Minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): study protocol for a multicentre, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Cervical spondylotic myelopathy: Changes of fractional anisotropy in the spinal cord and magnetic resonance spectroscopy of the primary motor cortex in relation to clinical symptoms and their duration.

OBJECTIVE: To determine the changes in fractional anisotropy (FA) at the proximal spinal cord and in magnetic resonance spectroscopy (MRS) of the precentral gyrus in patients with cervical spondylotic myelopathy (CSM) with respect to clinical symptoms and their duration. MATERIAL AND METHODS: 20 patients with CSM (7 female; mean age 64.6 ± 10.5 years) and 18 age/sex matched healthy controls (9 female; mean age 63.5 ± 6.6 years) were prospectively included. Clinical data (modified Japanese Orthopaedic Association Score (mJOA) and Neck Disability Index (NDI)) and 3T MR measurements including DTI at the spinal cord (level C2/3) with FA and MRS of the left and right precentral gyrus were taken. Clinical correlations and regression analyses were performed. RESULTS: Mean clinical scores of patients were significantly different to controls (mJOA; CSM: 10.2 ± 2.9; controls: 18.0 ± 0.0, p < 0.001; NDI; CSM: 41.4±23.5; controls: 4.4±6.6, p<0.001); FA was significantly lower in patients (CSM: 0.645 ± 0.067; controls: 0.699 ± 0.037, p = 0.005). MRS showed significantly lower metabolite concentrations between both groups: creatine (Cr) (CSM: 46.46±7.64; controls: 51.36±5.76, p = 0.03) and N-acetylaspartate (NAA) (CSM: 93.94±19.22; controls: 107.24±20.20, p = 0.05). Duration of symptoms ≤6 months was associated with increased myo-inositol (Ins) (61.58±17.76; 44.44±10.79; p = 0.02) and Ins/Cr ratio (1.36±0.47; 0.96±0.18; p = 0.014) compared to symptoms >6 months. CONCLUSION: Metabolic profiles of the precentral gyrus and FA in the uppermost spinal cord differ significantly between patients and healthy controls. Ins, thought to be a marker of endogenous neuroinflammatory response, is high in the early course of CSM and normalizes over time.

Predictors of Outcomes of Living Kidney Donation: Impact of Sex, Age and Preexistent Hypertension.

CONTEXT: Living kidney donation is considered a safe procedure with excellent outcomes. The great demand for organs has changed the suitability criteria for donation and older or hypertensive donors are increasingly accepted. METHODS: We reviewed the charts of 200 adults who donated a kidney at the University Hospital Hannover. Data regarding diastolic, systolic, mean blood pressure, renal function, and proteinuria at baseline and post-donation follow-up visits were recorded. A Mann-Whitney U test was performed to compare the post-nephrectomy development of blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria between men and women, hypertensives and normotensives, and older (≥65 years) and younger (<65 years) donors. Multivariable time-dependent Cox regression models were used to evaluate eGFR decline post-donation, after adjustment for covariates. RESULTS: The majority of donors were female (64.5%), and 29.0% had pre-existing hypertension. The mean age at donation was 49 years, and 9.5% were older than 65 years. During a median follow-up of 3 years, no significant differences in proteinuria and change in renal function were observed between both sexes or hypertensive and normotensive donors. In contrast, older donors exhibited a faster decline in renal function. Mean eGFR (chronic kidney disease epidemiology collaboration equation) pre-donation was 99.6 ± 21.9 mL/min in younger donors and 77.6 ± 17.7 mL/min in older donors (P < .001). The respective mean values at the last follow-up visit were 81.3 ± 24.0 and 46.8 ± 17.9 mL/min (P < .001). After adjustment for sex and preexisting hypertension, compared to younger donors, older donors had a 2.39 hazard ratio for eGFR decline. CONCLUSION: Older adults display a faster decline in renal function after donation and thus should be carefully evaluated for suitability before donation.

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

BACKGROUND: Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). METHODS: Going beyond earlier studies, a systems-level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale - Revised (CRS-R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients' behavioural repertoire (CRS-R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax ), i.e. when cognitive performance is expected to peak. RESULTS: The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS-R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre-specified time of occurrence of BTmax . CONCLUSIONS: In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain-injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre-assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.

Allergenic proteases cleave the chemokine CX3CL1 directly from the surface of airway epithelium and augment the effect of rhinovirus.

CX3CL1 has been implicated in allergen-induced airway CD4+ T-lymphocyte recruitment in asthma. As epidemiological evidence supports a viral infection-allergen synergy in asthma exacerbations, we postulated that rhinovirus (RV) infection in the presence of allergen augments epithelial CX3CL1 release. Fully differentiated primary bronchial epithelial cultures were pretreated apically with house dust mite (HDM) extract and infected with rhinovirus-16 (RV16). CX3CL1 was measured by enzyme-linked immunosorbent assay and western blotting, and shedding mechanisms assessed using inhibitors, protease-activated receptor-2 (PAR-2) agonist, and recombinant CX3CL1-expressing HEK293T cells. Basolateral CX3CL1 release was unaffected by HDM but stimulated by RV16; inhibition by fluticasone or GM6001 implicated nuclear factor-κB and ADAM (A Disintegrin and Metalloproteinase) sheddases. Conversely, apical CX3CL1 shedding was stimulated by HDM and augmented by RV16. Although fluticasone or GM6001 reduced RV16+HDM-induced apical CX3CL1 release, heat inactivation or cysteine protease inhibition completely blocked CX3CL1 shedding. The HDM effect was via enzymatic cleavage of CX3CL1, not PAR-2 activation, yielding a product mitogenic for smooth muscle cells. Extracts of Alternaria fungus caused similar CX3CL1 shedding. We have identified a novel mechanism whereby allergenic proteases cleave CX3CL1 from the apical epithelial surface to yield a biologically active product. RV16 infection augmented HDM-induced CX3CL1 shedding-this may contribute to synergy between allergen exposure and RV infection in triggering asthma exacerbations and airway remodeling.

Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review.

Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.

Differences in clinical presentation, intraoperative findings and outcome between petroclival and lateral posterior pyramid meningioma.

OBJECTIVE: The goal of this study was to determine the impact of the location of the most frequent skull base meningioma of the posterior fossa, i.e. petroclival (PCM) and lateral posterior pyramid meningioma (LPPM) on clinical presentation, surgical treatment and treatment results. PATIENTS AND METHODS: We retrospectively reviewed a consecutive series of patients operated on for PCM (n=46) and LPPM (n=32). Uni- and multivariate analyses were performed to identify differences in clinical presentation, surgical treatment and pre-, intra- and postoperative factors of influence upon the outcome parameters: Complications rate, mortality, tumour recurrence/progress, hospital stay, Karnofsky Performance Score (KPS). RESULTS: At Presentation, the rate of dizziness was higher in LPPM (56% vs. 7%, p<0,001) and trigeminal nerve impairment was more frequent in PCM (50% vs. 3%, p<0,001). Complete tumour resections were more often achieved (91% vs. 39%, p<0,001), and surgery lasted shorter (median: 247 min vs. 500 min, p<0,001) with less blood loss (median: 525 ml vs. 1000 ml, p<0,001) in LPPM compared to PCM. The overall complication rates (73% vs. 31%, p<0,001) as well the rate of irreversible complications (57% vs. 9%, p<0,004) were higher in PCM than in LPPM. The most frequent complications of PCM surgery were eye movement (46% vs. 6%, p<0,001), facial nerve (28% vs. 3%, p<0.02) and swallowing impairments (21% vs. 3%, p<0.02). The perioperative mortality was 11% in PCM and 0% in LPPM patients. In the multivariate analyses, KPS at discharge correlate positively with age (p=0.034) and preoperative KPS (p=0.0048) in LPPM and positively with staged resection (p=0.056) and negatively with the occurrence of surgical complications (p=0,0427) in PCM. Hospitalization time correlated with the blood loss (p<0,001) for PCM, negatively with the preoperative KPS (p=0.0002) for PCM and LPPM and positively with tumour diameter (p=0.0001) and non-surgical complications rate (p=0.0001) for LPPM. CONCLUSION: As compared to LPPM, surgical treatment of PCM is associated with higher morbidity and mortality. The outcome of LPPM was primarily influenced by preoperative factors: Patients age, tumour size, preoperative KPS. The outcome of PCM was primarily influenced by intraoperative factors like: blood loss, surgery duration, staged tumour resection and the surgical complications rate.

Surgical management of ipsilateral breast tumor recurrence.

PURPOSE: Approximately 10-15% of breast cancer patients treated by breast conserving surgery (BCS) and adjuvant radiotherapy (RT) will develop ipsilateral breast tumor recurrence (IBTR). International guidelines suggest total mastectomy as treatment of choice for IBTR following lumpectomy and RT. Nevertheless, there is evidence that second BCS might be equally sufficient. PATIENTS AND METHODS: Patients with IBTR diagnosed between 1990 and 2014 after BCS and RT were included (n = 170). 34.1% women underwent secondary BCS, whereas 65.9% were treated by mastectomy. We determined predictive factors for time to local progression (TTP), disease free survival (DFS), and overall survival (OS) comparing these two groups. RESULTS: Median follow-up after primary IBTR was 49 months (59 months for patients still alive at time of analysis). Five-year IBTR-free rate after secondary BCS was 77.6% (SD ± 6.1%) and 75.0% (SD ± 4.5%) for patients after mastectomy. Five-year DFS was 57.3% (SD ± 8.2%), and 61.9% (SD ± 5.5%), five-year OS was 84.7% (SD ± 5.8%), and 72.6% (SD ± 5.1%), respectively. Prior adjuvant systemic therapy, muscular invasion, and skin infiltration were independent significant risk factors for a shorter TTP. Additionally, lymphovascular infiltration (LVI) in the IBTR increased the risk for a shorter DFS. LVI, muscular invasion, and skin infiltration were identified as independent significant risk factors for a shorter OS. CONCLUSION: No significant difference in local control, DFS, and OS was seen between IBTR patients treated either by secondary BCS or mastectomy. Our data suggest that secondary BCS for IBTR patients after initial BCS and RT is feasible in selected patients.

Lost signature: progress and failures in in vivo tracking of implanted stem cells.

Stem cell therapy as a part of regenerative medicine provides promising approaches for the treatment of injuries and diseases. The increasing use of mesenchymal stem cells in various medical treatments created the demand for long-term in vivo cell tracking methods. Therefore, it is necessary to analyze post-transplantational survival, biodistribution, and engraftment of cells. Furthermore, stem cell treatment has been discussed controversially due to possible association with tumor formation in the recipient. For therapeutic purpose, stem cells must undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to the occurrence of genetic aberrations and altered expression of both tumor suppression and carcinogenic factors. To control therapy, it is necessary to find a reliable and general method to track and identify implanted cells in the recipient. This is especially challenging for autologous transplantations, as standard fingerprinting methods cannot be applied. An optimal technique for in vivo cell monitoring does not yet exist, and its development holds several challenges: small numbers of transplanted cells, possibility of cell number quantification, minimal transfer of the contrast agent to non-transplanted cells, and no genetic modification. This review discusses most of the proposed solutions, including magnetic resonance imaging, magnetic particle imaging, positron emission tomography, single-photon emission computed tomography, and optical imaging methods. Additionally, the recent research on cell labeling for stem cell monitoring after transplantation including in vitro, ex vivo, and in vivo imaging studies is described. Promising future imaging modalities for stem cell monitoring after transplantation are shown.

p53-dependent non-coding RNA networks in chronic lymphocytic leukemia.

Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We exploited the impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by small RNA sequencing. We describe the landscape of p53-dependent microRNA/non-coding RNA induced in response to DNA damage in CLL. Besides the key p53 target miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7-5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs) nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA p21 (lincRNA-p21) are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA-p21 are closely correlated to the induction of cell death after DNA damage. We used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and lincRNA-p21. The current work describes the p53-dependent miRNome and identifies lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage response machinery in CLL and lymphoma.

Pregnancies in liver and kidney transplant recipients: a review of the current literature and recommendation.

In this article, we focus on the biggest groups of organ transplant recipients, patients with a kidney or liver graft. Among these patients, about one sixth included women of childbearing potential. Therefore, the wish of getting pregnant is frequent in these peculiar patients, and careful planning and management of the pregnancies requires the expertise of obstetricians, midwives and transplant experts. Altogether, the outcome of the pregnancies in these women is acceptable. About 75% off all pregnancies ended successfully with live births, and this is comparable if not superior to pregnancies in healthy women. This success might be caused not only by the special and intensive care provided to these high-risk pregnancies by the transplant centres but also by the low rate of unplanned pregnancies. The risk of rejections and organ loss after delivery is about 10%, and it is slightly enhanced in liver transplant recipients (LTRs) in comparison to kidney graft recipients (KTRs) but the number of organ losses in direct association with a pregnancy is rare. However, there is not only a higher frequency of pregnancy-associated disorders such as pre-eclampsia and preterm delivery but also an acceleration of hypertension, new-onset diabetes mellitus and newly arising infections also favoured by the maintained immunosuppressive therapy. This implies a specialized 'control system' for these pregnant women that comprises ultrasound and Doppler investigation for risk assessment, infection screening, suitable therapy and the choice of non-teratogenic immunosuppressives. Antihypertensive treatment must be well balanced and adjusted to the possible growth-retarding effect on the foetus as well as on the co-morbidity of the mother. Finally, supplementation of vitamin D and iron is much more important in these transplanted women than in healthy pregnant women as vitamin D deficiency and anaemia are discussed to have an impact on pre-eclampsia and preterm delivery. These claims are widely discussed. Furthermore, the current literature is systematically reviewed by Scopus analysis.

Epithelial function and dysfunction in asthma.

Asthma was previously defined as an allergic Th2-mediated inflammatory immune disorder. Recently, this paradigm has been challenged because not all pathological changes observed in the asthmatic airways are adequately explained simply as a result of Th2-mediated processes. Contemporary thought holds that asthma is a complex immune disorder involving innate as well as adaptive immune responses, with the clinical heterogeneity of asthma perhaps a result of the different relative contribution of these two systems to the disease. Epidemiological studies show that exposure to certain environmental substances is strongly associated with the risk of developing asthma. The airway epithelium is first barrier to interact with, and respond to, environmental agents (pollution, viral infection, allergens), suggesting that it is a key player in the pathology of asthma. Epithelial cells play a key role in the regulation of tissue homeostasis by the modulation of numerous molecules, from antioxidants and lipid mediators to growth factors, cytokines, and chemokines. Additionally, the epithelium is also able to suppress mechanisms involved in, for example, inflammation in order to maintain homeostasis. An intrinsic alteration or defect in these regulation mechanisms compromises the epithelial barrier, and therefore, the barrier may be more prone to environmental substances and thus more likely to exhibit an asthmatic phenotype. In support of this, polymorphisms in a number of genes that are expressed in the bronchial epithelium have been linked to asthma susceptibility, while environmental factors may affect epigenetic mechanisms that can alter epithelial function and response to environmental insults. A detailed understanding of the regulatory role of the airway epithelium is required to develop new therapeutic strategies for asthma that not only address the symptoms but also the underlining pathogenic mechanism(s) and prevent airway remodelling.

Different models of transition to adult care after pediatric kidney transplantation: a comparative study.

Transition from pediatric to adult care is a critical and difficult step for young people with transplants and for the multidisciplinary team involved. In our retrospective study, we investigated the clinical course in a two-yr period of transition. Data from 66 teenagers were collected one yr before and after their transfer to three different adult care settings: (i) a specialized transition clinic, (ii) a general transplantation clinic, and (iii) a nephrologist. Patient survival rate was 100%. Three patients developed graft loss. GFR development was comparable in the three settings (ΔGFR 1.4 ± 8.7 vs. 3.1 ± 10.6 vs. 0.8 ± 4.4 mL/min/1.73 m2 , p = ns). Immunosuppressive therapy was stable in setting 1, whereas the number of changes increased in setting 2 and even more in setting 3. The percentage of patients with steroids increased from 36% to 38% and 52% in settings 1-3. Patient satisfaction was highest in setting 1 (100% vs. 64% and 78%, p < 0.05). Setting 1 was associated with fewer changes in therapy (13% vs. 91% and 45%, p < 0.05). The use of a specialized transition clinic is associated with fewer changes in medication and care and a higher level of patient satisfaction. This was not associated with a lower increase in GFR one yr after transition. Long-term results are awaited.

Pollen-derived low-molecular weight factors inhibit 6-sulfo LacNAc+ dendritic cells' capacity to induce T-helper type 1 responses.

BACKGROUND: Evidence is accumulating that the pollen exsudate contains an array of non-allergenic, pro-inflammatory and immunomodulatory substances acting on the innate and adaptive immune system. In this context, pollen-associated E(1)-phytoprostanes (PPE(1)) were shown to licence human monocyte-derived dendritic cells for T-helper type 2 (Th2) polarization of naïve T cells. OBJECTIVE: This study aims at analysing the impact of pollen-associated lipid mediators on cytokine secretion and maturation of 6-sulfo LacNAc(+) dendritic cells (slanDCs), the most abundant native dendritic cell (DC) in human peripheral blood, and further dissecting the biologically active substance(s) within aqueous pollen extracts. RESULTS: Aqueous birch pollen extracts dose-dependently inhibited the lipopolysaccharide (LPS)-induced IL-12 p70 production, while the levels of IL-6 remained unaffected. PPE(1) inhibited secretion of both IL-12 p70 and IL-6. Aqueous pollen extracts, but not PPE(1) or F(1)-phytoprostanes significantly reduced the LPS-induced surface expression of the maturation markers CD80, CD83, CD40 and CCR-7, an effect that was independent of proteins and that was still present in a 3 kDa cut-off fraction of the pollen extract. These effects were observed irrespective of the atopy status of the donors. Finally, slanDCs exposed to aqueous pollen extracts were impaired in eliciting an IFN-gamma response in naïve CD4(+) T cells. CONCLUSION: Our data show that slanDCs, a subset of human blood DCs with constitutively high potency to induce Th1 responses, are susceptible to the Th2 polarizing effect of low molecular weight, non-protein factors derived from pollen.

Suppression of high-p{T} neutral pion production in central Pb+Pb collisions at sqrt[S{NN}]=17.3 GeV relative to p+C and p+Pb collisions.

Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at sqrt[S{NN}]=17.4 GeV at midrapidity (2.3 less than or approximately equal eta{lab} less than or approximately equal 3.0) over the range 0.7 less than or approximately equal p{T} less than or approximately equal 3.5 GeV/c. The spectra are compared to pi{0} spectra measured in Pb+Pb collisions at sqrt[S{NN}]=17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N{part} less than or approximately equal 300), the yield of pi{0}'s with p{T} greater than or approximately equal 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N{coll}), while for central Pb+Pb collisions with N{part}greater than or approximately equal 350, the pi{0} yield is suppressed.

[Economic evaluation of medically occupationally orientated rehabilitation in patients with musculoskeletal disorders--a cost-benefit analysis from the perspective of the German statutory pension insurance scheme]. / Okonomische Evaluation einer medizinisch-beruflich orientierten Massnahme bei Patienten mit muskuloskeletalen Erkrankungen - Eine Kosten-Nutzen-Analyse aus Rentenversicherungsperspektive.

BACKGROUND: Musculoskeletal disorders are the most common health problem in Germany and the most frequent cause for medical rehabilitation under the German statutory pension insurance scheme. There is evidence of a strong association between musculoskeletal disorders and work-related problems. Recent research has shown that work-related interventions are adequate and effective as a treatment for patients with strong work-related problems. AIM: This evaluation compares the "work-related" (German: MBO, medizinisch-beruflich orientiert) rehabilitation to the standard medical rehabilitation provided in a clinical setting. From the perspective of a regional German statutory pension insurance agency, DRV Westfalen, it measures the efficiency of both treatments in patients with a diagnosed MBO demand 18 months after completion of the treatment. METHOD: The effect of both treatments on pension insurance revenues and costs up to 18 months after treatment was determined. Rehabilitation balance sheets of both treatments were compared in a cost-benefit analysis. From the difference obtained, conclusions could be drawn relative to the efficiency of the respective treatments. RESULTS: The descriptive analysis indicated additional receipts as a result of the MBO rehabilitation. Considering total costs, an effect amounting to 1 245 euro concerning the total revenue of DRV Westfalen is found if a patient had completed the MBO rehabilitation instead of the standard medical rehabilitation programme. CONCLUSION: Compared to standard medical rehabilitation, "work-related" rehabilitation hardly causes higher follow-up costs within 18 months, while generating higher receipts. Consequently, a more favourable monetary development is realized within the balance total in contrast to the standard medical rehabilitation. Limitations and consequences of these results are discussed in detail.

Changes in fibrinogen and fibrin induced by a peptide analog of fibrinogen gamma365-380.

BACKGROUND: The effects of synthetic peptides with sequences derived from the gamma-chain of fibrinogen on the functional properties of fibrinogen and fibrin were investigated. METHODS: Methods included thrombelastography, clot turbidity measurement, clot elasticity measurement, platelet aggregation, and scanning transmission electron microscopy (STEM). RESULTS: Peptide gamma369-380 (NH(2)-WATWKTRWYSMK-COOH) showed the greatest impact on fibrin structure, compared with the 76 other overlapping dodecapeptides. Addition of this peptide, or peptide gamma365-380 (NH(2)-NGIIWATKTREWYSMK-COOH) to a mixture of fibrinogen and thrombin resulted a shorter clotting time, higher clot turbidity, lower clot elastic modulus, a higher degree of D-trimer and D-tetramer formation, and impaired plasmin proteolysis of the clot. In STEM, fibrin formed in the presence of peptide gamma369-380 consisted of a more extensive array of linear fibrils typically consisting of 20 or more molecules. Fibrils were better organized than those from non-peptide containing mixtures. CONCLUSIONS: Replacement of the tryptophan residue gamma376 massively reduced the effect of the peptide on fibrin structure. Binding of the peptide to fibrinogen induces conformational changes, which result in accelerated clotting and increased lateral association of fibrin protofibrils. The results imply a relevant functional role of sites interacting with peptide gamma369-380 region in the fibrinogen molecule.