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The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m 2 ). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m 2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m 2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m 2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences., (© 2024. The Author(s).)

Background: Vaccine champions are common in primary care, but little is known about which champions are effective., Methods: In 2022, we surveyed 2,144 US primary care professionals (PCPs) who reported working with vaccine champions. Respondents rated the champion with whom they worked most closely on their effectiveness at improving vaccination rates., Results: About half (49 %) of PCPs perceived their closest champion as highly effective. PCPs perceived advanced practice providers and nursing staff as highly effective somewhat more often than physicians (52 % and 58 % vs 43 %, p <.001). Other correlates of perceived effectiveness included being a formally appointed versus informal champion, working extremely versus less closely with PCPs, and using a high (4-5) versus low (0-1) number of implementation strategies to improve vaccination rates (all p <.001)., Conclusions: Results suggest vaccine champions may benefit from having formal roles and opportunities to work closely with colleagues to improve vaccination rates using multiple strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65-70%, 70-75%, and > 75%) and the URR < 65% group were 0.748 (0.623-0.898), 0.693 (0.578-0.829), and 0.640 (0.519-0.788), respectively. The HRs of high Kt/V groups (Kt/V 1.2-1.4, 1.4-1.7, and > 1.7) and the Kt/V < 1.2 group were 0.711 (0.580-0.873), 0.656 (0.540-0.799), and 0.623 (0.498-0.779), respec-tively. In subgroup analysis, Kt/V was not associated with all-cause mortality in women. The prognostic value of URR for all-cause mortality is as great as that of Kt/V. URR > 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women., (© 2023. The Author(s).)

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians ( N  = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shen, Lin, Tsai, Kuo, Chen, Chao, Niu, Hung and Chang.)

Background: The prevalence of diabetes mellitus (DM) in Taiwan between 2017 and 2020 was 11.05%, which is higher than the global prevalence (10.5%). Previous studies have shown that patients with DM have higher liver enzyme levels than those without DM. However, it is unclear whether there are sex differences in the association between incident DM and liver function. Therefore, the aim of this longitudinal study was to investigate this issue in a large Taiwanese cohort., Methods: We identified 27,026 participants from the Taiwan Biobank, and excluded those with baseline DM ( n = 2,637), and those without follow-up data on DM, serum fasting glucose or glycosylated hemoglobin A1c ( n = 43). The remaining 24,346 participants (male: 8,334; female: 16,012; mean age 50.5 ± 10.4 years) were enrolled and followed for a median of 4 years., Results: Of the enrolled participants, 1,109 (4.6%) had incident DM and 23,237 (95.4%) did not. Multivariable analysis showed that high levels of glutamic-oxaloacetic transaminase (AST) ( p < 0.001), glutamic-pyruvic transaminase (ALT) ( p < 0.001), albumin ( p = 0.003), α-fetoprotein ( p = 0.019), and gamma-glutamyl transpeptidase (GGT) ( p = 0.001) were significantly associated with incident DM in the male participants. In comparison, high levels of AST ( p = 0.010), ALT ( p < 0.001), albumin ( p = 0.001) and GGT ( p < 0.001), and low total bilirubin ( p = 0.001) were significantly associated with incident DM in the female participants. There were significant interactions between total bilirubin and sex ( p = 0.031), and GGT and sex ( p = 0.011) on incident DM., Conclusion: In conclusion, liver function parameters were significantly associated with incident DM. Further, there were differences in the associations between the male and female participants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Wu, Huang, Chen and Chang.)

Healthcare organizations have been early adopters of Covid-19 vaccine mandates as a strategy to end the pandemic. We sought to evaluate support for such mandates among pediatric primary care professionals (PCPs) in the United States. In February-March 2021, we conducted a national online survey of 1,047 PCPs (71% physicians). We used multivariable logistic regression to assess correlates of PCPs' support for Covid-19 vaccine mandates for health care workers. Most PCPs supported Covid-19 vaccine mandates for health care workers (83%). PCPs were more likely to support mandates if they perceived health care workers to be at highest risk of getting Covid-19 compared to other worker types (8 percentage points, p  < 0.01). PCPs were also more likely to support mandates if their clinic recommended or required vaccination (11 percentage points and 20 percentage points respectively, both p  < 0.01). However, PCPs were less likely to support mandates if their clinic offered incentives to vaccinate (10 percentage points, p  < 0.05). Clinic recommendations and requirements for Covid-19 vaccination may increase support for mandates. Incentives may decrease support, perhaps by creating the perception that viable alternatives to mandates exist., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation., Methods: The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis., Results: Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression., Conclusion: Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Li, Li, Li, Wang, Wang, Yu, Zhu, Cheng and Du.)

Background: Endometriosis (EMS), a typical endocrine immune disorder, associates with dramatically increased estrogen production and disorganized immune response in ectopic focus. Peritoneal regulatory T cells (Tregs) expansion in women with EMS and their pathogenic role attributable to endometriotic immunotolerance has been reported. Whether local high estrogen promotes EMS by discipling Tregs needs to be further explored. Up to date, there is no effective medicine for the treatment of EMS. SCM-198 is a synthetic leonurine with multiple physiological activities. Whether SCM-198 could regulate Tregs via estrogen and facilitate the radical cure of EMS has not yet been reported. Methods: Proportion of Tregs in peritoneal fluid of patients with EMS was firstly analyzed via flow cytometry. Peritoneal estrogen concentration and the mRNA levels of estrogen receptor α (ERα) and estrogen receptor β (ERβ) of Tregs were detected by ELISA and RT-PCR, respectively. Grouped in vitro induction assays were performed to explore the effects of SCM-198 and estrogen signaling on Tregs. Cell invasion and viability assays were utilized to detect the crosstalk between Tregs and ectopic endometrial stromal cells (eESCs), with or without SCM-198 treatment. Furthermore, EMS mice models were established to verify the therapeutic effects of SCM-198. Results: Increased Tregs were found in peritoneal fluid of EMS patients, accompanied with estrogen-ERα overactivation. Estrogen-ERα triggered the expansion of Tregs and their cytokine production (IL-10 and TGF-β1), which could be reversed by SCM-198 treatment. Moreover, SCM-198 abated the invasion and viability of eESCs enhanced by Tregs. In vivo experiments confirmed that SCM-198 obviously retarded the growth of ectopic lesions and downregulated the functions of Tregs via estrogen-ERα inactivation. Conclusions: These data suggest that SCM-198 attenuates Tregs expansion via the inhibition of estrogen-ERα signaling in EMS and offer a promising therapy for such a refractory disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Urinary tract infections (UTI) represent one of the most common problem within the urological disorders, and it is mainly caused by biofilm formation which leads to bacterial infection. Anti-adhesion and antibacterial agents are two primary mechanisms to prevent biofilm formation; however, current strategies are insufficiently effective. In this study, we developed an effective antibiofilm biodegradable polymer with high biocompatibility. Here we embedded silver nanoparticles (AgNPs) in poly(glycerol sebacate) acrylate (PGSA) followed by superhydrophilic modification on the polymer surfaces. The modified surfaces were characterized using SEM, AFM and contact angle measurements. This anti-adhesive surface prevented the adhesion of E. coli and limited the biofilm coverage percentage to less than 3% in 24 h. In the in vitro degradation, the long-term antibiofilm performance was evaluated in Nowatzki-Stoodley artificial urine (NSAU). The surface modified AgNPs embedded PGSA (sPGSA-AgNPs) was able to effectively inhibit the formation of biofilm by reducing the biofilm coverage to less than 0.01%, and it also showed low cytotoxicity with human bladder carcinoma cell. With the effective antibiofilm, biocompatibility and biodegradability, it is possible to be applied in urological devices to ameliorate the situation of UTIs., (Copyright © 2021. Published by Elsevier B.V.)

The assembly-disassembly of hyaluronic acid (HA) with a bovine serum albumin-conjugated gold nanoparticle (BSA-AuNP) was demonstrated using a gas-phase electrophoresis approach, electrospray-differential mobility analysis (ES-DMA). Physical sizes, number and mass concentrations, and degrees of aggregation of HA, BSA, and AuNP were successfully quantified using ES-DMA hyphenated with inductively coupled plasma mass spectrometry. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy was employed complementarily for an orthogonal characterization of the assembly of HA with BSA-AuNP and the subsequent HA detachment. The results show that the surface packing density of HA on BSA-AuNP was proportional to the concentration of HA ( C HA ) when C HA ≤ 5 × 10 -3 μmol/L, and the equilibrium binding constant of HA on BSA-AuNP was identified as ≈ 4 × 10 5 L/mol at pH 3. The pH-sensitive and enzyme-induced detachments of HA from BSA-AuNP were both successfully characterized using ES-DMA and ATR-FTIR. In the absence of enzymatic catalysis, the rate constant of HA detachment ( k ) was shown to increase by at least 3.7 times on adjusting the environmental acidity from pH 3 to pH 7. A significant enzyme-induced HA detachment was identified at pH 7, showing a remarkable increase of k by at least two times in the presence of an enzyme. This work provides a proof of concept for assembly of HA-based hybrid colloidal nanomaterials through the tuning of surface chemistry in the aqueous phase with the ability of in situ quantitative characterization, which has shown promise for the development of a variety of HA-derivative biomedical applications (e.g., drug delivery).

Trace element analysis of soft materials, to determine the content of low concentration elements, is important in many industries such as food quality control and medical biopsy analysis. Many of these applications would benefit from faster analysis with smaller sample requirements. Further, some natural samples are soft and have high water content, which brings challenges to element analysis. Here, we develop a cryogenic pelletization pretreatment to address those challenges. The soft samples are cryogenically milled, freeze-dried, and pelletized before elemental analysis. Analysis is performed by laser ablation spectroscopy, the combination of laser-induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS), to rapidly analyze light and heavy analytes. For this initial study, aluminum (Al) content in soft samples is determined by LIBS and lead (Pb) content by LA-ICP-MS. The standard addition method is performed to build calibration curves for element quantification. The measurements are compared with a Hong Kong government certified acid digestion and ICP-MS procedure. The experiment is performed on standard reference materials and selected food samples. The relative errors compared with certified measurements are less than 10% for all samples, with Al content ranging from 63-1466 µg/g and Pb content from 0.37-2.35 µg/g (dry mass). Microscopy of pellets shows that laser ablation spectroscopy can be performed with 100 µg of sample (dry mass). Total analysis time from raw sample to final measurement, including preparation, is under 1 h. The results indicate that the laser ablation spectroscopy with cryogenic pelletization is a promising technique for many applications such as screening of small food samples for toxic metals and trace element analysis of millimeter biopsies.

The regeneration of damaged or lost tissue is considered to be a critical step toward realizing full organ regeneration in modern medicine. Although surgical techniques continue to advance, treatment for missing tissues in irregular wounds remains particularly difficult. With increasing interest in the application of additive manufacturing in tissue engineering, the fabrication of customized scaffolds for the regeneration of missing tissue via three-dimensional (3D) printing has become especially promising. Amongst the work on the regeneration of many important organs, liver regeneration is particularly interesting because liver diseases are increasingly prevalent in many countries around the world, resulting in a greater need for liver transplantation. The generation of hexagonal scaffolds for the regeneration of liver lobules is highly demanding, but their 3D structure has been proved difficult to reproduce by traditional fabrication methods. In this work, various hexagonal scaffolds are developed for liver lobule regeneration via 3D printing using novel biodegradable polymeric materials, including poly(glycerol sebacate) acrylate and poly(ethylene glycol) diacrylate. Through fine-tuning of printing parameters, a series of hexagonal scaffolds were designed and printed to mimic liver lobule units. The scaffolds were printed with various structures together with varying surface areas and 3D structures to enhance cell seeding density and diffusivity of the culture medium. Analysis of cell metabolic activities showed that the high-diffusion staircase (HDS) scaffold could support potential differences in cell proliferation rate. Furthermore, the HDS scaffolds composed of different copolymers were cultured with cells for up to 16 days to investigate the relationship between physical properties and hepatocyte proliferation. The results indicate that the combination of the high flexibility 3D printing with biodegradable, photocurable copolymers shows great promise for the regeneration of 3D liver lobules.

Leonurus japonicus Houtt, a Chinese traditional herbal medicine, has been widely used to cure gynecological diseases, such as incomplete abortion and menoxenia. Leonurine, a major active alkaloid compound only be found in Leonurus japonicus Houtt, has been successfully extracted and purified. Recent evidence has shown that leonurine can regulate a variety of pathologic processes including oxidative stress, inflammation, fibrosis, apoptosis, and multiple metabolic disorders. Here, we have reviewed the pharmacological actions and biological functions of leonurine, with a focus on the role of leonurine in the amelioration of various pathological processes. Insights into the related signaling pathways and molecular mechanisms have strengthened our understanding on the function of leonurine in the alleviation of multiple pathological states. Our summary of the existing researches should help direct future research into the basic science and clinical applications in related diseases.

We report a case of acute myeloid leukemia with complex cytogenetic abnormalities suggestive of preexisting myelodysplastic syndrome in a patient with habitual ingestion of colloidal silver as nutritional supplement for over 10 years and the medical literature is reviewed.

We report an unusual case of spontaneous intramuscular hematoma associated with antiproteinase 3 antibody in a patient with metastatic squamous cell carcinoma receiving nivolumab and the medical literature is reviewed.

Boron neutron capture therapy (BNCT) is a promising radiotherapy for treating glioblastoma multiforme (GBM). However, the penetration of drugs (e.g., sodium borocaptate and BSH) for BNCT into brain tumors is limited by cerebral vesicular protective structures, the blood-brain barrier, and the blood-brain tumor barrier (BTB). Although BSH has been reported to be selectively taken up by tumors, it is rapidly excreted from the body and cannot achieve a high tumor-to-normal brain ratio (T/N ratio) and tumor-to-blood ratio (T/B ratio). Despite the development of large-molecular weight boron compounds, such as polymers and nanoparticles, to enhance the permeation and retention effect, their effects remain insufficient for clinical use. To improve the efficiency of boron delivery to the tumor site, we propose combinations of self-assembled boron-containing polyanion [polyethylene glycol- b-poly(( closo-dodecaboranyl)thiomethylstyrene) (PEG- b-PMBSH)] nanoparticles (295 ± 2.3 nm in aqueous media) coupled with cationic microbubble (B-MB)-assisted focused ultrasound (FUS) treatment. Upon FUS sonication (frequency = 1 MHz, pressure = 0.3-0.7 MPa, duty cycle = 0.5%, sonication = 1 min), B-MBs can simultaneously achieve safe BTB opening and boron drug delivery into tumor tissue. Compared with the MBs of the PEG- b-PMBSH mixture group (B + MBs), B-MBs showed 3- and 2.3-fold improvements in the T/N (4.4 ± 1.4 vs 1.3 ± 0.1) and T/B ratios (1.4 ± 0.6 vs 0.1 ± 0.1), respectively, after 4 min of FUS sonication. The spatial distribution of PEG- b-PMBSH was also improved by the complex of PEG- b-PMBSH with MBs. The findings presented herein, in combination with the expanding clinical application of FUS, may improve BNCT and treatment of GBM.

5-fluorouracil and capecitabine are chemotherapeutic agents commonly used to treat solid malignancies. Increased susceptibility to 5-fluorouracil or capecitabine, caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, or other genetic mutations in the enzymes that metabolize 5-fluorouracil can lead to severe life-threatening toxicities and are typically manifested by an early onset of symptoms. We report and discuss the management and outcome of capecitabine toxicity with the recently FDA approved antidote, uridine triacetate (Vistogard), in a 57-year-old female breast cancer patient with homozygous dihydropyrimidine dehydrogenase deficiency who received treatment beyond the recommended 96 h window from the last dose of capecitabine.

As acrylated polymers become more widely used in additive manufacturing, their potential applications toward biomedicine also raise the demand for biodegradable, photocurable polymeric materials. Polycaprolactone diacrylate (PCLDA) and poly(ethylene glycol) diacrylate (PEGDA) are two popular choices of materials for stereolithography (SLA) and digital light processing additive manufacturing (DLP-AM), and have been applied to many biomedical related research. However, both materials are known to degrade at a relatively low rate in vivo, limiting their applications in biomedical engineering. In this work, biodegradable, photocurable copolymers are introduced by copolymerizing PCLDA and/or PEGDA with poly(glycerol sebacate) acrylate (PGSA) to form a network polymer. Two main factors are discussed: the effect of degree of acrylation in PGSA and the weight ratio between the prepolymers toward the mechanical and degradation properties. It is found that by blending prepolymers with various degree of acrylation and at various weight ratios, the viscosity of the prepolymers remains stable, and are even more 3D printable than pure substances. The formation of various copolymers yielded a database with selectable Young's moduli between 0.67⁻10.54 MPa, and the overall degradation rate was significantly higher than pure substance. In addition, it is shown that copolymers fabricated by DLP-AM fabrication presents higher mechanical strength than those fabricated via direct UV exposure. With the tunable mechanical and degradation properties, the photocurable, biodegradable copolymers are expected to enable a wider application of additive manufacturing toward tissue engineering.

The direct cell control by surface topographic patterns in the micrometer and nanometer range has been proven to be important for the maintenance of tissue structures. This study presents the application of direct laser writing to fabricate micro-gratings on the biodegradable material 1,3-diamino-2-hydroxypropane-co-polyol sebacate (APS). The 193 nm excimer laser is applied to form microgrooves with widths of 2 to 10 μm and depths of 400 to 2884 nm. Two kinds of cells, fibroblasts of the rabbit synoviocyte cell line (HIG-82) and endothelial cells of human umbilical vein endothelial cells (HUVECs), were cultured on the flat and patterned APS to evaluate the biocompatibility of APS as well as the influence of contact guidance for cellular behaviours, respectively. The results show that both HIG-82 and HUVECs grow actively on APS scaffolds with directional growth, which was observed through cell morphology and proliferation rate, indicating their applicability in tissue regeneration. HIG-82 was observed to exhibit directional growth with the highest cell spreading area and density on the scaffolds with 7 μm width and 1350-1500 nm depth of gratings. Meanwhile, high cell spreading area and cell density of HUVECs were observed on laser ablated APS with 5 μm gratings and at depths greater than 1485 nm. The proposed microgrooves on APS could significantly enhance the cell growth, adhesion and even promote selective cell proliferation, which poses potential application for further tissue engineering studies.

Aim: This study was conducted to compare predictive accuracy of the available pharmacogenetics (PGx)-guided warfarin dosing algorithms derived from Caucasian, Asian, and mixed population to identify a suitable algorithm for Thai population., Methods: Ten warfarin dosing algorithms derived from different population including Caucasian, East Asian, South-East Asian, and mixed races were selected and tested with clinical and genetic data of Thai patients. Comparative performances of these algorithms were tested using mean dose error (MDE) between actual warfarin maintenance dose (AWMD) and predicted dose generated by each dosing algorithm, and percentage of ideal dose prediction (IDP). Sensitivity analysis for predictive accuracy was also conducted by stratifying patients into low (AWMD ≤21 mg/wk), intermediate (AWMD >21 to <49 mg/wk), and high maintenance dose (AWMD ≥49 mg/wk) groups., Results: Data of 165 patients were included for the analyses. Mean actual warfarin dose of the study population was 25.03 ± 10.53 mg/wk. Large variability of MDE, ranging from -12.11 to 11.24 mg/wk, among algorithms was observed. International Warfarin Pharmacogenetics Consortium, Gage et al, and Ohno et al algorithms had comparable performances to Sangviroon et al algorithm, as observed by MDE of <1 mg/wk with percentage of IDP ≥40%. Further sensitivity analyses among patients requiring low and intermediate maintenance doses confirmed such findings with IDP percentage ranging from 37.8% to 59.2%. Among high-dose group, only Ohno et al and Sarapakdi et al algorithms had acceptable performance., Conclusions: Warfarin PGx-guided dosing algorithms derived from large, mixed population performed comparably to Sangviroon et al algorithm. Certain algorithms should be avoided due to significant dose prediction error., (© 2017 John Wiley & Sons Ltd.)

Laser patterning on polymeric materials is considered a green and rapid manufacturing process with low material selection barrier and high adjustability. Unlike microelectromechanical systems (MEMS), it is a highly flexible processing method, especially useful for prototyping. This study focuses on the development of polymer surface modification method using a 193 nm excimer laser system for the design and fabrication of a microfluidic system similar to that of natural vasculatures. Besides from poly(dimethyl siloxane) (PDMS), laser ablation on biodegradable polymeric material, poly(glycerol sebacate) (PGS) and poly(1,3-diamino-2-hydroxypropane- co -polyol sebacate) (APS) are investigated. Parameters of laser ablation and fabrication techniques to create microchannels are discussed. The results show that nano/micro-sized fractures and cracks are generally observed across PDMS surface after laser ablation, but not on PGS and APS surfaces. The widths of channels are more precise on PGS and APS than those on PDMS. Laser beam size and channel depth are high correlation with a linear relationship. Repeated laser ablations on the same position of scaffolds reveal that the ablation efficiencies and edge quality on PGS and APS are higher than on PDMS, suggesting the high applicability of direct laser machining to PGS and APS. To ensure stable ablation efficiency, effects of defocus distance into polymer surfaces toward laser ablation stability are investigated. The depth of channel is related to the ratio of firing frequency and ablation progression speed. The hydrodynamic simulation of channels suggests that natural blood vessel is similar to the laser patterned U-shaped channels, and the resulting micro-patterns are highly applicable in the field of micro-fabrication and biomedical engineering., Competing Interests: The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

During pregnancy, CD8 + T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8 + T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3 + PD-1 + CD8 + T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy. Furthermore, normal pregnant CBA/J females challenged with Tim-3- and/or PD-1-blocking antibodies were more susceptible to fetal resorption. These findings indicate that Tim-3 and PD-1 pathways play critical roles in regulating CD8 + T cell function and maintaining normal pregnancy.

Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono- and co-culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation. From mono-culture, ALT took up the most AgNPs and had the lowest cell viability within three cells. Moreover, AgNPs induced H 2 O 2 and NO from ALT/activated ALT and BV-2, respectively. However, AgNPs did not induce cytokines release (IL-6, TNF-α, MCP-1). LPS-activated BV-2 took up more AgNPs than normal BV-2, while the induction of ROS and cytokines from activated cells were diminished. Ca 2+ -regulated clathrin- and caveolae-independent endocytosis and phagocytosis were involved in the AgNP uptake in ALT, which caused more rapid NP translocation to lysosome than in macropinocytosis and clathrin-dependent endocytosis-involved BV-2. AgNPs directly caused apoptosis and necrosis in N2a cells, while by indirect NP exposure to bottom chamber ALT or BV-2 in Transwell, more apoptotic upper chamber N2a cells were observed. Cell viability of BV-2 also decreased in an ALT-BV-2 co-culturing study. The damaged cells correlated to NP-mediated H 2 O 2 release from ALT or NO from BV-2, which indicates that toxic response of AgNPs to neurons is not direct, but indirectly arises from AgNP-induced soluble factors from other glial cells., (© 2017 Wiley Periodicals, Inc.)

In these years, the artificial nerve guidance conduit (NGC) has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial NGC without proper stimulating factors and guidance cues still cannot obtain satisfactory prognosis for clinical patients. In this study, a biodegradable polymer-based implantable device has been developed and characterized. By incorporating three stimulating factors: (1) micro-patterned surface that can directionally guide the axon as physical cue; (2) neurotrophic gradient membrane that can continually attract axon outgrowth from the proximal to distal stump as chemical cue; (3) Schwann cells (SCs) that can support the growth of neurite and form myelin sheath around axon as biological cue, we expect that this construct can be used as a promising NGC for peripheral nerve regeneration. The results showed that the micro-patterned surface with specific dimension of channels and chambers can be precisely fabricated by laser ablation. Attachment and directional extension of differentiated neural stem cells (NSCs) were observed in micro-channels. The gradient distribution of nerve growth factor 7S on gelatin membrane was successfully achieved. Significant improvement in neurite length and increase in neuronal gene expressions were also noticed in higher concentration region. When co-culturing with SCs, NSCs can differentiate toward neuronal cells with strong expression of mature neuronal markers: βIII tubulin and microtubule-associated protein-2 (Map 2). Meanwhile, myelin basic protein was also observed, suggesting that SCs can provide biological support to neuronal cells in vitro. In the future, this advanced artificial NGC may be used as implantable prosthesis for the treatment of peripheral nerve injury with better functional recovery.

Passivation of surface states is known to reduce the onset photocurrent potential by removing the Fermi level pinning effect at the Helmholtz layer and enhance the photocurrent plateau by suppressing recombination loss in the space charge region. We report for the first time that metal ions can effectively passivate surface states in situ that improves the photoelectrochemical (PEC) performance of hematite electrodes. Among metal ions studied, Cr(iii), Mn(ii), Fe(ii), Co(ii), Cu(ii) and Zn(ii) were found to enhance the photocurrent by 30-300%; whereas photocurrent density significantly dropped by 90% in Ni(ii) solution after 90 min of illumination. We further hypothesized that the surface states might be the high affinity adsorption sites on hematite surfaces. Once the surface states are occupied by metal ions, along with the Schottky barrier effect at the hematite/electrolyte interface formed by adsorbed metal ions, the PEC performance is enhanced. Our results also enable the design of a potential PEC based water treatment method to extract additional energy, for example, in the brines (containing concentrated metal ions and electrolyte) of membrane processed wastewater.

Although, titanium dioxide nanoparticles (TiO2NPs) are nanomaterials commonly used in consumer products, little is known about their hazardous effects, especially on central nervous systems. To examine this issue, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were exposed to 6 nm of 100% anatase TiO2NPs. A lipopolysaccharide (LPS) was pre-treated to activate glial cells before NP treatment for mimicking NP exposure under brain injury. We found that ALT and BV-2 cells took up more NPs than N2a cells and caused lower cell viability. TiO2NPs induced IL-1β in the three cell lines and IL-6 in N2a. LPS-activated BV-2 took up more TiO2NPs than normal BV-2 and released more intra/extracellular reactive oxygen species (ROS), IL-1β, IL-6 and MCP-1 than did activated BV-2. Involvement of clathrin- and caveolae-dependent endocytosis in ALT and clathrin-dependent endocytosis and phagocytosis in BV-2 both had a slow NP translocation rate to lysosome, which may cause slow ROS production (after 24 h). Although TiO2NPs did not directly cause N2a viability loss, by indirect NP exposure to the bottom chamber of LPS-activated BV-2 in the Transwell system, they caused late apoptosis and loss of cell viability in the upper N2a chamber due to H2O2 and/or TNF-α release from BV-2. However, none of the adverse effects in N2a or BV-2 cells was observed when TiO2NPs were exposed to ALT-N2a or ALT-BV-2 co-culture. These results demonstrate that neuron damage can result from TiO2NP-mediated ROS and/or cytokines release from microglia, but not from astrocytes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Pharmacogenetics is a study of how genetic variation of an individual affects the drug response. We report a case of recurrent pancytopenia resulting from maintenance chemotherapy in a patient with acute promyelocytic leukemia and two pharmacogenetic mutations, namely, methylene tetrahydrofolate reductase C677T homozygous mutation and thiopurine methyltransferase mutation., (© The Author(s) 2015.)

The consideration of water energy nexus inspires the environmental engineering community to pursue a more sustainable strategy in the wastewater treatment. One potential response would be to enhance the performance of the low-pressure driven filtration system. To reach this objective, it is essential to have a better understanding regarding the surface interaction between the target substance and the surface of membrane. In this study, the hollow fiber ceramic membranes were coated with a goethite layer in order to enhance the Co(2+) rejection. Experimental results indicate that higher Co(2+) rejections are always accompanied with the significant reduction in the permeability. Based on the consideration of electroviscous effect, the surface interactions including the induced changes in viscosity, pore radius and Donnan effect in the goethite layer are likely responsible for the pH dependent behaviors in the rejection and permeability. These results could be valuable references to develop the filtration system with high rejection along with acceptable degree of permeability in the future., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The elemental content of fish scales is known to be a reliable biogeochemical tag for tracing the origin of fishes. In this study, this correlation is further confirmed to exist on the surface of fish scales using a novel environmental analytical method, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), which bypasses several complicated sample preparation procedures such as acid digestion and pre-concentration. The results suggest that the elemental ratios of Sr/Ca, Ba/Ca, and Mn/Ca on the surface of fish scales are strongly correlated with the geochemical environment of their original habitat. This correlation is further demonstrated to be sensitive to variation of water in the habitat due to the adsorbed inorganic ions. In this sense, the limitation of fish scales as a biogeochemical tag is the sensitivity of LA-ICP-MS toward the studied elements. Graphical abstract Illustration of the connection between element distribution pattern over the surface of fish scales and biogeochemical environment of its habitat.

The so-called "Trojan-horse" mechanism, in which nanoparticles are internalized within cells and then release high levels of toxic ions, has been proposed as a behavior in the cellular uptake of Ag nanoparticles (AgNPs). While several reports claim to have proved this mechanism by measuring AgNPs and Ag ions (I) in cells, it cannot be fully proven without examining those two components in both intra- and extracellular media. In our study, we found that even though cells take up AgNPs similarly to (microglia (BV-2)) or more rapidly than (astrocyte (ALT)) Ag (I), the ratio of AgNPs to total Ag (AgNPs+Ag (I)) in both cells was lower than that in outside media. It could be explained that H2O2, a major intracellular reactive oxygen species (ROS), reacts with AgNPs to form more Ag (I). Moreover, the major speciation of Ag (I) in cells was Ag(cysteine) and Ag(cysteine)2, indicating the possible binding of monomer cysteine or vital thiol proteins/peptides to Ag ions. Evidence we found indicates that the Trojan-horse mechanism really exists.

Background Aims: Large amounts of human mesenchymal stromal cells (MSCs) are needed for clinical cellular therapy. In a previous publication, we described a microcarrier-based process for expansion of MSCs. The present study optimized this process by selecting suitable basal media, microcarrier concentration and feeding regime to achieve higher cell yields and more efficient medium utilization., Methods: MSCs were expanded in stirred cultures on Cytodex 3 microcarriers with media containing 10% fetal bovine serum. Process optimization was carried out in spinner flasks. A 2-L bioreactor with an automated feeding system was used to validate the optimized parameters explored in spinner flask cultures., Results: Minimum essential medium-α-based medium supported faster MSC growth on microcarriers than did Dulbecco's modified Eagle's medium (doubling time, 31.6 ± 1.4 vs 42 ± 1.7 h) and shortened the process time. At microcarrier concentration of 8 mg/mL, a high cell concentration of 1.08 × 10(6) cells/mL with confluent cell concentration of 4.7 × 10(4)cells/cm(2) was achieved. Instead of 50% medium exchange every 2 days, we have designed a full medium feed that is based on glucose consumption rate. The optimal medium feed that consisted of 1.5 g/L glucose supported MSC growth to full confluency while achieving the low medium usage efficiency of 3.29 mL/10(6)cells. Finally, a controlled bioreactor with the optimized parameters achieved maximal confluent cell concentration with 16-fold expansion and a further improved medium usage efficiency of 1.68 mL/10(6)cells., Conclusions: We have optimized the microcarrier-based platform for expansion of MSCs that generated high cell yields in a more efficient and cost-effective manner. This study highlighted the critical parameters in the optimization of MSC production process., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

In this paper, we demonstrate a means of simultaneously solving two serious environmental issues by reutilization of calcinated mixture of pulverized waste oyster shells blending with poly(methyl methacrylate) (PMMA) nanospheres to prepare CaO-based sorbents for CO2 capture. After 10 cycles of isothermal carbonation/calcination at 750°C, the greatest CO2 uptake (0.19 g CO2/g sorbent) was that for the sorbent featuring 70 wt% of PMMA, which was almost three times higher than that (0.07 g CO2/g sorbent) of untreated waste oyster shell. The greater CO2 uptake was likely a result of particle size reduction and afterwards surface basicity enhancement and an increase in the volume of mesopores and macropores. Following simplified life cycle assessment, whose all input values were collected from our experimental results, suggested that a significant CO2 emission reduction along with lesser human health and ecosystems impacts would be achieved immediately once waste is reutilized. Most importantly, the CO2 uptake efficiency must be greater than 20% or sorbents prepared from limestone mining would eventually produce a net positive CO2 emission., (Copyright © 2014 Elsevier B.V. All rights reserved.)

It has been suggested that a high concentration of Fe(3+) in solution, a low pH, and noncomplexing ions of high ionic strength are all essential for developing a high-quality hematite array. Our curiosity was piqued regarding the role of the electrolyte ions in the hydrothermal synthesis of hematite photoanodes. In this study, we prepared hematite photoanodes hydrothermally from precursor solutions of 0.1 M FeCl3 at pH 1.55 with a background electrolyte of 1.0 M sodium halide (NaF, NaCl, NaBr, or NaI). We compared the structures and properties of the as-obtained hematite photoanodes with those of the material prepared in 1.0 M NaNO3, the most widely adopted electrolyte in previous studies. Among our studied systems, we found that the hematite photoanode prepared in NaCl solution was the only one possessing properties similar to those of the sample obtained from the NaNO3 solution-most importantly in terms of photoelectrochemical performance (ca. 0.2 mA/cm(2) with +0.4 V vs SCE). The hematites obtained from the NaF, NaBr, and NaI solutions exhibited much lower (by approximately 2 orders of magnitude) photocurrent densities under the same conditions, possibly because of their relatively less ordered crystallinity and the absence of rodlike morphologies. Because the synthetic protocol was identical in each case, we believe that these two distinct features reflect the environments in which these hematite photoanodes were formed. Consistent with the latest studies reported in the literature of the X-ray photoelectron spectra of fast-frozen hematite colloids in aqueous solutions, it appears that the degree of surface ion loading at the electrolyte-hematite interface (Stern layer) is critical during the development of hematite photoanodes. We suspect that a lower ion surface loading benefits the hematite developing relatively higher-order and a rodlike texture, thereby improving the photoelectrochemical activity.

In this study, the laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was adopted to determine the distribution of inorganic elements, including Ca, Cu, Fe, Mg, Mn, S, P, Pb, and Zn, in honeybees (Apis melifera L.). Two features are particularly noteworthy. First, it was found there is a significant amount of Fe located at the fringe of the abdomen in worker bees; ultrasonic imaging, scanning electron microscopy, and magnetic resonance imaging revealed that it arose from magnetic Fe-bearing nanoparticles (NPs) having an average diameter of approximately 40 nm. Interestingly, only worker bees contained these magnetic Fe-bearing NPs; no similar features appeared in larvae, pupae, wasps, or drones. Second, a detectable amount of Pb accumulated particularly in the alimentary canals of worker bees. Again, no detectable amounts of Pb in larvae, pupae, drones, or wasps, yet a level of 0.24 ± 0.05 mg/kg of Pb in pollen; therefore, the diet appears to be the primary pathway for environmental pollutants entering the honeybees' food chain.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was first reported in remote regions of Western Australia and is now the predominant MRSA isolated in the state. The objective of this study is to determine the genetic relatedness of Western Australian CA-MRSA clones within different multilocus sequence type (MLST) clonal clusters providing an insight into the frequency of S. aureus SCCmec acquisition within a region., Results: The CA-MRSA population in Western Australia is genetically diverse consisting of 83 unique pulsed-field gel electrophoresis strains from which 46 MLSTs have been characterised. Forty five of these sequence types are from 18 MLST clonal clusters and two singletons. While SCCmec IV and V are the predominant SCCmec elements, SCCmec VIII and several novel and composite SCCmec elements are present. The emergence of MRSA in diverse S. aureus clonal clusters suggests horizontal transmission of the SCCmec element has occurred on multiple occasions. Furthermore DNA microarray and spa typing suggests horizontal transfer of SCCmec elements has also occurred within the same CC. For many single and double locus variant CA-MRSA clones only a few isolates have been detected., Conclusions: Although multiple CA-MRSA clones have evolved in the Western Australian community only three clones have successfully adapted to the Western Australian community environment. These data suggest the successful evolution of a CA-MRSA clone may not only depend on the mobility of the SCCmec element but also on other genetic determinants.

This paper describes a simple procedure for the direct analysis and determination of multiple elements in dried blood samples on a filter membrane using laser ablation coupled with inductively coupled plasma mass spectrometry (LA-ICP-MS). With this technique, we simultaneously quantified 13 elements in whole blood: Be, Mn, Co, Ni, Tl, Bi, Sb, Pb, Cu, Zn, Ba, Mg, and Cd. The measured accuracies was in agreement with the Seronorm CRM certified values, except for Mn, Zn, Ba and Cd, which presented absolute differences higher than the expanded uncertainty for these elements. The within-run precision was less than 5.7% (relative standard deviation, RSD), except for the analyses of Be, and Mn (8.6% and 11.1%, respectively). The reproducibility (between-run precision) was calculated in terms of the RSD obtained for 12 analyses (i.e., four replicates of each sample in three analytical runs). Apart from Be, Mn, and Zn, the reproducibilities of all the elements listed above ranged between 4.0% and 8.5%. In contrast, for Cd, the concentration obtained was significantly different from the certified value; analyses of this element exhibited low reproducibility. Applying the matrix-matched calibration method, the accuracy for Cd measured was in agreement with both SRM966 and BCR 635; thus, matrix-matched calibration is a practical means of overcoming matrix-enhancement effects for the quantification of Cd. Sample throughput (ca. 5 min per sample) made it possible to rapidly screen a larger number of samples relative to other techniques that require time-consuming sample preparation steps (e.g., removal of a portion of the solid sample or digestion)., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In this study, we employed laser ablation/inductively coupled plasma mass spectrometry (LA-ICP-MS) to map the spatial distribution of Gd-doped iron oxide nanoparticles (IONPs) in one tumor slice that had been subjected to magnetic fluid hyperthermia (MFH). The mapping results revealed the high resolution of the elemental analysis, with the distribution of Gd atoms highly correlated with that of the Fe atoms. The spatial distributions of C, P, S, and Zn atoms revealed that the effect of MFH treatment was significantly dependent on the diffusion of the magnetic fluid in the tissue. An observed enrichment of Cu atoms after MFH treatment was probably due to inflammation in the tumor. The abnormal distribution of Ni atoms suggests a probable biochemical reaction in the tumor. Therefore, this LA-ICP-MS mapping technique can provide novel information regarding the spatial distribution of elements in tumors after cancer therapy.

Background: We report a retrospective study of 452 patients with lymphoma from 1991 to 2006, with 274 men and 178 women, median age of 50 years (range, 16-76 years)., Patients and Methods: There were 85 patients with Hodgkin lymphoma (HL) and 367 with non-Hodgkin lymphoma (NHL). Eleven patients received a second autologous transplantation for progressive lymphoma, and another 4 received a second allogeneic transplantation for myelodysplastic syndrome (MDS). Twenty-seven patients had skin biopsies, and 2 patients had gastrointestinal biopsies consistent with graft-versus-host disease (GVHD), and 11 patients developed severe engraftment syndrome (ES), as defined by noninfectious fever and skin rash with or without pulmonary infiltrates requiring systemic steroids., Results: The median follow-up of the patients was 6.2 years, and median overall survival was 5.3 years. Twenty-four patients (5.3%) developed MDS with median time of onset of 4.2 years (range, 8 months to 7.5 years). An additional 5 patients developed clonal karyotypic abnormalities in the bone marrow without clinical MDS. Actuarial probabilities of developing MDS at 5 and 8 years after transplantation were 5% and 15%, respectively., Conclusion: The incidences of MDS are similar in HL and NHL. Multivariate analysis revealed older age, occurrence of ES/GVHD, and longer intervals between the initial diagnoses to transplantation as independent factors. It is conceivable that perturbation to the host immunity caused by either previous chemotherapy or conditioning regimens in the elderly might play a role in the development of MDS after autologous transplantation.

This work describes a simple procedure for blood lead level determination. The proposed method requires little sample pretreatment and subsequent direct analysis of a dried blood spot on a filter membrane using laser ablation coupled with inductively coupled plasma mass spectrometry (LA-ICP-MS). In general, LA-ICP-MS studies are somewhat limited by the lack of matrix-matched standards for calibration purposes. Here we describe aqueous standard calibration and matrix-matched calibration methods. This method was validated by analysis of the reference materials. With the matrix-matched calibration method, the recovery ranged from 97.8% to 112.8%, while the aqueous standard calibration method ranged 90.4% to 122.4%. The lower detection limit was estimated as 0.1 ng mL(-1). The determination precision, expressed as the relative standard deviation (RSD), was not worse than 10% for all results. A sample throughput of approximately 5 min per sample made it possible to rapidly screen a large number of samples.

Guillain-Barré syndrome (GBS) is an unusual complication after organ and hematopoietic stem cell transplantation. We report two cases of GBS associated with autologous and allogeneic stem cell transplantation along with a review of the literature.

Copper deficiency is a recognized but often overlooked cause of anemia and neutropenia. We began checking serum copper levels on patients referred for evaluation for unexplained anemia and neutropenia or myelodysplasia. Eight patients were identified as copper deficient (serum copper less than 70 microg/dL). The anemia was normochromic and normocytic in seven patients. Neutropenia was present in seven patients. Seven patients had been referred for evaluation of myelodysplasia. Three were seen for consideration for allogenic stem cell transplant. Five patients had concomitant peripheral neurological symptoms. Seven patients were treated with oral copper gluconate. All treated patients demonstrated a hematological response; seven had a complete remission. The improvement in anemia and neutropenia was rapid with normalization of blood counts within three to four weeks. In one patient, normalization of the underlying marrow dysplasia was demonstrated by bone marrow histology eight months after copper replacement. The cause of copper deficiency was felt to be gastrointestinal malabsorption in five of our patients. We conclude that copper deficiency should be considered in all patients with unexplained anemia and neutropenia or myelodysplasia.

Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC(50) in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24 - 36 h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-kappaB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.

Compared to primary thrombocytosis such as that caused by essential thrombocytosis, reactive thrombocytosis is generally regarded as benign. However, reactive thrombocytosis has infrequently been reported to cause severe and even fatal complications. Two fatal cases of reactive thrombocytosis and iron deficiency anemia associated with peripheral/pulmonary vascular and cerebrovascular thrombosis are described. The literature on thrombosis and reactive thrombocytosis associated with iron deficiency anemia is reviewed.

We conducted a retrospective study to define the significance of Philadelphia chromosome (Ph) in myelodysplastic syndrome and acute leukemia in the adults at this institution and the literature was reviewed. One hundred forty-eight cases of t(9;22)(q34;q11) were identified for the period September 1993 through August 2001. The presentation of 124 cases (84%) was that of typical CML in chronic phase. Nineteen cases (13%) presented as de novo ALL, two cases (1%) presented as de novo AML and three cases (2%) presented as myelodysplastic syndrome (MDS). The estimated incidences of t(9;22)(q34;q11) in ALL and AML are 21 and 0.6%, respectively. Ph+ AMLs are increasingly being reported with either M-BCR or m-BCR gene rearrangements, similar to those found with Ph+ ALL lending support to the notion that Ph+ AMLs are distinct entities and not merely blastic phases of undiagnosed CML. This is further supported by the existence of Ph+ MDS cases.

In view of the recent reports demonstrating delayed engraftment after autologous and allogeneic transplantation from donors with constitutional pericentric inversion of chromosome 9, [inv(9)], we conducted a retrospective study on six patients with acute leukemia and inv(9) to investigate if there is an impaired engraftment potential of the inv(9) hematopoietic stem cells. All but one of our patients had poor outcome. The hematopoietic recovery after induction chemotherapy was not prolonged. It is possible that the hematopoietic defects of inv(9) become more apparent after repeated courses of chemotherapy. Alternatively, the number of patients in our series may have been too small to detect a partial hematopoietic defect in patients with constitutional inv(9). Larger studies are required to confirm our findings.

Helicobacter pylori have been causally linked to primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Antibiotic therapy to eradicate H. pylori has been shown to induce remission of such lymphoma. We report a case of primary B-cell MALT lymphoma of the jejunum associated with H. pylori. The literature of intestinal MALT lymphoma is reviewed.