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The mammalian and avian auditory brainstem likely arose by independent evolution. To compare the underlying molecular mechanisms, we focused on Atoh7, as its expression pattern in the mammalian hindbrain is restricted to bushy cells in the ventral cochlear nucleus. We thereby took advantage of an Atoh7 centered gene regulatory network (GRN) in the retina including upstream regulators, Hes1 and Pax6, and downstream targets, Ebf3 and Eya2. In situ hybridization demonstrated for the latter four genes broad expression in all three murine cochlear nuclei at postnatal days (P) 4 and P30, contrasting the restricted expression of Atoh7. In chicken, all five transcription factors were expressed in all auditory hindbrain nuclei at embryonic day (E) 13 and P14. Notably, all five genes showed graded expression in the embryonic nucleus magnocellularis (NM). Atoh7 was highly expressed in caudally located neurons, whereas the other four transcription factors were highly expressed in rostrally located neurons. Thus, Atoh7 shows a strikingly different expression between the mammalian and avian auditory hindbrain. This together with the consistent absence of graded expression of GRN components in developing mammalian nuclei provide the first molecular support to the current view of convergent evolution as a major mechanism in the amniote auditory hindbrain. The graded expression of five transcription factors specifically in the developing NM confirms this nucleus as a central organizer of tonotopic features in birds. Finally, the expression of all five retinal GRN components in the auditory system suggests co-options of genes for development of sensory systems of distinct modalities., (© 2023. The Author(s).)

Background: Hsa-miR-495 (miR-495) has been extensively investigated in cancer initiation and progression. On the other hand, our bioinformatics analysis suggested that miR-495 exerts its effects through targeting of TGFβ signaling components., Methods & Results: In order to investigate such an effect, miR-495 precursor was overexpressed in HEK293T, SW480, and HCT116 cells, which was followed by downregulation of TGFβR1, TGFβR2, SMAD4, and BUB1 putative target genes, detected by RT-qPCR. Also, luciferase assay supported the direct interaction of miR-495 with 3'UTR sequences of TGFβR1, TGFβR2, SMAD4, and BUB1 genes. Furthermore, a negative correlation of expression between miR-495-3p and some of these target genes was deduced in a set of colorectal and breast cancer cell lines. Then, flow cytometry analysis showed that the overexpression of miR-495 in HCT116 and HEK293T resulted in an arrest at the G1 phase. Consistently, western blotting analysis showed a significant reduction of the Cyclin D1 protein in the cells overexpressing miR-495, pointing to downregulation of the TGFβ signaling pathway and cell cycle arrest. Finally, microarray data analysis showed that miR-495-3p is significantly downregulated in colorectal tumors, compared to the normal pairs., Conclusions: Overall, the results of the current study introduced miR-495-3p as a cell cycle progression suppressor, which may negatively regulate TGFβR1, TGFβR2, SMAD4, and BUB1 genes. This finding suggests miR-495-3p as a tumor suppressor candidate for further evaluation., Competing Interests: Declaration of Competing Interest The authors declare that the present research was conducted with no commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The avian auditory hindbrain is a longstanding model for studying neural circuit development. Information on gene regulatory network (GRN) components underlying this process, however, is scarce. Recently, the spatiotemporal expression of 12 microRNAs (miRNAs) was investigated in the mammalian auditory hindbrain. As a comparative study, we here investigated the spatiotemporal expression of the orthologous miRNAs during development of the chicken auditory hindbrain. All miRNAs were expressed both at E13, an immature stage, and P14, a mature stage of the auditory system. In most auditory nuclei, a homogeneous expression pattern was observed at both stages, like the mammalian system. An exception was the nucleus magnocellularis (NM). There, at E13, nine miRNAs showed a differential expression pattern along the cochleotopic axis with high expression at the rostromedial pole. One of them showed a gradient expression whereas eight showed a spatially selective expression at the rostral pole that reflected the different rhombomeric origins of this composite nucleus. The miRNA differential expression persisted in the NM to the mature stage, with the selective expression changed to linear gradients. Bioinformatics analysis predicted mRNA targets that are associated with neuronal developmental processes such as neurite and synapse organization, calcium and ephrin-Eph signaling, and neurotransmission. Overall, this first analysis of miRNAs in the chicken central auditory system reveals shared and strikingly distinct features between chicken and murine orthologues. The embryonic gradient expression of these GRN elements in the NM adds miRNA patterns to the list of cochleotopic and developmental gradients in the central auditory system., (© 2021 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Objective: The aim of the article is a theoretical and methodological justification for strengthening the role of international trade in medicines and equipment during the COVID-19 pandemic, to establish the benefits of free trade, to develop important international trade policy priorities in this field., Patients and Methods: Materials and methods: Legislation of foreign countries and international organizations, statistical data published by international organizations are the materials of the research. Methods of analysis, synthesis, generalization were applied during the research., Conclusion: Conclusions: It has been proved that the legal regulation of world trade activity by medical supplies are increasingly playing more important roles in the implementation of international development goals. The authors have offered three priorities to all countries: to cooperate globally around the deployment of life-saving medical supplies, publicly commit all countries not to implement export bans or limits on relevant medical supplies; to control all trade measures countries have taken in response to the COVID-19 outbreak; to bring together in a global form measures and procedures to eliminate this phenomenon.

PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In this pathway, PI3Kα enzyme is composed of a regulatory protein encoded by p85 gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is amplified in several cancers including lung and colorectal cancer (CRC). Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1 (EBI accession no. LN626315), which is located within PIK3CA gene. A DNA segment corresponding to PIK3CA-premir1 sequence was transfected in human cell lines that resulted in generation of mature exogenous PIK3CA-miR1. Following the overexpression of PIK3CA-miR1, its predicted target genes (APPL1 and TrkC) were significantly downregulated in the CRC-originated HCT116 and SW480 cell lines, detected by qRT-PCR. Then, dual luciferase assay supported the interaction of PIK3CA-miR1 with APPL1 and TrkC transcripts. Endogenous PIK3CA-miR1 expression was also detected in several cell lines (highly in HCT116 and SW480) and highly in CRC specimens. Consistently, overexpression of PIK3CA-premir1 in HCT116 and SW480 cells resulted in significant reduction of the sub-G1 cell distribution and apoptotic cell rate, as detected by flowcytometry, and resulted in increased cell proliferation, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PIK3CA-miR1 overexpression also resulted in Wnt signaling upregulation detected by Top/Fop assay. Overall, accumulative evidences indicated the presence of a bona fide novel onco-miRNA encoded within the PIK3CA oncogene, which is highly expressed in colorectal cancer and has a survival effect in CRC-originated cells.

Background: Postoperative emergency agitation (EA) is a common problem often observed in children undergoing general anesthesia. The purpose of this study was to evaluate whether a bolus of intraoperative low-dose ketamine followed by dexmedetomidine i.v. could reduce the incidence of EA in children undergoing adenotonsillectomy following sevoflurane-based anesthesia., Methods: A total of 92 children undergoing adenotonsillectomy, aged 3-7 years, were randomly allocated to receive either low-doseketamine 0.15 mg/kg followed by dexmedetomidine 0.3 μg/kg i.v. (KETODEX, n=45) or volume-matched normal saline (Control, n=47), about 10 min before the end of surgery. Anesthesia was induced and maintained with sevoflurane. Postoperative pain and EA were assessed with objective pain score (OPS) and the Pediatric Anesthesia Emergence Delirium scale (PAED), respectively. EA was defined as a PAED≥10 points. Recovery profile and postoperative complications were recorded., Result: The incidence and severity of EA was lower in KETODEX group than controls (11% vs. 47%) and (2% vs. 13%), respectively (P<0.05). The frequency of fentanyl rescue was lower in KETODEX group than in controls (13.3 vs. 38.3%, P<0.05). Heart rate during extubation was significantly higher in the control group compared with children who received KETODEX (P<0.05). The incidence of postoperative pain was significantly less in the KETODEX group (15.5% vs. 63.8%, P<0.05). Times to interaction and extubation were significantly longer in the KETODEX group (P<0.05)., Conclusion: KETODEX reduces the incidence and severity of EA in children undergoing adenotonsillectomy following sevoflurane-based anesthesia and provided smooth extubation., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Preoperative conditions may play a significant role in postoperative cognitive dysfunction (POCD) development in elderly patients. We aimed to investigate whether preoperative cognitive training could lower the incidence of POCD one week after surgery., Material and Methods: A total of 141 ASA I-III elderly patients who underwent gastrointestinal surgery were enrolled into the study. Patients were randomized into either the Intervention group (69 analyzed) or the Control group (72 analyzed). Patients in the intervention group were instructed and trained in a cognition mnemonic skill for a total of three 1-hour sessions with the method of loci (MoL). Controls did not receive any cognitive training during hospitalization. All patients were tested using neuropsychological battery tests (NPTs) on admission and one week after surgery., Results: The incidence of POCD in the intervention group (15.9%) was significantly lower than in the controls (36.1%) (P<0.05). Patients' performance in Brief Visuospatial Memory Test-Revised and Symbol-Digit Modalities Test were improved by the cognitive training. Increasing age, longer length of anesthesia and surgery, and lack of cognitive training were associated with a significantly higher risk of POCD (P<0.05)., Conclusions: Cognitive training with MoL can reduce the decline of early postoperative cognitive function in elderly patients undergoing major gastrointestinal surgery.

Objective: This study was designed to investigate whether a priming dose of ketamine-dexmedetomidine can effectively suppress fentanyl-induced coughing (FIC)., Methods: Altogether 400 patients of ASA I and II, aged 18-70 years, undergoing various elective surgical procedures, were randomly allocated into four groups of 100 patients each. Patients in the placebo group received volume-matched normal saline 0.15 mL/kg + normal saline 0.05 mL/kg. One group of patients was given ketamine 0.15 mg/kg + normal saline 0.05 ml/kg (KET), and another group dexmedetomidine 0.5 μg/kg + normal saline 0.05 ml/kg (DEX). Finally, one group of patients received ketamine 0.15 mg/kg + dexmedetomidine 0.5 μg/kg (KETODEX). After fentanyl administration, the onset time and severity of cough for 1 min were recorded. Cough severity was graded as mild (grade 1-2), moderate (grade 3-5), or severe (grade >5)., Result: The incidence of FIC was 53%, 34%, 20%, and 9% in the placebo, DEX, KET, and KETODEX groups, respectively. The incidence of cough was significantly lower in the KETODEX group. Likewise, the onset time of cough was significantly delayed in the KETODEX group. Only nine patients in the KETODEX group had either mild (6%) or moderate (3%) cough, with none suffering from severe cough., Conclusion: A priming dose of KETODEX effectively suppressed the cough reflex induced by fentanyl and delayed the onset time of cough. Therefore, treatment with KETODEX may be a clinically useful method for preventing FIC.

Background and Objectives: There is limited information regarding the outcome of patients treated for leukemia during pregnancy. This study was performed on all cases of leukemia during pregnancy identified in our institution leukemia database., Patients and Methods: It is a retrospective study from our existing database. Thirty two cases were identified among the cohort of patients treated for acute and chronic leukemia between January 1991 and July 2003., Results: Among the acute leukemia patients (n=21), 10 patients (47.6%) received chemotherapy during pregnancy, seven had live birth and three had spontaneous abortion. No teratogenicity or congenital malformations or postnatal complication were reported. The remaining 11 (52.4%) were not given chemotherapy while pregnant; three patients presented after 34 weeks of gestation ending in normal live births and then received chemotherapy and eight patients had abortion before starting chemotherapy. Among the chronic myeloid leukemia (CML) patients (n=11), nine patients received hydroxyurea, one patient received alfa-interferon and one patient was treated with leukapheresis. Eight patients had normal live births and three patients had abortion. Out of the 32 patients, 18 patients (56.2%) subsequently underwent HLA matched sibling allogeneic stem cell transplantation, seven for acute myeloid leukemia (AML), two for acute lymphocytic leukemia (ALL) and nine for CML. After a median follow up of 16 years, five patients (15.6%) are alive in remission (one from chemotherapy group and four from SCT group)., Conclusions: Our report lends credence to the safety and feasibility of administering anti-leukemic therapy in acute and chronic leukemias during pregnancy although acute leukemia patients had possibly a poor long term outcome compared to non-pregnant patients., (Copyright © 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The multi-walled carbon nanotubes (MWCNTs), electrophoretically deposited on fluorine-doped tin oxide (FTO), were employed as charge-collecting channels in the TiO2 photoelectrode of dye-sensitized solar cells (DSSCs) fabricated at 200 degrees C. The CNT-networks at the conducting substrate increased the charge collection efficiency of the porous TiO2 film, while the short circuit current increased up to ca. 43% under optimized condition. However, the significant decrease in the open-circuit voltage (Voc) up to ca. 132 mV resulted in the failure of the overall cell efficiency improvement. Findings reveal that the transfer process for the back electron is mainly responsible for the significant Voc drop when the MWCNTs were deposited at the electron-collecting substrate of the photoelectrode. The study demonstrates that electrophoretic deposition of MWCNTs on charge collecting substrate would be applicable to introduce an effective charge-collecting channel for the fabrication of flexible DSSCs under low temperature sintering condition.

Using a doctor-blade method, a highly viscous titanium dioxide (TiO2) paste was deposited on a glass substrate coated with fluorine doped tin oxide (FTO). The paste was mainly composed of commercially available TiO2 nanoparticles (P25) and hydroxypropyl cellulose (HPC) as organic filler. Varying the content of HPC in the TiO2 paste changed the physical properties of the mesoporous TiO2 layer, particularly its porosity and surface area. From the quantification of dyes on Ti2, layer and the electrochemical impedance spectroscopy (EIS) study of the dye-sensitized solar cells (DSSCs), the surface area of the TiO2 film was found to have decreased. This came with the increase of HPC content while the porosity of the film increased, consistent with the concurrent decrease of short-circuit current density (Jsc) and efficiency (eta). The increased porosity greatly affected the electron transport through the TiO2 film by decreasing the coordination number of the TiO2 particles resulting to a decrease of the electron diffusion coefficient.

Here, we find that doping sp(2) selective nitrogen, N sp(2), into carbon nanotube (CNT) channels induces a positive shift in the Fermi level of TiO(2) photoelectrodes. It is found that this results in the large diffusion coefficient of solar driven electrons for increasing the photocurrent as well as in the low recombination rate for improving open circuit voltage with 0.74 V, which could not be overcome by using pristine CNT channels with 0.66 V., (This journal is © the Owner Societies 2012)

Three electrode structures with different spatial arrangements of carbon nanotubes (CNTs) in the mesoporous TiO(2) layer were employed in dye-sensitized solar cells to study the effect of surface states at the interface formed by the incorporation of CNTs. It was found that the decay of open circuit voltage (V(oc)) was significantly minimized by avoiding the direct contact of nanotubes to the conducting substrate by introducing a thin buffer layer of TiO(2) while maintaining the superior electron collection efficiency from the incorporation of nanotubes.

An amperometric hydrogen peroxide (H2O2) biosensor was developed based on the immobilization of horseradish peroxidase (HRP) onto a gold-nanoparticle (GNP)-adsorbed conducting poly(thionine) (PTH) film. The modification process was characterized by scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The effects of experimental parameters such as the concentration of the mediator (hydroquinone, HQ), the pH of the solution, and the working potential were investigated for optimum analytical performance. In the presence of the mediator, the immobilized HRP showed excellent electrocatalytic activity towards the reduction of H2O2. The linear dynamic range of 5-150 microM with the regression coefficient of 0.999 was obtained. The detection limit was calculated to be 1.5 microM based on a signal-to-noise ratio of 3. The reproducibility, repeatability, and stability of the biosensor were studied, with satisfactory results. The biosensor performance was evaluated with respect to the possible interferences and the application of the biosensor to real-sample analysis.

Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 10(8)/kg (range, 0.60-6.7 × 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hemopoietic stem cell transplantation (HSCT) has been considered a curative treatment option for many hematological and non-hematological disorders. Despite the use of advanced methods of tissue typing and new therapies, graft versus host disease (GVHD) remains a major obstacle. Secondary malignancies are also among the most serious long-term complications after HSCT including leukemia, lymphomas, and to a lesser extent, solid tumors. The most commonly observed solid tumor is squamous cell carcinoma (SCC). We report two cases of SCC of the lower lip diagnosed several years after HSCT. Both cases were complicated with GVHD prior to the development of SCC and had a successful outcome with minimal surgical intervention.

Nanotechnology has opened new and exhilarating opportunities for exploring glucose biosensing applications of the newly prepared nanostructured materials. Nanostructured metal-oxides have been extensively explored to develop biosensors with high sensitivity, fast response times, and stability for the determination of glucose by electrochemical oxidation. This article concentrates mainly on the development of different nanostructured metal-oxide [such as ZnO, Cu(I)/(II) oxides, MnO(2), TiO(2), CeO(2), SiO(2), ZrO(2,) and other metal-oxides] based glucose biosensors. Additionally, we devote our attention to the operating principles (i.e., potentiometric, amperometric, impedimetric and conductometric) of these nanostructured metal-oxide based glucose sensors. Finally, this review concludes with a personal prospective and some challenges of these nanoscaled sensors.

Background: Dendritic cells (DCs) play a critical role in the immune response and are a candidate for immunotherapy in cancer. Since gibbon ape leukemia virus (GALV) transduction of CD34+ cells is reasonably efficacious, we assessed the efficacy of GALV transduction of CD34+ derived DCs as a possible approach to creating genetically modified DCs for immunotherapy., Methods: Peripheral blood CD34+ cells were transduced with retroviruses obtained from the PG13/LN C8 cell line, with the neomycin gene as a marker gene. After prestimulation of hematopoietic cells for 24 hours with 10 ng/mL interleukin (IL)-3, 10 ng/mL IL-6, 100 ng/mL stem cell factor, 100 ng/mL granulocyte-macrophage colony stimulating factor and 8 Amicrog/mL protamine sulfate, the cells were cultured in a transforming media prior to differentiating into DCs by GM-CSF, TNF-a and IL-4. Immunophenotyping analyses for confirmation of the generated DCs, colony formation assay and PCR were done for the expression of neomycin gene in the transduced cells., Results: Titration of viral vectors indicated a transduction efficiency of 1×10(5) CFU/mL. Transduction efficiency for the CD34+ cells transformed to DCs was 45% and 38% before and after DC differentiation, respectively. Additionally, a mean (SEM) of 26.9% (11.4%) and 41.4% (11.8%) of the genetically modified DCs were positive for CD86+ HLA-DR and CD1a+CD14, respectively, Conclusion: This study showed that the majority of transduced CD34+ cells were successfully differentiated into cells identical to DCs according to morphology and immunophenotyping features, which could be a potential application in immunotherapy.

Background: Cytomegalovirus (CMV) infection is a major infectious complication post-allogeneic hematopoietic stem cell transplantation (HSCT). CMV seropositivity in Eastern Mediterranean and certain Asian countries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganciclovir (VGC) is a prodrug of ganciclovir with high bioavailability., Patients and Methods: HSCT patients with documented CMV infection (as defined by positive CMV antigenemia) were treated as outpatients with VGC at a starting dose of 900 mg twice daily for 1 week. Those who were antigenemia negative after one week received 900 mg once daily for another week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice-daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity., Results: From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the episodes were considered refractory, requiring alternative therapy. No CMV disease was observed in this cohort., Conclusion: Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatient treatment of CMV infection with "short-course oral VGC" given as a one-week twice-daily treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study.

Background: Idiopathic thrombocytopenic purpura (ITP) in adults has a chronic course and may necessitate splenectomy. The current study was undertaken to study the systemic thromboembolic complications of laparoscopic splenectomy (LS) versus open splenectomy (OS) in patients with ITP at two large referral hospitals., Patients and Methods: We conducted a retrospective analysis of 49 patients who underwent splenectomy (21 LS and 28 OS) for primary/relapsing refractory ITP between June 1995 and November 2004. Clinically and/or radiologically confirmed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) were assessed within 2 weeks before and after splenectomy. None had prophylactic anticoagulants immediately after surgery. Follow up of those who developed complications continued for at least 2 additional years to assess for contributing factors that may have been masked at the time of occurrence., Results: Two (9.5%) LS group had acute PE within 5 days of LS and their platelet count reached 500A103/I(1/4)L within 4 days and 1000A103/I(1/4)L within 7 days after surgery. Three conversions to OS occurred; none had VTE. DVT occurred in 3 patients (10.7%) in the OS group; none were life threatening. There were no deaths., Conclusion: Life-threatening venous thromboembolic events are serious complications after LS and OS for ITP patients if prophylactic anticoagulants are not administered. Patients at risk are those who both have an exponential rise of the platelet count, although factors other than the platelet count may be contributing in OS. Postsplenectomy, ITP should be considered as a thrombophilic condition and studies of additional measures to prevent such events are warranted.

The Wilms tumor antigen 1 (WT1) antigen is over-expressed in human leukemias, making it an attractive target for immunotherapy. Most WT1-specific Cytotoxic T Lymphocytes (CTLs) described so far displayed low avidity, limiting its function. To improve the immunogenicity of CTL epitopes, we replaced the first-amino-acid of two known immunogenic WT1-peptides (126 and 187) with a tyrosine. This modification enhances 126Y analogue-binding ability, triggers significant number of IFN-gamma-producing T cells (P = 0.0003), induces CTL that cross-react with the wild-type peptide, exerts a significant lytic activity against peptide-loaded-targets (P = 0.0006) and HLA-A0201-matched-leukemic cells (P = 0.0014). These data support peptide modification as a feasible approach for the development of a leukemia-vaccine.

Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases.