OR = 0.217), respectively, are associated with higher ECAP motivation., Conclusion: The use of ECAP-measures by parents to protect their newborns from allergies is important, but there are deficiencies in their implementation. Based on a social cognitive model approach, predictive characteristics could be identified, which are associated with increased motivation to implement ECAP-measures. For public health our findings provide a promising basis for conception of behavioral and environmental ECAP prevention measures and their motivated implementation by parents., (© 2024. The Author(s).)

Background: Mobile health (mHealth) tools were developed during the past decades and are increasingly used by patients in cancer care too. Scientific research in the development of mHealth services is required in order to meet the various needs of patients and test usability., Objective: The aim of this study is to assess patients' needs, preferences, and usability of an app (My University Clinic [MUC] app) developed by the Comprehensive Cancer Center Freiburg (CCCF) Germany., Methods: Based on a qualitative cross-sectional approach, we conducted semistructured interviews with patients with cancer, addressing their needs, preferences, and usability of the designed MUC app. Patients treated by the CCCF were recruited based on a purposive sampling technique focusing on age, sex, cancer diagnoses, and treatment setting (inpatient, outpatient). Data analysis followed the qualitative content analysis according to Kuckartz and was performed using computer-assisted software (MAXQDA)., Results: For the interviews, 17 patients with cancer were selected, covering a broad range of sampling parameters. The results showed that patients expect benefits in terms of improved information about the disease and communication with the clinic staff. Demands for additional features were identified (eg, a list of contact persons and medication management). The most important concerns referred to data security and the potential restriction of personal contacts with health care professionals of the clinical departments of the CCCF. In addition, some features for improving the design of the MUC app with respect to usability or for inclusion of interacting tools were suggested by the patients., Conclusions: The results of this qualitative study were discussed within the multidisciplinary team and the MUC app providers. Patients' perspectives and needs will be included in further development of the MUC app. There will be a second study phase in which patients will receive a test version of the MUC app and will be asked about their experiences with it., Trial Registration: Deutsches Register Klinischer Studien DRKS00022162; https://drks.de/search/de/trial/DRKS00022162., (©Joachim Weis, Lucy Raphaela Wolf, Melanie Boerries, Daniela Kassahn, Martin Boeker, Carolin Dresch. Originally published in JMIR Cancer (https://cancer.jmir.org), 27.07.2023.)

Background: Ensuring motivated and successful study participation is a key challenge in the design and conduct of health research studies. Previously, recruitment barriers and facilitators have been identified mainly from experience, and rarely based on theoretical approaches. We developed a framework of intentional and actional components of engaged participation in public health research studies (INTACT-RS), informed by psychological behavioral models. We aimed a) to identify precise indicators for each framework component and b) to better understand which components and decision processes are essential for study participants., Methods: Within a multicenter research network, we applied various approaches to recruit parents of newborns, pediatricians, and midwives. All recruitment processes were documented from the perspective of both participants and researchers. We used different qualitative and quantitative data material, which we applied in a multistage process according to the basic principles of qualitative content analysis., Results: INTACT-RS encompasses pre-intentional, intentional and actional phases with a total of n = 15 components covering all aspects of an individual's involvement with a research study. During intention formation, an understanding of efforts and benefits, why participation is valuable beyond contributing to research, and how others perceive the study, were particularly important to (potential) participants. Subsequently (intentional phase), participants consider how and when participation is compatible with their own resources, ability and availability, and hence seek for close communication with, and flexibility and support from the research team. During and after (initial) participation (actional phase), participants' assessment of whether expectations and interests have been met impact crucial further steps, especially the willingness to continue and to recommend participation to others. A strong topic-wise and or supportive participation interest as well as active, continuous exchange with the researchers appeared to be central determinants of study completion and data validity., Conclusions: A theoretical framework is now available to plan and conduct recruitment of different target groups, which accounts for essential motivational and volitional decision-making processes. Based on empirically specified constructs, possible barriers can be addressed even before the initial recruitment process. Therefore, recommendations for scientific practice have been formulated., (© 2023. The Author(s).)

Health literacy (HL) is thought to be crucial for the management of the manifold demands relating to child health which parents are faced with. Albeit many studies have investigated parental HL and health behaviours (HBs) directed at the child, knowledge about the pathways which link parental HL with HB is scarce. The aim of this scoping review was to identify and comprehensively describe the variety of pathways linking parental HL with HBs directed at the child which were empirically analysed in previous studies. Following established scoping review methods database searches were conducted in MEDLINE, EMBASE, PsycINFO and WebofScience on 5 March 2020. Eligibility criteria included primary, empirical studies assessing parental HL and HB directed at the child in the general parent population. Titles and abstracts were screened independently by six reviewers for potentially relevant publications and data were extracted using standardized data extraction forms. The search identified 6916 articles for title and abstract screening. After full-text review, 50 studies were included in this review. Most studies (N = 24) assumed a direct association between HL and HBs and only few studies (N = 4) used more complex models investigating different pathways or mediation and/or moderation models. Overall, the evidence on the underlying pathways linking parental HL and HBs directed at the child is mixed and fairly limited. Therefore, hypothesis-driven research and integration of results into theoretical frameworks is needed for advancing both the research on HL and public health practice., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The goal of this study was to investigate barriers to utilisation of cancer rehabilitation by querying a large sample of various professionals in health care with a comprehensive set of barriers., Methods: We developed a questionnaire comprising 55 barriers to utilisation of cancer rehabilitation and administered it to four different types of medical, care and social work experts involved in the referral to cancer rehabilitation. An exploratory factor analysis was conducted and the extracted factors were ranked by mean values. Additionally, ANOVAs were calculated to test for group differences., Results: Our sample (N = 606) consisted of 249 physicians, 194 social workers, 105 nurses and 55 psychologists in Germany. We identified seven barrier-dimensions: low appreciation of rehabilitation by professionals, insufficient coordination, insufficient application procedure, rehabilitation requirements not met, patients' unfulfilled demands, patients' social responsibilities and patients' coping style, with the latter being rated as the most obstructive thereof. Furthermore, we found statistically significant group differences for six of these factors with small- to medium-sized effects., Conclusion: Our results support previous publications implicating the patients' coping style as a barrier. We furthermore found evidence for barriers relating to processes and organisational issues, thereby expanding on the scope of patient-oriented publications. Suggestions for improving patients' health services accessibility are made., (© 2021 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Purpose: In this study, which was funded by the German Federal Pension Fund (DRV), barriers in the application process for oncological rehabilitation services were examined from the perspective of various expert groups., Methods: In an exploratory multicentre qualitative cross-sectional study 61 semi-structured interviews with experts working in oncological care were conducted: Physicians (n=26), social workers (n=22), psychologists/psycho-oncologists (n=6), nurses/medical assistants (n=5), administrative staff of the DRV (n=2). In guided interviews the participants were asked about their experiences with rehabilitation applications as well as their estimations and evaluations regarding possible reasons for non-utilisation. The evaluation of the interviews was computerized and based on the qualitative content analysis by Mayring., Results: The respondents had an average age of 52.51 years (SD=10.06; min=25, max=71) and were working in the consultation or treatment of oncological patients for an average of 19.26 years (SD=10.15; min=1, max=42). In total, 854 statements were coded and assigned to the following three main categories: expert-related, system-related and patient-related barriers. In the first main category, scepticism about the benefits of rehabilitation services and an insufficiently met need for information on the part of experts became the focus of attention. In the main category of system-related barriers, aspects were mentioned that addressed the application procedure, the low availability of, for example, outpatient rehabilitation services and the absence of a functioning referral system. The main category of patient-related barriers included psychosocial factors such as subcategories on the topic of coping with the disease which include the patient's desire to come home, experience everyday life again and the fear of being confronted with the disease., Conclusion: The exploratory study revealed potential barriers in the application process for oncological rehabilitation services from an expert perspective. In particular, the findings form the basis for a multi-dimensional assessment instrument that can be used to analyze the barriers in a standardised way and to derive individual recommendations for action., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: From the perspective of various expert groups involved in the care of oncological patients, barriers to the application process of oncological rehabilitation programs will be identified. The study was funded by the German Pension Insurance Association (DRV)., Methods: Based on an interview study (N=61), a questionnaire instrument with 55 items describing possible barriers in the application process was designed and implemented online. Participants with more than 33% missing values were excluded from the analyses. Mean value analyses were used to identify the most significant relevance. To identify overall dimensions an explorative factor analysis was conducted ., Results: A total of 606 experts from the oncological field were included in the analyses. Among them were 249 doctors, 194 social workers, 105 nurses / medical assistants, 55 psychologists / psycho-oncologists and three other professional groups. The queried experts were on average 51 years old ( SD =10.4) and had been working in the oncological field for 17 years (SD=9.8). The barriers could be assigned to the following seven factor-analytically determined content sections: coping style, application procedure, rehabilitation requirements, coordination, social responsibilities, desires of patient and the priority of rehabilitation. According to the experts statements the main obstacles to an application were the patient's desire for normality, the rigid deadline for the application and the application procedure which is difficult for patients with a migration background to understand. It was also pointed out that it is difficult to place multimorbid patients in rehabilitation facilities., Conclusion: The following recommendations for action to facilitate access to rehabilitation can be derived from the expert study: optimization of the coordination between different expert groups, institutions and the cost units, flexibilisation of the deadline for follow-up, simplifying the application process, providing applications/information material in additional languages, orienting rehabilitation clinics towards specific patient groups., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals.

Delivering antigens in vivo by coupling them to mAbs specific for unique receptors on antigen-presenting cells (APCs) is a promising approach for modulating immune responses. Antigen delivery to receptors found on myeloid dendritic cell (DC) subsets, plasmacytoid DCs and B cells has shown them all to be viable targets to stimulate either the cellular or humoral arms of the immune system. It is now evident that antigen-targeting approaches can also be used to invoke antigen-specific inhibition of immune responses. The outcome of activation versus inhibition is determined by a combination of factors that include the choice of APC, the receptor that is targeted, whether to include an adjuvant and, if so, which adjuvant to employ. In addition to their use as a means to modulate immune responses, antigen-targeting systems are also a useful method to investigate the function of DC subsets and the early mechanistic events that underlie the initiation of both cellular and humoral immune responses. In this review, we focus on the literature surrounding the control of B-cell responses when antigen is delivered to various APC subsets.

Virus-like particles (VLPs) are promising vaccine candidates because they represent viral antigens in the authentic conformation of the virion and are therefore readily recognized by the immune system. As VLPs do not contain genetic material they are safer than attenuated virus vaccines. In this study, herpes simplex virus type 1 (HSV-1) amplicon vectors were constructed to coexpress the rotavirus (RV) structural genes VP2, VP6, and VP7 and were used as platforms to launch the production of RV-like particles (RVLPs) in vector-infected mammalian cells. Despite the observed splicing of VP6 RNA, full-length VP6 protein and RVLPs were efficiently produced. Intramuscular injection of mice with the amplicon vectors as a two-dose regimen without adjuvants resulted in RV-specific humoral immune responses and, most importantly, immunized mice were partially protected at the mucosal level from challenge with live wild-type (wt) RV. This work provides proof of principle for the application of HSV-1 amplicon vectors that mediate the efficient production of heterologous VLPs as genetic vaccines.

Cross-presentation by dendritic cells (DCs) of exogenous antigens on MHC class I is important for the generation of immune responses to intracellular pathogens, as well as for maintenance of self tolerance. In mice, the CD8(+) DC lineage is specialised for this role. However, DCs of this lineage are not born with cross-presentation capacity. Several studies have demonstrated that it must be induced as a later developmental step by cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF), or by microbial products such as toll-like receptor (TLR) ligands. Increased cross-presentation capacity is thus induced in peripheral CD8 lineage DCs during inflammation or infection. However, this capacity is already fully developed in steady-state thymic CD8(+) DCs, in accordance with their role in the deletion of self-reactive developing T cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for cross-presentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady-state thymic CD8(+) DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic CD8(+) DCs was dependent on licensing factors such as GM-CSF. In the absence of GM-CSF, antigen-MHC-class-I complexes were detected on thymic but not on splenic CD8(+) DCs, indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences between thymic and splenic CD8(+) DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall impairment of antigen presentation, as peptide-loaded splenic CD8(+) DCs were able to induce CD8(+) T-cell proliferation. The observation that thymic CD8(+) DCs are more efficient than splenic CD8(+) DCs in T-cell cross-priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Adeno-associated virus (AAV) has previously been shown to inhibit the replication of its helper virus herpes simplex virus type 1 (HSV-1), and the inhibitory activity has been attributed to the expression of the AAV Rep proteins. In the present study, we assessed the Rep activities required for inhibition of HSV-1 replication using a panel of wild-type and mutant Rep proteins lacking defined domains and activities. We found that the inhibition of HSV-1 replication required Rep DNA-binding and ATPase/helicase activities but not endonuclease activity. The Rep activities required for inhibition of HSV-1 replication precisely coincided with the activities that were responsible for induction of cellular DNA damage and apoptosis, suggesting that these three processes are closely linked. Notably, the presence of Rep induced the hyperphosphorylation of a DNA damage marker, replication protein A (RPA), which has been reported not to be normally hyperphosphorylated during HSV-1 infection and to be sequestered away from HSV-1 replication compartments during infection. Finally, we demonstrate that the execution of apoptosis is not required for inhibition of HSV-1 replication and that the hyperphosphorylation of RPA per se is not inhibitory for HSV-1 replication, suggesting that these two processes are not directly responsible for the inhibition of HSV-1 replication by Rep.

Dendritic cells (DCs) are important APCs able to induce both tolerance and immunity. Therefore, DCs are attractive targets for immune intervention. However, the ex vivo generation and manipulation of DCs at sufficient numbers and without changing their original phenotypic and functional characteristics are major obstacles. To manipulate DCs in vivo, we developed a novel DC-specific self-inactivating lentiviral vector system using the 5' untranslated region from the DC-STAMP gene as a putative promoter region. We show that a gene therapy approach with these DC-STAMP-lentiviral vectors yields long-term and cell-selective transgene expression in vivo. Furthermore, transcriptionally targeted DCs induced functional, Ag-specific CD4 and CD8 T cell tolerance in vivo, which could not be broken by viral immunization. Tolerized CTL were unable to induce autoimmune diabetes in a murine autoimmune model system. Therefore, delivering transgenes specifically to DCs by using viral vectors might be a promising tool in gene therapy.

Several mechanisms are in place to neutralize autoimmune CD8 T cells by tolerance induction. Developing self-specific CD8 T cells are eliminated in the thymus by Ag-presenting epithelial and dendritic cells (DCs). However, CD8 T cells escaping thymic central tolerance can also be inactivated by tolerance mechanisms in peripheral organs. In contrast to DCs, the role of B cells in generating CD8 T cell tolerance is not well-characterized. To investigate this question in more detail, we transcriptionally targeted Ag to B cells using B cell-specific retroviral vectors in vivo. Although Ag expression could be detected in B cells of thymus, lymph nodes, and spleen, B cells were unable to induce central tolerance of CD8 thymocytes. In contrast, in peripheral organs, we could identify clonal deletion and functional inhibition (anergy) of CD8 T cells as tolerance-inducing mechanisms. Although Ag expressed by B cells was acquired and cross-presented by DCs, B cells were also sufficient to tolerize CD8 T cells directly. These findings suggest exploitation of B cells for Ag-specific immunotherapy of CD8 T cell-mediated autoimmune diseases.

Considering the role of T-lymphocytes in rheumatoid arthritis (RA) and a possible involvement of the TCR in the pathology of this disease we analyzed allelic and genotypic frequencies of variants of two TCRBV gene segments (TCRBV3S1 and TCRBV18) in RA. A total of 95 caucasoid South Brazilian RA patients were genotyped for both TCRBV gene segment variants by restriction fragment length polymorphism preceded by PCR (PCR-RFLP) and the obtained frequencies were compared to those from healthy individuals. Allelic frequencies for the TCRBV3S1 gene segment were, respectively, for RA patients and controls, 0.447 and 0.545 (allele 1) and 0.553 and 0.455 (allele 2). Allelic frequencies for the TCRBV18 gene segment were, respectively, for RA patients and controls, 0.824 and 0.806 (allele 1) and 0.176 and 0.194 (allele 2). Neither allelic frequencies nor genotypic frequencies differ among RA and healthy individuals, suggesting that there is not a direct association among the TCRBV allelic variants studied and the development of RA and thus excluding the possibility of use of these gene segment polymorphisms as RA susceptibility markers.

The very-long-term follow-up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotomy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly. In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.