Lipocalin-2 protects the brain during inflammatory conditions.

Sepsis is a prevalent health issue that can lead to central nervous system (CNS) inflammation with long-term behavioral and cognitive alterations. Using unbiased proteomic profiling of over 100 different cytokines, we found that Lipocalin-2 (LCN2) was the most substantially elevated protein in the CNS after peripheral administration of lipopolysaccharide (LPS). To determine whether the high level of LCN2 in the CNS is protective or deleterious, we challenged Lcn2-/- mice with peripheral LPS and determined effects on behavior and neuroinflammation. At a time corresponding to peak LCN2 induction in wild-type (WT) mice injected with LPS, Lcn2-/- mice challenged with LPS had exacerbated levels of pro-inflammatory cytokines and exhibited significantly worsened behavioral phenotypes. To determine the extent of global inflammatory changes dependent upon LCN2, we performed an RNAseq transcriptomic analysis. Compared with WT mice injected with LPS, Lcn2-/- mice injected with LPS had unique transcriptional profiles and significantly elevated levels of multiple pro-inflammatory molecules. Several LCN2-dependent pathways were revealed with this analysis including, cytokine and chemokine signaling, nucleotide-binding oligomerization domain-like receptor signaling and Janus kinase-signal transducer and activator of transcription signaling. These findings demonstrate that LCN2 serves as a potent protective factor in the CNS in response to systemic inflammation and may be a potential candidate for limiting sepsis-related CNS sequelae.

Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice.

Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota ß-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.

Commutability of the First World Health Organization International Standard for Human Cytomegalovirus.

Quantitative detection of cytomegalovirus (CMV) DNA has become a standard part of care for many groups of immunocompromised patients; recent development of the first WHO international standard for human CMV DNA has raised hopes of reducing interlaboratory variability of results. Commutability of reference material has been shown to be necessary if such material is to reduce variability among laboratories. Here we evaluated the commutability of the WHO standard using 10 different real-time quantitative CMV PCR assays run by eight different laboratories. Test panels, including aliquots of 50 patient samples (40 positive samples and 10 negative samples) and lyophilized CMV standard, were run, with each testing center using its own quantitative calibrators, reagents, and nucleic acid extraction methods. Commutability was assessed both on a pairwise basis and over the entire group of assays, using linear regression and correspondence analyses. Commutability of the WHO material differed among the tests that were evaluated, and these differences appeared to vary depending on the method of statistical analysis used and the cohort of assays included in the analysis. Depending on the methodology used, the WHO material showed poor or absent commutability with up to 50% of assays. Determination of commutability may require a multifaceted approach; the lack of commutability seen when using the WHO standard with several of the assays here suggests that further work is needed to bring us toward true consensus.

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice.

Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock-in (KI) mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6months, by 12months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug-evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S KI mice, which are consistent with mitochondrial fission arrest. We anticipate that this G2019S mouse line will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.

Renal Transplantation in the Setting of Prior Urinary Diversion: A Case of Poorly Differentiated Adenocarcinoma in an Ileal Conduit.

Though rare, renal transplantation into a bowel containing urinary diversion is necessary in select clinical situations. Compared to renal transplant patients with functional native bladders, patients with urinary diversion have comparable long-term graft and patient survival rates. However, compounding the increased risk of malignancy in those on chronic immunosuppression are the inherent risks of urinary diversion. We present a case report of a high grade adenocarcinoma with neuroendocrine differentiation arising in an ileal conduit and discussion on the pathophysiology, management, and screening of this highly select population.

AQP4 autoantibody assay performance in clinical laboratory service.

OBJECTIVE: To compare performance of contemporary aquaporin-4-immunoglobulin (Ig) G assays in clinical service. METHODS: Sera from neurologic patients (4 groups) and controls were tested initially by service ELISA (recombinant human aquaporin-4, M1 isoform) and then by cell-based fluorescence assays: fixed (CBA, M1-aquaporin-4, observer-scored) and live (fluorescence-activated cell sorting [FACS], M1 and M23 aquaporin-4 isoforms). Group 1: all Mayo Clinic patients tested from January to May 2012; group 2: consecutive aquaporin-4-IgG-positive patients from September 2011 (Mayo and non-Mayo); group 3: suspected ELISA false-negatives from 2011 to 2013 (physician-reported, high likelihood of neuromyelitis optica spectrum disorders [NMOSDs] clinically); group 4: suspected ELISA false-positives (physician-reported, not NMOSD clinically). RESULTS: Group 1 (n = 388): M1-FACS assay performed optimally (areas under the curves: M1 = 0.64; M23 = 0.57 [p = 0.02]). Group 2 (n = 30): NMOSD clinical diagnosis was confirmed by: M23-FACS, 24; M1-FACS, 23; M1-CBA, 20; and M1-ELISA, 18. Six results were suspected false-positive: M23-FACS, 2; M1-ELISA, 2; and M23-FACS, M1-FACS, and M1-CBA, 2. Group 3 (n = 31, suspected M1-ELISA false-negatives): results were positive for 5 sera: M1-FACS, 5; M23-FACS, 3; and M1-CBA, 2. Group 4 (n = 41, suspected M1-ELISA false-positives): all negative except 1 (positive only by M1-CBA). M1/M23-cotransfected cells expressing smaller membrane arrays of aquaporin-4 yielded fewer false- positive FACS results than M23-transfected cells. CONCLUSION: Aquaporin-4-transfected CBAs, particularly M1-FACS, perform optimally in aiding NMOSD serologic diagnosis. High-order arrays of M23-aquaporin-4 may yield false-positive results by binding IgG nonspecifically.

Gastrointestinal hypomotility with loss of enteric nicotinic acetylcholine receptors: active immunization model in mice.

BACKGROUND: Autoimmune gastrointestinal dysmotility (AGID) is a limited form of dysautonomia. The only proven effector to date is IgG specific for ganglionic nicotinic-acetylcholine receptors containing α3 subunits [α3*- nicotinic acetylcholine receptor (nAChR)]. Rabbits immunized with recombinant α3-polypeptide produce α3*-nAChR autoantibodies, and profound AGID ensues. Human and rabbit α3*-nAChR-specific-IgGs induce transient hypomotility when injected into mice. Here, we describe success and problems encountered inducing gastrointestinal hypomotility in mice by active immunization. METHODS: We repeatedly injected young adult mice of seven different strains susceptible to autoimmunity (spontaneous diabetes or neural antigen immunization-induced myasthenia gravis or encephalomyelitis) with: (i) α3-polypeptide, intradermally or (ii) live α3*-nAChR-expressing xenogeneic cells, intraperitoneally. We measured serum α3*-nAChR-IgG twice monthly, and terminally assessed blue dye gastrointestinal transit, total small intestinal α3*-nAChR content (radiochemically) and myenteric plexus neuron numbers (immunohistochemically, ileal-jejunal whole-mount preparations). KEY RESULTS: Standard cutaneous inoculation with α3-polypeptide was minimally immunogenic, regardless of dose. Intraperitoneally injected live cells were potently immunogenic. Self-reactive α3*-nAChR-IgG was induced only by rodent immunogen; small intestinal transit slowing and enteric α3*-nAChR loss required high serum levels. Ganglionic neurons were not lost. CONCLUSIONS & INFERENCES: Autoimmune gastrointestinal dysmotility is inducible in mice by active immunization. Accompanying enteric α3*-nAChR reduction without neuronal death is consistent with an IgG-mediated rather than T cell-mediated pathogenesis, as is improvement of symptoms in patients receiving antibody-depleting therapies.

The prevalence and demographic distribution of treated epilepsy: a community-based study in Tasmania, Australia.

OBJECTIVES: To estimate the prevalence and demographic distribution of treated epilepsy in a community-based population. MATERIALS & METHODS: We surveyed all residents in Tasmania, Australia, who were supplied at least one antiepileptic drug prescription between July 1, 2001 and June 30, 2002, recorded on the national prescription database. We adjusted for the effect of disease-related non-response bias by imputation methods. RESULTS: After three mail contacts, 54.0% (4072/7541) responded, with 1774 (43.6%) indicating treatment for epilepsy, representing 86.0% of the estimated total possible cases in Tasmania. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00)); greater with increasing age (P < 0.001); similar in the three main geographic regions; and similar with socioeconomic status of postcode of residence. CONCLUSIONS: Although our estimates are likely to be affected by access to health services, overall treated epilepsy prevalence of 4.4 per 1000 is similar to previous studies. Our finding of high elderly prevalence has been reported in a few recent studies in developed countries and has important clinical and public health implications in populations with similar aging demographics.

The impact of MELD/PELD revisions on the mortality of liver-intestine transplantation candidates.

Patients listed for liver-intestine transplantation suffer higher waiting list mortality than those listed for liver-only, thus leading to policy revisions seeking to close the gap. We sought to determine the impact of key model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) policy modifications on the waiting list mortality of adult and pediatric liver-intestine candidates as compared to liver-only candidates. Analysis of UNOS data separated into adult and pediatric categories and based on time periods of policy implementation revealed higher mortality in liver-intestine candidates over all time periods studied (p < 0.001 pediatric and adult). After implementation of a revision to augment their MELD scores based on a sliding scale, adult liver-intestine candidates with calculated MELD > 15 no longer suffered higher mortality although this change did not completely eliminate the mortality disparity for candidates with MELD < 15 (p < 0.01). The waiting list mortality of pediatric liver-intestine candidates dropped significantly after a revision that gave them 23 additional MELD/PELD points (p < 0.01) although the mortality disparity with pediatric liver-only candidates was not eliminated. Following this revision, mortality in pediatric liver-only and liver-intestine Status 1 candidates was similar, however more liver-intestine candidates were listed as Status 1B. This data demonstrates that a mortality disparity remains for liver-intestine candidates compared with candidates listed for liver-only.

Academic careers and lifestyle characteristics of 171 transplant surgeons in the ASTS.

This manuscript reports the demographics, education and training, professional activities and lifestyle characteristics of 171 members of the American Society of Transplant Surgeons (ASTS). ASTS members were sent a comprehensive survey by electronic mail. There were 171 respondents who were 49 ± 8 years of age and predominantly Caucasian males. Female transplant surgeons comprised 10% of respondents. ASTS respondents underwent 15.6 ± 1.0 years of education and training (including college, medical school, residency and transplantation fellowship) and had practiced for 14.7 ± 9.2 years. Clinical practice included kidney, pancreas and liver organ transplantation, living donor surgery, organ procurement, vascular access procedures and general surgery. Transplant surgeons also devote a significant amount of time to nonsurgical patient care, research, education and administration. Transplant surgeons, both male and female, reported working approximately 70 h/week and a median of 195 operative cases per year. The anticipated retirement age for men was 64.6 ± 8.6 and for women was 62.2 ± 4.2 years. This is the largest study to date assessing professional and lifestyle characteristics of abdominal transplant surgeons.

Intestine transplantation in the United States, 1999-2008.

Improving short-term results with intestine transplantation have allowed more patients to benefit with nearly 700 patients alive in the United States with a functioning allograft at the end of 2007. This success has led to an increase in demand. Time to transplant and waiting list mortality have significantly improved over the decade, but mortality remains high, especially for infants and adults with concomitant liver failure. The approximately 200 intestines recovered annually from deceased donors represent less than 3% of donors who have at least one organ recovered. Consent practice varies widely by OPTN region. Opportunities for improving intestine recovery and utilization include improving consent rates and standardizing donor selection criteria. One-year patient and intestine graft survival is 89% and 79% for intestine-only recipients and 72% and 69% for liver-intestine recipients, respectively. By 10 years, patient and intestine survival falls to 46% and 29% for intestine-only recipients, and 42% and 39% for liver-intestine, respectively. Immunosuppression practice employs peri-operative antibody induction therapy in 60% of cases; acute rejection is reported in 30%-40% of recipients at one year. Data on long-term nutritional outcomes and morbidities are limited, while the cause and therapy for late graft loss from chronic rejection are areas of ongoing investigation.

What defines a transplant surgeon? A needs assessment for curricular development in transplant surgery fellowship training.

This study compares the perceptions of transplant surgery program directors (PDs) and recent fellowship graduates (RFs) regarding the adequacy of training and relevancy to practice of specific curricular content items in fellowship training. Surveys were sent to all American Society of Transplant Surgery approved fellowship PDs and all RFs in practice <5 years. For operative procedures, the RFs considered the overall training to be less adequate than the PDs (p = 0.0117), while both groups considered the procedures listed to be relevant to practice (p = 0.8281). Regarding nonoperative patient care items, although RFs tended to rank many individual items lower, both groups generally agreed that the training was both adequate and relevant. For nonpatient care related items (i.e. transplant-related ethics, economics, research, etc.), both groups scored them low regarding their adequacy of training although RFs scored them significantly lower than PDs (p = 0.0006). Regarding their relevance to practice, while both groups considered these items relevant, RFs generally considered them more relevant than PDs. Therefore, although there is consensus on many items, significant differences exist between PDs and RFs regarding their perceptions of the adequacy of training and the relevance to practice of specific curriculum items in transplant surgery fellowship training.

Perception versus reality?: Virtual crossmatch--how to overcome some of the technical and logistic limitations.

The goal of this work was to evaluate concordance between (a) actual flow cytometric crossmatch (FCXM) that is performed by the OPO laboratory servicing our transplant center and (b) virtual XM (vXM) prediction based on antibody identification by solid-phase methods performed in our laboratory. A total of 1586 FCXM, performed between June 2007 and September 2008, between all potential deceased donors in our region and sera from patients awaiting kidney or kidney-pancreas transplant, listed at Northwestern Memorial Hospital were evaluated. A key finding of this analysis was the understanding that a thorough vXM cannot be performed in some donor/recipient pairs due to the lack of certain antibody profile data specific to the donor in question. Obtaining more in depth and stringent information regarding antibody specificities, we demonstrate an excellent sensitivity and specificity of the vXM assays- 86.1% and 96.8%, respectively, with a positive likelihood ratio and negative likelihood ratios of 26.9 and 0.14, respectively. The vXM can serve as an outstanding tool to predict HLA compatibility between donor and recipient, with the caveat that the presence/absence of all antibodies against the potential donor and their strength have been thoroughly investigated.

Frequency of contamination of coagulation factor concentrates with novel human parvovirus PARV4.

Human parvovirus, PARV4 was identified in a plasma sample from a patient presenting with symptoms resembling acute HIV infection. Further strains of PARV4 and those of a closely related variant virus, were identified in plasma pools used in the manufacture of blood derivatives. DNA sequence analysis of these strains demonstrated two distinct PARV4 genotypes. It has subsequently been proposed that transmission of PARV4 occurs by parenteral routes. To investigate the risk of contamination of plasma-derived coagulation factor concentrates, we analysed 169 lots for PARV4 DNA by polymerase chain reaction. Positive samples were confirmed by nucleotide sequence analysis and quantification of the viral load. Twenty-one lots, representing eight different products were administered until the beginning of the 1980s and were not virally inactivated. Two lots examined were used in 1997, and 146 lots representing 13 products had been administered between October 2000 and February 2003. PARV4 DNA was detected in 7(33%) of the formerly administered lots, in one lot used in 1997, and in 13(9%) recently used lots. PARV4 genotype 2 DNA was predominantly present in the older concentrates, whilst genotype 1 was found more frequently in recently used lots. In three lots, both PARV4 genotypes were detected. Viral loads ranged between <100 and 10(5.8) copies mL(-1) of product, with higher viral loads in the older concentrates. The results show that PARV4 contamination can be detected in an appreciable proportion of clotting factor concentrates. Further studies are needed to determine whether or not PARV4 contamination of coagulation factors causes harm to the product recipients.

CNS aquaporin-4 autoimmunity in children.

BACKGROUND: In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood. METHODS: A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58. RESULTS: Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4-18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjögren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months). CONCLUSIONS: Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children.

Human parvovirus PARV4 in clotting factor VIII concentrates.

BACKGROUND AND OBJECTIVES: Parvoviruses are small non-enveloped DNA viruses, relatively resistant to virus inactivation procedures. The recently identified human parvovirus PARV4, including a related genotype 2 virus (also termed PARV5), has been found to be a contaminant of pooled plasma used in the manufacture of plasma-derived products. This report describes an investigation to determine whether PARV4 is present in clotting factor concentrates. MATERIALS AND METHODS: Factor VIII concentrates manufactured in the past 30-35 years were screened for PARV4 and human parvovirus B19 (B19V) sequences. Viral loads in products testing positive for PARV4 were quantified using a consensus TaqMan assay designed to a highly conserved region. DNA sequence analysis was performed to confirm the genotypes present. RESULTS: From a total of 175 lots of factor VIII concentrate, 28 of these contained PARV4 sequences, and in two lots both genotypes 1 and 2 were found to be present. The highest viral loads observed exceeded 10(5) copies per ml. The majority of factor VIII concentrates testing positive for PARV4 were manufactured in the 1970s and 1980s. Human B19V was also a frequent contaminant of these products. CONCLUSIONS: PARV4 was detected in 16% of factor VIII concentrates, particularly in older batches from the 1970s and 1980s. The significance in terms of the viral safety and potential transmission to recipients of these products is not yet known.

Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica.

BACKGROUND: Autoantibody specific for the aquaporin-4 astrocytic water channel is restricted to serum and CSF of patients with neuromyelitis optica (NMO) and related CNS inflammatory demyelinating disorders (relapsing optic neuritis and longitudinally extensive transverse myelitis). NMO-typical lesions are distinct from MS-typical lesions. Aquaporin-4 is lost selectively at vasculocentric sites of edema/inflammation coinciding with focal deposits of immunoglobulins (Ig) G, M, and terminal complement products, with and without myelin loss. Evidence for antigen-specific autoantibody pathogenicity is lacking. METHODS: We used confocal microscopy and flow cytometry to evaluate the selectivity and immunopathological consequences of Ig binding to surface epitopes of living target cells expressing aquaporin-4 fused at its cytoplasmic N-terminus with GFP. We tested serum, IgG-enriched and IgG-depleted serum fractions, and CSF from patients with NMO, neurologic control patients, and healthy subjects. We also analyzed aquaporin-4 immunoreactivity in myelinated adult mouse optic nerves and spinal cord, and plasma cell Ig isotypes in archived brain tissue from an NMO patient. RESULTS: Serum IgG from patients with NMO binds to the extracellular domain of aquaporin-4; it is predominantly IgG(1), and it initiates two potentially competing outcomes, aquaporin-4 endocytosis/degradation and complement activation. Serum and CSF lack aquaporin-4-specific IgM, and plasma cells in CNS lesions of NMO contain only IgG. Paranodal astrocytic endfeet highly express aquaporin-4. CONCLUSIONS: NMO patients' serum IgG has a selective pathologic effect on cell membranes expressing aquaporin-4. IgG targeting astrocytic processes around nodes of Ranvier could initiate demyelination.

Parvovirus B19 genotypes 1 and 2 detection with real-time polymerase chain reaction assays.

BACKGROUND AND OBJECTIVES: Parvovirus B19 (B19V) DNA screening has been introduced to comply with European regulations for certain plasma products. Current commercial and some in-house B19V DNA assays fail to detect or under-quantify the recently identified genotypes 2 and 3. In this report, we describe 2-year experience with B19V DNA screening using the commercial assay from Roche (detecting only genotype 1) combined with an in-house assay (detecting genotypes 1, 2 and 3). This dual testing approach enables the identification of molecular variants of B19V. MATERIALS AND METHODS: Between 2005 and 2007, approximately 2.6 million plasma donations were screened for B19V DNA loads exceeding 10(6) IU/ml using the Roche and the in-house real-time polymerase chain reaction assay. RESULTS: A total of 232 plasma units were identified with B19V DNA loads above 10(6) IU/ml. Concordant results were observed for the majority of B19V positive samples; however, three of these showed discrepant results between the two assay systems. One was a B19V genotype 2 strain not detected by the Roche assay; another was a B19V genotype 1 strain with a mismatch in the 3'-end of the reverse primer and therefore under-quantified by the Roche assay; and the third one was also a B19V genotype 1 strain that gave an unusual amplification plot in the in-house assay due to a mismatch in the probe-binding site. CONCLUSIONS: New, high viral load, B19V genotypes 2 and 3 infections are rare in blood donors tested by Sanquin. One case was found while testing 2.6 million donations. The prevalence of B19V genotype 1 variants not detected by commercial or in-house assays might be in the same range or even higher than the prevalence of B19V genotype 2 viruses, which remain undetected.

Liver and intestine transplantation in the United States, 1996-2005.

The number of liver transplants performed yearly has slowly and steadily increased over the last 10 years, reaching 6441 procedures in 2005. The number of living donor liver transplants performed rose steadily from 1996 to 2001, when it peaked at 519; since 2003 there have been approximately 320 such procedures performed each year. The continual increase in the size of the waiting list for a liver transplant, which peaked in 2001 at 14 897 patients, was interrupted in 2002 by the implementation of the allocation system based on the model for end-stage liver disease and pediatric end-stage liver disease (MELD/PELD). Activity in all areas of intestinal transplantation continues to increase. One-year patient and graft survival following intestine-alone transplantation now seem to be superior to outcomes following liver-intestine transplantation. Other topics covered here include the recent 'Share 15' component of the MELD allocation system; liver transplantation following donation after cardiac death; simultaneous liver-kidney transplantation and waiting list and post-transplant outcomes for both liver and intestine transplantation, broken out by a variety of clinical and demographic factors.

The association between non-melanoma skin cancer and osteoporotic fractures--a population-based record linkage study.

UNLABELLED: We studied the association between osteoporotic fractures and prior non-melanoma skin cancer (NMSC, a biomarker for cumulative sun exposure). The risk of prior NMSC in our fracture cohort was significantly reduced (standardised incidence ratio 0.69, 95% CI 0.61, 0.78). Adequate lifetime sun exposure may be necessary to protect against osteoporotic fractures in later life. INTRODUCTION: The relationship between cumulative sun exposure and osteoporotic fractures is uncertain. We aimed to study the association between non-melanoma skin cancer (NMSC), a marker of cumulative sun exposure, and osteoporotic fractures in an older cohort. METHODS: A retrospective cohort study in southern Tasmania in people aged at least 50 years with incident radiographic fracture (n = 2,283) was carried out. By record linkage to the Tasmanian Cancer Registry the cohort was followed backwards through time until the occurrence of NMSC or end-of follow-up. Relative risk was estimated by the standardised incidence ratio (SIR) using sex-, age- and calendar year-specific cancer incidence rates in southern Tasmania as reference. RESULTS: The incidence of prior NMSC in the fracture cohort was 31% lower than for the general population (SIR 0.69, 95% CI 0.61, 0.78). This effect was significant for most fracture subtypes except pelvic and wrist fractures and observed for both NMSC subtypes, squamous cell carcinoma and basal cell carcinoma. CONCLUSIONS: Older people with osteoporotic fractures may have had lifestyles linked to lower cumulative sunlight exposure. Achieving a balance between adequate lifetime sun exposure and protection against its adverse effects (such as fractures and skin cancer) may require assessment of individual risks.