Too little or too much: nonlinear relationship between sleep duration and daily affective well-being in depressed adults.

BACKGROUND: In addition to having higher negative affect and lower positive affect overall, depressed individuals exhibit heightened affective reactivity to external stimuli than non-depressed individuals. Sleep may contribute to day-to-day fluctuations in depressed individuals, given that sleep disturbance is a common symptom of depression. Yet, little is known about changes in daily affect as a function of nightly sleep duration in depressed adults and non-depressed adults. The current study examined whether and how naturally-occurring sleep duration is associated with negative and positive affect, and how these associations differ between depressed vs. non-depressed adults. METHODS: Data were drawn from the second wave of the National Study of Daily Experiences (NSDE), a daily diary project of the Midlife in the United States (MIDUS) study. The sample of 2,012 adults (Mage=56.5; 57% female; 84% white) completed eight-day diary interviews via telephone on their daily experiences including nightly sleep duration and negative and positive affect. They also completed assessments of the Composite International Diagnostic Interview-Short form, and depressed status was determined based on DSM-III. Multilevel regression models with linear, quadratic, and cubic terms of sleep duration examined the nonlinear relationship between nightly sleep duration and daily affect. Interaction terms with depression status were added to examine differences between depressed and non-depressed adults. RESULTS: Depressed adults exhibited significant and greater fluctuations in daily affect as a function of nightly sleep duration than non-depressed adults. Specifically, the degree of decrease in positive affect and increase in negative affect was greater when depressed adults slept 2 or more hours less or longer than their usual sleep hours. Non-depressed adults exhibited relatively stable daily affect regardless of their nightly sleep hours. CONCLUSIONS: Sleep duration is nonlinearly associated with affect in daily lives of depressed adults, highlighting that both having too little sleep and excessive sleep are associated with adverse daily affective well-being. Implementing sleep interventions to promote an appropriate sleep duration may help improve daily affect among depressed adults.

Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.

Mechanical properties of the tumor microenvironment play a critical role in cancer progression by activation of cancer mechano-responses. The biophysical interactions between cancer cells and their dynamic microenvironment are attributed to force-dependent alterations in molecular pathways that trigger the structural reorganization of intracellular organelles and their associated genetic modifications. Recent studies underscore the role of oxygen concentration in cancer metastasis. Suppressed oxygen levels promote the development of invasive phenotypes and aggressive proliferation of cancer cells, accompanied by remodeling of tumor microenvironment encompassing the modulation of physical settings of extracellular matrix. This review summarizes the role of biophysical interactions between cancer cells and their surroundings in determining cancer progression. Biophysical interpretation of the tumor microenvironment and cancer progression could provide further insights into the development of novel biomedical technologies for therapeutic cancer treatment.

Affective reactivity to daily stressors and immune cell gene expression in the MIDUS study.

Affective reactivity to stress is a person-level measurement of how well an individual copes with daily stressors. A common method of measuring affective reactivity entails the estimation of within-person differences of either positive or negative affect on days with and without stressors present. Individuals more reactive to common stressors, as evidenced by affective reactivity measurements, have been shown to have increased levels of circulating pro-inflammatory markers. While affective reactivity has previously been associated with inflammatory markers, the upstream mechanistic links underlying these associations are unknown. Using data from the Midlife in the United States (MIDUS) Refresher study (N = 195; 52% female; 84% white), we quantified daily stress processes over 10 days and determined individuals' positive and negative affective reactivities to stressors. We then examined affective reactivity association with peripheral blood mononuclear cell (PBMC) gene expression of the immune-related conserved transcriptional response to adversity. Results indicated that individuals with a greater decrease in positive affect to daily stressors exhibited heightened PBMC JUNB expression after Bonferroni corrections (p-adjusted < 0.05). JUNB encodes a protein that acts as a transcription factor which regulates many aspects of the immune response, including inflammation and cell proliferation. Due to its critical role in the activation of macrophages and maintenance of CD4+ T-cells during inflammation, JUNB may serve as a potential upstream mechanistic target for future studies of the connection between affective reactivity and inflammatory processes. Overall, our findings provide evidence that affective reactivity to stress is associated with levels of immune cell gene expression.

Daily Affective Dynamics in Major Depressive Disorder: The Role of Daily Stressors and Positive Events.

This study examined daily affective dynamic indices among individuals with a major depressive disorder (MDD) diagnosis in the past one year at the time of the interview, focusing on affective variability and change in affect in response to daily events (affective reactivity). Data were from the main survey and daily diary project of the Midlife in the United States (MIDUS) study. Participants (N = 1,970; nMDD = 202; nnon-MDD = 1,768) completed structured clinical interviews on mental health and telephone interviews about their daily experiences spanning eight consecutive days. Multilevel models revealed that the MDD group experienced greater positive (PA) and negative affect (NA) variability than the non-MDD group. On days that at least one stressful event was reported, the MDD group experienced a greater decrease in PA and a greater increase in NA. On days that at least one positive event was reported, the MDD group experienced a greater increase in PA and a greater decrease in NA. Changes in affect to daily events, particularly the mood brightening effect, may be indicators of depression and potential targets for intervention. Limitations of the study include a community sample, reliance on self-reported measures of daily stressors and positive events, inclusion of remitted and current MDD participants, and the DSM-III-R based criteria for MDD diagnosis.

Treatment decision for cancer patients with fever during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGRUOUND: Cancer patients have been disproportionally affected by the coronavirus disease 2019 (COVID-19) pandemic, with high rates of severe outcomes and mortality. Fever is the most common symptom in COVID-19 patients. During the COVID-19 pandemic, physicians may have difficulty in determining the cause of fever (COVID-19, another infection, or cancer fever) in cancer patients. Furthermore, there are no specific guidelines for managing cancer patients with fever during the COVID-19 pandemic. Thus, this study evaluated the clinical characteristics and outcomes of cancer patients with fever during the COVID-19 pandemic. METHODS: This study retrospectively reviewed the medical records of 328 cancer patients with COVID-19 symptoms (fever) admitted to five hospitals in Daegu, Korea from January to October 2020. We obtained data on demographics, clinical manifestations, laboratory test results, chest computed tomography images, cancer history, cancer treatment, and outcomes of all enrolled patients from electronic medical records. RESULTS: The most common COVID-19-like symptoms were fever (n=256, 78%). Among 256 patients with fever, only three (1.2%) were diagnosed with COVID-19. Most patients (253, 98.8%) with fever were not diagnosed with COVID-19. The most common solid malignancies were lung cancer (65, 19.8%) and hepatobiliary cancer (61, 18.6%). Twenty patients with fever experienced a delay in receiving cancer treatment. Eighteen patients discontinued active cancer treatment because of fever. Major events during the treatment delay period included death (2.7%), cancer progression (1.5%), and major organ dysfunction (2.7%). CONCLUSION: Considering that only 0.9% of patients tested for COVID-19 were positive, screening for COVID-19 in cancer patients with fever should be based on the physician's clinical decision, and patients might not be routinely tested.

Patterns of multimorbidity trajectories and their correlates among Korean older adults.

OBJECTIVE: This study aims to identify distinct patterns of 10-year multimorbidity trajectory among Korean older adults and examine factors associated with the patterns. METHODS: Data were drawn from the six waves of the Korean Longitudinal Study of Ageing (KLoSA, 2006-2016). We examined trajectories of multimorbidity of 1,705 older adults aged 65 and older using Growth Mixture Modeling. Then, the identified patterns were used as dependent variables to examine the correlates of multimorbidity trajectories. Explanatory variables considered were sociodemographic, psychological, health behavioural and interpersonal factors at baseline. RESULTS: Four distinct patterns of multimorbidity trajectories were identified: 'maintaining-low' (59.4%), 'chronically-high' (7.5%), 'moderately-increasing' (26.0%) and 'rapidly- increasing' (7.1%). Gender, depressive symptoms, life satisfaction and frequency of contacts with others were associated with trajectory membership. Specifically, women were more likely to be in the 'chronically-high' group than any other groups. Compared to the 'maintaining-low' group, those with higher levels of depressive symptoms and lower levels of life satisfaction were more likely to belong to the 'chronically-high' group and 'moderately-increasing' group, respectively. Respondents who had less frequent meetings with others in close relationships were more likely to be in the 'rapidly-increasing' group than the 'maintaining-low' group. DISCUSSION: These findings are suggestive of distinct trajectories of multimorbidity across older adulthood, indicating that multimorbidity experiences might differ among older adults. Moreover, results suggest that there may be gender inequalities in multimorbidity trajectories, and that levels of psychological well-being and social engagement could be useful in identifying older adults who are at higher risk of worsening multimorbidity.

Interobserver Reproducibility in Sonographic Measurement of Diameter and Volume of Papillary Thyroid Microcarcinoma.

Background: Active surveillance is recommended as an alternative to immediate surgery for low-risk papillary thyroid microcarcinoma (PTMC), and determining meaningful changes in diameter and volume on ultrasonography (US) is critical. However, interobserver reproducibility of the sonographic measurement of maximum diameter and volume of PTMC has not been well established. We aimed to determine the reproducibility in the measurement of maximum diameter and volume of PTMC on US. Methods: Consecutive patients who underwent US for pathologically proven PTMC between December 2018 and December 2019 were retrospectively reviewed. Two observers independently performed sonographic measurement of each nodule using standardized measurement methods. Each observer measured maximum transverse, anteroposterior, and longitudinal nodule diameters, and using these, nodule volume was calculated using the ellipsoid formula. Interobserver reproducibility in the measurement of the maximum diameter and volume was assessed using percentage reproducibility coefficient (RC). Z-tests of the intraclass correlation coefficients (ICCs) were used to compare the interobserver reproducibility in subgroups defined according to sonographic characteristics, such as the presence of microcalcification, nodule size, and parenchymal heterogeneity. Results: A total of 197 thyroid nodules from 188 patients were included in the study series. The percentage RCs were 71.8% [95% confidence interval, CI 65.4-79.7%] and 23.7% [CI 21.6-26.3%] for volume and maximum diameter measurements, respectively. There were no significant differences noted in the ICC values according to nodule orientation, presence of calcifications, size, or parenchymal heterogeneity. Conclusion: For PTMC, a difference of up to 24% in the maximum diameter and 72% in the volume may be considered to be within measurement error on US. This value may be used to determine the cutoff for defining meaningful change in the maximum diameter and volume for PTMC during active surveillance.

Comparison of three risk stratification models for non-clear cell renal cell carcinoma patients treated with temsirolimus as first-line therapy.

BACKGROUND/AIMS: For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. METHODS: This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. RESULTS: Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). CONCLUSION: All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte.

BACKGROUND: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. METHODS: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. RESULTS: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. CONCLUSIONS: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Clinical significance of systemic chemotherapy after curative resection of metachronous pulmonary metastases from colorectal cancer.

PURPOSE: The use of systemic chemotherapy after resection remains controversial in patients with resectable metachronous pulmonary metastases from colorectal cancer (CRC). This retrospective study compared systemic chemotherapy with observation alone after resection of pulmonary metastases from CRC. METHODS: Between 2001 and 2015, 91 patients with metachronous pulmonary metastases underwent curative surgical resection at five centers. Patients with stage IV at diagnosis were excluded. Overall survival (OS) was defined as the time from pulmonary resection until death. The disease-free interval (DFI) was defined as the time from pulmonary resection until recurrence or death. RESULTS: Among the 91 patients, 63 were in the chemotherapy group, while 28 were in the observation alone group. The characteristics were similar between the two groups, except for the carcinoembryonic antigen level after pulmonary metastases and the use of adjuvant treatment after resection of the primary tumor. With a median follow-up duration of 46 months (11-126), the estimated 5-year DFI and OS rates were 32.8 and 61.4%, respectively. The chemotherapy following pulmonary resection was not significantly associated with the DFI (p = 0.416) and OS (p = 0.119). CONCLUSION: Systemic chemotherapy after pulmonary resection was not found to have a significant effect on survival.

Preparation of Chitosan-Coated Nanostructured Lipid Carriers (CH-NLCs) to Control Iron Delivery and Their Potential Application to Food Beverage System.

Nanostructured lipid carriers (NLCs) and chitosan-coated NLCs (CH-NLCs) were prepared by a combined double emulsion and melt dispersion method. The physicochemical properties of them were investigated to determine the optimum conditions. At 3% emulsifier concentration, the NLCs showed about 191.0 ± 4.1 nm mean particle size and low polydispersity index value compared to those observed under other conditions. The encapsulation efficiency of CH-NLCs was 83.9% which was about 10% higher than that of NLCs. In vitro release test showed that low release amount of iron from the NLCs (11%) and CH-NLCs (5%) in simulated gastric condition within 3 h, whereas the iron release amounts of the NLCs and CH-NLCs were high (over 77%) in simulated intestinal condition because both NLCs and CH-NLCs were totally destructed in the intestinal condition after 3 h. In the thiobarbituric acid test, the absorbance of milk-fortified NLC and CH-NLCs was lower than that of original milk. Based on these results, CH-NLCs showed great potential for iron fortification in milk.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer.

PURPOSE: Genexol-PM is a Cremophor EL-free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Application of mutant JAK2V617F for in vitro generation of red blood cells.

BACKGROUND: In vitro generation of red blood cells (RBCs) from hematopoietic stem cells (HSCs) has been reported, but the collection of 1 × 10(5) to 1 × 10(6) CD34+ cells present in cord and peripheral blood is too small for expansion to 1 × 10(12) cells in 1 unit of RBCs. We transduced JAK2V617F gene, the most common mutation with polycythemia vera (PV), into cord blood-derived CD34+ cells. This PV model was expected to increase cell proliferation without the addition of erythropoietin (EPO) in early phase of differentiation. STUDY DESIGN AND METHODS: Empty vector (control), wild-type JAK2 (wJAK2), and mutant JAK2V617F (mJAK2) were transduced into CD34+ cells using a lentivirus system. The CD34+ cells were then differentiated to the RBCs in a culture system. The cells were analyzed for cell number, differential count, and morphologic changes. Cultured RBCs were tested for oxygen equilibrium. RESULTS: wJAK2- and mJAK2-transduced cells showed higher proliferation capacity until Day 21 than control cells; interestingly, only mJAK2-transduced cells were highly increased on Day 7 during EPO-free culture. However, both wJAK2- and mJAK2-tranduced cells had more delayed differentiation than control, but they had a higher portion of completely matured RBCs and orthochromatic erythroblasts. Furthermore, mJAK2-tranduced cells showed more differentiation into RBCs than wJAK2-transduced cells and they had a normal hemoglobin dissociation curve. CONCLUSION: This is the first trial to use a PV erythropoiesis model for RBC differentiation from stem cells. The transduction of HSCs with mJAK2 increased their proliferation capacity in EPO-free culture conditions. This model may also be useful for investigating the pathogenesis of PV.

Multi-center Randomized Phase II Study of Weekly Docetaxel Versus Weekly Docetaxel-plus-Oxaliplatin as a Second-line Chemotherapy for Patients with Advanced Gastric Cancer.

AIM: The current phase II clinical study was conducted to evaluate the efficacy and safety of weekly docetaxel alone, and weekly docetaxel-plus-oxaliplatin, as a second-line chemotherapy in patients with cisplatin-refractory advanced gastric cancer. PATIENTS AND METHODS: We enrolled patients with histologically confirmed gastric adenocarcinoma whose disease had progressed after cisplatin-based regimens. Patients were randomly assigned to receive docetaxel alone (36 mg/m(2), days 1 and 8) or docetaxel (36 mg/m(2), days 1 and 8) and oxaliplatin (80 mg/m(2), day 1) combination therapy every three weeks. RESULTS: This trial was terminated early due to poor patient accrual rate. From January 2009 to January 2012, a total of 52 patients were enrolled in the current study from six centers: 27 patients in the docetaxel monotherapy arm and 25 patients in the docetaxel/oxaliplatin combination arm. Fifty-two patients were assessable for efficacy, and response rates as follows (response rate: 14.8% in the monotherapy arm, 24.0% in the combination arm; disease control rate: 48.1% in the monotherapy arm, 76.0% in the combination arm. The median progression-free survival was 2.0 (95% confidence interval=1.2-2.9) months in the monotherapy arm and 4.9 (95% confidence interval=3.6-6.6) months in the combination arm (p=0.002). The most common grade 3 or 4 adverse event was neutropenia (14% for monotherapy versus 32% for combination). No treatment-related mortality was observed. CONCLUSION: Weekly docetaxel and weekly docetaxel-plus-oxalipaltin regimens were found to be well-tolerated and effective as a second-line chemotherapy for patients with advanced gastric cancer.

Analysis of immunoglobulin and T cell receptor gene rearrangement in the bone marrow of lymphoid neoplasia using BIOMED-2 multiplex polymerase chain reaction.

The evaluation of bone marrow (BM) involvement is important for diagnosis and staging in patients with lymphoid neoplasia. We evaluated of immunoglobulin (Ig) and/or T-cell receptor (TCR) gene rearrangements in the BM using the standardized BIOMED-2 multiplex PCR clonality assays and compared the results with microscopic findings such as histology and CD10, CD20, CD79a, CD3 and CD5 immunohistochemistry. A total of 151 samples were enrolled; 119 B cell neoplasia, 29 T cell neoplasia, and 3 Hodgkin's lymphoma. The molecular clonality assay and microscopic diagnosis were concordant in 66.9% (n=101) and discordant in 33.1 % (n=50). Ig/TCR gene clonality assay detected 43 cases of BM involvement which was not presented in the morphology. Two cases among them turned into microscopic BM involvement during a close follow up. Clonal TCR gene rearrangements were detected in 12.6% of B cell neoplasia and Ig gene rearrangement were found in 3.4% of T cell neoplasia. This molecular clonality assay is valuable particularly in diagnosing BM involvement of lymphoid neoplasia if it is morphologically uncertain. But it should be carefully interpreted because molecular clonality may be present in the reactive lymphoproliferation. Therefore, comprehensive analysis with morphologic analysis should be important to reach a final diagnosis.

Clinical effectiveness and safety of OROS® hydromorphone in break-through cancer pain treatment: a multicenter, prospective, open-label study in Korean patients.

OBJECTIVE: To evaluate the effectiveness of OROS® hydromorphone in reducing breakthrough pain (BTP) medication frequency in Korean patients with chronic cancer pain. SETTINGS AND DESIGN: Multicenter, prospective, open-label, phase IV study. PARTICIPANTS: Patients with chronic malignant pain using immediate-release oxycodone more than two times per day for BTP. INTERVENTIONS: Patients were stabilized on their ongoing drug for 3 days immediately before baseline measurements (day 0). Medication was changed to OROS® hydromorphone at a dose equianalgesic to oxycodone using a 2.5:1 controlled-release oxycodone to hydromorphone hydrochloride conversion ratio; the patients were observed for 7 days. Dose was titrated, if required, and the patients were observed for another 7 days. Effectiveness and safety parameters were measured at baseline, day 7, and day 14. MAIN OUTCOMES: BTP medication frequency on days 7 and 14, compared to baseline. RESULTS: Of the 141 patients screened, 114 received study drug and 98 completed the study. Compared to day 0, daily BTP medication frequency on day 14 decreased from 2.93 to 2.00 (p > 0.0001), daily BTP frequency decreased from 3.67 to 2.44 (p > 0.0001), and end-of-dose pain frequency decreased by 44 percent. Pain was controlled adequately during daytime and night-time. Pain intensity decreased by 11 percent as assessed using the Korean Brief Pain Inventory and by 17 percent as assessed using the numerical rating scale. About 61.2 percent patients and 60.2 percent physicians were satisfied with the treatment. Common adverse events, which occurred in 91.2 percent patients, were constipation, somnolence, and dizziness. CONCLUSION: Once-daily OROS® hydromorphone is efficient in the reduction of cancer pain-related BTP episodes, including end-of-dose pain.

Comparative study of immunofluorescent antinuclear antibody test and line immunoassay detecting 15 specific autoantibodies in patients with systemic rheumatic disease.

Based on the currently proposed algorithms, antibodies specificities (sp-ANAs) are identified mainly in samples positive for fluorescent antinuclear antibodies (FANA) screening tests. The purpose of the present study was to compare diagnostic performances of FANA and line immune assay (LIA) detecting 15 sp-ANAs in patients with systemic rheumatic diseases (SRD). In 948 sera from the patients with SRD (n = 590) and non-SRD (n = 358), we evaluated the fluorescent patterns and intensities in the FANA test, and compared the FANA results with sp-ANAs against nRNP, Sm, SS-A, Ro52, SS-B, Scl-70, PM/Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosome, histone, ribosomal-P, and M2. The sensitivity and specificity was 75.9% and 52.5% of FANA test and 62.0% and 84.4% of sp-ANAs test for SRD detection. The overall agreement between FANA and sp-ANAs results was 69.2% (Kappa coefficient; 0.404). According to the clinical diagnosis, the levels of agreement varied from 33.3% to 83.1%. The positive predictive values of each FANA pattern for the detection of sp-ANAs were less than 50% except for the discrete speckled pattern (91.7%). The 1:100 intensity of FANA as well as the monoreactivity of LIA, anti-SSA(-)/anti-Ro52(+), or FANA(-)/sp-ANAs(+) was associated with non-SRD. Antibodies against ribosomal-P or PCNA were specific for systemic lupus eryhthematosus. This study highlights the need for careful interpretation of FANA test results to assess sp-ANAs and the application of sp-ANAs tests including less-common autoantibodies. In patients with clinical suspicion of SRD, screening with both FANA and sp-ANAs tests could improve diagnostic efficiency.

A facile synthesis of highly functionalized 4-arylcoumarins via Kostanecki reactions mediated by DBU.

An efficient synthesis of 4-arylcoumarins has been accomplished via Kostanecki reactions of 2-hydroxybenzophenones with acetic anhydride employing DBU at ambient temperature. Using the same strategy, several 2-acyloxybenzophenone derivatives were readily converted to 3,4-difunctionalized coumarins. This protocol offers a notable improvement in reaction conditions for coumarin synthesis and takes advantage of its synthetic capability, especially for highly functionalized 4-arylcoumarins with structural diversity.

Highly enantioselective synthesis of cyclic sulfamidates and sulfamides via rhodium-catalyzed transfer hydrogenation.

We achieved highly enantioselective synthesis of cyclic 1,2-sulfamidates and -sulfamides via rhodium-catalyzed transfer hydrogenation, and also revealed one-pot preparation of cyclic N-sulfonylimines from α-hydroxy ketones.

[A case of t(3;3)(q21;q26.2) associated with severe multilineage dysplasia and multi-drug resistance in blastic crisis of chronic myelogenous leukemia].

The t(3;3)(q21;q26.2) is known to be mainly observed in hematologic myeloid malignancies, as a form of 3q21q26 syndrome. Cytogenetic abnormalities of 3q21q26 syndrome result in RPN1-EVI1 fusion transcripts involving ecotropic viral integration site-1 (EVI1) at 3q26.2 and ribophorin I (RPN1) at 3q21, and the fusion transcripts play an important role in leukemogenesis and disease progression. They are usually associated with dysplasia, especially of megakaryocytes. Patients with these cytogenetic abnormalities show extremely poor prognosis even with aggressive anti-leukemic therapy. We report a case of blastic crisis of CML with both t(3;3)(q21;q26.2) and t(9;22)(q34;q11.2) and associated severe multilineage dysplasia. The patient showed a poor response to imatinib, dasatinib and aggressive induction therapy. When both t(3;3)(q21;q26.2) and t(9;22)(q34;q11.2) are observed in cases of leukemia with increased blasts, they are best considered as aggressive phases of CML with t(3;3)(q21;q26.2), rather than AML with t(9;22)(q34;q11.2) by 2008 WHO classification.