Lower Dose Requirement Research Articles

Human solid-phase gastric-emptying measurement by AMS using 14C tracer

Determining solid-phase gastric emptying (GE) in a human being is an important application in clinical practice as it can provide valuable information for the diagnosis of related digestive diseases. Currently, 99mTc gastric scintigraphy is considered as the gold standard for measuring GE. However, this method suffers from clinical drawback, such as radiation exposure. This study focuses on identifying alternative methods for GE measurement. Carbon-14 accelerator mass spectrometry (AMS) is a useful tool for biomedical projects due to its inherently high sensitivity and dynamic range, low dose and sample size requirements, and relatively short measurement time. However, it has not yet been implemented in GE tests. In this work, 14C AMS methodology was developed for breath samples. Measurements were conducted on a compact, single-stage AMS device at China Institute of Atomic Energy (CIAE). To investigate GE, micro-doses of 14C-octanoic acid, 13C-octanoic acid, and 99mTc were marked along with tracers in the same test meal and subsequently ingested by volunteers. The 14C-octanoic acid breath test (14C-OBT) in combination with AMS showed better counting statistics than those obtained for the 13C-OBT measured using infrared spectroscopy. The results also demonstrate a considerably lower radiation dose than that in 99mTc gastric scintigraphy. This work establishes an alternative method of 14C-AMS tracing to determine solid-phase GE in a human being, which could provide clinical technical support for a GE test and further expand the range of 14C-AMS applications in biomedicine.

Bioflocculation Activity in Harvesting System: A Biotechnology Approach for Microalgae Biomass

A study on Ankistrodesmus sp.—a freshwater green microalgae species—as a bioflocculant based on its physicochemical properties and flocculation rate has been carried out. The molecular identification via 16S rDNA showed 99% resemblance of this green microalga to the Ankistrodesmus fumigatus strain. The optimum batch culture condition for the bioflocculant production was initiated by 10% inoculum (v/v). The low-concentrated bioflocculant of 10% (v/v) is considered as thermostable with a high flocculation rate to harvest the biomass of Chlorella sp. at a pH range of 5 to 9. The source of molasses, the mixture of yeast extract were used as the optimum sources of carbon and Ammonium sulfate were used as the optimum sources of nitrogen in the growth medium. Ankistrodesmus sp. bioflocculant has a high flocculation efficiency over a wide range of pH (5–9) with a low dose requirement of 10% v/v at 25°C. Hence, it is immensely competitive to promote the economic viability of the production process. Accordingly, Ankistrodesmus sp. bioflocculant has a high potential to be applied on an industrial scale in tropical regions as it does not require additional production cost.

Dynamic beam filtering for miscentered patients.

Accurate centering of the patient within the bore of a CT scanner takes time and is often difficult to achieve precisely. Patient miscentering can result in significant dose and image noise penalties with the use of traditional bowtie filters. This work describes a system to dynamically position an x-ray beam filter during image acquisition to enable more consistent image performance and potentially lower dose needed for CT imaging. We propose a new approach in which two orthogonal low-dose scout images are used to estimate a parametric model of the object describing its shape, size, and location within the field of view (FOV). This model is then used to compute an optimal filter motion profile by minimizing the variance of the expected detector fluence for each projection. Dynamic filtration was implemented on a cone-beam CT (CBCT) test bench using two different physical filters: 1) an aluminum bowtie and 2) a structured binary filter called a multiple aperture device (MAD). Dynamic filtration performance was compared to a static filter in studies of dose and reconstruction noise as a function of the degree of miscentering of a homogeneous water phantom. Estimated filter trajectories were found to be largely sinusoidal with an amplitude proportional to the amount of miscentering. Dynamic filtration demonstrated an improved ability to keep the spatial distribution of dose and reconstruction noise at baseline levels across varying levels of miscentering, reducing the maximum noise and dose deviation from 53% to 15% and 42% to 14% respectively for the bowtie filter, and 25% to 8% and 24% to 15% respectively for the MAD filter. Dynamic positioning of beam filters during acquisition improves dose utilization and image quality over static filters for miscentered patients. Such dynamic filters relax positioning requirements and have the potential to reduce set-up time and lower dose requirements.

Adjustments to warfarin dosing after gastric bypass and sleeve gastrectomy

BackgroundWarfarin dosing after bariatric surgery may be influenced by alterations in gastrointestinal pH, transit time, absorptive surface area, gut microbiota, food intake, and adipose tissue. ObjectivesThe aim of this study was to describe trends in warfarin dosing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SettingSingle academic center. MethodsAll patients chronically on warfarin anticoagulation before RYGB or SG were retrospectively identified. Indications for anticoagulation, history of bleeding or thrombotic events, perioperative complications, and warfarin dosing were collected. ResultsFifty-three patients (RYGB n = 31, SG n = 22) on chronic warfarin therapy were identified (56.6% female, mean 54.4 ± 11.7 yr of age). Of this cohort, 34.0% had prior venous thromboembolic events, 43.4% had atrial fibrillation, and 5.7% had mechanical cardiac valves. Preoperatively, the average daily dose of warfarin was similar in the RYGB group (8.3 ± 4.1 mg) and SG group (6.9 ± 2.8 mg). One month after surgery, mean daily dose of warfarin was reduced 24.1% in the RYGB group (P<.001) and 23.2% in the SG group (P = .002). At 12 months postoperatively, the required daily warfarin dose compared with baseline remained statistically different (RYGB: 6.8 ± 3.8 mg; SG: 6.1 ± 2.0 mg). ConclusionsThe warfarin dose is expected to be decreased by approximately 25% from preoperative levels after both RYGB and SG. Lower dose requirement within the first month after bariatric surgery is followed by a trend toward increased warfarin dose requirements, but remain less than baseline. Because dose requirements change constantly over time, frequent postoperative monitoring of the international normalized ratio is recommended.

The effect of CYP2C9*2, CYP2C9*3, and VKORC1-1639 G>A polymorphism in patients under warfarin therapy in city of Kermanshah.

Polymorphism in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence warfarin dose requirement since patients with CYP2C9*2, CYP2C9*3 and VKORC1 mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of VKORC1-1639 G>A, CYP2C9*2, and CYP2C9*3. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of MspI, AVAII and KpnI, respectively. The frequencies of VKORC1-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for CYP2C9 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of VKORC1-1639A allele was 42.3% and the frequencies of CYP2C9*2 and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of CYP2C9 and VKORC1-1639 variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.

Thiopurine metabolite level and toxicity in Indians with inflammatory bowel disease.

Background and AimA lower dose requirement and higher toxicity of thiopurine is reported in Asian patients with inflammatory bowel disease (IBD) as compared with Caucasian patients. These reports are based on thiopurine methyltransferase measurement studies rather than metabolite estimation.We studied the utility of thiopurine metabolite estimation in Indian patients with IBD and compared dose and toxicity with Asian and Caucasian patients.MethodsIn this prospective study, 6‐thioguanine nucleotide (6‐TGN) and 6‐methylmercaptopurine levels were determined by HPLC in 76 IBD patients treated with thiopurines. The levels were correlated with dose, disease activity, and toxicity. The dose‐related metabolite levels and toxicity were compared with Caucasian and Asian patients reported in literature.ResultsOf the 76 patients (32 women, mean age: 35.9 [SD: 14.54] years, 36 Crohn's disease and 40 ulcerative colitis), 1 non‐compliant patient had undetectable level of metabolites. Of the 75 patients, 21(28%) had therapeutic level of 6‐TGN, 37(49%) had subtherapeutic level and 17(23%) had supratherapeutic level. The 6‐methylmercaptopurine levels ranged up to 4971 pmol/8 × 108 red blood cells. Six (8%) patients showed toxicity. Thiopurine dose was optimized in 20 (26.31%) patients. Dose‐based metabolite levels were comparable to Asian and Caucasian patients. The toxicity (8%) observed in our patients was less than that reported (12–39%).ConclusionHalf of the patients in this study had low and a quarter had high 6‐TGN levels. One‐fourth of the patients needed dose modification. The dose‐based metabolite levels were comparable and the toxicity was less than that reported in Asian and Caucasian patients.

Optimizing structural and mechanical properties of cryogel scaffolds for use in prostate cancer cell culturing

Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate. Cryogel scaffolds represent a valid alternative to 2D culturing systems for studying the normal and pathological behavior of the prostate cells thanks to their 3D pore architecture that reflects more closely the physiological environment in which PCa cells develop. In this work the 3D morphology of three potential scaffolds for PCa cell culturing was investigated by means of synchrotron X-ray computed micro tomography (SXCμT) fitting the according requirements of high spatial resolution, 3D imaging capability and low dose requirements very well. In combination with mechanical tests, the results allowed identifying an optimal cryogel architecture, meeting the needs for a well-suited scaffold to be used for 3D PCa cell culture applications. The selected cryogel was then used for culturing prostatic lymph node metastasis (LNCaP) cells and subsequently, the presence of multi-cellular tumor spheroids inside the matrix was demonstrated again by using SXCμT.

Efficient use of Mg-modified zeolite in the treatment of aqueous solution contaminated with heavy metal toxic ions

The aim of this study was to investigate adsorption using modified zeolite with magnesium (Mg-zeolite) in aqueous solutions for removal of heavy metal ions. The adsorption capacity of Mg-zeolite was determined to be 1.5-fold higher than that of zeolite modified with Na or K and 1.5- to 2.0-fold higher compared to that of natural zeolite. The Mg-zeolite successfully adsorbed >98% of the Pb2+, Cd2+, and Cu2+ in the aqueous solutions at the following optimal conditions: 40mg/L dosage and 1.5–1.75 Mg/zeolite ratio. The maximum binding capacity increased with an increase in pH to >5 for Pb and Cu and to >7 for Cd. The adsorbent, Mg-zeolite, could be promising for adsorption due to its high efficiency and low dose requirements. In addition, Mg-zeolite does not contaminate treated wastewater, so it can be recycled to reduce not only cost and demand for water, but also extra operational costs for reuse of wastewater.

Parametric study of a dyeing wastewater treatment by modified sericite

ABSTRACTThe aim of this study was to investigate color, suspended solids (SS), chemical oxygen demand (COD) and biological oxygen demand (BOD) removal using modified sericite with magnesium (Mg–Sericite) flocculants in dyeing wastewater. Mg–Sericite flocculants successfully removed >95% of color, SS. COD and BOD in dyeing wastewater at the following optimal conditions: Mg–Sericite dosage of 40 mg/L, pH of 11, Mg/Sericite ratio of 1.5, settling time of 20 min, mixing time of 10 min and mixing rate of 100 rpm. The bioflocculant, Mg–Sericite, can be a promising flocculants due to its high efficiency and low dose requirements in dyeing wastewater treatment. In addition, Mg–Sericite does not contaminate treated wastewater, which can be recycled to reduce not only the cost and the demand for water but also the extra operational costs for reusing wastewater.

Genotype-guided tacrolimus dosing in African-American kidney transplant recipients.

Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AA) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AA have primarily evaluated the CYP3A5*3 variant; however, there are common nonfunctional variants in AA (CYP3A5*6 and CYP3A5*7) which do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AA are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AA using a development and validation cohort. Time posttransplant, steroid and antiviral use, age, CYP3A5*1, *3, *6 and *7 alleles were significant towards clearance. This study is the first to develop an AA specific genotype-guided tacrolimus dosing model to personalize therapy.

Magnetophoretic harvesting of freshwater microalgae using polypyrrole/Fe3O4 nanocomposite and its reusability

A magnetophoretic harvesting agent, a polypyrrole/Fe3O4 magnetic nanocomposite, is proposed as a cost and energy efficient alternative to recover biomass of the microalgae Botryococcus braunii, Chlorella protothecoides, and Chlorella vulgaris from their culture media. The maximal recovery efficiency reached almost 99 % for B. braunii, 92.4 % for C. protothecoides, and 90.8 % for C. vulgaris. The maximum adsorption capacity (Q 0) of the magnetic nanocomposite for B. braunii (63.49 mg dry biomass mg−1 PPy/Fe3O4) was higher than that for C. protothecoides (43.91 mg dry biomass mg−1 PPy/Fe3O4) and C. vulgaris (39.98 mg dry biomass mg−1 PPy/Fe3O4). The highest harvesting efficiency for all the studied microalgae were at pH 10.0, and measurement of zeta-potential confirmed that the flocculation was induced by charge neutralization. This study showed that polypyrrole/Fe3O4 can be a promising flocculant due to its high efficacy, low dose requirements, short settling time, its integrity with cells, and with great potential for saving energy because of its recyclability.

개질한 sericite를 이용한 염색공장 폐수처리

Abstract The aim of this study was to investigate the nutrient removal using Mg-Sericite flocculant in the dyeing wastewater. Mg-Sericite flocculant was removed successfully > 98% of the Color, SS. COD and BOD in the dyeing wastewater at the following optimal Mg-Sericite dosage: 100 mg/L for Colour and SS, 300 mg/L for BOD and COD. The removal of TN and TP was obtained 92.00% with 50 mg/L and 87.80% with 100 mg/L Mg-Sericite dosage, respectively. These results was indicated that the amount of 0.79~1.31, 0.22~0.37, 0.5 and 0.16 mg/L Mg-Sericite was necessary for 1 mg/L removal BOD, COD, TN and TP, respectively. The biopolymer, Mg-Sericite, can be a promising flocculants due to its high efficiency and low dose requirements. In addition, Mg-Sericite does not contaminate treated wastewater, which can be recycled to reduce not only the cost and the demand for water but also the extra operational costs for reusing wastewater. This flocculation method is helpful to lower the wastewater treatment cost.

Effect of Mg-sericite flocculant for treatment of brewery wastewater

The aim of this study was to investigate organic/inorganic matter removal using Mg-sericite flocculant in brewery wastewater. Mg-sericite flocculant successfully removed 98–100% of organic/inorganic substances in brewery wastewater at the following optimal Mg-sericite dosage: 30mg/L for turbidity and SS, 100mg/L for COD, 50mg/L for BOD, 30mg/L for TN and NH4-N and 20mg/L for TP and PO4-P. These results indicated that approximately 12.3mg/L, 11.0mg/L, 1.0mg/L, 0.5mg/L, 0.3mg/L and 0.4mg/L of COD, BOD, TN, NH4-N, TP and PO4-P were removed by 1mg/L Mg-sericite, respectively. The biopolymer, Mg-sericite, can be a promising flocculant due to its high efficiency and low dose requirements. In addition, Mg-sericite does not contaminate treated wastewater, which can be recycled to reduce not only the cost and the demand for water but also the extra operational costs for reusing brewery wastewater. This flocculation method can be used to reduce brewery wastewater treatment costs.

Abstract 4502: Identification of an aspirin-derived small molecule as a potential therapeutic for colorectal cancer

Abstract In the US, colorectal cancer (CRC) remains the second leading cause of cancer-related death. The 5-year survival rate for patients with CRC is 64%, although for patients who present with distant metastases at diagnosis the 5 year survival is only 12%. Currently used standard care for CRC can only marginally extend the survival of patients and is associated with numerous adverse events. Hence, there remains an urgent need for more effective and less toxic treatments, which can increase CRC patient survival with better quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. Aspirin, Ibuprofen, Naproxen), which are widely used for their anti-inflammatory and analgesic effects, have also been shown to be effective in reducing colon cancer incidences and are proposed to be effective chemopreventive agents. However, these NSAIDs are not potent enough to be used as cancer therapeutics and also carry a liability of gastrointestinal bleeding mainly associated with COX inhibition. Through extensive structure activity relationship (SAR) studies based on newly synthesized NSAID-analogs, we have identified a novel aspirin analog, ASD-49, as the most effective small molecule that showed efficacy in different cancer cell lines, including CRC cells with an EC50 ranging between 1 to 2.5 μM at 48 h treatment in culture. This unique compound selectively killed cancer cells and is &amp;gt;50-times more potent than the current therapy for CRC and &amp;gt;100-times more potent than the parent compound, aspirin. Our preliminary results show that ASD-49 induces G1 and G2 cell cycle arrest in HT29 cells. In addition, ASD-49 induced apoptosis as indicated by PARP cleavage in HCT116 and RKO cells. Furthermore, we observed down-regulation of anti-apoptotic protein Bcl-2 in a dose-dependent manner in both HCT116 and RKO cell lines. Unlike aspirin, the novel analog did not alter COX-2 protein expression, suggesting that ASD-49 may not possess adverse effects related to COX-2 inhibition. In addition, &amp;gt;100-times lower dose requirement as compared to aspirin is expected to further minimize side effects associated with aspirin structure. Taken together, our results suggest that ASD-49 may be a promising agent for CRC treatment. Detailed results regarding the efficacy and mechanism of action of ASD-49 will be presented. Citation Format: Deepkamal Karelia, Manoj Pandey, Daniel Plano, Satya Narayan, Jitesh Jani, Jay Sharma, Shantu Amin, Arun K. Sharma. Identification of an aspirin-derived small molecule as a potential therapeutic for colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4502. doi:10.1158/1538-7445.AM2015-4502

Mg으로 개질한 Zeolite를 이용하여 염색공장 폐수처리 평가

The aim of this study was to investigate the bio-adsorption using modified zeolite with Mg (Mg-zeolite) in the dyeing wastewater treatment. Mg-zeolite adsorbed successfully 100% of the color, suspended solid (SS). chemical oxygen demand (COD), biological oxygen demand (BOD), total nitrogen (TN) and total phosphorus (TP) in the dyeing wastewater at the following optimal Mg-zeolite loading: 20 mg/L for colour, SS, TN and TP, 30 mg/L for BOD and COD. These results indicated that the amount of 1 mg/L Mg-zeolite adsorbed 11.6 mg/L for color, 9.5 mg/L for SS, 45.0 mg/L for COD, 12.7 mg/L for BOD, 0.91 mg/L for TP and 2.25 mg/L for TN. The bio-adsorbent, Mg-zeolite, can be a promising adsorption due to its high efficiency and low dose requirements.

Mg-Sericite 응집제를 이용하여 미세조류 회수 최적화 연구

In this study, Mg-Sericite was used as a flocculant to harvest freshwater microalgae, Chlorella. vulgaris. Mg-Sericite separated successfully >95% of the C. vulgaris at the following optimal parameters: Mg/Si mol ratio 1.25 to 1.50, mixing time of 20 min and settling time of 20 min. The harvesting efficiency was pH dependent. The highest harvesting efficiency (<TEX>$99{\pm}0.3%$</TEX>) was obtained at Mg/Si mol ratio 1.5 and pH 9 to 11. These results indicated that a biopolymer, Mg-Sericite, can be a promising flocculant due to its high efficiency, low dose requirements, short mixing and settling times. This harvesting method is helpful to lower the production cost of algae for biodiesel.

Effect of eggshells for the harvesting of microalgae species

The aim of this study was to determine the optimal conditions for adding eggshells as a bioflocculant (including concentration dosage, pH, mixing time, mixing rate and settling time) in harvesting Chlorella vulgaris cells from liquid cultures, using the well-known jar-test experimental method. Eggshells separated successfully 99 ± 0.4% of the C. vulgaris biomass at the following optimal parameters: eggshell concentration 80 mg/L, mixing time 20 min, mixing rate 150 r/min and settling time 20 min at pH 6. These results indicated that eggshells, as a biopolymer, are a promising flocculant due to their high separation efficiency, low dose requirements and short mixing and settling time. Eggshells not only act as an adsorbent, but also spontaneously coagulate to agglomerate the microalgae cells.

Utilization of Total Body Irradiation Is Not Necessary for Unrelated Donor Umbilical Cord Blood Transplants: a Single-Center Experience

▪Background: Umbilical cord blood (UCB) is rich in primitive hematopoietic stem cells (HSC) and progenitor cells that can reconstitute the hematopoietic system in recipients under proper conditioning. Initially umbilical cord blood transplantation was limited to children because of the low cell dose requirement. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders in the pediatric setting. To overcome the disadvantage of low cell dose in a single unit of UCB, the double-units umbilical cord blood transplantation (dCBT) strategy was introduced to adult patients with various hematological malignant diseases who had no suitable related or unrelated stem cell donor. Over the last decade, this dCBT strategy has been validated in several elegant adult HSC transplantation studies. Because of its loose HLA-matching requirement and abundant UCB resource available, UCB transplantation (UCBT) has emerged as an effective alternative therapy for both pediatric and adult HSC transplantations. However, the optimal conditioning regimens prior to UCBT remains unclear in regards to engraftment, treatment related mortality (TRM), graft-versus-host-disease (GVHD), and prevention of disease relapse. Further more, most published UCBT conditioning regimens have utilized total body irradiation (TBI), but there is no stringent study to evaluate the efficacy of this treatment in regards to UCBT outcome.Method: This is a retrospective study to analyze the outcomes of 47 patients with various hematological diseases receiving UCBT at Pennsylvania State University Hershey Cancer Institute in last 13 years. In this study, individual patient was characterized by his/her gender, age and weight at the time of receiving UCBT, disease status, the HLA compatibilities among UCB units and recipient, the conditioning regimens prior to UCBT, the ABO and gender compatibilities among UCB units and recipient, time to engraftment and chimerism status post UCBT, the incidence and severity of GVHD (acute and chronic), and the incidence of systemic infection. The rates for TRM, event free survival (EFS), and overall survival (OS) were calculated and compared among patients who received different conditioning regimens that contained TBI and those that did not.Result: This study analyzed 47 patients with an age range from 0.5 years old to 65.4 years old (mean: 14.3) at the time of UCBT. The lengths of individual patient follow up ranged from 0.9 years to 12.8 years (mean: 6.8 years). The long term OS rate was 55.3%, which was comparable to progress-free survival rate. Twenty-six patients were male (55%) and 21 patients were female (45%). Days to neutrophil engraftment (absolute neutrophil count ≥500/dl) post UCBT ranged from 10 days to 38 days (mean: 21.8 days). Nine patients (19%) developed severe acute GVHD (≥degree 3) and 8 patients (8%) had severe chronic GVHD. Twenty eight patients (58%) had a systemic infection, of which 5 patients (11%) had systemic CMV infection. Thirty eight patients underwent a busulfan and cyclophosphamide (Bu/Cy) combination as conditioning regimen, 9 patients used fludarabine and cyclophosphamide (Flu/Cy) combination as conditioning regimen. Thirty four patients didn’t utilize TBI as part of conditioning regimens and 13 patients utilized TBI. The long term OS rate of patients not receiving TBI was 55.9% (19/34) and the long term OS rate of patients receiving TBI was 53.8% (7/13). The TRM rate of patients not receiving TBI was 32.4% (11/34) and receiving TBI was 38.5% (5/13).Conclusion:1.UCBT has a comparable outcome to HSC transplantation from suitable related or unrelated blood or bone marrow donors in regards to TRM, EFS, and OS.1.The conditioning regimens not utilizing TBI are not inferior to the conditioning regimens utilizing TBI for unrelated donor UCBT. DisclosuresNo relevant conflicts of interest to declare.

Multipinhole collimator with 20 apertures for a brain SPECT application.

Several new technologies for single photon emission computed tomography (SPECT) instrumentation with parallel-hole collimation have been proposed to improve detector sensitivity and signal collection efficiency. Benefits from improved signal efficiency include shorter acquisition times and lower dose requirements. In this paper, the authors show a possibility of over an order of magnitude enhancement in photon detection efficiency (from 7.6 × 10(-5) to 1.6 × 10(-3)) for dopamine transporter (DaT) imaging of the striatum over the conventional SPECT parallel-hole collimators by use of custom-designed 20 multipinhole (20-MPH) collimators with apertures of 0.75 cm diameter. Quantifying specific binding ratio (SBR) of (123)I-ioflupane or (123)I-iometopane's signal at the striatal region is a common brain imaging method to confirm the diagnosis of the Parkinson's disease. The authors performed imaging of a striatal phantom filled with aqueous solution of I-123 and compared camera recovery ratios of SBR acquired between low-energy high-resolution (LEHR) parallel-hole collimators and 20-MPH collimators. With only two-thirds of total acquisition time (20 min against 30 min), a comparable camera recovery ratio of SBR was achieved using 20-MPH collimators in comparison to that from the LEHR collimator study. Their systematic analyses showed that the 20-MPH collimator could be a promising alternative for the DaT SPECT imaging for brain over the traditional LEHR collimator, which could give both shorter scan time and improved diagnostic accuracy.

The CYP3A4*22 C>T single nucleotide polymorphism is associated with reduced midazolam and tacrolimus clearance in stable renal allograft recipients.

Tacrolimus, a dual substrate of CYP3A4 and CYP3A5 has a narrow therapeutic index and is characterized by high between-subject variability in oral bioavailability. This study investigated the effects of the recently described CYP3A4*22 intron 6 C>T single nucleotide polymorphism on in vivo CYP3A4 activity as measured by midazolam (MDZ) clearance and tacrolimus pharmacokinetics in two cohorts of renal allograft recipients, taking into account the CYP3A5*1/*3 genotype and other determinants of drug disposition. In CYP3A5 non-expressers, the presence of one CYP3A4*22T-allele was associated with a 31.7-33.6% reduction in MDZ apparent oral clearance, reflecting reduced in vivo CYP3A4 activity. In addition, at ⩾12 months after transplantation, steady-state clearance of tacrolimus was 36.8% decreased compared with homozygous CYP3A4*22CC-wild type patients, leading to 50% lower dose requirements. Both concurrent observations in stable renal allograft recipients are consistent with a reduced in vivo CYP3A4 activity for the CYP3A4*22T-allele.