Head movement kinematics are differentially altered for extended versus short duration gait exercises in individuals with vestibular loss.

Head kinematics are altered in individuals with vestibular schwannoma (VS) during short duration gait tasks [i.e., Functional Gait Assessment (FGA)], both before and after surgery, yet whether these differences extend to longer duration gait exercises is currently unknown. Here we examined the effects of vestibular loss and subsequent compensation on head kinematics in individuals with VS during gait exercises of relatively extended versus short duration (< 10 versus 30 s), compared to age-matched controls. Six-dimensional head movements were recorded during extended and short duration gait exercises before and then 6 weeks after sectioning of the involved vestibular nerve (vestibular neurectomy). Standard functional, physiological, and subjective clinical assessments were also performed at each time point. Kinematics were differentially altered in individuals with vestibular loss at both time points during extended versus short duration exercises. Range of motion was significantly reduced in extended tasks. In contrast, movement variability predominately differed for the short duration exercises. Overall, our results indicate that quantifying head kinematics during longer duration gait tasks can provide novel information about how VS individuals compensate for vestibular loss, and suggest that measurements of range of motion versus variability can provide information regarding the different strategies deployed to maintain functional locomotion.

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.

Hemorrhagic complications in individuals with liver disease submitted to minor oral surgery.

Individuals with chronic liver disease (CLD) have an increased risk of bleeding from thrombocytopenia and changes in hemostasis. The aim of this study was to evaluate the frequency of and the factors associated with the occurrence of bleeding in CLD patients who underwent dental surgical procedures. This was a retrospective study whose data were collected in a hospital dentistry service between 2010 and 2016. The patients were referred from the gastroenterology and liver transplantation services of a university hospital for dental treatment. The study followed the STROBE guidelines. Among the 71 surgical procedures performed, there were 17 (24%) perioperative and postoperative bleeding episodes, 14 of which were in pretransplant patients and 11 received blood transfusion before dental surgery. Individuals with a previous history of bleeding (PR = 2.67, CI = 1.07-6.67, P  = 0.035) and those with a platelet count before surgery 50 × 10 9 /l or less (PR = 7.48, CI = 1.70-32.86, P  = 0.008) had a higher prevalence of perioperative and postoperative bleeding episodes than their peers without a previous history of bleeding, and those with platelet count greater than 50 × 10 9 /l. The approach to individuals with CLD is complex and represents a challenge to the clinician. A careful anamnesis combined with laboratory screening of coagulation disorders appears to be useful to identify individuals at a major risk of bleeding. Studies identifying the predisposing factors of bleeding in CLD patients support well tolerated protocols for oral surgery in this group.

Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer.

We aimed to explore the genetic and environmental contributions to variation in the risk of hematologic malignancies and characterize familial dependence within and across hematologic malignancies. The study base included 316,397 individual twins from the Nordic Twin Study of Cancer with a median of 41 years of follow-up: 88,618 (28%) of the twins were monozygotic, and 3459 hematologic malignancies were reported. We estimated the cumulative incidence by age, familial risk, and genetic and environmental variance components of hematologic malignancies accounting for competing risk of death. The lifetime risk of any hematologic malignancy was 2.5% (95% CI 2.4-2.6%), as in the background population. This risk was elevated to 4.5% (95% CI 3.1-6.5%) conditional on hematologic malignancy in a dizygotic co-twin and was even greater at 7.6% (95% CI 4.8-11.8%) if a monozygotic co-twin had a hematologic malignancy. Heritability of the liability to develop any hematologic malignancy was 24% (95% CI 14-33%). This estimate decreased across age, from approximately 55% at age 40 to about 20-25% after age 55, when it seems to stabilize. In this largest ever studied twin cohort with the longest follow-up, we found evidence for familial risk of hematologic malignancies. The discovery of decreasing familial predisposition with increasing age underscores the importance of cancer surveillance in families with hematological malignancies.

Patient-derived xenografts of a case of ameloblastic fibrodentinoma.

OBJECTIVES: The establishment of animal models of xenotransplantation can contribute to the elucidation of the molecular pathogenesis of ameloblastic fibrodentinomas (AFD) and it also provides an opportunity for drug tests. We aimed to evaluate the possibility of AFD tumour growth in a patient-derived xenograft (PDX) model. In addition, we characterized the human tumour and the PDXs. MATERIALS AND METHODS: A sample of a recurrent AFD was obtained and two fragments were contralaterally implanted subcutaneously in an 8-week old female NUDE mouse. After 250 days, the PDXs were removed and submitted to histopathological and molecular analysis. Immunohistochemical reactions for Ki67 and the phosphorylated form of ERK1/2 were carried out in both, PDXs and human tumour, and the presence of BRAFV600E was assessed. RESULTS: From day 135 onwards, the PDXs presented a growth peak and remained stable until day 250. Histopathologically, the PDXs presented the same features of the patient's tumour. Tumour cells exhibited Ki67 and pERK1/2 immunoexpression in the patient's tumour and PDX. The AFD was wild-type for BRAFV600E. CONCLUSION: The PDX model recapitulated well the human tumour after a long implantation time, representing a possible model to study the AFD and other odontogenic tumours pathobiology.

Bioinspired Flexible and Tough Layered Peptide Crystals.

One major challenge of functional material fabrication is combining flexibility, strength, and toughness. In several biological and artificial systems, these desired mechanical properties are achieved by hierarchical architectures and various forms of anisotropy, as found in bones and nacre. Here, it is reported that crystals of N-capped diphenylalanine, one of the most studied self-assembling systems in nanotechnology, exhibit well-ordered packing and diffraction of sub-Å resolution, yet display an exceptionally flexible nature. To explore this flexibility, the mechanical properties of individual crystals are evaluated, assisted by density functional theory calculations. High-resolution scanning electron microscopy reveals that the crystals are composed of layered self-assembled structures. The observed combination of strength, toughness, and flexibility can therefore be explained in terms of weak interactions between rigid layers. These crystals represent a novel class of self-assembled layered materials, which can be utilized for various technological applications, where a combination of usually contradictory mechanical properties is desired.

Dental management for patients undergoing heart valve surgery.

This study sought to review current guidelines and the most optimal dental management for patients undergoing cardiac valve surgery.

Long-Term Biomechanical and Histologic Results of WST-D/NIR Corneal Stiffening in Rabbits, Up to 8 Months Follow-up.

Purpose: To determine the long-term safety and efficacy of WST-D/near-infrared (NIR) corneal stiffening. Methods: One eye of 23 New Zealand White rabbits was de-epithelialized mechanically followed by topical application of 2.5 mg/mL WST11, combined with dextran-500 (WST-D) for 20 minutes. Subsequently, samples were irradiated with a NIR (755 nm) laser at 10 mW/cm2 for 30 minutes. Untreated fellow eyes served as controls. One week (n = 4), 1 month (n = 6), 4 months (n = 9), or 8 months (n = 4) after treatment rabbits were euthanized. Corneal strips were cut in superior-inferior direction for extensiometry testing (1, 4, and 8 months), and histologic sections were prepared for evaluation of keratocyte distribution (1 week and 8 months). Results: Elastic modulus after treatment was significantly higher than in paired controls (16.0 ± 2.3 MPa versus 9.6 ± 3.6 MPa [P = 0.008], 18.1 ± 4.5 MPa versus 12.6 ± 2.3 MPa [P = 0.003], and 18.6 ± 3.6 MPa versus 14.2 ± 3.6 MPa [P = 0.010], at 1, 4, and 8 months, respectively). A significant decrease in keratocyte count at the anterior stroma was observed directly after treatment (1.5 ± 1.7 vs. 19.0 ± 4.1 [P = 0.002]). At 8 months keratocyte repopulation appeared completed, with similar distribution in treated and untreated corneas (15.9 ± 1.1 vs. 14.5 ± 2.5 [P = 0.562]). Corneal thickness was comparable between treated and untreated corneas at all time points. Conclusions: WST-D/NIR treatment resulted in significant and persistent long-term increase in corneal stiffness. Initial keratocyte apoptosis in the anterior stroma is followed by repopulation to normal level at 8 months after treatment. The safe nature of NIR light allows treatment of corneas of any thickness without endangering corneal endothelium or deeper ocular structures, potentially benefiting patients deemed unsuitable for riboflavin/UV-A cross-linking.

Cannabis use disorder and suicide attempts in Iraq/Afghanistan-era veterans.

The objective of the present research was to examine the association between lifetime cannabis use disorder (CUD), current suicidal ideation, and lifetime history of suicide attempts in a large and diverse sample of Iraq/Afghanistan-era veterans (N = 3233) using a battery of well-validated instruments. As expected, CUD was associated with both current suicidal ideation (OR = 1.683, p = 0.008) and lifetime suicide attempts (OR = 2.306, p < 0.0001), even after accounting for the effects of sex, posttraumatic stress disorder, depression, alcohol use disorder, non-cannabis drug use disorder, history of childhood sexual abuse, and combat exposure. Thus, the findings from the present study suggest that CUD may be a unique predictor of suicide attempts among Iraq/Afghanistan-era veterans; however, a significant limitation of the present study was its cross-sectional design. Prospective research aimed at understanding the complex relationship between CUD, mental health problems, and suicidal behavior among veterans is clearly needed at the present time.

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann­Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.

A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair.

The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-ß3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration.

Effect of pegylated phosphatidylserine-containing liposomes in experimental chronic arthritis.

BACKGROUND: Phosphatidylserine-containing liposomes (PSL) have been shown to reduce inflammation in experimental models of acute arthritis, by mimicking the apoptotic process. The aim of this study was to evaluate the effect of pegylated PSL (PEG-PSL) on chronic inflammation of collagen induced arthritis (CIA) in DBA/1J mice. METHODS: CIA was induced in 24 DBA/1J mice (n = 6/group), which were divided into control (0.9 % saline) or treated with PEG-PSL (5, 10 and 15 mg/kg/day, subcutaneously for 20 days). Clinical score, limb histology and measurement of cytokines in knee joints of animals by ELISA and cytometric bead array (CBA) were evaluated. The in vitro study employed macrophage cultures stimulated with 100 ng/ml of LPS plus 10 ng/ml of PMA and treated with 100 µM PEG-PSL. RESULTS: Resolution of the disease in vivo and the inflammatory process in vitro were not observed. PEG-PSL, in doses of 10 and 15 mg/kg, were not shown to reduce the score of the disease in animals, whereas with the dose of 5 mg/kg, the animals did not show the advanced stage of the disease when compared to the controls. The PEG- PSL 5, 10 and 15 mg/kg treatment groups did not show significant reduction of TNF-α, IL-1ß, IL-6, IL-2 and IFN-γ when compared to the controls. Disease incidence and animal weights were not affected by treatment. Regarding the paw histology, PEG-PSL did not yield any reductions in the infiltrating mononuclear, synovial hyperplasia, extension of pannus formation, synovial fibrosis, erosion of cartilage, bone erosion or cartilage degradation. The concentration of 100 µM of PEG-PSL has not been shown to reduce inflammation induced by LPS/PMA in the in vitro study. Treated groups did not show any reduction in inflammatory cytokines in the knee joints of animals affected by the disease compared to the control, although there were higher concentrations of TGF-ß1 in all experimental groups. CONCLUSION: The experimental model showed an expression of severe arthritis after the booster. TGF-ß1 as well other pro inflammatory cytokines were presented in high concentrations in all groups. PEG-PSL had no impact on the clinical score, the histopathology from tibial-tarsal joints or the production of cytokines in the knee joints. Other alternatives such as dosage, route of administration, and as an adjunct to a drug already on the market, should be evaluated to support the use of PEG-PSL as a new therapeutic tool in inflammatory diseases.

BRAFV600E Mutation in Melanotic Neuroectodermal Tumor of Infancy: Toward Personalized Medicine?

The melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that primarily affects the maxilla of infants during their first year of life. Complete resection is the conventional treatment and recurrence rates vary from 10% to 60%. The recurrent tumors grow more aggressively and can invade other anatomic structures, such as the nasal cavity, the orbit, and the skull base. The aggressive behavior of MNTIs may require radical resection, which may not be possible in some cases because of its rapid and invading growth together with invasion of vital structures. In these situations, adjunct radiotherapy or chemotherapy has been used. However, as there are no conclusive data regarding the molecular profile of this tumor, currently there is no targeted therapy that may be used in the treatment of selected aggressive cases. On the basis of MNTI similarities with melanomas, such as derivation from the neural crest cells and presence of large melanin-containing cells, we hypothesized that MNTIs also may harbor the BRAFV600E oncogenic mutation. We show for the first time that this important pediatric tumor may harbor the oncogenic BRAFV600E mutation, providing the first insights to their personalized treatment.

Use of Psychotropic Medications among Youth in Treatment Foster Care.

We describe the use of psychotropic medications among youth in treatment foster care (TFC). Data from 240 youth were coded to examine rates of medication use, including polypharmacy and an indicator of "questionable polypharmacy." Fifty-nine percent of youth in TFC had taken a psychotropic medication within the past two months. Of the youth taking psychotropics, 61% took two or more and 22% met criteria for questionable polypharmacy. The majority of youth taking psychotropics also received psychosocial mental health services and were more likely to receive such services than youth not taking medication. Use of psychotropic medication use was not significantly related to demographic factors, maltreatment history, or custody. However, youth with more severe symptoms were more likely to be on medications and to be on multiple medications. Youth with "questionable polypharmacy" were less likely than other youth on multiple medications to have a recent visit to a psychiatrist.

Screening for violence risk in military veterans: predictive validity of a brief clinical tool.

OBJECTIVE: Violence toward others is a serious problem among a subset of military veterans. The authors evaluated the predictive validity of a brief decision support tool to screen veterans for problems with violence and identify potential candidates for a comprehensive risk assessment. METHOD: Data on risk factors at an initial wave and on violent behavior at 1-year follow-up were collected in two independent sampling frames: a national random-sample survey of 1,090 Iraq and Afghanistan veterans and in-depth assessments of 197 dyads of veterans and collateral informants. Risk factors (lacking money for basic needs, combat experience, alcohol misuse, history of violence and arrests, and anger associated with posttraumatic stress disorder) were chosen based on empirical support in published research. Scales measuring these risk factors were examined, and items with the most robust statistical association with outcomes were selected for the screening tool. Regression analyses were used to derive receiver operating characteristic curves of sensitivities and specificities, with area under the curve providing an index of predictive validity. RESULTS: The resultant 5-item screening tool, called the Violence Screening and Assessment of Needs (VIO-SCAN), yielded area-under-the-curve statistics ranging from 0.74 to 0.78 for the national survey and from 0.74 to 0.80 for the in-depth assessments, depending on level of violence analyzed. CONCLUSIONS: Although the VIO-SCAN does not constitute a comprehensive violence risk assessment and cannot replace fully informed clinical decision making, it is hoped that the screen will provide clinicians with a rapid, systematic method for identifying veterans at higher risk of violence, prioritizing those in need a full clinical workup, structuring review of empirically supported risk factors, and developing plans collaboratively with veterans to reduce risk and increase successful reintegration in the community.

Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis.

Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosoma mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.

Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light.

PURPOSE: We evaluated the efficacy and safety of photochemical corneal stiffening by palladium bacteriochlorin 13'-(2-sulfoethyl)amide dipotassium salt (WST11) and near infrared (NIR) illumination, using ex vivo and in vivo rabbit eye models. METHODS: Corneas of post mortem rabbits and living rabbits were pretreated topically with 2.5 mg/mL WST11 in saline or in 20% dextran T-500 (WST-D), washed and illuminated with an NIR diode laser (755 nm, 10 mW/cm(2). Studies with corneas of untreated fellow eyes served as controls. Tensile strength measurements, histopathology, electron spin resonance, and optical spectroscopy and fluorescence microscopy were used to assess treatment effects. Comparative studies were performed with standard riboflavin/ultraviolet-A light (UVA) treatment. RESULTS: WST11/NIR treatment significantly increased corneal stiffness following ex vivo or in vivo treatment, compared to untreated contralateral eyes. The incremental ultimate stress and Young's modulus of treated corneas increased by 45, 113, 115%, and 10, 79, and 174% following 10, 20, and 30 minutes of incubation with WST11, respectively. WST-D/NIR had a similar stiffening effect, but markedly reduced post-treatment edema and shorter time of epithelial healing. WST11/NIR and WST-D/NIR generate hydroxyl and superoxide radicals, but no singlet oxygen in the cornea. Histology demonstrated a reduction in the keratocyte population in the anterior half of the corneal stroma, without damage to the endothelium. CONCLUSIONS: Treatment of rabbit corneas, with either WST11/NIR or WST-D/NIR, increases their biomechanical strength through a mechanism that does not involve singlet oxygen. The WST-D/NIR treatment showed less adverse effects, demonstrating a new potential for clinical use in keratoconus and corneal ectasia after refractive surgery.

Comparison of six different specimen types for Epstein-Barr viral load quantification in peripheral blood of pediatric patients after heart transplantation or after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Epstein-Barr Virus (EBV) a gamma-herpes virus is associated with a spectrum of lymphoid and epithelial malignancies including posttransplant lymphoproliferative disorders (PTLD). EBV-load measurement has been shown to be important for the monitoring of these patients. However, in contrast to the viral quantification of human immunodeficiency virus or human hepatitis C virus, the EBV-load measurement has not been completely standardized as yet. OBJECTIVES: In this study, we compared the EBV DNA levels in whole blood (WB), plasma, peripheral mononuclear cells (PBMC) and B-cells (BC) in children and adolescents after heart transplantations (HTx) and allogeneic hematopoietic stem cell transplantations (HSCT). STUDY DESIGN: In a period of 2 years (from May 2007 to May 2009) we collected 547 samples of 96 cardiac transplant recipients and 248 samples of 37 patients who underwent HSCT. For EBV DNA quantification we used a duplex real-time PCR (ABI Prism 7500, Applied Biosystems). Additionally, EBV-load of PBMC and BC were normalized with respect to endogenous cell DNA. RESULTS: In both patient populations we found no significant difference of test sensitivity for the EBV detection. In PBMC as well as BC, there was a high correlation between the analysis of cells with and without normalization in both populations. Spearman's correlation coefficient ρ between PBMC without and PBMC with normalization was ρ=0.98 (P<0.0001) in patients after HTx and ρ=0.99 (P<0.0001) in patients after HSCT. Correlation between BC with and without normalization was ρ=0.98 (P<0.0001) in patients after HTx and ρ=0.995 (P<0.0001) in patients after HSCT. When comparing the different blood compartments for EBV quantification in both populations, the strongest correlations were found between the EBV DNA levels in WB and PBMC (HTx: ρ=0.93, P<0.0001; HSCT: ρ=0.81, P<0.0001) followed by PBMC and BC (HTx: ρ=0.87, P<0.0001; HSCT: ρ=0.81, P<0.0001) as well as WB and BC (HTx: ρ=0.86, P<0.0001; HSCT: ρ=0.75, P<0.0001). In contrast, the correlation coefficients between plasma and the other blood compartments (WB as well as PBMC or BC) were lower. Six patients developed seven episodes of PTLD (five patients after HTx and one after renal transplantation). Analyzing the different blood compartments, we found that a threshold of WB ≥20,000EBV-copies/ml and plasma ≥1000EBV-copies/ml had the highest sensitivities and specificities (WB: sensitivity 100%, specificity 87% and plasma: sensitivity 88%, specificity 98%). CONCLUSION: Normalization towards an endogenous control does not seem to be necessary for EBV quantification in peripheral blood. The analysis of whole blood correlates well with B-cells and PBMC. Routine screening of EBV DNA in whole blood appeared to be a useful tool supplemented by EBV-load measurement in plasma to discriminate chronic high EBV-load carrier without risk for PTLD from those who are at risk for PTLD. Values in whole blood higher than 20,000EBV-copies/ml WB and plasma values higher than 1000EBV-copies/ml plasma indicated PTLD in our series.