Sleep quality according to chronotype in nurses working 8-hour shifts.

BACKGROUND: To date, studies have been focused on sleep disturbances of nurses working during night shifts. There is a lack of understanding regarding the sleep quality of nurses working in the rapid rotation system for each type of shift work. AIMS: To determine the relationship between chronotype and sleep quality according to shift type (i.e. day, evening and night shifts) in nurses working 8-hour rotating shifts. METHODS: A cross-sectional, descriptive study was conducted from two tertiary hospitals in South Korea from December 2021 to September 2022, including nurses working 8-hour rotating shifts (N = 74). They completed questionnaires to measure general, occupational and sleep-related characteristics, chronotype, insomnia severity and daytime sleepiness. Additionally, sleep parameters were collected from actigraphy and sleep diaries for 7 days. RESULTS: A total of 64% of nurses had an evening chronotype and 37% of nurses had an intermediate chronotype. Nurses had significantly less total sleep time and worsened sleep latency and efficiency during the day shift compared to other shift types. Compared to nurses with an intermediate chronotype, those with an evening chronotype had poorer sleep quality during day shift work. CONCLUSIONS: Strategies to enhance nurses' sleep quality during day shifts should consider a two-level approach: individual approaches, such as improving sleep hygiene, and administrative approaches, such as establishing a chronotype-based shift system for scheduling.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Orbitofacial dermatofibrosarcoma protuberans with intranasal extension.

A 25-year-old Chinese woman presented with recurrent painless swelling over the left medial canthus region for 3 months and intranasal mass for an indeterminate duration. Initial incision biopsy of the mass was reported as nodular fasciitis but the lesion recurred 3 weeks later. Intraoperative findings during repeat biopsy showed a mass extending from the deep dermal tissue into the anterior orbit and polyp-like nasal mass. Histopathology findings were that of dermatofibrosarcoma protuberans (DFSP). The mass recurred 4 months later without orbital or intranasal recurrence. Wide excision biopsy under frozen section guidance was attempted however; clear surgical margins could not be achieved despite extensive resection. She was subsequently referred for adjuvant radiotherapy. We report an exceptionally rare case of local recurrence of DFSP in an unusual anatomic location. This case was surgically challenging in achieving negative margins, and thus neoadjuvant therapy may improve overall outcome to prevent local relapse.

Effects of platelet-rich plasma and prolotherapy on supraspinatus tendinopathy: a double blind randomized clinical trial.

BACKGROUND: Supraspinatus tendinopathy is a significant cause of pain and function loss. It has been suggested that platelet-rich plasma (PRP) and prolotherapy are effective treatments for this condition. This study was done to assess and compare the effects of PRP and prolotherapy on shoulder function and pain. The secondary aim was to evaluate the effect of the treatment on shoulder range of motion, supraspinatus tendon thickness, patient satisfaction, and adverse effects. METHODS: This was a randomized, double-blind clinical trial. The study included 64 patients over the age of 18 who had supraspinatus tendinopathy and had not responded to at least three months of conventional treatment. Patients were assigned to either receive 2 mL of PRP (N.=32) or prolotherapy (N.=32). The Shoulder Pain and Disability Index (SPADI) and the Numerical Rating Scale (NRS) were the primary outcomes. Secondary outcomes included shoulder range of motion (ROM), supraspinatus tendon thickness, and adverse effects, which were measured at baseline, 3, 6, and 6 months after injection. At six months, patient satisfaction was assessed. RESULTS: Repeated measures ANOVA showed there was a statistically significant effect of time on total SPADI scores (F [2.75, 151.11], = 2.85, P=0.040) and the NRS (F [2.69, 147.86], = 4.32, P=0.008) within each group. There were no other significant changes over time or between groups. Significantly more patients in the PRP group experienced increased pain lasting less than two weeks after injection (χ2=11.94, P=0.030). CONCLUSIONS: PRP and prolotherapy resulted in improved shoulder function and pain for patients with chronic supraspinatus tendinopathy who did not response to conventional treatment.

A 26-week, placebo- and pioglitazone-controlled monotherapy study of rivoglitazone in subjects with type 2 diabetes mellitus.

AIMS: To evaluate the efficacy and safety of rivoglitazone, a peroxisome proliferator-activated receptor γ agonist in the thiazolidinedione class, in subjects with suboptimally controlled type 2 diabetes mellitus (T2DM). METHODS: Subjects aged ≥18 years with T2DM and haemoglobin A1c (HbA1c) >7.0% and ≤8.5%, who were treatment naïve or receiving a non-thiazolidinedione antidiabetes monotherapy, entered a 2-week washout and single-blind placebo run-in period and were then randomized 2 : 4 : 11 : 11 to double-blind treatment with placebo, rivoglitazone 1.0 mg/day, rivoglitazone 1.5 mg/day, or pioglitazone 45 mg/day, for 26 weeks. RESULTS: A total of 1912 subjects received placebo (n = 137), rivoglitazone 1.0 mg (n = 274), rivoglitazone 1.5 mg (n = 750) or pioglitazone (n = 751). Rivoglitazone 1.5 mg was statistically superior (p = 0.0339) and rivoglitazone 1.0 mg was non-inferior (p = 0.0339) to pioglitazone in reducing HbA1c from baseline (changes of -0.7%, -0.4% and -0.6%, respectively). Rivoglitazone also significantly reduced fasting plasma glucose from baseline (p < 0.0001). Rivoglitazone significantly improved estimates of insulin sensitivity, high-density lipoprotein cholesterol levels, and other metabolic and inflammatory biomarkers. Rivoglitazone was generally well tolerated at both doses, with treatment-emergent adverse event (TEAE) rates similar to pioglitazone. The most common drug-related TEAEs were peripheral oedema (active, 5.2-6.2%; placebo 0.7%), increased weight (active, 1.6-3.1%; placebo, 0%) and pitting oedema (active, 1.3-2.2%; placebo, 0%). CONCLUSIONS: In subjects with suboptimally controlled T2DM, rivoglitazone 1.5 mg was associated with statistically superior glycaemic control to pioglitazone 45 mg, while rivoglitazone 1.0 mg was non-inferior; the safety profiles of the two drugs appeared similar.

Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients.

BACKGROUND: To analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr). RESULTS: Median age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum ß(2) microglobulin level, and platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.

Dual roles of CD40 on microbial containment and the development of immunopathology in response to persistent fungal infection in the lung.

Persistent pulmonary infection with Cryptococcus neoformans in C57BL/6 mice results in chronic inflammation that is characterized by an injurious Th2 immune response. In this study, we performed a comparative analysis of cryptococcal infection in wild-type versus CD40-deficient mice (in a C57BL/6 genetic background) to define two important roles of CD40 in the modulation of fungal clearance as well as Th2-mediated immunopathology. First, CD40 promoted microanatomic containment of the organism within the lung tissue. This protective effect was associated with: i) a late reduction in fungal burden within the lung; ii) a late accumulation of lung leukocytes, including macrophages, CD4+ T cells, and CD8+ T cells; iii) both early and late production of tumor necrosis factor-α and interferon-γ by lung leukocytes; and iv) early IFN-γ production at the site of T cell priming in the regional lymph nodes. In the absence of CD40, systemic cryptococcal dissemination was increased, and mice died of central nervous system infection. Second, CD40 promoted pathological changes in the airways, including intraluminal mucus production and subepithelial collagen deposition, but did not alter eosinophil recruitment or the alternative activation of lung macrophages. Collectively, these results demonstrate that CD40 helps limit progressive cryptococcal growth in the lung and protects against lethal central nervous system dissemination. CD40 also promotes some, but not all, elements of Th2-mediated immunopathology in response to persistent fungal infection in the lung.

Th2 but not Th1 immune bias results in altered lung functions in a murine model of pulmonary Cryptococcus neoformans infection.

Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known if Cryptococcus neoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C. neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show that C. neoformans can significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.

Morphology of Peeled Internal Limiting Membrane in Macular Hole Surgery.

PURPOSE: The aim of this work was to describe the ultrastructure and behavior of peeled internal limiting membrane (ILM) in macular hole (MH) surgery. METHODS: Seven patients with MH were included, and vitrectomy with ILM peeling was performed in all patients. The ILM inverted flap technique was used. Two other flaps of ILM of the same patient were collected and studied using light and transmission electron microscopy (TEM). ILM cell type, distribution, and morphology were analyzed, and the proliferation or fusion potential of the ILM interface was evaluated. RESULTS: ILM vitreous sides in apposition showed signs of proliferative fibrotic activity, producing a basal membrane that merges ILM sides. CONCLUSIONS: Epiretinal cells in ILM show proliferative capacity, with formation of microfibrils between adjacent sides of the ILM, which may explain adherence of ILM flaps to the hole border, contributing to closure of the hole in MH surgery. This trail is registered with NCT03799575.

A New Biomedical Passage Retrieval Framework for Laboratory Medicine: Leveraging Domain-specific Ontology, Multilevel PRF, and Negation Differential Weighting.

Clinical decision support (CDS) search is performed to retrieve key medical literature that can assist the practice of medical experts by offering appropriate medical information relevant to the medical case in hand. In this paper, we present a novel CDS search framework designed for passage retrieval from biomedical textbooks in order to support clinical decision-making using laboratory test results. The framework utilizes two unique characteristics of the textual reports derived from the test results, which are syntax variation and negation information. The proposed framework consists of three components: domain ontology, index repository, and query processing engine. We first created a domain ontology to resolve syntax variation by applying the ontology to detect medical concepts from the test results with language translation. We then preprocessed and performed indexing of biomedical textbooks recommended by clinicians for passage retrieval. We finally built the query-processing engine tailored for CDS, including translation, concept detection, query expansion, pseudo-relevance feedback at the local and global levels, and ranking with differential weighting of negation information. To evaluate the effectiveness of the proposed framework, we followed the standard information retrieval evaluation procedure. An evaluation dataset was created, including 28,581 textual reports for 30 laboratory test results and 56,228 passages from widely used biomedical textbooks, recommended by clinicians. Overall, our proposed passage retrieval framework, GPRF-NEG, outperforms the baseline by 36.2, 100.5, and 69.7 percent for MRR, R-precision, and Precision at 5, respectively. Our study results indicate that the proposed CDS search framework specifically designed for passage retrieval of biomedical literature represents a practically viable choice for clinicians as it supports their decision-making processes by providing relevant passages extracted from the sources that they prefer to refer to, with improved performances.

Internal retinal layer thickness and macular migration after internal limiting membrane peeling in macular hole surgery.

PURPOSE: To provide a spectral-domain optical coherence tomography (SD-OCT)-based analysis of retinal layers thickness and nasal displacement of closed macular hole after internal limiting membrane peeling in macular hole surgery. METHODS: In this nonrandomized prospective interventional study, 36 eyes of 32 patients were subjected to pars plana vitrectomy and 3.5 mm diameter internal limiting membrane (ILM) peeling for idiopathic macular hole (IMH). Nasal and temporal internal retinal layer thickness were assessed with SD-OCT. Each scan included optic disc border so that distance between optic disc border and fovea were measured. RESULTS: Thirty-six eyes had a successful surgery with macular hole closure. Total nasal retinal thickening (p<0.001) and total temporal retinal thinning (p<0.0001) were observed. Outer retinal layers increased thickness after surgery (nasal p<0.05 and temporal p<0.01). Middle part of inner retinal layers (mIRL) had nasal thickening (p<0.001) and temporal thinning (p<0.05). The mIRL was obtained by deducting ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness from overall thickness of the inner retinal layer. Papillofoveal distance was shorter after ILM peeling in macular hole surgery (3,651 ± 323 µm preoperatively and 3,361 ± 279 µm at 6 months; p<0.0001). CONCLUSIONS: Internal limiting membrane peel is associated with important alteration in inner retinal layer architecture, with thickening of mIRL and shortening of papillofoveal distance. These factors may contribute to recovery of disrupted foveal photoreceptor and vision improvement after IMH closure.

Novel deletion mutation of HLA-B*40:02 gene in acquired aplastic anemia.

Despite prevalence of clonal evolution in patients with aplastic anemia (AA), somatic mutation of human leukocyte antigen (HLA) gene is rarely reported. Herein, we reported a case of acquired AA (aAA) harboring a new four-base-pair deletion mutation within exon 4 of HLA-B*40:02 leading to frameshift and premature stop codon. The HLA-B*40:02 mutant allele was detected in the patient's peripheral blood sample not in patient's buccal epithelial cells. The patient received allogenic hematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donor. On day 30 after HSCT, the mutant HLA allele was not detected by high-resolution sequence-based HLA typing. Serial chimerism analyses showed mixed chimeric status indicative of coexisting donor and recipient hematopoietic cells. Our data could provide additional support in view of pathophysiology of aAA that somatic mutation of HLA-B*40:02 allele is one of the possible origin of clonal escape to evade immune attack in patient with aAA.

Management of dislocated intraocular lenses with iris suture.

PURPOSE: Subluxated or malpositioned intraocular lenses (IOLs) and inadequate capsular support is a challenge for every ophthalmic surgeon. Iris suture of an IOL seems to be an easy technique for the management of dislocated 3-piece IOL, allowing the IOL to be placed behind the iris, far from the trabecular meshwork and corneal endothelium. The purpose of this study is to assess the results of pars plana vitrectomy (PPV) and iris suture of dislocated 3-piece acrylic IOLs. METHODS: In this retrospective, nonrandomized, interventional case consecutive study, of a total of 103 dislocated IOLs, 36 eyes were considered for analysis. All 36 eyes had subluxated or totally luxated 3-piece IOL and underwent iris suture at the Ophthalmology Department of Santa Maria Hospital-North Lisbon Hospital Center, Portugal, from January 2011 until November 2015. All patients underwent 3-port 23-G PPV. The optic zone of the dislocated IOL was placed anterior to the iris with the haptics behind, in the posterior chamber. Haptics were sutured to iris followed by placement of the optics behind iris plane. Postoperative measures included best-corrected visual acuity (BCVA), IOL position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, and development of macular edema. RESULTS: A total of 36 eyes of 36 patients were included. All underwent successful iris fixation of dislocated 3-piece IOL. Mean overall follow-up was 15.9 months (range 3-58 months). At presentation, 16 eyes (44.4%) had a luxated IOL and 20 eyes (55.6%) a subluxated IOL. As underlying cause, 17 eyes (47.2%) had a history of complicated cataract surgery, 5 eyes (13.9%) had a traumatic dislocation of the IOL, and 6 eyes (16.7%) had a previous vitreoretinal surgery. A total of 8 eyes (22.2%) had late spontaneous IOL dislocation after uneventful cataract surgery. The mean preoperative BCVA was 1.09 ± 0.70 logarithm of the minimal angle of resolution (logMAR) units and mean postoperative BCVA was 0.48 ± 0.58 of logMAR units. The mean visual acuity improvement was 4.08 ± 5.33 lines on the logMAR scale. In this study, every IOL was stable at the last follow-up. As late complications, macular edema occurred in 1 patient and retinal detachment occurred in 2 patients. There were no cases of endophthalmitis. CONCLUSIONS: Iris suture fixation of subluxated IOL is a good treatment option for eyes with dislocated IOLs, leading to long-term stability of the IOL. The advantage of this procedure is using the same IOL in a closed eye surgery. No astigmatic difference is expected as no large corneal incision is needed.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Evaluation of Immunoprotection Conferred by the Subunit Vaccines of GRA2 and GRA5 against Acute Toxoplasmosis in BALB/c Mice.

Toxoplasmosis is a foodborne disease caused by Toxoplasma gondii, an obligate intracellular parasite. Severe symptoms occur in the immunocompromised patients and pregnant women leading to fatality and abortions respectively. Vaccination development is essential to control the disease. The T. gondii dense granule antigen 2 and 5 (GRA2 and GRA5) have been targeted in this study because these proteins are essential to the development of parasitophorous vacuole (PV), a specialized compartment formed within the infected host cell. PV is resistance to host cell endosomes and lysosomes thereby protecting the invaded parasite. Recombinant dense granular proteins, GRA2 (rGRA2) and GRA5 (rGRA5) were cloned, expressed, and purified in Escherichia coli, BL21 (DE3) pLysS. The potential of these purified antigens as subunit vaccine candidates against toxoplasmosis were evaluated through subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Results obtained demonstrated that rGRA2 and rGRA5 elicited humoral and cellular-mediated immunity in the mice. High level of IgG antibody was produced with the isotype IgG2a/IgG1 ratio of ≈0.87 (p < 0.001). Significant increase (p < 0.05) in the level of four cytokines (IFN-γ, IL-2, IL-4, and IL-10) was obtained. The antibody and cytokine results suggest that a mix mode of Th1/Th2-immunity was elicited with predominant Th1-immune response inducing partial protection against T. gondii acute infection in BALB/c mice. Our findings indicated that both GRA2 and GRA5 are potential candidates for vaccine development against T. gondii acute infection.

Induction of Protective Immunity against Toxoplasmosis in BALB/c Mice Vaccinated with Toxoplasma gondii Rhoptry-1.

Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1) is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1) was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1) was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA) and rROP1 from pVAX1-ROP1 and rROP1-immunized mice, respectively, readily proliferated and secreted large amount of IFN-γ (712 ± 28.1 pg/ml and 1457 ± 31.19 pg/ml, respectively) and relatively low IL-4 level (94 ± 14.5 pg/ml and 186 ± 14.17 pg/ml, respectively). These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis.

A prospective randomized study on the mobilization of CD34+ cells comparing continuous intravenous vs subcutaneous administration of rhG-CSF in normal donors.

The efficacy of mobilizing peripheral blood progenitor cells (PBPC) with continuous intravenous (c.i.v.) administration of rhG-CSF was randomly compared to subcutaneous (s.c.) administration, in 15 normal donors in each arm of the study for 6 days. The percentage and absolute numbers of CD34+ cells in the c.i.v. and s.c. groups increased maximally at day 3 and 5, respectively, when compared with the steady-state (day 0) level. Peak CD34+ cell levels were achieved on day 3 in the c.i.v. group, with more rapid results than in the s.c. group (49.3/microl vs 35.9/microl, P=0.043). Plasma rhG-CSF levels declined progressively during mobilization in each group as the WBC increased. The serum level of rhG-CSF did not correlate with CD34+ cell counts in the peripheral blood. Toxicity profiles in the c.i.v. and s.c. groups were similar. Each regimen was effective in successfully mobilizing the target CD34 cell number.

Comparison of IgG-ELISA and IgG4-ELISA for Toxocara serodiagnosis.

Diagnosis of human toxocariasis, caused by Toxocara canis or Toxocara cati, normally relies on a combination of the presence of clinical signs and symptoms backed by positive serology. The use of Toxocara excretory-secretory antigen (TES) in ELISA assays increases the test specificity. However, in tropical countries where soil-transmitted helminths are endemic, cross-reactivity from antibodies to these intestinal parasites poses a significant limitation for Toxocara serodiagnosis. To increase the specificity of serodiagnosis, we compared the use of IgG-ELISA to the use of IgG4-ELISA using commercially manufactured TES-coated plates. The sensitivity of the IgG-ELISA was 97.1%, while that of the IgG4-ELISA was 45.7%; the specificities were 36.0 and 78.6%, respectively. The study shows that employing both assays can improve the serodiagnosis of toxocariasis. An IgG4 immunoassay would also be useful in the secondary screening of antigen clones in the effort to develop improved serological tests for toxocariasis.

Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.

INTRODUCTION: Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) may transform into secondary myelofibrosis (MF) or evolve into acute myeloid leukemia (AML). The genetic mechanisms underlying disease progression in MPN and MDS/MPN patients remain unclear. The purpose of this study was to investigate sequential genomic aberrations identified by single nucleotide polymorphism array (SNP-A)-based karyotyping that can detect cryptic aberrations or copy neutral loss of heterozygosity (CN-LOH) in the chronic phase and during disease progression of MPN and MDS/MPN patients. METHODS: The study group included 13 MPN and four MDS/MPN patients (seven polycythemia vera (PV); four essential thrombocythemia (ET); two MPN-unclassifiable (MPN-U); one chronic myelomonocytic leukemia (CMML); one atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML); and two MDS/MPN-unclassifiable (MDS/MPN-U)). Among them, five patients (two PV, two MPN-U, and one MDS/MPN-U) progressed to MF and three patients (one CMML, one aCML, and one MDS/MPN-U) transformed to AML. The median follow-up period was 70 months (range, 7-152). Whole-genome SNP-A (SNP 6.0; Affymetrix, Santa Clara, CA, USA)-based karyotyping and JAK2 mutation analysis were performed according to the manufacturer's instructions. RESULTS: SNP-A showed 19 kinds of genomic aberrations, including seven gains, eight deletions, and four CN-LOH. CN-LOH of 9p involving JAK2 was the most common aberration, followed by 5q deletion and 9p gain. The incidence of genomic changes identified by SNP was not different in patients with disease progression (75%), compared with those without disease progression (56%) (P = 0.4). However, when excluding 9p CN-LOH, the incidence of genomic changes was significantly higher in patients with disease progression than in patients without disease progression (63% and 0%, respectively, P = 0.01). Among eight patients with disease progression, two patients (two MPN-U) showed abnormal SNP-A results, whereas metaphase cytogenetics (MC) analysis showed normal results at diagnosis and during follow-up. In nine patients without disease progression, SNP-A did not show any genomic aberrations except for 9p CN-LOH. In three patients (one PV, one aCML, and one MDS/MPN-U), clonal evolutions were identified by both MC and SNP-A according to disease progression. One PV patient who progressed to MF at 45 months after diagnosis showed sequential genomic changes from 9p CN-LOH to 9p gain by SNP-A. Results of JAK2 mutation analysis were variable depending on the patient. Most of the patients with 9p CN-LOH or 9p gain showed more than 50% of the JAK2 mutant alleles. In one patient (MDS/MPN-U) evolving to AML, the number of JAK2 mutant alleles decreased according to disease progression. CONCLUSION: This study suggests sequential genomic changes identified by SNP-A may be associated with disease progression.

Primary diaphragmatic schwannoma with a typical target appearance: correlation of CT and MR imagings and histologic findings.

A rare case of benign diaphragmatic schwannoma in a 38-year-old female is reported. Precontrast computed tomography (CT) showed an encapsulated well-defined round homogeneous tumor with central calcification, measuring approximately 5 cm in diameter, arising from the left diaphragm. Contrast-enhanced CT and gadolinium-enhanced T1-weighted magnetic resonance (MR) imaging showed focal enhancement in the central portion of the tumor. The tumor showed a typical target appearance of increased peripheral signal intensity and decreased central signal intensity on unenhanced T2-weighted images. Pathological examination of resected specimens of the tumor showed two zonal histological components: a hypercellular portion of spindle cells with nuclear palisading (Antoni A tissue) and a hypocellular portion of cells with cystic degeneration, together with focal calcification and hemangeomatous vascular changes (Antoni B tissue). We consider the radiological characteristics of diaphragmatic schwannoma on CT and MR imagings to represent the geographic difference between the histologic zones of the tumor.