Comparative transcriptomic analysis of races 1, 2, 5 and 6 of Fusarium oxysporum f.sp. pisi in a susceptible pea host identifies differential pathogenicity profiles.

BACKGROUND: The fungal pathogen Fusarium oxysporum f.sp. pisi (Fop) causes Fusarium wilt in peas. There are four races globally: 1, 2, 5 and 6 and all of these races are present in Australia. Molecular infection mechanisms have been studied in a few other F. oxysporum formae speciales; however, there has been no transcriptomic Fop-pea pathosystem study. RESULTS: A transcriptomic study was carried out to understand the molecular pathogenicity differences between the races. Transcriptome analysis at 20 days post-inoculation revealed differences in the differentially expressed genes (DEGs) in the Fop races potentially involved in fungal pathogenicity variations. Most of the DEGs in all the races were engaged in transportation, metabolism, oxidation-reduction, translation, biosynthetic processes, signal transduction, proteolysis, among others. Race 5 expressed the most virulence-associated genes. Most genes encoding for plant cell wall degrading enzymes, CAZymes and effector-like proteins were expressed in race 2. Race 6 expressed the least number of genes at this time point. CONCLUSION: Fop races deploy various factors and complex strategies to mitigate host defences to facilitate colonisation. This investigation provides an overview of the putative pathogenicity genes in different Fop races during the necrotrophic stage of infection. These genes need to be functionally characterised to confirm their pathogenicity/virulence roles and the race-specific genes can be further explored for molecular characterisation.

Phylogenetic relationship between Australian Fusarium oxysporum isolates and resolving the species complex using the multispecies coalescent model.

BACKGROUND: The Fusarium oxysporum species complex (FOSC) is a ubiquitous group of fungal species readily isolated from agroecosystem and natural ecosystem soils which includes important plant and human pathogens. Genetic relatedness within the complex has been studied by sequencing either the genes or the barcoding gene regions within those genes. Phylogenetic analyses have demonstrated a great deal of diversity which is reflected in the differing number of clades identified: three, five and eight. Genetic limitation within the species in the complex has been studied through Genealogical Concordance Phylogenetic Species Recognition (GCPSR) analyses with varying number of phylogenetic 'species' identified ranging from two to 21. Such differing views have continued to confuse users of these taxonomies. RESULTS: The phylogenetic relationships between Australian F. oxysporum isolates from both natural and agricultural ecosystems were determined using three datasets: whole genome, nuclear genes, and mitochondrial genome sequences. The phylogenies were concordant except for three isolates. There were three concordant clades from all the phylogenies suggesting similar evolutionary history for mitochondrial genome and nuclear genes for the isolates in these three clades. Applying a multispecies coalescent (MSC) model on the eight single copy nuclear protein coding genes from the nuclear gene dataset concluded that the three concordant clades correspond to three phylogenetic species within the FOSC. There was 100% posterior probability support for the formation of three species within the FOSC. This is the first report of using the MSC model to estimate species within the F. oxysporum species complex. The findings from this study were compared with previously published phylogenetics and species delimitation studies. CONCLUSION: Phylogenetic analyses using three different gene datasets from Australian F. oxysporum isolates have all supported the formation of three major clades which delineated into three species. Species 2 (Clade 3) may be called F. oxysporum as it contains the neotype for F. oxysporum.

[What are the predictive factors of the pain during the treatment of kidney stones by extra-corporeal shockwave lithotripsy?]. / Quels sont les facteurs prédictifs de la douleur lors du traitement des calculs rénaux par lithotritie extracorporelle ?

PURPOSE: Identify predictors for selecting patients who requires analgesia during lithotripsy. METHODS: This is a prospective study over a period of 13 months, 100 patients with kidney stones treated by an electromagnetic lithotripter (siemens; lithoskop) were selected. For the study of subjective pain caused by the ESWL at different times of the session, a visual analog scale (VAS) was used at different times (T) of the session (T0 before shots, T1 at 500 shots, T2 at 1500 shots, T end of treatment). A session was considered painless if VAS≤3. To identify predictors, were investigated association between pain and the different characteristics of patients, kidney stones and the shock wave specifications. RESULTS: The analytical study showed that pain was correlated with female gender, anxiety score, skin distance stones, parietal distance and the energy of the shock wave. While age, waist circumference, the circumstance found, the projection of stones on the rib and the number of shots had no impact on the level of pain. CONCLUSION: Our study showed that even with an electromagnetic lithotripter third generation; ESWL is still painful leading to the interruption of the session in 29% of cases. Four major predictors of pain leading to the use of sedo-analgesia early in the session were identified. LEVEL OF EVIDENCE: 3.

Native portal vein embolization for persistent hyperoxaluria following kidney and auxiliary partial liver transplantation.

Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM-R). Following initial combined APLT-KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM-R could be corrected by trans-hepatic native PVE. The resulting increased APLT/NLM-R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT-KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function.

Early readmissions post kidney transplantation: lessons learned.

INTRODUCTION: Kidney transplantation (KT) is the gold standard treatment for end-stage renal disease (ESRD) patients. Hospital readmissions post-transplant is a common complication and can be considered an indication of avoidable morbidity and hospital quality, and there is a significant correlation between EHR and adverse patient outcomes. This study aimed to assess the readmission rate following kidney transplants, the underlying causes, and possible ways to prevent it. MATERIAL AND METHODS: We retrospectively reviewed the medical records of recipients from January 2016 to December 2021 in a single center. The primary objective of this study is to find the readmission rate for kidney transplants and the variables that contribute to readmission. Post-transplant complications that were resulted in the readmission categorized into surgical complications, graft-related complications, infections, DVT, and other medical complications. RESULTS: Four hundred seventy-four renal allograft recipients met our inclusion criteria and were included in the study. 248 (52.3%) of the allograft recipients had at least one readmission during the first 90 days after the transplantation. 89 (18.8%) allograft recipients had more than one readmission episode in the first 90 days post-transplant. The perinephric fluid collection was the most common surgical complication (52.4%), and UTI was the most common infection (50%), causing readmission in the first 90 days post-transplant. The readmission odd ratio was significantly higher in patients above 60 years old and in kidneys with KDPI ≥ 85, and in recipients with DGF. CONCLUSION: Early hospital readmission (EHR) following a kidney transplant is a common complication. Identifying the causes not only helps the transplant centers to take further steps to prevent some incidents and help to improve the patients' morbidities and mortalities, but also it can reduce the unnecessary costs of readmissions.

Diagnosis of Fusarium oxysporum f. sp. ciceris causing Fusarium wilt of chickpea using loop-mediated isothermal amplification (LAMP) and conventional end-point PCR.

Fusarium oxysporum (Fo) is ubiquitous in soil and forms a species complex of pathogenic and putatively non-pathogenic strains. Pathogenic strains cause disease in over 150 plant species. Fusarium oxysporum f. sp. ciceris (Foc) is a major fungal pathogen causing Fusarium wilt in chickpeas (Cicer arietinum). In some countries such as Australia, Foc is a high-priority pest of biosecurity concern. Specific, sensitive, robust and rapid diagnostic assays are essential for effective disease management on the farm and serve as an effective biosecurity control measure. We developed and validated a novel and highly specific PCR and a LAMP assay for detecting the Indian Foc race 1 based on a putative effector gene uniquely present in its genome. These assays were assessed against 39 Fo formae speciales and found to be specific, only amplifying the target species, in a portable real-time fluorometer (Genie III) and qPCR machine in under 13 min with an anneal derivative temperature ranging from 87.7 to 88.3 °C. The LAMP assay is sensitive to low levels of target DNA (> 0.009 ng/µl). The expected PCR product size is 143 bp. The LAMP assay developed in this study was simple, fast, sensitive and specific and could be explored for other Foc races due to the uniqueness of this marker to the Foc genome.

Relationship between conventional sperm parameters and motile sperm organelle morphology examination (MSOME).

With the motile sperm organelle morphology examination (MSOME), spermatozoa morphology may be assessed directly on motile spermatozoa at high magnification (up to 6600×). This procedure describes more precisely spermatozoa abnormalities, especially head vacuoles. However, no consensus has been established concerning normal or abnormal MSOME criteria. The aim of our study was to define MSOME vacuole criteria assessed objectively with a digital imaging system software to establish a potential relationship between conventional semen parameters. A total of 440 semen samples were obtained from males consulting in Rouen University Hospital Reproductive Biology Laboratory. Conventional semen analysis (volume, sperm concentration, progressive motility, vitality and morphology) and MSOME assessment {sperm head length, width and area as well as vacuole number, vacuole area and relative vacuole area to sperm head [RVA (%) = [vacuole area (µm(2))/head area (µm(2))] × 100)]} were performed for each semen sample. Among our 440 males, 109 presented normal conventional semen parameters and 331 abnormal ones. Sperm head vacuoles were significantly larger in abnormal semen samples (p < 0.0001). RVA was the most discriminative MSOME criterion between normal and abnormal semen samples according to ROC curves analysis, and was negatively correlated with poor sperm morphology (r = -0.53, p < 0.0001). We concluded to (i) the normal occurrence of vacuoles in sperm head whatever the normality or abnormality of semen parameters, (ii) the discriminative function of the RVA to distinguish semen samples with normal and abnormal parameters, and (iii) the strong correlation between high RVA and poor sperm morphology.

Changing pattern of organ donation at a single center: are potential brain dead donors being lost to donation after cardiac death?

Donation after cardiac death (DCD) has proven effective at increasing the availability of organs for transplantation.We performed a retrospective examination of Massachusetts General Hospital (MGH) records of all 201 donors from 1/1/98 to the 11/2008, including 54 DCD, 115 DBD and 32 DCD candidates that did not progress to donation (DCD-dnp). Comparing three time periods, era 1 (01/98-12/02), era 2 (01/03-12/05) and era 3 (01/06-11/08), DCD's comprised 14.8,48.4% and 60% of donors, respectively (p = 0.002). A significant increase in the incidence of cardiovascular/cerebrovascular as cause of death was evident in era 3 versus eras 1 and 2; 74% versus 57.1% (p<0.001),as was a corresponding decrease in the incidence of traumatic death. Interestingly, we noted an increase in utilization of aggressive neurological management over time, especially in the DCD group.We detected significant changes in the make-up of the donor pool over the past decade. That the changes in diagnosis over time did not differ between DCD and DBD groups suggests this difference is not responsible for the increase in DCD rates. Instead, we suggest that changes in clinical practice, especially in management of patients with severe brain injury may account for the increased proportion of DCD.

[Febrile algo-eruptive illness in a French foreign legionnaire returning from Djibouti: gonococcal arthritis]. / Fièvre algo-éruptive chez un légionnaire au retour de Djibouti.

A French foreign legionnaire returning from Djibouti developed feverish polyarthritis with acral purpura. Diagnostic workup demonstrated gonococcemia contracted during unprotected fellatio. Based on this case report, diagnostic and therapeutic management is described.

[Congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency]. / Anémie hémolytique congénitale par déficit en Glucose-6-Phosphate Déshydrogénase.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme defect with a wide range of clinical manifestations that can be severe. A variety of factors including many medications can induce hemolytic episodes. Screening for G6PD deficiency is required before use of some drugs especially primaquine or dapsone.

[Which photon energy for intensity-modulated radiotherapy and volumetric-modulated arctherapy in 2019?] / Quelle énergie de photons pour la modulation d'intensité et l'arcthérapie volumétrique en 2019 ?

For more than a decade, the majority of radiation oncology centres have been delivering intensity-modulated radiotherapy (then volumetric-modulated arctherapy) with 6 MV photons as their standard of care. This « dogma ¼ had been supported by the usual absence of dosimetric advantages with high-energy photons (15 to 18 MV or more), at least for the planning target volume and the dose received by the adjacent organs at risk, and by the neutron component as soon as the photon energy exceeds 10 MV. Recent data could question such a dogma. First, in 2019, one cannot avoid taking into account the integral dose, delivered outside the treated volume. Actually, most available data show that integral dose is higher with low energy photons (as 6 MV) than with higher energies. Moreover, recent studies have shown that the neutron component at high energies may have been overestimated in the past; in fact, the neutron dose appears to be lower, and sometimes much lower, than the dose we accept for imaging. Finally, a few cohort studies did not show any increase in second cancers incidence after high-energy photon radiotherapy. In such a context, the American Association of Physicists in Medicine (AAPM) TG 158 document, released a few months ago, clearly states that there is a trade-off between high- and low-energy treatments. High-energy therapy is associated with neutron production, while low-energy therapy results in higher stray photon dose. According to the AAPM, « the optimal energy is likely an intermediate such as 10 MV ¼.

The market of human organs: a window into a poorly understood global business.

The global demand for human organs has set the stage for an exploding and poorly understood global business in human organs. Whenever there is demand for a product, the opportunity for business arises. The form that a business takes is dependent on a complex network of inputs and outputs, each affecting the others. Historically, the details of any specific market are drastically underestimated. Nowhere is this truer than in the market of human organs. The drivers, which propel the "goods" of human organs, form a flourishing business. Critical analysis is essential to understanding of the supply and demand sides and to determine the role of government in regulating the industry. Governmental groups have dismissed formation of a regulated market for organ sales. The concept is nonetheless a topic of active discussion, motivated by the suffering of patients in need of organs and exploitation of the victims of human trafficking. Ethical principles have been invoked on each side of the ensuing debate. Theory in the absence of sufficient data is shaky ground for enactment of new policy. The Aristotelian concept of "practical wisdom" and the pragmatism of William James illuminate the importance of scientific investigation as guide to policy formation. How will stakeholders benefit or lose? What impact might be anticipated in regard to organized medicine's social contract? What can we learn about cross-cultural differences and their effect on the global landscape?

Impact of donor kidney recovery method on lymphatic complications in kidney transplantation.

INTRODUCTION: Prolonged lymphatic drainage and lymphocele are undesirable complications following kidney transplantation. We evaluated the impact of kidney recovery methods (deceased donor vs laparoscopic nephrectomy) on the lymphatic complications of the kidney transplant recipients. METHOD: The incidence of lymphatic complications was retrospectively analyzed in recipients of deceased donor kidneys (DD, n = 62) versus laparoscopically procured kidneys from living donors (LP, n = 61). A drain was placed in the retroperitoneal space in all recipients. The drain was maintained until the output became less than 30 mL/d with no evidence of fluid collection by ultrasound examination. RESULTS: There was no statistically significant difference in the patient demographics (age, gender, and original disease and procedure time) between two groups. The incidence of lymphocele that required therapeutic intervention was comparable in both groups (3.2%). However, the duration of drain placement was significantly longer in the LP group than in the DD group, 8.6 +/- 2.5 days versus 5.4 +/- 2.5 day, respectively (P < .05). CONCLUSION: The recipients of laparoscopically removed kidneys had a higher incidence of prolonged lymphatic leakage. More meticulous back table preparation may be required in LP kidneys to prevent prolonged lymphatic drainage after kidney transplantation. These observations may indicate that the major source of persistent lymphatic leakage is lymphatics of the allograft rather than severed recipient lymphatics.

Deceased donor kidney transplantation in elderly patients: is there a difference in outcomes?

INTRODUCTION: There is a paucity of data on long-term outcomes of older kidney recipients. Our aim was to compare the early and long-term outcomes of deceased donor kidney transplantation in patients aged >or=60 years with outcomes in younger recipients. MATERIALS AND METHODS: From 1998 to 2005, we performed 271 deceased donor kidney transplants. There were 76 recipients (28.1%) >60 years old. Older candidates were carefully selected based on their physiologic, cardiac, and performance status. Demographic data, including clinical characteristics, early complications, mortality, and patient and graft survival rates, were collected and analyzed. RESULTS: Older patients had comparable perioperative mortality and morbidity, incidence of delayed graft function (DGF), length of stay, and readmissions compared with younger patients. The rates of acute rejection and major infections were also comparable between the 2 study groups. Among older recipients, 25/76 (32.1%) patients received extended criteria donor kidneys compared with only 35/195 (17.9%) of younger patients (P < .001). Nevertheless, equivalent 1-, 3-, and 5-year allograft survival rates were observed in elderly and young patients; 91.5% versus, 92.5%, 78.5% versus 81.9%, and 75.6% versus 78.5%, respectively. Overall patient survival was also comparable in both groups. CONCLUSION: Kidney transplantation in appropriately selected elderly recipients provides equivalent outcomes compared with those observed in younger patients. These observations support the notion that older recipients should not lose access to deceased donor kidney transplantation in the effort to achieve a perceived gain in social utility.

Ischemic preconditioning and intermittent clamping increase the tolerance of fatty liver to hepatic ischemia-reperfusion injury in the rat.

INTRODUCTION: Liver ischemia-reperfusion (I/R) injury is a well-known cause of morbidity and mortality following liver surgery and transplantation. Hepatic steatosis increases the extent of cellular injury incurred during I/R injury. We sought to identify measures that reduced the untoward sequelae of liver I/R injury. METHODS: Male Zucker rats were subjected to 75 minutes of 70% hepatic ischemia, and 3 hours of reperfusion. The ischemic periods were based on the following protocols: continuous clamping (CC) for 75 minutes; intermittent clamping (IC) with five cycles of 15 minutes clamp on and 5 minutes clamp off; or ischemic preconditioning (IP) with 10 minutes clamp on, 15 minutes off, and 60 minutes on (n=7 in each group). Warm I/R injury was evaluated using serum levels of aspartate aminotransferase (AST), serum interleukin (IL)-6, as well as hematoxylin and eosin staining. RESULTS: Hepatocellular injury was significantly reduced with IP or IC compared with CC (AST: 3285+/-122.3 and 2875+/-285.4 compared with 5436.3+/--984.7 units/L, respectively; P<.01). Serum IL-6 level was also significantly reduced with IP and IC compared with CC (70+/-8.8 and 76+/-6.2 compared with 147+/-8.5 ng/l, respectively (p<.01). Histological analysis also revealed that IC and IP provided significant protection compared with the CC group. CONCLUSION: IC and IP increased the tolerance of a fatty liver to hepatic I/R injury.

Recent Progress in Cell Therapy in Solid Organ Transplantation.

There has been ample of preclinical and animal studies showing efficacy and safety of using various cells, such as stem cells or T regulatory cells, after transplantation for tissue repair, immunosuppression or tolerance induction. However, there has been a significant progress recently using cell therapy in solid organ transplantation in small clinical trials. Recent results have been promising and using cell therapy in solid organ transplantation seems feasible and safe. However, there are more hurdles to overcome such as dose and timing of the infusions. Current studies mainly focused on live donor kidney transplantation. Expansion of current regimes to other organs and deceased donor transplantation would be crucial.

Outcomes of Full-Right-Full-Left Split Liver Transplantation in Adults in the USA: A Propensity-Score Matched Analysis.

BACKGROUND: Splitting a liver for utilization in adult/pediatric recipients has been shown to decrease mortality on the wait list without increasing the overall risk of long-term graft failure compared to a whole graft. However, splitting a single donor organ for two adult recipients, full-right-full-left split liver transplantation (FRFLSLT), to overcome organ shortage is still considered controversial. OBJECTIVE: This study assessed the outcome of FRFLSLT comparing full-right (FR) and full-left (FL) with whole liver (WL) allografts in adults (1998-2010) using UNOS standard transplant analysis and research (STAR) file. Methods: Unadjusted allograft and patient survival were estimated using Kaplan-Meier survival curves. Adjusted analyses of survival were conducted controlling for propensity for WL allograft. RESULTS: There were 83,313 cases of WL, 651 FR and 117 FL. Significant differences were evident in the unadjusted cohort between recipients who received FR and FL including donor, cold ischemic time, and days on transplant waiting list. Use of FL allograft resulted in a trend toward lower graft and patient survival compared to WL and FR, which was not statistically significant (p=0.07). In the matched cohort, FL hemiliver allograft had no detrimental effect on the allograft or patient survival after split liver transplantation when compared to FR and WL. CONCLUSION: After adjusting for donor and recipient characteristics, there was no difference in allograft or patient survival with the use of FL, FR, or WL after liver transplantation in adults. FRFLSLT is a valuable and safe option to expand the donor pool.

Mesenchymal Stem Cells and Co-stimulation Blockade Enhance Bone Marrow Engraftment and Induce Immunological Tolerance.

BACKGROUND: Organ transplantation currently requires long-term immunosuppression. This is associated with multiple complications including infection, malignancy and other toxicities. Immunologic tolerance is considered the optimal solution to these limitations. OBJECTIVE: To develop a simple and non-toxic regimen to induce mixed chimerism and tolerance using mesenchymal stem cell (MSC) in a murine model. METHODS: Wild type C57BL6 (H2D(k)) and Bal/C (H2D(d)) mice were used as donors and recipients, respectively. We studied to achieve tolerance to skin grafts (SG) through mixed chimerism (MC) by simultaneous skin graft and non-myeloablative donor bone marrow transplantation (DBMT) +/- MSC. All recipients received rapamycin and CTLA-4 Ig without radiation. RESULTS: DBMT+MSC combined with co-stimulation blockage and rapamycin led to stable mixed chimerism, expansion of Tregs population and donor-specific skin graft tolerance. The flow cytometry analysis revealed that recipient mice developed 15%-85% chimerism. The skin allografts survived for a long time. Elimination of MSC failed to induce mixed chimerism and tolerance. CONCLUSION: Our results demonstrate that donor-specific immune tolerance can be effectively induced by non-myeloablative DBMT-MSC combination without any additional cytoreductive treatment. This approach provides a promising and non-toxic allograft tolerance strategy.

Competitive Market Analysis of Transplant Centers and Discrepancy of Wait-Listing of Recipients for Kidney Transplantation.

BACKGROUND: There are over 250 kidney transplant programs in the USA. OBJECTIVE: To determine if highly competitive regions, defined as regions with a higher number of transplant centers, will approve and wait-list more end-stage renal disease (ESRD) candidates for transplant despite consistent incidence and prevalence of ESRD nationwide. METHODS: ESRD Network and OPTN data completed in 2011 were obtained from all transplant centers including listing data, market saturation, market share, organs transplanted, and ESRD prevalence. Herfindahl-Hirschman Index (HHI) was used to measure the size of firms in relation to the industry to determine the amount of competition. RESULTS: States were separated into 3 groups (HHI<1000 considered competitive; HHI 1000-1800 considered moderate competition; and HHI>1800 considered highly concentrated). The percentage of ESRD patients listed in competitive, moderate, and highly concentrated regions were 19.73%, 17.02%, and 13.75%, respectively. The ESRD listing difference between competitive versus highly concentrated was significant (p<0.05). CONCLUSION: When there is strong competition without a dominant center as defined by the HHI, the entire state tends to list more patients for transplant to drive up their own center's market share. Our analysis of the available national data suggests a discrepancy in access for ESRD patient to transplantation due to transplant center competition.

Nonthermal ablation of malignant esophageal strictures. Photodynamic therapy, endoscopic intratumoral injections, and novel modalities.

Several novel nonthermal ablative modalities for the palliation of malignant esophageal stenoses have been developed over the past decade. In this article, the authors review techniques and clinical experience with photodynamic therapy as well as the intratumoral injection of alcohol, cytotoxins, and immunomodulators.