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Identification of new potential drug target proteins and their plausible mechanisms for stroke treatment is critically needed. We previously showed that genetic deletion and short-term pharmacological inhibition of P2X4R, a purinergic receptor for adenosine triphosphate ATP, provides acute cerebroprotection. However, potential mechanisms remain unknown. Therefore, we employed RNA-seq technology to identify the gene expression profiles, pathway analysis, and qPCR validation of differentially expressed genes (DEGs). This analysis identified roles of DEGs in certain biological processes responsible for P2X4R-dependent cerebroprotection after stroke. We subjected both young and aged male and female global P2X4 KO and littermate WT mice to ischemic stroke. After 3 days, mice were sacrificed, total RNA was isolated using Trizol, and subjected to RNA-seq and Nanostring-mediated qPCR. DESeq2, Gene Ontology (GO), and Ingenuity Pathway Analysis (IPA) were used to identify mRNA transcript expression profiles and biological pathways. We found 2246 DEGs in P2X4R KO vs WT tissue after stroke. Out of these DEGs, 1920 gene were downregulated, and 325 genes were upregulated in KO. GO/IPA analysis of the top 300 DEGs suggests an enrichment of inflammation and extracellular matrix component genes. qPCR validation of the top 30 DEGs revealed downregulation of two common age-independent genes in P2X4R KO mice: Interleukin-6 (IL-6), an inflammatory cytokine, and Cytotoxic T Lymphocyte-Associated Protein 2 alpha (Ctla2a), an immunosuppressive factor. These data suggest that P2X4R-mediated cerebroprotection after stroke is initiated by attenuation of immune modulatory pathways in both young and aged mice of both sexes.

PDF file, 173K, Transient transfection of SOX10-specific siRNAs in 0380-MMU and UACC 1022 cells.

Supplementary Tables 1-2, Figures 1-3 from Mutational Inactivation of PTPRD in Glioblastoma Multiforme and Malignant Melanoma

PDF file, 122K, Senescence associated heterochromatin foci (SAHF) are more pronounced in melanoma cells when SOX10shRNA is expressed compared to non-silencing (NS) control.

PDF file, 164K, KitlacZ and Mitfvga are not sufficient genetic alterations to suppress melanoma in Grm1Tg mice.

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (

The SARS-CoV-2 virus emerged and spread quickly, leading to a pandemic within weeks of the first recognized cases. In this chapter, we describe a successful effort to develop and maintain situational awareness of COVID-19 presence and effects across Southwestern Ohio. Healthcare, public health, schools, and businesses organized and worked together to characterize the threat, align on common goals, share data, and spread messages in pursuit of disease suppression. The resulting communication across sector lines was key for understanding and managing the evolving phases of the COVID-19 pandemic in Southwestern Ohio.

Intracellular calcium (Ca(2+)) homeostasis is a vital process to nerve cell survival and function with an intricate regulatory network. It is well established that the endoplasmic reticulum (ER) is a major intraneuronal Ca(2+) storage and that the sarco/endoplasmic reticulum (SR/ER) calcium (Ca(2+))-ATPase (SERCA) pump is a key regulator of cytosolic Ca(2+) levels. SERCA pumps play a critical role in brain pathophysiology, thus SERCA comprises an emerging pharmacological target for the treatment of brain diseases. Interestingly, preclinical studies in rodents suggest that chronic pharmacological activation of SERCA2 by the quinoline derivative CDN1163 comprises a potential pharmacotherapeutic target in Alzheimer’s and Parkinson’s diseases. As little is known about the behavioral and neurochemical consequences of CDN1163 administration, in the current study we investigated the potential effects of acute (i.e., at 1h) and chronic (i.e., 17 days) CDN1163 administration (i.e., 10mg/kg and 20mg/kg; intraperitoneally) on locomotor activity and relevant affective behaviors, as well as on monoaminergic neurotransmission in naive C57BL/6J mice of both sexes. Interestingly, chronic, but not acute, CDN1163 administration induced anxiogenic and depressive-like behavioral effects in mice, as assessed in the open field test (OFT) and the forced swim test (FST), respectively. In addition, chronic CDN1163 administration induced sustained sex- and brain region-dependent noradrenergic and serotonergic neurochemical effects ex vivo. Taken together, present findings support the critical role of SERCA-dependent Ca(2+) handling in regulating behavior and neurochemical activity, and further highlights the need to consider sex in the development of SERCA-targeting pharmacotherapies for the treatment of debilitating brain disorders.

Imaging plays an important role in the diagnosis of urolithiasis as well as its pre-treatment planning and post-treatment follow-up. Proper imaging technique is essential to provide appropriate clinical care to affected patients. This article reviews the clinically relevant imaging findings most likely to influence management decisions.

A 19-year-old man presented with a 2-day history of hematuria, without pain, after hiking. Imaging revealed a well-circumscribed 4.6-cm retroperitoneal mass. A procedure was performed.

Aims To analyse all paediatric patients who presented with diabetic ketoacidosis (DKA) from 2012 to 2017. Methods A retrospective observational study was carried out analysing all cases of diabetic ketoacidosis admitted to a regional centre from 2012-2017. Results We identified 133 cases of DKA, 81 (61%) were newly diagnosed patients and 52 (39%) were patients with known T1DM. There were 215 new diagnoses of T1DM during the study period giving a DKA rate at diagnosis of 38%. Among the 52 cases with established T1DM, 13 cases (25%) presented in severe DKA and 37 cases (71%) occurred in adolescents aged over 12 years. Precipitating factors included chronic suboptimal control and psychosocial factors (28/52), acute illness (16/52), and pump technical failure (5/52). There were two cases treated for suspected cerebral oedema and one case each of subarachnoid haemorrhage and cardiac arrhythmia. Conclusion The current proportion of new T1DM presenting in DKA is higher than international data. The high frequency of DKA in known T1DM indicates a need for particular focus on adolescents.

Systemic vasoplegia is common in patients undergoing liver transplantation. In this report, we present a case in which treatment with conventional vasopressors caused peripheral arterial spasm, rendering arterial blood pressure monitoring impossible. Administration of methylene blue resolved the vasospasm; however, concern for toxic dose requirements limited its use. Hydroxocobalamin administration resolved the vasospasm and increased blood pressure without the potential adverse effects seen with methylene blue. This case represents the first report of hydroxocobalamin use in liver transplantation and may represent a new option for the treatment of vasoplegia and the potential vasospasm that may result from traditional vasopressors.

Shortage of donor organs has increased consideration for use of historically excluded grafts. Ex-vivo machine perfusion is an emerging technology that holds the potential for organ resuscitation and reconditioning, potentially increasing the quality and number of organs available for transplantation. This article aims to review the recent advances in machine perfusion and organ preservation solutions.Flow and pressure-based machine perfusion has shown improved kidney graft function and survival, especially among expanded criteria donors. Pressure-based machine perfusion is demonstrating promising results in preservation and resuscitation of liver, pancreas, heart, and also lung grafts. August 2014 marked Food and Drug Administration approval of XPS XVIVO Perfusion System (XVIVO Perfusion Inc., Englewood, Colorado, USA), a device for preserving and resuscitating lung allografts initially considered unsuitable for transplantation. Although there is no consensus among physicians about the optimal preservation solution, adding antiapoptotic and cell protective agents to preservation solutions is an interesting research area that offers potential to improve preservation.Ex-vivo machine perfusion of solid organs is a promising method that provides the opportunity for resuscitation and reconditioning of suboptimal grafts, expanding the number and quality of donor organs.

The transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression. The suppression of SOX10 in melanoma cells activates TGF-β signaling and can promote resistance to BRAF and MEK inhibitors. Since resistance to BRAF/MEK inhibitors is seen in the majority of melanoma patients, there is an immediate need to assess the underlying biology that mediates resistance and to identify new targets for combinatorial therapeutic approaches. Previously, we demonstrated that SOX10 protein is required for tumor initiation, maintenance and survival. Here, we present data that support phosphorylation as a mechanism employed by melanoma cells to tightly regulate SOX10 expression. Mass spectrometry identified eight phosphorylation sites contained within SOX10, three of which (S24, S45 and T240) were selected for further analysis based on their location within predicted MAPK/CDK binding motifs. SOX10 mutations were generated at these phosphorylation sites to assess their impact on SOX10 protein function in melanoma cells, including transcriptional activation on target promoters, subcellular localization, and stability. These data further our understanding of SOX10 protein regulation and provide critical information for identification of molecular pathways that modulate SOX10 protein levels in melanoma, with the ultimate goal of discovering novel targets for more effective combinatorial therapeutic approaches for melanoma patients.

Melanoma, a melanocyte origin neoplasm, is the most lethal type of skin cancer, and incidence is increasing. Several familial and somatic mutations have been identified in the gene encoding the melanocyte lineage master regulator, MITF; however, the neoplastic mechanisms of these mutant MITF variants are mostly unknown. Here, by performing unbiased analysis of the transcriptomes in cells expressing mutant MITF, we identified calcium-binding protein S100A4 as a downstream target of MITF-E87R. By using wild-type and mutant MITF melanoma lines, we found that both endogenous wild-type and MITF-E87R variants occupy the S100A4 promoter. Remarkably, whereas wild-type MITF represses S100A4 expression, MITF-E87R activates its transcription. The opposite effects of wild-type and mutant MITF result in opposing cellular phenotypes, because MITF-E87R via S100A4 enhanced invasion and reduced adhesion in contrast to wild-type MITF activity. Finally, we found that melanoma patients with altered S100A4 expression have poor prognosis. These data show that a change in MITF transcriptional activity from repression to activation of S100A4 that results from a point mutation in MITF alters melanoma invasive ability. These data suggest new opportunities for diagnosis and treatment of metastatic melanoma.

The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGFβ1) pathways, or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extended this knowledge by discovering that melanoma cell lines with these two expression programs exhibit distinctive microRNA (miRNA) expression patterns. We also demonstrated that hypoxia-inducible factor 1 alpha (HIF1A) is increased in TGFβ1 pathway-expressing melanoma cells and that HIF1A upregulates miR-210, miR-218, miR-224, and miR-452. Reduced expression of these four miRNAs in TGFβ1 pathway-expressing melanoma cells arrests the cell cycle, while their overexpression in mouse melanoma cells increases the expression of the hypoxic response gene Bnip3. Taken together, these data suggest that HIF1A may regulate some of the gene expression and biological behavior of TGFβ1 pathway-expressing melanoma cells, in part via alterations in these four miRNAs.

Background:Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings.Methods:A multi-site database, including motor symptom assessments conducted in 487 patients from palliative care, adult and old age consultation-liaison psychiatry services was used to document motor activity disturbances as per the Delirium Motor Checklist (DMC). Latent class analysis (LCA) was used to identify the class structure underpinning DMC data and also items for a brief subtyping scale. The concordance of the abbreviated scale was then compared with the original Delirium Motor Subtype Scale (DMSS) in 375 patients having delirium as per the American Psychiatric Association's Diagnostic and Statistical Manual (4th edition) criteria.Results:Latent class analysis identified four classes that corresponded closely with the four recognized motor subtypes of delirium. Further, LCA of items (n = 15) that loaded >60% to the model identified four features that reliably identified the classes/subtypes, and these were combined as a brief motor subtyping scale (DMSS-4). There was good concordance for subtype attribution between the original DMSS and the DMSS-4 (κ = 0.63).Conclusions:The DMSS-4 allows for rapid assessment of clinical subtypes in delirium and has high concordance with the longer and well-validated DMSS. More consistent clinical subtyping in delirium can facilitate better delirium management and more focused research effort.

The transcription factor SOX10 is essential for survival and proper differentiation of neural crest cell lineages, where it plays an important role in the generation and maintenance of melanocytes. SOX10 is also highly expressed in melanoma tumors, but a role in disease progression has not been established. Here, we report that melanoma tumor cell lines require wild-type SOX10 expression for proliferation and SOX10 haploinsufficiency reduces melanoma initiation in the metabotropic glutamate receptor 1 (Grm1Tg) transgenic mouse model. Stable SOX10 knockdown in human melanoma cells arrested cell growth, altered cellular morphology, and induced senescence. Melanoma cells with stable loss of SOX10 were arrested in the G1 phase of the cell cycle, with reduced expression of the melanocyte determining factor microphthalmia-associated transcription factor, elevated expression of p21WAF1 and p27KIP2, hypophosphorylated RB, and reduced levels of its binding partner E2F1. As cell-cycle dysregulation is a core event in neoplastic transformation, the role for SOX10 in maintaining cell-cycle control in melanocytes suggests a rational new direction for targeted treatment or prevention of melanoma. Cancer Res; 73(18); 5709–18. ©2013 AACR.

In liver transplantation, a left lateral section (LLS) graft may have an unusual variant left hepatic vein (LHV) anatomy. This study was designed to analyze the incidence of unusual LHV variants and to determine technical methods for effective reconstruction in infant recipients weighing approximately 10 kg or less. The study comprised 3 parts: an LHV variation analysis, a simulation-based design for the technical modification of graft LHV venoplasty, and its clinical application. The LHV anatomy of 300 potential LLS graft donors was classified into 4 types according to the number and location of the hepatic vein openings: (1) a single opening (n = 218 or 72.7%); (2) 2 large adjacent openings (n = 29 or 9.7%); (3) 2 adjacent openings, 1 large and 1 small (n = 34 or 11.3%); and (4) 2 widely spaced openings (n = 19 or 6.3%). Types 2 and 3 required wedged unification venoplasty, and type 4 required additional vein interposition. In a series of 49 cases using LLS grafts, the graft hepatic vein complication rate was 4.5% at 3 years; stenting was necessary for 1 of the 36 type 1 LHV grafts (2.8%) and for 1 of the 13 type 2-4 LHV grafts (7.7%, P = 0.46). A customized interposition-wedged unification venoplasty technique for coping with type 4 vein variations was developed with a simulation-based approach, and it was successfully applied to a 10-month-old male infant receiving an LLS graft with a type 4 LHV. In conclusion, nearly all LHV variations can be effectively managed with customized unification venoplasty. These venoplasty techniques represent beneficial surgical options as part of graft standardization for hepatic vein reconstruction in pediatric living donor liver transplantation.

Pediatricians are required by law to notify child protection agencies if parents are neglecting their child’s medical needs. Sometimes, however, it is difficult to determine when a particular parental choice ought to be reported. If the treatment is standard therapy and the consequences of nontreatment are dire, than parental refusal is usually considered neglectful. Organ transplants, however, represent a unique situation for 2 reasons. First, because there is a dire scarcity of organs, there are more people who need organs than there are organs to transplant. In this situation, it seems odd to force a transplant on a child whose parents do not want it, knowing that other parents are eager to have their child undergo a transplant. Second, transplantation is risky and requires lifelong follow-up and treatment. Thus, parental cooperation is essential. We present a case of a child who needs a liver transplant and whose parents refuse, and ask 2 surgeons, a gastroenterologist, and a child abuse specialist to comment on the case. David C. Cronin is director of the liver transplant program at the Medical College of Wisconsin. Robert Squires is a gastroenterologist, George Mazariegos is a transplant surgeon, and Janet Squires is chief of the child advocacy center, all at the University of Pittsburgh. A 10-month-old girl, Baby A, was admitted to the hospital because of worsening jaundice. She had been diagnosed with biliary atresia at 1 month of age, and a Kasai procedure was performed when she was 10 weeks old. Since then, she had been failing to thrive and had worsening jaundice. On the current admission, the patient’s weight was 8 kg (

In September 2016, the University of Chicago and Peking Union Medical Center co-sponsored a conference in Beijing, People’s Republic of China marking the twentieth anniversary of the Milan criteria (1).

Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent/hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets – GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 – are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0.0013) and ROC curve analysis (AUC= 0.826, P-value

Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI).Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy. The change in MR signal intensity from the baseline before the contrast injection (ΔSI) was analyzed every minute for 30 min. Dynamic signal intensity retention ratio (DSR) was defined as the mean ΔSI of the third 10-minmin period divided by the first 10-minmin period. Real-time PCR was utilized to quantify mRNA expressions.Compared to the control, cirrhosis group demonstrated lower mRNA levels of OATP1 (0.038 ± 0.020 vs. 0.232 ± 0.0979; p = 0.004), MRP2 (0.201 ± 0.084 vs. 0.7567 ± 0.254; p = 0.002), and OATP1/MRP2 mRNA ratio (0.193 ± 0.065 vs. 0.342 ± 0.206; p = 0.032). DSR was higher in the cirrhosis group (0.678 ± 0.554 vs -0.125 ± 0.839; p = 0.033). In the cirrhosis group, there was an inverse correlation between the ratios of OATP1/MRP2 mRNA and DSR (R = -0.709, p = 0.01).Bile transporters OATP1/MRP2 mRNA expression ratio in rat liver tissue decreased with DMN-induced liver injury. The expressions of bile transporters correlated with GE-MRI DSR. The GE-MRI DSR has potential utility in qualifying OATP1/MRP2 mRNA expression.

Successful liver transplantation typically results in an immediate decrease in intrahepatic resistance accompanied by an initial increased hepatopedal portal flow. Within a short period of time, the portal hypertension resolves and the variceal shunts involute. However, in situations in which intrahepatic vascular resistance to venous flow remains elevated, significant hepatofugal portal flow may continue through persistent mesenteric shunts. This situation, portal steal, can result in decreased perfusion of the liver graft leading to graft dysfunction, failure, and potentially recipient death. This report details a case and the surrounding literature to highlight appropriate diagnosis and management in these patients.

A 28-year-old woman gravida 4 Para 0 presented with a history of cervical insufficiency following three midtrimester miscarriages, two at 16 weeks and one at 17 weeks. The last two mid-trimester miscarriages presented with painless rupture of membranes and cervical shortening was demonstrated on ultrasound in one. She also had one early miscarriage at 6 weeks. There was no patient history of cervical instrumentation, cervical surgery, congenital abnormality or uterine anomaly. There was also no history of thrombophilia, translocation or maternal family history of recurrent miscarriage. She was appropriately counselled and offered an interval robot-assisted abdominal cerclage (Interval RA-AC). The procedures were carried out using the da Vinci System. The ports were sited as per Fig. 1. The procedure was performed as previously described [1, 2] using steep Trendelenburg position, uterine manipulation with a size 10 Hagar dilator in order to prevent over-tightening of the cervix, bladder reflection (Fig. 2) and broad ligament fenestration bilaterally (Fig. 3). A one Ethibond (Ethicon Inc., Johnson & Johnson, USA) suture was placed medial to the uterine artery bilaterally (Fig. 4) and tied posteriorly (Fig. 5). She was discharged without complication later that day and remained well. She subsequently became spontaneously pregnant. Her pregnancy was uncomplicated and she delivered a healthy female infant (weighing 2.58 kg) by elective caesarean section (CS) at 37 weeks gestation. There were no intraoperative difficulties. The suture was neither visualised nor felt at CS, and it was presumably deep in the substance of the myometrium. The cerclage remains in place for subsequent pregnancies.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

Transplant patients are at risk for a variety of gastrointestinal complications due to long-term immunosuppression. One such complication is colonic perforation in the setting of diverticular disease. While complicated diverticulitis has been reported in heart, lung, and kidney transplant patients, here we report the first case of complicated sigmoid diverticulitis in a patient after an orthotopic liver transplant. We also present a case where complicated diverticulitis can progress to free perforation in the setting of immunosuppression in transplant patients. Although not associated with an increased risk of development of diverticular disease, long-term immunosuppression not only increases risk of colonic perforation in the setting of diverticular disease but also masks the clinical signs and symptoms. Therefore, transplant patients with vague symptoms of abdominal pain should be evaluated and followed vigilantly for diverticulitis and signs of perforation.

The photophysical properties of a range of fluorescent sensors with β-aminobisphosphonate receptors have been studied. The compounds were designed according to the fluorophore–spacer–receptor format of photoinduced electron transfer-based sensors. The sensors displayed unusual fluorescence intensity–pH profiles that were attributed to a receptor–fluorophore H-bonding interaction that resulted in a quenching of fluorescence. The number of receptors and the nature of the fluorophore were both shown to have an effect on the pH profiles of the sensors. In addition, compound 1 was also shown to be selective for Cu2+ ions, in water at pH 7.4 with sensitivity in the micromolar range.

Tyrosine phosphorylation is important in signaling pathways underlying tumorigenesis. We performed a mutational analysis of the protein tyrosine kinase (PTK) gene family in cutaneous metastatic melanoma. We identified 30 somatic mutations affecting the kinase domains of 19 PTKs and subsequently evaluated the entire coding regions of the genes encoding these 19 PTKs for somatic mutations in 79 melanoma samples. We found ERBB4 mutations in 19% of individuals with melanoma and found mutations in two other kinases (FLT1 and PTK2B) in 10% of individuals with melanomas. We examined seven missense mutations in the most commonly altered PTK gene, ERBB4, and found that they resulted in increased kinase activity and transformation ability. Melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4 or treatment with the ERBB inhibitor lapatinib. These studies could lead to personalized therapeutics specifically targeting the kinases that are mutationally altered in individual melanomas.

BACKGROUND: A widely reported ABO-mismatch accident in March of 2003 raised concerns about the reliability of the transplantation system. Because this type of failure is rare and significant, we performed a probabilistic risk assessment (PRA) of the donor-recipient matching processes for thoracic organ transplantation. METHODS: A probabilistic risk assessment was performed. RESULTS: The likelihood of accidental incompatible implantation was already low in 2003. The PRA model indicates that the likelihood of such an event was 1.38x10 per donated organ. This estimate correlates closely with the observed rate of these accidents. Based on this model, process changes put in place shortly after the accident reduced the probability to approximately 3.08x10 and changes put in place in October 2004 further reduced the probability to approximately 2.22x10 per organ donated. CONCLUSIONS: The observed and predicted likelihoods of accidental incompatible thoracic organ transplantation are comparable. These likelihoods are several orders of magnitude smaller than other hazards associated with solid organ transplantation. The PRA model indicates that changes that followed the March 2003 accident further reduced the likelihood of accidental incompatible implantation by roughly two orders of magnitude. Quantitative estimates from PRA can be used to assess risks in healthcare and to gauge the impact of system changes on these risks.

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR 1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients. Median follow-up is 7.1 years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA 80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR 1 year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility.

29. Delmonico FL, Arnold R, Scheper-Hughes N, Siminoff LA, Kahn J, Youngner SJ. Ethical incentives—not payment—for organ donation. N Engl J Med. 2002;346(25):2002-2005. 30. Salim A, Malinoski D, Schulman D, Desai C, Navarro S, Ley EJ. The combination of an online organ and tissue registry with a public education campaign can increase the number of organs available for transplantation. J Trauma. 2010;69(2): 451-454.

The long-term impact of allosensitization between ABO compatible donor/recipient pairs in liver transplantation is unclear. Accumulating clinical evidence suggests that donor-specific antibody formation may lead to antibody-mediated rejection and is causally linked to pathologic injury, graft loss, and death. Although this immune-mediated graft dysfunction is increasingly being associated with poor outcomes, the specific pathologic sequelae are not defined. Herein, we examine the relationship between allosensitization, antibody-mediated rejection, and subsequent graft pathology.

Objectives Follow-up of celiac disease diagnosed in childhood is variable or nonexistent after transition to adulthood. Outcome, continuity of care, and adherence to a gluten-free diet are poorly documented. We report a 28-yr follow-up of 50 adults in whom the original childhood diagnosis could be confirmed. Methods Original pediatric charts were reviewed, and subjects were invited to undergo dietary evaluation, measurement of bone mineral density, and quality-of-life assessment. The mean duration of celiac was 28.5 yr, median 28.7 yr (range 22-45 yr). The mean and median age of the group was 35 yr. Results Only 22% of patients were enrolled in an adult gastroenterology clinic. Fifty percent were fully compliant with a gluten-free diet; 18% were partially compliant; and 32% were not adhering to diet. The main motivating factor for dietary compliance was avoidance of symptoms rather than avoidance of complications. Eighty-six percent of the females and 21% of the males had iron deficiency. Bone mineral density was subnormal in 32%; 28.9% were osteopenic and 2.6% were osteoporotic. Quality-of-life scores were normal. Conclusions Most patients diagnosed with celiac in childhood receive no medical or dietary supervision after transition to adulthood. One-third are not compliant with diet; the primary motivating factor for those who do comply is avoidance of symptoms rather than fear of complications. The prevalence of preventable and treatable disorders in these young adults highlights a failure of health services after transition from pediatric to adult health care.

Background: Investigation of a suspected peri-prosthetic infection post joint arthroplasty typically involves an index of clinical suspicion and the use of inflammatory markers, radiological assessment and joint aspiration. Joint aspiration remains the gold standard, but the risk of false positives limits its accuracy. We describe a novel technique of joint aspiration that addresses its inherent shortcomings by limiting the exposure to contamination by skin commensals. Methods: In a laminar airflow theatre, a spinal needle is introduced into the joint space via a truncated 5 ml syringe, (with the plunger removed). The trajectory and position of the advancing spinal needle is confirmed using intermittent anteroposterior (AP) fluoroscopy.Results: The technique described here isolates the aspirating needle and the subsequent sample(s) obtained from the skin flora, thus it also has the advantage of isolating the joint in the same manner. This technique has the added advantages of being simple, cost effective, easy to employ and easy to teach. As it is based on a simple principle it can also be modified for use in prosthetic knee aspirations or in cases where septic arthritis is suspected.Conclusions: Joint aspiration is a useful technique in providing a diagnostic sample to assist in the diagnosis of suspected joint infections. Its sensitivity is affected owing to the risk of sample contamination when obtaining the sample. This technique aims to address the shortcomings of traditional joint aspiration by isolating the aspirating needle and the subsequently obtained sample from the surrounding skin.