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Objective: The growing number of adults with childhood onset chronic conditions (COCC) is reflected in the increase of adult-aged admissions to pediatric institutions. Despite national bodies advising pediatric institutions to have a pediatric to adult healthcare transition (HCT) policy, little guidance is available on if or how to include inpatient care. We sought to create a framework-based Pediatric to Adult Transitional Care in the Hospital Context (PATCH) tool to assess how inpatient care of adults is addressed in pediatric institutional guidelines or policies (hereafter guidelines) as a first step towards informing future PATCH guideline development., Methods: We used convenience and snowball sampling to obtain 11 pediatric institutional guidelines. Combining the GotTransition® core elements with Coller et al's inpatient transition conceptual model through iterative consensus building, we developed the PATCH tool. Interrater reliability was assessed by using mean percent agreement amongst raters. A three-phase content validity process utilizing existing guidelines refined the finalized tool., Results: The PATCH tool included 42 items within nine domains. There was a high degree of agreeability amongst reviewers, and qualitative analysis revealed no missing items. Twenty-five (59%) of our 42 PATCH tool items were present in at least one of the reviewed guidelines, with age being present in all., Conclusion: We developed the PATCH tool as a guide for pediatric institutions regarding the care of adolescent and adult patients. The PATCH tool, embedded in multidisciplinary stakeholder discussion and patient- and system-specific knowledge, may help institutions incorporate HCT into processes for adolescent and adult patients with COCCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Pathologies of the shoulder, i.e. rotator cuff tears and labral injuries are very common. Most patients receive MRI examination prior to surgery. A correct assessment of pathologies is significant for a detailed patient education and planning of surgery., Materials and Methods: Sixty-nine patients were identified, who underwent both, a standardised shoulder MRI and following arthroscopic shoulder surgery in our hospital. For this retrospective comparative study, the MRIs were pseudonymised and evaluated separately by an orthopaedic surgeon and a radiologist. A third rater evaluated images and reports of shoulder surgery, which served as positive control. Results of all raters were then compared. The aim was an analysis of agreement rates of diagnostic accuracy of preoperative MRI by a radiologist and an orthopaedic surgeon., Results: The overall agreement with positive control of detecting transmural cuff tears was high (84% and 89%) and lower for partial tears (70-80%). Subscapularis tears were assessed with moderate rates of agreement (60 - 70%) compared to intra-operative findings. Labral pathologies were detected mostly correctly. SLAP lesions and pulley lesions of the LHB were identified with only moderate agreement (66.4% and 57.2%) and had a high inter-rater disagreement., Conclusion: This study demonstrated that tears of the rotator cuff (supraspinatus, infraspinatus) and labral pathologies can be assessed in non-contrast pre-operative shoulder MRI images with a high accuracy. This allows a detailed planning of surgery and aftercare. Pathologies of the subscapularis tendon, SLAP lesions and biceps instabilities are more challenging to detect correctly. There were only small differences between a radiologic and orthopaedic interpretation of the images., Competing Interests: All authors declare that there is no conflict of interest., (© 2024 Malaysian Orthopaedic Association (MOA). All Rights Reserved.)

Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1-60 and TRA-1-81, two 'stemness' cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1-60+/TRA-1-81+ cells are chemoresistant compared to TRA-1-60-/TRA-1-81- cells. Transcriptome profiling identified UGT1A10, shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10, eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway., (© The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Objectives: Pediatric Hospital Medicine fellowship programs need to abide by Accreditation Council for Graduate Medical Education requirements regarding communication and supervision. Effective communication is critical for safe patient care, yet no prior research has explored optimal communication practices between residents, fellows, and attending hospitalists. Our objective is to explore communication preferences among pediatric senior residents (SRs), Pediatric Hospital Medicine fellows, and hospitalists on an inpatient team during clinical decision-making., Methods: We conducted a cross-sectional survey study at 6 institutions nationwide. We developed 3 complementary surveys adapted from prior research, 1 for each population: 200 hospitalists, 20 fellows, and 380 SRs. The instruments included questions about communication preferences between the SR, fellow, and hospitalist during clinical scenarios. We calculated univariate descriptive statistics and examined paired differences in percent agreement using χ2 tests, accounting for clustering by institution., Results: Response rates were: 53% hospitalists; 100% fellows; 39% SRs. Communication preferences varied based on role, scenario, and time of day. For most situations, hospitalists preferred more communication with the fellow overnight and when a patient or family is upset than expressed by fellows (P < .01). Hospitalists also desired more communication between the SR and fellow for an upset patient or family than SRs (P < .01), but all respondents agreed the SR should call the fellow for adverse events. More fellows and hospitalists felt that the SR should contact the fellow before placing a consult compared with SRs (95%, 86% vs 64%)., Conclusions: Hospitalists, fellows, and SRs may have differing preferences regarding communication, impacting supervision, autonomy, and patient safety. Training programs should consider such perspectives when creating expectations and communication guidelines., (Copyright © 2023 by the American Academy of Pediatrics.)

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14 + and CD16 + myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16 + myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To describe supervision preferences among pediatric hospitalists, Pediatric Hospital Medicine (PHM) fellows, and senior residents (SRs), and to better define the ideal role of a PHM fellow., Methods: We conducted a cross-sectional survey study at 6 institutions nationwide. We developed 3 complementary surveys, one for each population (hospitalists, fellows, SRs). We calculated univariate descriptive and bivariate statistics for categorical variables using Chi-square tests with the Rao-Scott correction to account for clustering by institution., Results: Survey respondents included 106 of 200 hospitalists (53%), all 20 fellows (100%), and 149 of 380 SRs (39%). Most hospitalists and all fellows preferred the supervising hospitalist to have 3+ years of experience or be fellowship-trained. Nearly all fellows preferred the attending round in-person providing progressive independence; while hospitalists and SRs desired greater attending presence on rounds. Hospitalists and fellows wanted more frequent communication when the attending does not round with the team, and more hospitalists desired at least 2 points of contact regardless of attending presence on rounds. Fifty-five percent of SRs reported experiencing much less/less autonomy when on with a fellow than when supervised by a hospitalist only. Regarding the fellow's role, most participants agreed SRs should lead rounds and contact the fellow first with questions. The majority agreed teaching should be a shared responsibility but lacked consensus about how to provide feedback., Conclusions: Study results reveal preferences about supervising fellows in this new subspecialty. Hospitalists, fellows, and SRs may have differing opinions regarding workflow, communication, and teaching, impacting team leadership and autonomy., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2/5i), in combination with αPD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by αPD-1 and prolonged treatment with CCR2/5i conferred better antitumor efficacy than other combination treatments tested. The combination of RT + αPD-1 + CCR2/5i enhanced intratumoral effector and memory T cell infiltration but suppressed regulatory T cell, M2-like tumor-associated macrophage, and myeloid-derived suppressive cell infiltration. RNA sequencing showed that CCR2/5i partially inhibited RT-induced TLR2/4 and RAGE signaling, leading to decreased expression of immunosuppressive cytokines including CCL2/CCL5, but increased expression of effector T cell chemokines such as CCL17/CCL22. This study thus supports the clinical development of CCR2/5i in combination with RT and ICIs for PDAC treatment., (© 2022 Wang et al.)

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy, due in large part to its resistance to conventional therapies, including radiotherapy (RT). Despite RT exerting a modest antitumor response, it has also been shown to promote an immunosuppressive tumor microenvironment. Previous studies demonstrated that focal adhesion kinase inhibitors (FAKi) in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory (T regs) cells, and subsequently enhance effector T cell infiltration. FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies. Thus, we investigated the impact of FAK inhibition on RT, its potential as an RT sensitizer and immunomodulator in a murine model of PDAC., Methods: We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT., Results: In this study we showed that IN10018, a small molecular FAKi, enhanced antitumor response to RT. Antitumor activity of the combination of FAKi and RT is T cell dependent. FAKi in combination with RT enhanced CD8+ T cell infiltration significantly in comparison to the radiation or FAKi treatment alone ( P < 0.05). FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone ( P < 0.01)., Conclusions: These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy., Competing Interests: Conflict of interest statement Lei Zheng receives grant support from Bristol-Meyer Squibb, Merck, iTeos, Amgen, NovaRock, Inxmed, and Halozyme. Lei Zheng is a paid consultant/Advisory Board Member at Biosion, Alphamab, NovaRock, Akrevia, Datarevive, and Mingruzhiyao. Lei Zheng holds shares at Alphamab and Mingruzhiyao. Yanan Liu and Zaiqi Wang are employees of InxMed. Zaiqi Wang is a shareholder of InxMed. No potential conflicts of interest were disclosed by the other authors., (Copyright: © 2021, Cancer Biology & Medicine.)

Background: Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia of PDACs following neoadjuvant therapy including RT, suggesting RT may prime PDAC for PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i) treatments. In this study, we investigated the antitumor efficacy of the combination therapies with radiation and PD-1 blockade or IDO1 inhibition or both., Methods: We developed and used a mouse syngeneic orthotopic model of PDAC suitable for hypofractionated RT experiments., Results: The combination therapy of αPD-1 and RT improved survival. The dual combination of RT/IDO1i and triple combination of RT/αPD-1/IDO1i did not improve survival compared with RT/αPD-1, although all of these combinations offer similar local tumor control. RT/αPD-1 appeared to result in the best systemic interferon-γ response compared with other treatment groups and the highest local expression of immune-activation genes, including Cd28 and Icos ., Conclusion: Our RT model allows examining the immune-modulatory effects of RT alone and in combination with immune-checkpoint inhibitors in the pancreas/local microenvironment. This study highlights the importance of choosing the appropriate immune-modulatory agents to be combined with RT to tip the balance toward antitumor adaptive immune responses., Competing Interests: Competing interests: LZ receives grant support from Bristol-Meyer Squibb, Merck, iTeos, Amgen, NovaRock, Inxmed, and Halozyme, and received the royalty for licensing GVAX to Aduro Biotech. LZ is a paid consultant/Advisory Board Member at Biosion, Alphamab, NovaRock, Akrevia, Sound Biologics, FusunBiopharmaceutical, Foundation Medicine, Datarevive, and Mingruzhiyao. LZ holds shares at Alphamab and Mingruzhiyao., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with pancreatic cancer have not benefited from recent improvements in overall survival brought about by precision medicine in other malignancies. This failure is not due to a dearth of precision-medicine research in pancreatic ductal adenocarcinoma (PDAC), the main type of pancreatic cancer. In fact, the stalled progress in precision therapies for this type of cancer is due to the absence of agents that are able to target the common genetic alterations in PDAC. Several studies have attempted to phenotypically stratify PDAC at the transcriptional level. However, the value of such classifications will only be revealed through prospective studies and, crucially, only after development of new treatment options for this disease. Therefore, it is essential to learn from breakthrough discoveries in other cancer types that could benefit subpopulations of patients with PDAC and convert them from ordinary to exceptional responders. Identifying these exceptional patients will help to bring PDAC in line with other cancer types in terms of availability of precision therapies. Thus, the true challenge to precision medicine for PDAC might be the poor consensus on which genetic and phenotypic alterations across the spectrum of this disease are actionable; not the absence of actionable variables themselves. To reach consensus, knowledge and tools must be developed and disseminated for individuals who provide pancreatic cancer care, to enable the real-time identification of exceptional patients, more precise subgroup classifications, and effective disease management strategies; all informed by immediate feedback from clinical outcome data., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8 + T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

Purpose: Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy. Experimental Design: Archival or prospectively acquired FFPE samples and matched normal DNA from N = 336 patients with pancreatic cancer were analyzed using a hybridization capture-based, next-generation sequencing assay designed to perform targeted deep sequencing of all exons and selected introns of 410 key cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles. Results: The median time from protocol consent to reporting of the genomic results was 45 days with a median time from tissue delivery of 20 days. All genetic alterations identified were stratified based upon prior evidence that the mutation is a predictive biomarker of drug response using the MSKCC OncoKB classification. Three of 225 patients (1%) received a matched therapy based upon the sequencing results. Conclusions: The practical application of molecular results to guide individual patient treatment is currently limited in patients with pancreatic adenocarcinoma. Future prospective molecular profiling efforts should seek to incorporate routine germline genetic analysis and the identification of DNA profiles that predict for clinical benefit from agents that target DNA damage repair and or immunotherapy. Clin Cancer Res; 23(20); 6094-100. ©2017 AACR ., (©2017 American Association for Cancer Research.)

This study investigates multi-dimensional impacts of adopting new technology in agriculture at the farm/village and watershed scale in sub-Saharan Africa using the Integrated Decision Support System (IDSS). Application of IDSS as an integrated modeling tool helps solve complex issues in agricultural systems by simultaneously assessing production, environmental, economic, and nutritional consequences of adopting agricultural technologies for sustainable increases in food production and use of scarce natural resources. The IDSS approach was applied to the Amhara region of Ethiopia, where the scarcity of resources and agro-environmental consequences are critical to agricultural productivity of small farm, to analyze the impacts of alternative agricultural technology interventions. Results show significant improvements in family income and nutrition, achieved through the adoption of irrigation technologies, proper use of fertilizer, and improved seed varieties while preserving environmental indicators in terms of soil erosion and sediment loadings. These pilot studies demonstrate the usefulness of the IDSS approach as a tool that can be used to predict and evaluate the economic and environmental consequences of adopting new agricultural technologies that aim to improve the livelihoods of subsistence farmers.

Traumatic brain injuries (TBI) are common in sports accidents. Helmets are generally known to provide protection to the head. However, the effectiveness of helmets in mitigating a TBI may be compromised due to the impact location and impact speed. Although it is known that the helmet decreases the linear head accelerations and the resulting head injury potential, to the best of our knowledge, limited research effort has been devoted to the study of the biomechanics of TBI in side impact conditions. The present work is designed to delineate the biomechanics of TBI in a fall impacting the parietal/temporal regions. A standing Hybrid III male dummy with pedestrian pelvis was used. The dummy was placed on a swinging platform for the fall simulation. The drop was achieved by stopping the platform with a block. The platform was swung from a predetermined height and stopped to allow the free fall of the dummy. The test was conducted with and without a skate board helmet. The impact on the dummy’s head was in the parietal and temporal regions. The head impact speed with the floor was approximately 24 kph (6.7 m/sec) The dummy was instrumented with tri-axial linear and tri-axial angular head accelerometers to measure the biomechanical injury responses. Results from three tests were compared. The linear head CG acceleration, Head Injury Criteria (HIC) and angular head accelerations were compared. Results suggest that the helmet reduced the linear head acceleration, HIC and angular head acceleration compared to the impact without a helmet. Although the linear head accelerations and HIC were reduced, the angular head accelerations even with the helmet were above nearly all proposed rotational head injury threshold in the literature. The higher angular head accelerations indicate a higher probability of concussion, acute subdural hematoma and diffuse axonal injuries. The present study is an additional step to better understand the biomechanics of TBI and the role of protective headgear systems in sports and recreational accidents.

Airbag related injuries to infants in rear facing child seats are common in frontal crashes. Several vehicular modifications such as deactivated passenger airbags, manual cut-off switches, depowered airbags and smart airbags have been advanced to mitigate the effect of airbag deployment on child seats. However, there is limited research effort to address the biomechanics of airbag injuries due to modification in child restraint systems. The purpose of this research is to evaluate the biomechanical effects of a protective barrier between the rear facing child restraint and the frontal passenger airbag of the vehicle. An experimental study was conducted using an Anthropometric Test Dummy (ATD) in a vehicular partial structure (buck). The rear facing child seat was placed in the right front passenger seat of the vehicle. The child seat was restrained using the three-point restraint in the vehicle. The six-month-old instrumented ATD was restrained in the child seat. The ATD was instrumented with the head tri-axial and two uni-axial linear accelerometers. The uni-axial linear acceleration was used to calculate the angular acceleration. Two different rear facing child seats, the standard rear facing infant seat and the rear facing infant seat inside the protective barrier structure were tested. In each test, the Head Injury Criteria (HIC) and angular head acceleration were measured. Results show that the HIC was reduced by 95% and the angular head acceleration was reduced by 85% by the protective barrier. The head injury values were well below the tolerance limit for the child with the barrier. The protective barrier deflected the airbag away from the ATD’s head and also acted as a shield to minimize airbag force on the child seat. In the typical infant seat, the airbag contacted the ATD’s head and exerted significant force on the child seat which rotated the seat rearward. These kinematic responses may explain the clinical observation of severe head injuries by infants in rear facing seats due to forces transmitted through the child seat and downward force from the top of the head. The present study is a first step in better understanding the injury mitigating aspects of the safety protective structure in child restraints.

Objectives: To assess attitudes and perceptions towards oral hygiene tasks among geriatric nursing home staff, before and after a dental hygiene education., Methodology: A survey questionnaire was distributed to the nursing staff (n = 105), at a geriatric nursing home in Stockholm, Sweden., Results: The response rate to the questionnaire was 83%. A vast majority (87%) of the nursing staff considered oral hygiene tasks unpleasant. The main reason for considering oral care unpleasant was a perceived unwillingness from the residents. The perceived unwillingness from the residents among the nursing staff was reduced after the dental hygiene education (chi-square test, P = 0.02). A vast majority of the nursing staff experienced, always or sometimes, resistance from the residents towards oral care., Conclusions: Nursing home staff members consider oral care tasks unpleasant, and frequently experience resistance from the nursing home residents towards oral care. The perceived unwillingness from the residents is reduced after an advanced dental hygiene education. Further studies are needed to evaluate the effects of education on nursing staff's attitudes and perceptions towards oral care tasks, with the overall aim of improving the oral health among older people in hospitals and nursing homes., (© 2010 John Wiley & Sons A/S.)

The aim of this survey was to test the impact of an oral hygiene educational model on attitudes and perceptions toward oral hygiene among nursing home staff members. A pilot questionnaire was distributed to the nursing staff before and after a course on oral hygiene at a geriatric nursing home in Stockholm in 2008. The nursing staff was of the opinion that they had sufficient time to carry out oral hygiene tasks but considered such tasks unpleasant, mainly because of unwillingness and resistance from the residents. These attitudes and perceptions among the nursing staff did not change significantly after oral hygiene education. Future oral hygiene educational models need to be developed with an aim to alter the perceptions and behavior of the nursing home staff., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Aim: This paper is a report of a study evaluating the effect of a repeated education programme for nursing staff in a home for older people., Background: A strong relationship exists between oral infections and general health complications (especially aspiration pneumonia) among nursing home residents and hospitalized older people. Thus, nursing staff need to be educated in oral hygiene measures., Methods: Forty-three nursing home resident older people (12 men, 31 women, age range 69-99 years) were included in a dental hygiene and gingivitis evaluation using gingival bleeding scores and modified plaque scores. Evaluation was conducted before and 3 weeks after a repeated dental hygiene education for nursing staff at a nursing home in Sweden in 2008. Dental hygiene education had been given 1.5 years previously., Findings: Forty-one residents (12 men and 29 women) were available for evaluation after the repeated dental hygiene education (one died, one had had teeth extracted). There was a reduction in gingival bleeding scores (P < 0.001), and in plaque scores (P < 0.001)., Conclusion: Repeated dental hygiene education improves the dental hygiene among nursing home resident older people. In order to succeed it may be necessary to address attitudes and perceptions towards oral care in such a dental hygiene education programme for nursing staff. Improved oral hygiene contributes to reducing the incidence of healthcare-associated pneumonia among nursing home resident older people, and thus to reduced healthcare costs.

Aim: This paper is a report of a study evaluating the long-term effects on the oral hygiene status of older nursing home residents one and a half years after dental hygiene education was given to the staff., Background: A strong relationship exists between oral infections and general health complications (especially aspiration pneumonia) among nursing home residents and hospitalized older people. It is therefore important to educate nursing home staff in oral hygiene measures and to follow up the effects of the education over time., Methods: Dental plaque measurements were conducted at a Swedish nursing home in 2006-2008. Forty-one residents (12 men, 31 women, aged 69-99 years) fulfilled the inclusion criteria and participated in a dental hygiene evaluation 1.5 years after dental hygiene education was given to the staff at the nursing home. Plaque index scores (year 2008) were compared to those soon after the education (year 2006)., Findings: After the dental hygiene education in 2006, 60 nursing home residents (14 men, 46 women) were available for plaque index measurements, whereas 41 residents (12 men, 29 women) were available 1.5 years later. The median plaque index scores were 17.0 (n = 60) in 2006, and 18.0 (n = 41) in 2008 (Mann-Whitney U-test, P > 0.05)., Conclusion: Dental hygiene education for nursing home staff is important to maintain an adequate level of oral hygiene among older nursing home residents over time. Follow-up of dental hygiene education for nursing home staff is recommended to maintain a sufficient level of oral hygiene among the residents.

The aim of this study was to describe a new dental hygiene education program for nursing staff and to report experiences from the program at a nursing home in Stockholm, Sweden (2006). This strategy comprises 3 steps. The first is individual instruction for nursing staff about oral care for patients and hands-on training in toothbrushing technique using an electric toothbrush. The second step was small discussion groups of 4 to 8 nursing staff, led by a dental hygienist and a psychologist. The third step was a theoretical lecture focusing on the associations among dental hygiene, oral health, and general health among the elderly. During the dental hygiene education program, a negative attitude toward oral care was noted among members of the nursing staff, although they did consider oral care important for their patients. Increased self-confidence of staff in providing oral care was noted after completing the dental hygiene education program. Nursing staff members stated that they had received more detailed knowledge about oral care during the program. This dental hygiene education program appears to result in increased knowledge and interest in oral hygiene tasks among the nursing staff and may lead to improved dental hygiene among nursing home residents.

This study investigates the influence of pelvic tilt on conventional alignment of acetabular cups. Cementless cups were aligned into a synthetic replica of the pelvis 300 times at different pelvic tilts. At +10 degrees pelvic tilt, average cup inclination was 46.2 degrees (32 degrees to 65 degrees ; +/-7.0 degrees ), and average cup anteversion was 19.8 degrees (4 degrees to 37 degrees ; +/-9.1 degrees ). At neutral pelvic tilt, inclination was 44.5 degrees (28 degrees to 59 degrees ; +/-7.2 degrees ), and anteversion was 15.6 degrees (-5 degrees to 33 degrees ; +/-8.1 degrees ). At -10 degrees pelvic tilt, inclination was 42.6 degrees (25 degrees to 61 degrees ; +/-7.2 degrees ), and anteversion was 10.5 degrees (-10 degrees to 37 degrees ; +/-12.2 degrees ). Overall, 50% of the cups were positioned outside the safe zone: 46% in pelvic inclination, 42% in neutral position, and 63% in pelvic reclination (P = .007). This study shows the considerable inaccuracies of conventional cup implantation by experienced and trainee surgeons and shows the influence of pelvic tilt on acetabular cup alignment.

Aim: Ultrasound may be a cheap alternative to scintigraphic determination of splenic function. We directly compared nanocolloid scintigraphy (NS), scintigraphy with heat-altered erythrocytes (ES), and colour-coded Doppler sonography (DS) in patients with chronic inflammatory bowel disease (CIBD)., Patients, Methods: 35 patients were included into the study. Clearance rates were determined in ES, spleen/liver ratios (SLR) were measured scintigraphically in ES/NS. In DS, spleen size, echogenicity, and vascular resistance indices (RI) were determined. The results were compared to each other, to the clinical activity scores for CIBD, and to the course of the disease., Results: Based on the blood erythrocyte clearance serving as standard, patients had a good (19 patients), impaired (5), or missing splenic function (11). There was a good correlation of the clearance to SLR in ES (0.63, p < 0.01). The 10 min / 45 min ES clearance showed a high correlation (Spearman-Rho 0.87, p < 0.01). The SLR in ES at 2, 5, 10 and 45 min also correlated well with each other (Spearman-Rho > 0.9, p < 0.01; SLR > 3.45 normal splenic function, SLR < 1.22 indicated hyposplenia). There were no correlations between the results of NS, DS, Howell-Jolly-bodies, or clinical parameters. Only ES and the erythrocyte clearance correlated well. Howell-Jolly-Bodies detected 1 of 11 patients with hyposplenia while false-positive in 4., Conclusion: Ultrasound and colloid scintigraphy show a low correlation with clearance of heat-altered erythrocytes. Only ES shows a good correlation in patients with CIBD. The clearance at 10 min already reliably determines splenic function. SLR may be determined after 10 minutes and is predictive of normal function if above 3.45 while SLR < 1.2 indicated hyposplenia.

The National Highway Traffic Safety Administration (NHTSA) has concluded that there is a relationship between roof intrusion and the risk of injury to belted occupants in rollovers events [1]. Previous testing on many different production vehicle types indicates that damage consistent with field rollover accidents can be achieved through inverted drop testing from small drop heights. It has been shown in previous drop test pairs with Hybrid III dummies, that the amount of roof intrusion is related to occupant neck injury [2,3]. In 1990, a study was reported by General Motors which involved 8 dolly rollover tests and 5 inverted drop tests performed on both production and rollcaged vehicles with Hybrid III dummies [4]. These studies were conducted to investigate the relationship between roof strength and occupant injury potential. In this paper, the authors further analyze the relationship between roof intrusion and occupant neck injury potential through inverted drop testing performed on Ford Econoline E-350 15-Passenger production and reinforced vans. Each of these van tests used Hybrid III test dummies in order to evaluate the resulting occupant injury potential in relation to the roof intrusion. The resulting roof intrusion and occupant neck loading experienced during the reinforced van drop test were significantly less than that of the production van test. As previously observed, the results of these tests indicate that the reduction of roof crush resulted in a direct reduction in neck loading and therefore an increase in occupant protection. Additionally, the inverse relationship between restraint loading and neck loading of the dummies was confirmed.

Under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) clinical practice guidelines were systematically developed by 88 experts from 20 different countries between spring 2004 and winter 2005 in a predefined evidence and consensus based process. Evidence was gathered by a structured literature search, and the quality and strength of the evidence was graded according to published standards. On this basis recommendations were formulated which were then finalised in a consensus conference. The recommendations and their grades were summarized in table form. The German translation of these tables is now published for the following chapters: Intensive care, surgery including organ transplantation, non-surgical oncology, gastroenterology, pancreas, liver disease, adult renal failure, cardiology and pulmonology, wasting in HIV and chronic infectious diseases, geriatrics. The full text and the comments are available in ,,Clinical Nutrition" as well as on the internet under www.espen.org and www.dgem.de. The ESPEN guidelines enteral nutrition reflect the current medical knowledge in the field of enteral nutrition therapy and may help to decide when enteral nutrition is indicated and which therapeutic goals can be reached.

Nutritional intake is often compromised in elderly, multimorbid patients. Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in geriatric patients. It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for geriatric patients at nutritional risk, in case of multimorbidity and frailty, and following orthopaedic-surgical procedures. In elderly people at risk of undernutrition ONS improve nutritional status and reduce mortality. After orthopaedic-surgery ONS reduce unfavourable outcome. TF is clearly indicated in patients with neurologic dysphagia. In contrast, TF is not indicated in final disease states, including final dementia, and in order to facilitate patient care. Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

Under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) clinical practice guidelines on enteral nutrition were systematically developed between spring 2004 and winter 2005 in a both evidence and consensus based process. A steering committee implemented 13 disease-specific working groups with a total of 88 experts in clinical nutrition from 20 countries. Evidence was gathered by conducting a structured literature search applying a defined search strategy, inclusion criteria and specified keywords. The quality and strength of the supporting evidence was then graded according to published standards. On this basis recommendations were spelled out which were not only based on the evidence levels of the studies but also on the judgement of the working groups concerning the consistency, clinical relevance and validity of the evidence. Preparation of the drafts was accomplished in interactive small group work processes. The voting of statements took place in a consensus conference and final refinements and voting were done using the Delphi technique. The ESPEN guidelines enteral nutrition reflect the current medical knowledge in the field of enteral nutrition therapy and summarize the evidence when enteral nutrition is indicated and which goals can be reached in regard to nutritional state, quality of life and outcome.

The National Highway Traffic Safety Administration has concluded that there is a relationship between roof intrusion and the risk of injury to belted occupants in rollovers events. Previous testing on many different production vehicle types indicates that damage consistent with field rollover accidents can be achieved through inverted drop testing from small drop heights. It has been shown in previous drop test pairs with Hybrid III dummies, that the amount of roof intrusion is related to occupant neck injury. This paper analyzes inverted drop testing performed on Ford F250 Crew Cab production and reinforced pickups. Each of these pickup tests used Hybrid III test dummies in order to evaluate the occupant injury potential in relation to roof intrusion. The reinforced truck's residual crush was an order of magnitude less than the production truck crush. These tests indicated that the reduction of roof crush resulted in a direct reduction in neck loading and therefore an increase in occupant protection. In addition, it was found that the restraint loading was inversely related to the neck loading of the dummies.

Static signatures originate as handwritten images on documents and by definition do not contain any dynamic information. This lack of information makes static signature verification systems significantly less reliable than their dynamic counterparts. This study involves extracting dynamic information from static images, specifically the pen trajectory while the signature was created. We assume that a dynamic version of the static image is available (typically obtained during an earlier registration process). We then derive a hidden Markov model from the static image and match it to the dynamic version of the image. This match results in the estimated pen trajectory of the static image.

A better understanding of occupant kinematics in rollover accidents helps to advance biomechanical knowledge and to enhance the safety features of motor vehicles. While many rollover accident simulation studies have adopted the static approach to delineate the occupant kinematics in rollover accidents, very few studies have attempted the dynamic approach. The present work was designed to study the biomechanics of restrained occupants during rollover accidents using the steady-state dynamic spit test and to address the importance of keeping the lap belt fastened. Experimental tests were conducted using an anthropometric 50% Hybrid III dummy in a vehicle. The vehicle was rotated at 180 degrees/second and the dummy was restrained using a standard three-point restraint system. The lap belt of the dummy was fastened either by using the cinching latch plate or by locking the retractor. Three configurations of shoulder belt harness were simulated: shoulder belt loose on chest with cinch plate, shoulder belt under the left arm and shoulder belt behind the chest. In all tests, the dummy stayed within the confinement of the vehicle indicating that the securely fastened lap belt holds the dummy with dynamic movement of 3 1/2" to 4". The results show that occupant movement in rollover accidents is least affected by various shoulder harness positions with a securely fastened lap belt. The present study forms a first step in delineating the biomechanics of occupants in rollover accidents.

Roof crush occurs and potentially contributes to serious or fatal occupant injury in 26% of rollovers. It is likely that glazing retention is related to the degree of roof crush experienced in rollover accidents. Occupant ejection (including partial ejection) is the leading cause of death and injury in rollover accidents. In fatal passenger car accidents involving ejection, 34% were ejected through the side windows. Side window glass retention during a rollover is likely to significantly reduce occupant ejections. The inverted drop test methodology is a test procedure to evaluate the structural integrity of roofs under loadings similar to those seen in real world rollovers. Recent testing on many different vehicle types indicates that damage consistent with field rollover accidents can be achieved through inverted drop testing at very small drop heights. Drop test comparisons were performed on 16 pairs of vehicles representing a large spectrum of vehicle types. Each vehicle pair includes a production vehicle and a vehicle with a reinforced roof structure dropped under the same test conditions. This paper offers several examples of post-production reinforcements to roof structures that significantly increase the crush resistance of the roof as measured by inverted drop tests. These modifications were implemented with minimal impact on vehicle styling, interior space and visual clearances. The results of these modifications indicate that roof crush can be mitigated by nearly an order of magnitude, as roof crush was reduced by 44-91% with only a 1-2.3% increase in vehicle weight. Additionally, this paper analyzes the glazing breakage patterns in the moveable tempered side windows on the side adjacent to the vehicle impact point in the inverted drop tests. A comparison is made between the production vehicles and the reinforced vehicles in order to determine if the amount roof crush is related to glazing integrity in the side windows. Lastly, two drop test pairs, performed with Hybrid III test dummies, indicates that the reduction of roof crush resulted in a direct reduction in neck loading and therefore an increase in occupant protection.

Seat belt system restrains and protects occupants in motor vehicle crashes and any slack in seat belt system induces additional loading on occupant. Signs of belt loading are more obvious in high-speed frontal collisions with heavy occupants. However subtle changes may occur at low speeds or with low forces from occupants during rollovers. In certain cases, the seat belt webbing is twisted and loaded by the occupant. The loading of webbing induces an observable fold/crimp on the seat belt. The purpose of the study is to biomechanically evaluate the force required to produce such marks using an anthropometric physical test dummy. Two tests were conducted to determine the amount of force required to put an observable fold/crimp in a shoulder belt. A head form designed by Voight Hodgson was used to represent the neck which interacted with the belt. The force was applied with a pneumatic pull ram (central hydraulic 89182 N) and the force was measured with a 44,000 N transducer load cell (DSM-10K). Results indicate that the force of over 1,000 N produced a fold or crimp in the belt.

Recent statistics highlight the significant risk of serious and fatal injuries to occupants involved in rollover collisions due to excessive roof crush. The government has reported that in 2002. Sports Utility Vehicle rollover related fatalities increased by 14% to more than 2400 annually. 61% of all SUV fatalities included rollovers [1]. Rollover crashes rely primarily upon the roof structures to maintain occupant survival space. Frequently these crashes occur off the travel lanes of the roadway and, therefore, can include impacts with various types of narrow objects such as light poles, utility poles and/or trees. A test device and methodology is presented which facilitates dynamic, repeatable rollover impact evaluation of complete vehicle roof structures with such narrow objects. These tests allow for the incorporation of Anthropomorphic Test Dummies (ATDs) which can be instrumented to measure accelerations, forces and moments to evaluate injury potential. High-speed video permits for detailed analysis of occupant kinematics and evaluation of injury causation. Criteria such as restraint performance, injury potential, survival space and the effect of roof crush associated with various types of design alternatives, countermeasures and impact circumstances can also be evaluated. In addition to presentation of the methodology, two representative vehicle crash tests are also reported. Results indicated that the reinforced roof structure significantly reduced the roof deformation compared to the production roof structure.

Various studies have reported that inertially sensitive buckles are susceptible to impact unlatching. The present work synthesizes the results from various experimental studies conducted over the years to study the mechanical behavior of buckles and subsequent injuries to occupants. First, the side press button seat buckle due to impact a lateral impact from an adjacent child restraint seat component indicated that the side button RCF-67 buckle released at a speed of 2.2 m/sec with a force range of 264 to 440 N and acceleration range of 100 to 175 G. In contrast, the top button Autoliv Lockarm buckles did not release up to 1300 vertical G's. Second, side release RCF-67 buckles when loaded with the webbing required approximately three times more force to open than top press buckles. Inverted occupants in a three-point belt could not release the RCF-67 buckle. Third, a side sled impact on the drivers side of a production vehicle buck with a three-point belt and a RCF-67 buckle was done at 7 m/s to 8 m/s. A convertible child seat with a dummy in the passenger seat moved inboard toward the buckle and unlatched it. Fourth, an intact vehicle drop study at 0.3 m showed that the accelerations on a JDC buckle on a metal stalk are large compared to acceleration of the floor pan. The present study provides comprehensive data to evaluate the mechanical behavior of seat buckles under various motor vehicle crash conditions.

The multi-planar and multiple impact long duration accident sequence of a real world rollover results in multidirectional vehicle acceleration pulses and multiplanar occupant motions not typically seen in a planar crash sequence. Various researchers have documented that, while contemporary production emergency locking seatbelt retractors (ELRs) have been found to be extremely effective in the planar crashes in which they are extensively evaluated, when subjected to multi-planar acceleration environments their response may be different than expected. Specifically, accelerations in the vertical plane have been shown to substantially affect the timeliness of the retractors inertial sensor moving out of its neutral position and locking the seat belt. An analysis of the vehicle occupant motions relative to the acceleration pulses sensed at the retractor location indicates a time phase shift that, under certain circumstances, can result in unexpected seat belt spool out and occupant excursions in these multi-planar, multiple impact crash sequences. This paper will review the various previous studies focusing on the retractors response to these multidirectional, including vertical, acceleration environments and review statistical studies based upon U.S. government collected data indicating a significant difference in belt usage rates in rollover accidents as compared to all other planar accident modes. A significant number of real world accident case studies will be reviewed wherein the performance of ELR equipped seatbelt systems spooled out. Finally, the typical occupant injury and the associated mechanism due to belt spool out in real world accidents will be delineated.

Inverted drop testing of vehicles is a methodology that has long been used by the automotive industry and researchers to test roof integrity and is currently being considered by the National Highway Traffic Safety Administration as a roof strength test. In 1990 a study was reported which involved 8 dolly rollover tests and 5 inverted drop tests. These studies were conducted with restrained Hybrid III instrumented Anthropometric Test Devices (ATD) in production and rollcaged vehicles to investigate the relationship between roof strength and occupant injury potential. The 5 inverted drop tests included in the study provided a methodology producing "repeatable roof impacts" exposing the ATDs to the similar impact environment as those seen in the dolly rollover tests. Authors have conducted two inverted drop test sets as part of an investigation of two real world rollover accidents. Hybrid-III ATD's were used in each test with instrumented head and necks. Both test sets confirm that reduction of roof intrusion and increased headroom can significantly enhance occupant protection. In both test pairs, the neck force of the dummy in the vehicle with less crush and more survival space was significantly lower. Reduced roof crush and dynamic preservation of the occupant survival space resulted in only minor occupant contact and minimal occupant loading, establishing a clear causal relationship between roof crush and neck injuries.

Occupant kinematics and the potential for injury in vehicular rollover crashes are dramatically affected by various restraint system characteristics. This study reviews previous research that utilized various methodologies and test fixtures to evaluate restrained occupant motions, primarily in the vertical direction, during both inverted and quasi-static simulated rollover environments. Additional laboratory tests were conducted in order to understand the static and dynamic excursion of restrained humans and surrogates in typical production motor vehicles under inverted circumstances. These tests indicated that volunteer occupants restrained within a complete vehicle by typical production 3 point seat belts will move vertically towards the vehicle roof structure by approximately 50-150 mm in production vehicles, depending on occupant size and belt configuration, when inverted and subjected to a static 1 g acceleration. Dynamic inverted vehicle drop testing in 3-point belt production vehicles, resulting in 4 to 11 g impacts, resulted in surrogates moving only about an additional 23 to 55 mm beyond the static inverted 1 g excursions.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can be used for vaccination purposes, to induce a specific T-cell response in vivo against melanoma-associated antigens. We have shown that the sequential use of early-acting hematopoietic growth factors, stem cell factor, IL-3 and IL-6, followed by differentiation with IL-4 and granulocyte-macrophage colony-stimulating factor allows the in vitro generation of large numbers of immature DCs from CD34(+) peripheral blood progenitor cells. Maturation to interdigitating DCs could specifically be induced within 24 hr by addition of TNF-alpha. Here, we report on a phase I clinical vaccination trial in melanoma patients using peptide-pulsed DCs. Fourteen HLA-A1(+) or HLA-A2(+) patients received at least 4 i.v. infusions of 5 x 10(6) to 5 x 10(7) DCs pulsed with a pool of peptides including either MAGE-1, MAGE-3 (HLA-A1) or Melan-A, gp100, tyrosinase (HLA-A2), depending on the HLA haplotype. A total of 83 vaccinations were performed. Clinical side effects were mild and consisted of low-grade fever (WHO grade I-II). Clinical and immunological responses consisted of anti-tumor responses in 2 patients, increased melanoma peptide-specific delayed-type hypersensitivity reactions in 4 patients, significant expansion of Melan-A- and gp100-specific cytotoxic T lymphocytes in the peripheral blood lymphocytes of 1 patient after vaccination and development of vitiligo in another HLA-A2(+) patient. Our data indicate that the vaccination of peptide-pulsed DCs is capable of inducing clinical and systemic tumor-specific immune responses without provoking major side effects., (Copyright 2000 Wiley-Liss, Inc.)

The Federal Motor Vehicle Safety Standard 571.201 discusses occupant protection with interior impacts of vehicles. Rule making by the National Highway Traffic Safety Administration (NHTSA) has identified padding for potential injury reduction in vehicles. In these studies, head injury mitigation with padding on vehicular roll bars and brush bars was evaluated. Studies were conducted with free falling Hybrid 50% male head form drops on the forehead and side of the head and a 5% female head. Marked reductions in angular acceleration, as well as Head Injury Criterions (HIC), were observed when compared to unpadded roll bars and brush bars.

The article describes the application of lime as a method for treatment and hygienisation of sewage sludges with lime products such as quicklime, slake lime and dolomitic lime. As a result of the increase in temperature and pH-value during sludge and lime mixing most pathogenic vectors of disease (i.e. bacteria, worms, viruses and parasites) are reduced in concentration and viability to manufacture a safe product for further application on agricultural land.

The expression of MHC class I and class II molecules in the cerebral cortex of rats was investigated at daily intervals from day 3 to day 6 after fully allogeneic (DA-->LEW) and isogeneic (LEW-->LEW) kidney transplantation. MHC class II molecules were temporarily induced on the previously negative microglial cells and on the endothelia of arterioles and venules during acute rejection. On the endothelia of all brain vessels MHC class I expression was enhanced. MHC class I+ cells with microglial cell morphology were discernible within the diffusely MHC class I+ brain parenchyma. In contrast, the brain parenchyma of isograft recipients and untreated control animals did not express detectable levels of MHC molecules. In conclusion, we demonstrate that a strong immune reaction in the periphery is able to activate microglial cells in the central nervous system.

Epithelia-associated dendritic cells (DC) including Langerhans cells in the skin (LC) are precursors of lymph node located interdigitating DC (iDC). CD1a+ LC are known to be derived from CD34+ haemopoietic progenitor cells (HPC); however, cells of an intermediate differentiation state that are CD34- and CD1a- have not been identified. Monitoring the differentiation pathway of HPC in the presence of GM-CSF+IL-4, we observed the emergence of a distinct LC precursor population that was CD33+ CD13+ CD4+ CD38+ CD44+ CD34- CD14- CD1a-. The cells could be separated by FACS due to a unique CD44/CD38 expression pattern or by CD44 expression in conjunction with the SSC profile. It was found that they were similarly generated in the presence of GM-CSF alone and were detectable in culture for at least a week. Irrespective of being generated in the presence of GM-CSF+IL-4 or GM-CSF alone, CD44/SSC-sorted precursor cells matured to MHC class II compartments (MIIC) and Birbeck granules (BG) expressing LC, when subsequently cultured in the presence of GM-CSF+IL-4. When IL-4 was omitted, however, the same cells matured to phagocytically active adherent macrophages (Mphi). These culture conditions were associated with a > 4-fold increase in the concentration of IL-6 when compared to those used for LC differentiation. The identification of a distinct oligopotent precursor cell population that can deliberately be induced to give rise to BG+ MIIC+ CD1a+ CD14- LC or to adherent CD14+ Mk further substantiates the close relationship of monocytes and DC and may help to identify its in vivo equivalent.

We examined the infiltration of acutely rejecting renal allografts (DA-->LEW) by ED1+ and ED2+ macrophages and T lymphocytes at intervals of 24 h after transplantation. Donor and recipient macrophages were differentiated by MHC class II antigen expression in double-staining experiments with ED1. Proliferation was assayed after pulse-labelling with BrdU. We subdivided allograft infiltration into three consecutive phases: 1) During phase I on days 1 to 2 after allogeneic kidney transplantation, perivascular infiltrates developed that contained numerous donor and recipient macrophages. Allograft rejection could already be diagnosed 24 h after transplantation by perivascular infiltration of T lymphocytes, whereas T cells were rarely found in isografts. 2) Phase II of allograft rejection from day 3 to 4 was characterized by massive propagation of the infiltrate. About equal numbers of interstitial donor and recipient macrophages were counted. Both macrophages and T lymphocytes proliferated in situ and macrophages outnumbered T cells until complete rejection. 3) During phase III the allograft was destroyed. Large intravascular monocytes surprisingly expressed the ED2 antigen. In the interstitium of viable graft regions, the population of recipient macrophages grew, whereas the population of donor macrophages and of T lymphocytes decreased.

The Gastro-Entero-Pancreatic System (GEP) defined a group of highly differentiated neuroendocrine tumors (Insulinomas, Gastrinomas, PP-omas, Somatostatinomas, Carcinoids). In this kind of tumors the multistage carcinogenesis is really unknown. Activated ras oncogenes could play an important role in initiation or process of carcinogenesis in different human cancers. The purpose of our study was to determe if H-ras or K-ras play a role in the carcinogenesis of GEP tumors. 20 paraffin embedded tumor tissues (1 Vipom, 1 Somatostatinom, 10 Carcinoids, 1 Gastrinoma, 4 livermetastasis of a Carcinoid, 3 Insulinomas) were analysed immunohistologic of H-ras and K-ras oncogene protein expression. Immunohistologic investigations showed a H-ras expression in 65% (13/20). K-ras protein could detected in 10% (2/20). On the basis of these data H-ras oncogene expression could play a role in the multistage carcinogenesis of GEP tumors.

Dendritic cells (DC) have been generated in vitro from either CD34+ haemopoietic progenitor cells (HPC) or peripheral blood monocytes (Mo) in the presence of specific cytokine combinations, including granulocyte-macrophage colony-stimulating factor (GM-CSF). Since differences between DC from either source may be important for the clinical use of these antigen-presenting cells (APC), a comparative analysis was performed. HPC were expanded in the presence of interleukin (IL)-3, IL-6 and stem cell factor (SCF) (days 1-7) and subsequently induced by IL-4+ GM-CSF (days 8-26) to differentiate to Langerhans-type cells (pLC). The latter cytokines were similarly used to generate Mo-derived LC (mLC). Maturation of both cell types, pLC and mLC, to interdigitating DC-type cells (iDC) was induced by tumour necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS). Analysis of mLC/pLC and miDC/piDC with respect to morphology, phenotype, antigen uptake and presentation revealed a high similarity of DC from either source. The majority of mLC, however, exhibited a more mature differentiation stage, compared to pLC, evidenced from lower numbers of multilaminar MHC class II compartments and less efficient APC function for extracellular protein antigens. Although macropinocytosis was performed by LC, neither LC nor iDC from either source were able to take up > or = 0.5 microm latex beads. However, phagocytosis of 0.5 microm and 1 microm beads was performed by Mo that could subsequently be induced to become iDC, thus providing the unique opportunity to present phagocytosed material in DC-type fashion. Mo may be the preferential source for clinical use of iDC-type cells since preparation and culture are easier to perform and are less costly while APC function is similar to HPC-derived iDC.

The microanatomical structure of human and rat splenic white pulp is compared, with special emphasis on the localization of the marginal zone occupied by immunoglobulin M (IgM)+ IgD-/dull B lymphocytes and its specialized macrophages. Our study reveals that in contrast to rats, the marginal zone of humans primarily exists in the vicinity of primary and secondary splenic follicles and that it is almost absent around the periarteriolar T-cell zones. We demonstrate that in humans there is an additional compartment, the perifollicular zone, located between the marginal zone and the red pulp. The perifollicular zone is a dynamic region of variable cellular and phenotypic composition, which can be regarded either as a part of the red pulp or of the follicles. In most cases the perifollicular zone appears as a compartment of the red pulp containing erythrocyte-filled spaces which differ from the typical red pulp sinusoids. Similar to the splenic cords, the perifollicular zone mostly harbours scattered B and T lymphocytes. However, sometimes B lymphocytes clearly predominate in the perifollicular area. In addition, strongly sialoadhesin-positive macrophages form sheaths around capillaries in the perifollicular zone. Such capillary sheaths are not observed in rats. In humans weakly sialoadhesin-positive macrophages are also present in the perifollicular zone and in the red pulp. In some specimens sialoadhesin is, however, strongly expressed by a large number of dispersed perifollicular macrophages. Interestingly, in striking contrast to rats, the human marginal zone does not contain sialoadhesin-positive macrophages and marginal metallophilic macrophages are also absent in humans. Thus, sialoadhesin-positive macrophages and IgM+ IgD- memory B lymphocytes both share the marginal zone as a common compartment in rats, while they occupy different compartments in humans. We show that the human splenic marginal zone does not contain a marginal sinus and assume that in humans the perifollicular region is the compartment where antigen and recirculating lymphocytes enter the organ.