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Park, Chan-ran, Eun-ji Kim, Chang-gue Son, Jung-hyo Cho, and Nam-hun Lee. "3 Cases of Cancer Patients Whose Natural Killer Cell Activity Improved with Traditional Korean Medicine Treatment: A Case Series." Journal of Internal Korean Medicine 42, no. 3 (June 30, 2021): 444–54. http://dx.doi.org/10.22246/jikm.2021.42.3.444.
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Objectives: High natural killer cell activity (NKA) is associated with a clinically favorable status in patients with cancer. This study explores whether traditional Korean medicine (TKM) improves NKA in patients with cancer.Methods: We report three clinical cases involving patients with cancer who underwent NKA tests while they received TKM treatment, including acupuncture, moxibustion, wild ginseng pharmacopuncture, and Korean herbal medicines. We analyzed the treatment process and NKA test results of each patient.Results: The NKA of all three patients presented with an increasing tendency during the treatment process. Patient 1, who had been diagnosed with breast cancer, received inpatient treatment 3 times between September 16, 2017 and February 27, 2019. The NKA increased from 7.2 pg/mL to 571.7 pg/mL. Patient 2, who had thyroid cancer, was hospitalized 4 times between July 23, 2019 and August 27, 2020. The NKA improved from 317.4 pg/mL to 2000 pg/mL. Patient 3, who had liver cancer, received inpatient treatment 4 times between May 27, 2016 and January 10, 2017. The NKA increased from 22.2 pg/mL to 459.5 pg/mL. The chief complaints of these patients also were alleviated.Conclusions: TKM may be an effective treatment for accelerating NKA. Further research is needed to establish evidence that TKM stimulates NKA.
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Kaplan, David Edward, Tamar H. Taddei, Ayse Aytaman, Kristel Hunt, Astrid Knott, Eric Dieperink, Michelle Baytarian, et al. "Interim analysis of hepatocellular carcinoma (HCC) screening and survival in 4,087 veterans diagnosed with HCC from 2008 to 2010." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 243. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.243.
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243 Background: The Veterans Health Administration (VHA) is the largest provider of liver disease care in the US. From 2000-2007, there was a 5-fold increase in the incidence of hepatocellular carcinoma (HCC) among Veterans. The aim of the VOCAL group is to study outcomes and cost of Veterans diagnosed with cirrhosis and HCC from 2008-2010. Methods: The VA Corporate Data Warehouse was queried to identify all patients with ICD9 codes for HCC (155.0, 155.2) and cirrhosis (571.2, 571.5, 571.6). Chart abstraction was performed for each HCC patient to determine tumor characteristics, BCLC stage, and eligibility for transplantation. Results: This is an interim analysis of the first 4087 of 7,111 patients with HCC. HCC was confirmed in 3,207/4,087 (78%). Of these 3,207 patients, 778 (24%) were managed outside the VHA and 156 (6%) were diagnosed prior to 2008. Thus, 2,323 patients were analyzed. Median age was 60y (38-91). Males comprised 99% of the cohort; 61% were white, 24% were black, and 0.5% were Asian. Etiologies of cirrhosis were hepatitis C (HCV) (27%), alcohol-related (11%), HCV+alcohol (49%), hepatitis B (HBV) (9%), and other (metabolic, NASH) (2%). 63 (3%) were HIV-infected. Cirrhosis was coded in 83% (1918) prior to HCC diagnosis. Of cirrhotics, 11% (248) were optimally screened and 14% (335) were near-optimally screened; 75% of HCC were diagnosed incidentally or due to symptoms. AJCC stage was I/II/IIIA/IIIB/IIIC/IVA/IVB in 42/23/10/13/1/4/7%, respectively. 963 (41%) of patients were within Milan Criteria. BCLC staging was 0/A/B/C/D in 8/39/27/13/13%, respectively. Median OS was 400d and 1214/857/404/163/107d in BCLC 0/A/B/C/D, respectively. In multivariate survival model, age, the presence of ascites, serum albumin, serum bilirubin, serum sodium, CirCom score, Charlson-Deyo index, number of tumors, largest tumor size, and total tumor size were all statistically significantly predictive of survival. Conclusions: ICD9 codes for HCC have a PPV of ~80% for identifying true HCC cases in the CDW. Approximately 1/4 of patients received screening within AASLD 2010 guidelines. The majority of Veterans diagnosed with HCC present with intermediate to advanced disease with median survival 4.5-9.2 months.
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Ebadi, Mona, Nurul Asikin-Mijan, Mohd Suzeren Md. Jamil, Anwar Iqbal, Emad Yousif, Ahmad Rifqi Md Zain, Tengku Hasnan Tengku Aziz, and Muhammad Rahimi Yusop. "Palladium Nanoparticles on Chitosan-Coated Superparamagnetic Manganese Ferrite: A Biocompatible Heterogeneous Catalyst for Nitroarene Reduction and Allyl Carbamate Deprotection." Polymers 15, no. 1 (January 1, 2023): 232. http://dx.doi.org/10.3390/polym15010232.
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Although metallic nanocatalysts such as palladium nanoparticles (Pd NPs) are known to possess higher catalytic activity due to their large surface-to-volume ratio, however, in nanosize greatly reducing their activity due to aggregation. To overcome this challenge, superparamagnetic chitosan-coated manganese ferrite was successfully prepared and used as a support for the immobilization of palladium nanoparticles to overcome the above-mentioned challenge. The Pd-Chit@MnFe2O4 catalyst exhibited high catalytic activity in 4-nitrophenol and 4-nitroaniline reductions, with respective turnover frequencies of 357.1 min−1 and 571.4 min−1, respectively. The catalyst can also be recovered easily by magnetic separation after each reaction. Additionally, the Pd-Chit@MnFe2O4 catalyst performed well in the reductive deprotection of allyl carbamate. Coating the catalyst with chitosan reduced the Pd leaching and its cytotoxicity. Therefore, the catalytic activity of Pd-Chit@MnFe2O4 was proven to be unrestricted in biology conditions.
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Kratochvíl, Bohumil, Jan Ondráček, Karel Malý, and László Csordás. "The molecular and crystal structure of benzamidinium bromoacetate." Collection of Czechoslovak Chemical Communications 53, no. 2 (1988): 294–300. http://dx.doi.org/10.1135/cccc19880294.
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The molecular and crystal structure of benzamidinium bromoacetate was solved on the basis of Patterson and Fourier synthesis. The position of all the atoms were localized and the least squares method was employed to refine the coordinates of all the atoms together with their thermal vibration parameters. A final R factor value of 0.067 was obtained for 1 349 observed reflections (I 1.96 σ(I)). The substance crystallizes in the P21/n monoclinic space group with lattice parameters of a = 1 145.7(2), b = 1 571.3(3), c = 578.3(1) pm, γ = 90.65(1)°, Z = 4. Intramolecular hydrogen bonds form ion pairs in the structure between the nitrogen atoms of the amidinium group and the oxygen atoms of the bromoacetate. Intramolecular hydrogen bonds, also between nitrogen and oxygen atoms, connect the molecules in an infinite chain. The molecular chains are joined together by van der Waals forces. The N···O distance in the hydrogen bonds varies between 280.3(8) and 284.5(8) pm.
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Shahinul, M., MJ Hussain, MMR Salim, B. Ahamed, and M. Rahman. "Determination of Optimum Rate of Nitrogen, Phosphorus, Potassium and Boron for Leaf and Seed Yield of Lettuce." Bangladesh Journal of Agricultural Research 45, no. 4 (December 15, 2022): 455–71. http://dx.doi.org/10.3329/bjar.v45i4.63251.
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The experiment was conducted at Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur, during October 2012 to May 2013 to determine the optimum rate of nutrients for sustainable lettuce production. Nineteen treatment combinations were considered with five levels of each elements such as nitrogen viz. 0, 50, 100, 150 and 200 kg ha-1; phosphorus viz. 0, 25, 50, 75 and 100 kg ha-1; potassium viz. 0, 50, 100, 150 and 200 kg ha- 1; boron viz. 0, 0.5, 1.0, 1.5 and 2.0 kg ha-1. Results revealed that treatment T3 (N100P50K100B1.0) showed the maximum leaf and seed yield of lettuce. Fertilizer doses under T3 also showed the highest gross margin Tk. 305825 and Tk. 2816675 ha-1 and BCR 7.50 and 70.0 for leaf and seed yield, respectively. But, from regression analysis optimum doses of nitrogen, phosphorus, potassium and boron for maximum leaf yield (23.11 ton ha-1) and seed yield (571.5 kg ha-1) were N143P74K95B1.26 and N136.4P67.8K118.0B1.0, respectively that could be recommended as the best combination of nutrients for achieving higher leaf and seed yield of lettuce.
Bangladesh J. Agril. Res. 45(4): 455-471, December 2020
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Gori, Eleonora, Alessio Pierini, Ilaria Lippi, Noemi Boffa, Francesca Perondi, and Veronica Marchetti. "Urinalysis and Urinary GGT-to-Urinary Creatinine Ratio in Dogs with Acute Pancreatitis." Veterinary Sciences 6, no. 1 (March 13, 2019): 27. http://dx.doi.org/10.3390/vetsci6010027.
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In acute pancreatitis (AP), kidney injury (KI) can occur. Urinalysis and some urinary biomarkers have been proposed as prognostic tools in human AP. The aim of the study was to evaluate urinalysis and urinary GGT-to-urinary creatinine (uGGT/uCr) in canine AP and their association with possible outcomes. AP diagnosis was based on clinical and laboratory parameters, abnormal SNAP® cPL™ test and compatible imaging. Urinary KI (uKI) was defined if dogs had urinary casts and/or proteinuria. Dogs (n = 70) were divided in survivors and non-survivors according to the 15-day outcome. Data were analyzed using statistical software. Seventy dogs were retrospectively included, of which 24 dogs (34%) died. uKI was detected in 36 dogs (37%) which was associated with mortality (p = 0.01, Odds ratio (OR) 3.9, 95% CI 1.3–11.56). Non-survivors showed higher dipstick bilirubin levels than survivors (p = 0.0022). By excluding active sediments, urine protein-to-creatinine ratio (UPC) ≥2 was associated with mortality (p = 0.001, OR 47.5, 95% CI 4–571.9). The uGGT/uCr was available in 40 dogs, although no association of this factor with any outcome was found. The UPC ≥2 can be a negative prognostic factor in canine AP and further studies on uGGT/uCr are warranted.
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Syarifuddin, S., H. Husin, M. Mahidin, J. Jakfar, N. Nurhazanah, F. Nasution, F. R. Nasri, and H. D. Ramadhan. "Experimental study of calcium carbonate solution saturation in the separation process of palm kernel-shell mixtures using water clay bath systems." IOP Conference Series: Earth and Environmental Science 1356, no. 1 (June 1, 2024): 012117. http://dx.doi.org/10.1088/1755-1315/1356/1/012117.
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Abstract Continual use of CaCO3 in the separation of the palm kernel-shell mixture causes CaCO3 solution saturation. In this study, we aimed to evaluate the causes of CaCO3 solution saturation during the separation process of palm kernel-shell mixtures. The process was carried out in the laboratory clay bath system using several factors in the separation process, including calcium carbonate to water ratios (1:2 and 1:3), palm kernel-shell mixture feed rates (2.5, 3.0, and 3.5 kg/batch), and times (1, 2, 3, 4, and 5 h) with density, pH, and oil content as the quantitative control. The results show that the density and pH of the separating solution dropped per unit length of processing, with the lowest values being around 1.0916 g/ml and 6.65 (CaCO3 to H2O ratios of 1:3; feed rates 3.0 kg/batch; and times 5 h), respectively. In addition, the oil content of the separating solution was raised from 0.145 mg/L to 571.87 mg/L. Owing to the results, the dissolved oil in the solution was discovered as the cause of the saturation of the separating solution (decanting agent) during the process, corresponding to the inefficient separation of palm kernels and shells.
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Gallocchio, Federica, Alessandra Moressa, Francesco Pascoli, Alessia Vetri, Anna Toffan, Tobia Pretto, Giuseppe Arcangeli, Roberto Angeletti, and Antonia Ricci. "Effect of TiO2 Nanoparticle on Bioaccumulation of ndl-PCBs in Mediterranean Mussels (Mitilus galloprovincialis)." Animals 13, no. 7 (March 30, 2023): 1208. http://dx.doi.org/10.3390/ani13071208.
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The interaction of nanomaterials with pollutants in the marine environment might alter bioavailability, as well as toxicity, of both nanomaterials and pollutants, representing a risk, not only for marine organisms, but also for consumers through the marine food chain.The aim of this study was to evaluate the effect of titanium dioxide nanoparticles (TiO2NPs) in terms of bioaccumulation and toxicity on Mediterranean mussels (Mytilus galloprovincialis) exposed to six-indicator non-dioxin-like polychlorinated biphenyls (ndl-PCBs). Mussels were exposed to ndl-PCBs (20 µg/mL) (groups 3–4) or to a combination of ndl-PCBs (20 µg/mL) and TiO2NPs (100 µg/mL) (groups 5–6) for four consecutive days. TiO2NPs was detected in groups 5–6 (3247 ± 567 and 1620 ± 223 µg/kg respectively), but their presence did not affect ndl-PCBs bioaccumulation in mussels. In fact, in groups 3–4, the concentration of ndl-PCBs (ranging from 3818.4 ± 166.0–10,176 ± 664.3 µg/kg and 2712.7 ± 36.1–9498.0 ± 794.1 µg/kg respectively) was not statistically different from that of groups 5–6 (3048.6 ± 24.0–14,635.9 ± 1029.3 and 5726.0 ± 571.0–9931.2 ± 700.3 µg/kg respectively). Histological analyses showed alterations to the structure of the gill tissue with respect to the control groups, with more severe and diffuse dilatation of the central hemolymphatic vessels of the gill lamellae in groups 5–6 (treated with TiO2NPs and ndl-PCBs concurrently) compared to groups 3–4 (ndl-PCBs only). Finally, in mussels submitted to a seven-day depuration process, most TiO2NPs were eliminated, and NPs had a synergistic effect on ndl-PCBs elimination; as a matter of fact, in groups 5–6, the percentage of concentration was statically inferior to the one observed in groups 3–4. In any case, consumers might be exposed to TiO2NPs and ndl-PCBs (both concurrently and separately) if edible mussels, harvested in a contaminated environment, are consumed without a proper depuration process.
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Erber, Luke, Samantha Goodman, Caitlin Jokipii Krueger, Ivan Rusyn, and Natalia Tretyakova. "Quantitative NanoLC/NSI+-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine DNA-DNA Cross-Links in Urine." Toxics 9, no. 10 (October 2, 2021): 247. http://dx.doi.org/10.3390/toxics9100247.
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1,3-Butadiene (BD) is a common environmental and industrial chemical widely used in plastic and rubber manufacturing and also present in cigarette smoke and automobile exhaust. BD is classified as a known human carcinogen based on evidence of carcinogenicity in laboratory animals treated with BD by inhalation and epidemiological studies revealing an increased risk of leukemia and lymphohematopoietic cancers in workers occupationally exposed to BD. Upon exposure via inhalation, BD is bioactivated to several toxic epoxides including 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein crosslinks, which can cause base substitutions, genomic rearrangements, and large genomic deletions. In this study, we developed a quantitative nanoLC/NSI+-HRMS methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to quantify bis-N7G-BD in urine of mice treated with 590 ± 150 ppm BD for 2 weeks (6 h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female BD-exposed mice (574.6 ± 206.0 and 571.1 ± 163.4 pg/mg of creatinine, respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This method will be useful for future studies of 1,3-butadiene exposure and metabolism.
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Feyerabend, S., S. Stefanovic, C. Gouttefangeas, M. Widenmeyer, D. Wernet, J. Hennenlotter, J. Bedke, et al. "HLA-associated multipeptide vaccination in biochemically relapsed prostate cancer patients." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 5134. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.5134.
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5134 Background: We conduct a phase I/II monocenter clinical trial using multi peptide vaccination in patients with hormone naive, biochemically relapsed prostate cancer. The synthetic peptides applied are MHC-class I (HLA-A2) and -class II binders for activating CD4+ and CD8+ T- effector cells in vivo. Study endpoints are side effects as well as PSA- and T-cell response. Methods: Patients (pts) with rising PSA after primary curative surgical treatment without metastatic imageable lesions receive 14 peptides emulsified in Montanide ISA51 subcutaneously, combined with one of four T-cell stimulatory adjuvants versus no adjuvant for 18 months (mo) or until progression. PSA doubling time (DT) and clinical performance are monitored. T-cell activity and specifity are assessed with Elispot assay, tetramer staining and intracellular cytokine stainings. Results: 25 out of 35 pts have terminated the study treatment so far. During the vaccination period, geometric mean PSA DT increased from 7.8 mo (range 1.5 - 44.8 mo, 25 pts) to 11.8 months (range 2.2 - 571.3 mo, 24pts) whereas 1 pt showed a decreasing PSA value. Overall 8/25 pts (32%) had a mean rise of PSA DT of 81.6 mo and four of them did not receive any further treatment and were evaluable for follow-up (FU) after peptide vaccination (FU median 16 mo, range 5–33). These four pts raised their mean geometric PSA DT from 8.2 mo prior study treatment to 51.9 mo at treatment end and 52.5 mo at end of FU. PSA progressed unchanged in 10 patients (40%) or increased intermittently only in 4 pts. Two pts had PSA decline or DT increase during FU but not during the treatment period. Four patients (16%) exhibited an allergic reaction CTCAE II°. All pts reacted to at least one of the tumor antigen-derived HLA-class I epitopes after the fourth vaccine injection and up to six peptides were recognized simultaneously by CD8+ T cells in some individuals. Conclusions: Multi peptide vaccination stabilized or slowed down PSA progress in 11 of 25 cases. Stimulation of specific T-cell response is observed. Rise of PSA DT delaying standard treatment up to 33 mo and thus, delaying disease specific mortality is feasible. No significant financial relationships to disclose.
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Rambojun, A., A. Antony, Y. Hughes-Roberts, and W. Tillett. "AB1575 A RELIABLE METHOD FOR ANNOTATING HAND AND WRIST X-RAYS FOR SUPERVISED MACHINE LEARNING ALGORITHMS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 2020.2–2021. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3434.
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BackgroundMachine learning (ML) algorithms could facilitate the standardisation of joint damage assessment in Psoriatic Arthritis (PsA) and improve its accessibility in clinical and research settings. ML algorithms trained on manually annotated hand and wrist radiographs have promising performance characteristics[1]. A large volume of annotated radiographs is needed, and annotation is time consuming and subject to reliability issues given X-Rays (XRs) are 2D representations.ObjectivesTo develop a reliable method for the annotation of hand and wrist bones on XRs in order to facilitate the development of supervised ML algorithms for joint damage detection.Methods10 bilateral hand and wrist XRs were selected at random from the Bath PsA XR database. 5 XRs were independently annotated by 3 annotators; (AA & WT (rheumatologist) and YHR (radiologist)) using the ASPAX software[2]. Annotations were visually inspected for areas of discordance and consensus annotation guidelines were developed. Annotation was repeated using the annotation guidelines on second set of 5 XRs. With annotator 1 (WT) representing ground truth, the mean error (ME; in pixels) of the annotation (deviation from ground truth) and the mean fractional error (MFE; corrects for the perimeter measurements of the bone), was estimated in pre- and post-training annotations. The ME and MFE within a single annotator (AA) were estimated in 5 radiographs after a 2-month interval.ResultsVisual inspection determined that the areas of discordance in annotation were the 1stinterphalangeal joint, the metacarpal bases, the hamate and capitate bones, and the trapezium and trapezoid bones (Figure 1). The MFE between the annotators and ground truth improved for all bones following the development of annotation guidelines, with the largest improvement evident in the annotation of the metacarpal bones (Table 1). The intra-reader and inter-reader MFEs were comparable (Table 1).ConclusionStandardised instructions may facilitate reliable hand and wrist bone annotation and enable the acquisition of large volumes of annotated training data for supervised ML algorithms.References[1]Adwaye Rambojun, William Tillett, Tony Shardlow, Neill D. F. Campbell; Proceedings of the IEEE/CVF Winter Conference on Applications of Computer Vision (WACV), 2021, pp. 2043-2052[2]Machine Learning and Rheumatic Diseases (Website)https://people.bath.ac.uk/amr62/Projects/malard/malard.htmlTable 1.Reliability ExerciseExercise 1: Inter-rater errorExercise 2: Inter-rater errorExercise 2: Intra-rater errorMean Error (±sd)PixelsMean Fractional Error (±sd)Mean Error (±sd)PixelsMean Fractional Error (±sd)Mean Error (±sd)PixelsMean Fractional Error (±sd)Distal phalanges201.02 (119.282)3.97 x 10-4(3.747 x 10-3)550.54(85.201)1.66 x10-5(1.293 x10-5)1.39 x10-2(8.740 x10-3)2.40 x10-5(1.335 x10-5)Middle phalanges218.83 (119.891)7.43 x 10-4(3.232 x 10-3)544.37(76.012)4.33 x 10-4(1.178 x 10-3)7.85 x10-3(2.368 x10-3)1.02 x10-5(4.055 x10-5)Proximal phalanges231.48 (116.095)8.52 x10-6(8.113 x10-6)585.33(104.098)7.13 x10-6(3.119 x10-6)7.80 x10-3(3.554 x10-3)6.88 x10-6(3.972 x10-6)Metacarpals184.94(115.208)1.74 x 10-4(1.345 x 10-3)571.73(62.721)8.65 x10-6(4.308 x10-6)9.82 x10-3(6.102 x10-3)6.07 x10-6(3.307 x10-6)Radius232.90(122.620)1.75 x 10-4(2.086 x 10-4)552.12(79.655)3.25 x10-5(1.775 x10-5)1.83215 x10-2(9.617 x10-3)1.25 x10-5(6.534 x10-6)Ulna236.60(121.709)3.31 x 10-4(3.778 x 10-4)557.25(80.019)2.19 x10-5(1.793 x10-5)1.68 x10-2(1.842 x10-2)1.41 x10-5(1.656 x10-5)Carpal bonesa197.42 (141.548)2.75 x 10-4(3.009 x 10-4)Carpal bonesb542.31(77.896)8.89 x10-5(1.025 x 10-4)2.86 x10-2(3.285 x10-2)5.28 x10-5(7.673 x10-5)a. Trapezium, Trapezoid, Scaphoid, Lunate, Pisiform, Triquetrum, Hamate Capitateb. Trapezium, Hamate/Capitate, Lunate, ScaphoidFigure 1.Pre- and Post-training annotation examplesAcknowledgements:NIL.Disclosure of InterestsAdwaye Rambojun: None declared, Anna Antony Speakers bureau: Eli Lilly, AbbVie, Ynyr Hughes-Roberts: None declared, William Tillett Speakers bureau: Abbvie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Ono Pharma, Pfizer, UCB, Grant/research support from: Janssen, UCB, Pfizer, Eli-Lilly.
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Regnault, TR, RJ Orbus, FC Battaglia, RB Wilkening, and RV Anthony. "Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency." Journal of Endocrinology 162, no. 3 (September 1, 1999): 433–42. http://dx.doi.org/10.1677/joe.0.1620433.
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Pregnant ewes were exposed chronically to thermoneutral (TN; 20+/-2 degrees C, 30% relative humidity; n=8) or hyperthermic (HT; 40+/-2 degrees C 12 h/day, 35+/-2 degrees C 12 h/day, 30% relative humidity, n=6) environments between days 37 and 93 of pregnancy. Ewes were killed following 56 days of exposure to either environment (days in treatment (dit)), corresponding to 93+/-1 day post coitus (dpc). Maternal core body temperatures (CBT) in HT ewes were significantly elevated above the TN ewes (HT; 39.86+/-0.1 degrees C vs TN; 39.20+/-0.1 degrees C; P<0.001). Both groups of animals displayed circadian CBT, though HT ewes had elevated amplitudes (HT; 0.181+/-0.002 degrees C vs TN; 0.091+/-0.002 degrees C; P<0.001) and increased phase shift constants (HT; 2100 h vs TN; 1800 h; P<0.001). Ewes exposed to chronic heat stress had significantly reduced progesterone and ovine placental lactogen (oPL) concentrations from 72 and 62 dpc respectively (P<0.05), corresponding to approximately 30 dit. However, when compared with the TN ewes, HT cotyledonary tissue oPL mRNA and protein concentrations were not significantly different (P>0.1). Prolactin concentrations rose immediately upon entry into the HT environment, reaching concentrations approximately four times that of TN ewes, a level maintained throughout the study (HT; 216.31+/-32.82 vs TN; 54. 40+/-10.0; P<0.0001). Despite similar feed intakes and euglycemia in both groups of ewes, HT fetal body weights were significantly reduced when compared with TN fetuses (HT; 514.6+/-48.7 vs TN; 703. 4+/-44.8; P<0.05), while placental weights (HT; 363.6+/-63.3 vs TN; 571.2+/-95.9) were not significantly affected by 56 days of heat exposure. Furthermore, the relationship between body weight and fetal length, the ponderal index, was significantly reduced in HT fetuses (HT; 3.01+/-0.13 vs TN; 3.57+/-0.18; P<0.05). HT fetal liver weights were also significantly reduced (HT; 27.31+/-4.73 vs TN; 45.16+/-6.16; P<0.05) and as a result, the brain/liver weight ratio was increased. This study demonstrates that chronic heat exposure lowers circulating placental hormone concentrations. The observation that PL mRNA and protein contents are similar across the two treatments, suggests that reduced hormone concentrations are the result of impaired trophoblast cell development, specifically trophoblast migration. Furthermore, the impact of heat exposure during maximal placental growth is great enough to restrict early fetal development, even before the fetal maximal growth phase (100 dpc-term). These data highlight that intrauterine growth retardation (IUGR) may result primarily from placental trophoblast cell dysfunction, and secondarily from later reduced placental size.
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林大偉, 林大偉, and 湯欽達 湯欽達. "宜蘭清水地區二氧化碳增強型地熱系統之孔隙熱水模型研究." 理工研究國際期刊 13, no. 1 (April 2023): 79–94. http://dx.doi.org/10.53106/222344892023041301006.
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本研究之目的為探討以超臨界二氧化碳（supercritical CO2）為取熱流體之二氧化碳增強型地熱系統（CO2-EGS）開發之可行性並預估其取熱產能以活化暫停開發之地熱井。為此，本研究以紅柴林2號井（HCL-2）與結元井（JY-1）為基礎，使用有限元素分析法建立了結合裂隙網路（fracture network）、孔隙熱傳與達西流（Darcy’s law）的孔隙-熱-水模型（porous-thermal-hydraulic model），並探討了儲集層於不同注入條件下的溫度變化趨勢及CO2-EGS之總產能。<br>由本研究可知當注入質量流率愈大，注入井底溫度變化大，生產井產出溫度愈高，使得EGS總產能愈高；大的注入質量流率可有效降低工作流體沿生產井流出時的溫降；然注入流體溫度對儲集層溫度分布幾乎沒有影響，生產井溫度對之亦較不敏感。在本研究中，CO2-EGS在注入質量流率為4 ton/hr與0.0005 ton/hr之條件比較發現，生產井口溫度增加約21.5%；溫降降低約16.96%，僅為約0.04%；總產能由23.6 kW增加到219 MW。而流量為4 ton/hr之比產能為571.4 kJ/kg，相較0.0005 ton/hr之比產能增加約11.8%。<br>未來本研究可結合更進一步之現地示蹤劑試驗數據做產能預估，評估以此二井為基礎建立CO2-EGS之產能與效益，可為活化已暫停開發之地熱井做出貢獻。The re-utilization and activation of the abandon geothermal well was an economic concept for increasing the geothermal potential. The purpose of this study was to evaluate the feasibility of CO2 enhanced geothermal systems (CO2-EGS) based on the geothermal well HCL-2 and JY-1 and to estimate their capacity. A porous-fracture thermal-hydraulic model combined the fracture network, porous heat transfer model and Darcy's Law was established by finite element analysis. The temperature variation of the reservoir under different injected conditions and the total geothermal capacity of CO2-EGS are discussed. <br>The results show that the higher the mass flow rate of injection, the higher the outer temperature of the production well, the higher the total EGS capacity. The temperature difference of the production well decreased as the injected mass flow rate increased. The reservoir temperature distribution could be affected by the injected fluid temperature slightly. In this study, the temperature of the production wellhead of CO2-EGS increased about 21.5% when the injected mass flow rate was from 0.0005 ton/hr to 4 ton/hr. The specific capacity increased about 11.8%. <br>In future, this study can be combined with further in-situ tracer test data to estimate the capacity realistically, which can contribute to the activation of the abandon geothermal wells.
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Peres, M. A., A. B. Nascimento, V. P. Oliveira, C. Yamada, A. C. Nicacio, J. A. Visintin, and M. E. O. A. Assumpção. "228 COLLECTION AND EVALUATION OF SEMEN OF SLOTH (BRADYPUS TRIDACTYLUS)." Reproduction, Fertility and Development 18, no. 2 (2006): 222. http://dx.doi.org/10.1071/rdv18n2ab228.
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Sloths are animals that suffer with the destruction and fragmentation of forests. They experience a low population growth rate and need to be studied further for the preservation of the species. The objective of this study was to contribute data relevant to the reproductive physiology of this species, selecting a semen collection method and evaluating seminal characteristics that have never before been described in the literature. Fifteen Bradypus tridactylus males were captured in Manaus, Brazil. Nine of them were captured during the first half of 2004 (Group 1) and the others during the second half (Group 2). The animals were anesthetized with an i.m. injection of a combination of ketamine (10 mg/kg) and xylasine (1 mg/kg). Semen was collected by electroejaculaton using a rectal probe designed for domestic cats. Electrostimulations were given with a 0-100 mA/0-12 V variable electrostimulator in sequences of three progressive intensities, with ten repetitions at each intensity and variation of 10 mA between them. They started with 20 mA and peaked at 60 mA. Each stimulus lasted about 3 s. It was not possible to define the best intensity of stimulus to use and ejaculation could take place at any time of the stimulation (Fisher's exact test). Sperm motility and vigor were immediately analyzed. Sperm count was determined in a Neubauer chamber at a 1:50 (v:v) dilution in formol-saline. Morphology was examined at the same dilution. Fresh semen smears were made and stained using Spermac Stain� (Minit�b, Tiefenbach, Germany) protocol for a better evaluation of the spermatozoa acrosome and midpiece. In both methods 200 cells were counted for morphological evaluation. All animals ejaculated approximately 30 �L to 90 �L of semen. In some ejaculates the semen was too thin and flowed down the penis, so that the volume effectively collected was not sufficient for a complete spermiogram. Spermatozoa presented a wide variety of defects, and some physical characteristics differed (not significantly) between samples collected during the first and second halves of the year. Motility and vigor were very low, the sperm did not show forward progression, only oscillatory movement. However, a high percentage (80%) of spermatozoa were moving. The concentration in Group 1 ranged from 5000 spermatozoa/mm3 to 685 500 spermatozoa/mm3 (mean � 218 571.4 � 242 499.4). Sperm concentation was not assessed in Group 2. The morphology of the head could be elongated or squared, or the head could have a base narrower than the apex. The tail showed a unique feature: the midpiece narrowed abruptly, forming a nip in its transition to the tail. This was similar in appearance to the segmental aplasia of the mitochondrial sheath, but it was considered normal because it was observed in all spermatozoa. Although further studies are necessary to standardize the semen evaluation of sloths and to define the best protocol for electroejaculation, this pioneering study has shown the characteristics of sloth spermatozoa and the possibility of collecting semen throughout the electroejaculation process in this species. This work was supported by Fapesp 03/07457-4.
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Goldrich, Adam, Anuja Kriplani, Andriane Melanthiou, Daniel Fein, Elizabeth Helzner, Arvind Babu, Jason Gonsky, and Olcay Batuman. "Cytogenetic Profile Of Multiple Myeloma In The Inner City: Clinical Presentation and Survival." Blood 122, no. 21 (November 15, 2013): 5355. http://dx.doi.org/10.1182/blood.v122.21.5355.5355.
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Abstract Multiple Myeloma (MM), a plasma-cell neoplasia characterized by bone marrow (BM) infiltration, monoclonal protein production, and end organ dysfunction, is the most common hematologic neoplasm in blacks. The subclinical syndrome monoclonal gammopathy of undetermined significance (MGUS) precedes MM, and SEER data as well as more recent reports show that blacks have a 2-3-fold higher risk of developing MGUS and MM suggesting a genetic predisposition that causes the marked racial disparity in the incidence of both conditions. In addition, the recent rate of survival improvement observed in Caucasian patients has not been observed in blacks implying that the clinical course and development of resistance are varied between black and Caucasian MM patients. We have recently reported that in our inner-city, largely Caribbean-African patients MM occurs more frequently in women and at a younger age compared to literature. In this report we present cytogenetic information on 146 of these newly-diagnosed MM patients and their survival data. Patients were identified by tumor registries at UH and Kings County Hospital based on tumor histopathology. Data were collected from hospital records of patients treated between 2001-2011 (n=242).Downstate’s inner-city MM patients in Brooklyn, NY are largely Caribbean-African individuals and descendants. Demographics, disease indicators, and vital statistics were collected. In 146 patients, baseline cytogenetics by chromosome banding studies were available. In 63 of these patients baseline FISH used locus-specific probes del13 (13q14), IGH translocation (14q32), del17 and t(11;14)(q13;q32). Patients were treated with standard combination therapies. 146 patients had active, advanced newly-diagnosed MM. Median age=66 (range 36-91), male/female= 0.8, and evidence for the degree of tumor burden included: median % infiltration with CD138-positive cells within BM=50% (range 7%-99%), median serum M protein 3.3 g/dL (range 0.2-9.1). International Staging System level: Stage II: 28%, Stage III: 72%; median serum creatinine=2 mg/dL (range 0.38-14), median serum beta-2 microglobulin= 5.8 mg/dl (range 0.96-20.2). Further, 58% of patients with cytogenetic information had diffuse skeletal involvement with multiple lytic lesions (48%) and fractures (10%). Contrary to expectations from patients with advanced MM, chromosome banding and FISH showed abnormal cytogenetics (AC) in only 26% (n=38). At present, 50% of the patients have expired in both the normal cytogenetics (NC) and AC groups. In the AC group who expired, average time with MM was 2 years (range 0.5-5.6), whereas in the NC patients, average survival was 3.4 years (range, 0.6-5.2). Frequency of trisomies 5 and 9 indicative of hyperdiploidy, were twice as common in patients who are surviving with AC. In these latter patients as well as in surviving patients with NC, average survival time with MM is 4 years (range 0.4-15). In addition, IGH translocation was twice as common in AC patients who expired compared to the NC group. Other AC findings including hypodiploidy, del13, chr1 loss, and trisomies involving chromosomes 1, 7, 11, 19, and 21 were equally frequent in expired and living patients with AC. Using clinically available methods we found IGH translocation, trisomy 5 and trisomy 9 to be prognostically significant in this cohort of 145 inner-city, largely Carribean-African patients. Subtle presentation of cytogenetic abnormalities suggest that genome-wide analyses are needed to asses this patient populations’ MM biology.Cytogenetic Abnormality (frequency)Alive (n)Expired (n)Mean Survival in Years of Expired Patients with AC (Range)del 13 (12.3%)8101.2 (0.1-3.6)IGH translocation (13.0%)7121.7 (0.1-4.1)Chr 1 gain (8.2%)571.1 (0.1-2.4)Chr 1 loss (4.8%)342.3 (0.5-4.1)Hyperdiploidy (19.9%)15141.8 (0.1-5.6)Hypodiploidy (8.9%)761.7 (0.1-4.1)Trisomy 5 (12.3%)1261.7 (0.1-5.6)Trisomy 7 (6.9%)641.2 (0.5-2.3)Trisomy 9 (15.1%)1482.1 (0.1-5.6)Trisomy 11 (12.3%)992.0 (0.1-5.6)Trisomy 15 (11.6%)1161.5 (0.1-5.6)Trisomy 19 (13.7%)1371.7 (0.1-4.1) Disclosures: No relevant conflicts of interest to declare.
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Kumar, Rathan, Lotus Neidermire-Colley, Charlie Spencer, David Aslaner, Yandi Gao, Simran Surana, Matthew W. Gorr, et al. "Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins Alleviates Chronic Graft- Versus-Host-Disease Via Modulating the CXCR5/CXCL13 Axis." Blood 142, Supplement 1 (November 28, 2023): 2047. http://dx.doi.org/10.1182/blood-2023-182354.
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Introduction: Chronic graft-versus-host disease (cGVHD) is a severe complication of allogeneic hematopoietic cell transplant (allo-HCT) often leading to transplant-mediated mortality. Studies have shown that T follicular helper cells (Tfh) upregulate CXCR5 and migrate into the lymphoid organ follicles in response to CXCL13 promoting germinal center (GC) B cell proliferation and differentiation of plasma cells resulting in pathogenic antibody production and profibrotic pathways associated with cGVHD. In contrast, T follicular regulatory cells (Tfr) modulate the magnitude of the GC response; thus, the balance of Tfr/Tfh could be crucial to mitigating cGVHD.Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers influencing transcription of a multitude of inflammatory genes and our lab has previously reported pharmacological inhibition of BET, through OPN-51107, improves survivability and limits disease progression in murine models of acute GVHD that led to opening the first-in-human clinical trial of OPN-51107 in steroid refractory acute GVHD. We demonstrated BET proteins to be important in modulating acute GVHD pathogenesis, however, mechanisms of BET regulation within cGVHD are largely unknown. Here, using OPN-51107 we aim to further investigate mechanisms of cGVHD pathogenesis and identify successful BET inhibition-based therapeutic approaches. Methods: We used a Bronchiolitis Obliterans model (B6->B10.br) of cGVHD. Mice were administered 120mg/kg cyclophosphamide (D-3 and D-2) and 8Gy irradiation (D-1) as a conditioning regimen followed by B6 T-cell depleted bone marrow cells with and without CD45.1 B6 splenocytes. Mice that did not receive allogeneic splenocytes served as controls and did not develop GVHD. Recipients of allogeneic splenocytes were treated with a BET inhibitor - OPN-51107 at 10mg/kg 3x/weekly, or vehicle, from D28-54(+ 4) via oral gavage. Resting lung elastance and resistance was measured using the Flexivent system. At the time of lung function analysis, lung and liver tissue was harvested and stained via Hesson's Trichrome to identify and quantify collagen deposition. We performed immunofluorescence to quantify alveolar alloantibody deposition. Spleen and lung cells were stimulated with PMA/I and analyzed via spectral flow cytometry. An inflammatory murine cytokine array (#ARY006, R&D Systems) was used to analyze circulating plasma cytokine levels. Results: BET inhibition via OPN-51107 treatment decreased lung resistance (vehicle vs OPN-51107 =1.16Rrs vs 0.83Rrs p<0.05) and elastance (vehicle vs. OPN-51107=62Ers vs. 45Ers p<0.05). OPN-51107 treatment also significantly reduced alveolar antibody (Ig) deposition per area compared to vehicle (vehicle vs. OPN-51107= 4.91% vs. 3.3% p=0.01) and collagen deposition (vehicle vs. OPN-51107=19.0% vs. 12.9% p<0.05) and liver (vehicle vs. OPN-51107=19.3% vs. 2.35% p<0.0001). Congruently, BET inhibition decreased B220-CD19- CD138+mature plasma cells (vehicle vs. OPN-51107=15% vs 9.1% p<0.05) in the lung. Serum cytokine array analysis revealed a significant decrease in circulating CXCL13, relevant to Tfh migration as well as a decrease in other proinflammatory cytokines - CXCL9, MCP-1, IL3, RANTES and G-CSF important for macrophage activation and pathogenicity in OPN-51107 compared to vehicle treated mice. BET inhibition reduced splenic Tfh while increasing Tfr, thereby increasing Tfr:Tfh ratio (vehicle vs. OPN-51107= 5% vs. 9% p<0.05). Furthermore, total splenic CD19+ B-cells (vehicle vs. OPN51107= 70% vs. 33% p<0.001) as well as CXCR5 expression on B-cells were decreased in OPN-51107 treated mice (MFI vehicle vs. OPN-51107= 4744 vs. 571.5 p<0.0001). Conclusion: OPN-51107 improved lung function which correlated with significantly decreased lung fibrosis and antibody deposition in a BO model of cGVHD. BET inhibition reduces cGVHD immune pathology through decreased inflammatory cytokine production, promotion of GC Tfr cell population and modulates B-cell proliferation and/or trafficking. Significance: Using OPN-51107 in a BO model of cGVHD we demonstrate that BET inhibition is a feasible therapeutic strategy to reduce disease severity and improve lung function.
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Hernandez-Nieto, Carlos, Joseph A. Lee, Tamar Alkon-Meadows, Martha Luna-Rojas, Tanmoy Mukherjee, Alan B. Copperman, and Benjamin Sandler. "Late follicular phase progesterone elevation during ovarian stimulation is not associated with decreased implantation of chromosomally screened embryos in thaw cycles." Human Reproduction 35, no. 8 (July 10, 2020): 1889–99. http://dx.doi.org/10.1093/humrep/deaa123.
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Abstract STUDY QUESTION What is the impact of a late follicular phase progesterone elevation (LFPE) during controlled ovarian hyperstimulation (COH) on embryonic competence and reproductive potential in thaw cycles of preimplantation genetic testing for aneuploidy (PGT-A) screened embryos? SUMMARY ANSWER Our study findings suggest that LFPE, utilizing a progesterone cutoff value of 2.0 ng/ml, is neither associated with impaired embryonic development, increased rate of embryonic aneuploidy, nor compromised implantation and pregnancy outcomes following a euploid frozen embryo transfer (FET) cycle. WHAT IS KNOWN ALREADY Premature progesterone elevation during COH has been associated with lower pregnancy rates due to altered endometrial receptivity in fresh IVF cycles. Also, increased levels of progesterone (P) have been suggested to be a marker for ovarian dysfunction, with some evidence to show an association between LFPE and suboptimal embryonic development. However, the effect of LFPE on embryonic competence is still controversial. STUDY DESIGN, SIZE, DURATION Retrospective cohort analysis in a single, academic ART center from September 2016 to March 2020. In total, 5244 COH cycles for IVF/PGT-A were analyzed, of those 5141 were included in the analysis. A total of 23 991 blastocysts underwent trophectoderm biopsy and PGT analysis. Additionally, the clinical IVF outcomes of 5806 single euploid FET cycles were evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS Cohorts were separated in two groups: Group 1: oocytes retrieved from cycles with normal P levels during ovulation trigger (P ≤ 2.0 ng/ml); Group 2: oocytes retrieved after cycles in which LFPE was noted (P > 2.0 ng/ml). Extended culture and PGT-A was performed. Secondly, IVF outcomes after a single euploid FET were evaluated for each cohort. MAIN RESULTS AND THE ROLE OF CHANCE Four thousand nine hundred and twenty-five cycles in Group 1 were compared with 216 cycles on Group 2. Oocyte maturity rates, fertilization rates and blastulation rates were comparable among groups. A 65.3% (n = 22 654) rate of utilizable blastocysts was found in patients with normal P levels and were comparable to the 62.4% (n = 1337) observed in those with LFPE (P = 0.19). The euploidy rates were 52.8% (n = 11 964) and 53.4% (n = 714), respectively, albeit this difference was not statistically significant (P = 0.81). Our multivariate analysis was fitted with a generalized estimating equation (GEE) and no association was found with LFPE and an increased odds of embryo aneuploidy (adjusted odds ratio 1.04 95% CI 0.86–1.27, P = 0.62). A sub-analysis of subsequent 5806 euploid FET cycles (normal P: n = 5617 cycles and elevated P: n = 189 cycles) showed no differences among groups in patient’s BMI, Anti-Müllerian hormone (AMH), endometrial thickness at FET and number of prior IVF cycles. However, a significant difference was found in patient’s age and oocyte age. The number of good quality embryos transferred, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate and clinical pregnancy loss rates were comparable among groups. Of the registered live births (normal P group: n = 2198; elevated P group: n = 52), there were no significant differences in gestational age weeks (39.0 ± 1.89 versus 39.24 ± 1.53, P = 0.25) and birth weight (3317 ± 571.9 versus 3 266 ± 455.8 g, P = 0.26) at delivery, respectively. LIMITATIONS, REASONS FOR CAUTION The retrospective nature of the study and probable variability in the study center’s laboratory protocol(s), selected progesterone cutoff value and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. WIDER IMPLICATIONS OF THE FINDINGS Based on robust sequencing data from a large cohort of embryos, we conclude that premature P elevation during IVF stimulation does not predict embryonic competence. Our study results show that LFPE is neither associated with impaired embryonic development nor increased rates of aneuploidy. Embryos obtained from cycles with LFPE can be selected for transfer, and patients can be reassured that the odds of achieving a healthy pregnancy are similar to the embryos exposed during COH cycles to physiologically normal P levels. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for the realization of this study. Dr A.B.C. is advisor and/or board member of Sema 4 (Stakeholder in data), Progyny and Celmatix. The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NA
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SMD, ROSITA, OTIH ROSTIANA, and W. HARYUDIN W. HARYUDIN. "RESPON LIMA NOMOR UNGGUL KENCUR TERHADAP PEMUPUKAN." Jurnal Penelitian Tanaman Industri 13, no. 4 (June 25, 2020): 130. http://dx.doi.org/10.21082/jlittri.v13n4.2007.130-135.
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<p>ABSTRAK<br />Kencur (Kaempferia galanga) banyak dimanfaatkan oleh rumah<br />tangga, industri obat maupun makanan serta minuman dan industri rokok<br />kretek. Peningkatan pemakaian simplisia kencur dalam berbagai industri di<br />dalam negeri akan meningkatkan konsumsi simplisia ini, sehingga upaya<br />peningkatan produksi masih perlu dilakukan melalui budidaya, di<br />antaranya dengan penggunaan varietas unggul yang didukung dengan<br />pemupukan yang optimal. Di dalam penelitian ini dikaji respon lima<br />nomor unggul kencur terhadap paket pemupukan organik dan anorganik<br />pada tanah latosol di dataran rendah, Cileungsi, Bogor, Jawa Barat.<br />Penelitian dilaksanakan mulai bulan Oktober 2003 sampai Agustus 2004,<br />dengan RAK dalam pola faktorial. Faktor I nomor unggul kencur (V1, V2,<br />V3, V4 dan V5) dan faktor II paket pemupukan (6 paket), diulang 2 kali.<br />Jarak tanam yang digunakan 20 x 20 cm, ukuran petak 4 x 1,2 m. Hasil<br />penelitian menunjukkan, empat nomor unggul kencur (V1, V3, V4, V5),<br />dari lima nomor yang diuji, mempunyai kemampuan untuk menghasilkan<br />rimpang segar dan kering yang sama, dengan kisaran bobot rimpang segar<br />62,27-70,22 g/tanaman dan kisaran bobot rimpang kering 16,95-19,33 g/<br />tanaman. Paket pemupukan yang dianjurkan untuk semua nomor yang<br />diuji adalah pupuk kandang 20 ton/ha + urea 250 kg/ha + SP36 200 kg/ha<br />+ KCl 200 kg/ha, atau pemupukan organik dengan pupuk kandang kerbau<br />40 ton/ha. Respon lima nomor unggul kencur terhadap aplikasi paket<br />pemupukan memberikan mutu dengan hasil yang berbeda, yaitu kadar<br />minyak atsiri V3 (2,03%) tergolong mutu I, sedangkan empat nomor<br />lainnya tergolong mutu II (1,08 -1,97%), dengan hasil minyak atsiri 0,325<br />– 0,466 ml/tanaman. Serapan hara lima nomor unggul kencur terhadap<br />paket teknologi yang diuji memperlihatkan, serapan hara N berkisar antara<br />149,60 – 415,60 mg/tanaman, hara P 41,50 – 112,50 mg/tanaman, hara K<br />236,10 – 571,70 mg/tanaman.<br />Kata kunci : Kencur, Kaempferia galanga, varietas unggul, pemupukan,<br />serapan hara, produksi, mutu</p><p><br />ABSTRACT<br />Response of five galanga promising lines to fertilization<br />India galanga (Kaempferia galanga) is commonly used for<br />household consumption, medicines, food and drink supplement industries<br />as well as cigarette sauce. Increase in demand of this commodity for<br />domestic industries will raise the consumption of symplicia. Therefore,<br />effort in increasing yield of the plant through cultivation technique<br />improvement, i.e. application of superior variety and fertilization, is worth<br />to be accomplished. In this experiment five Galanga promising lines of<br />India galanga were subjected to organic and inorganic fertilizations at<br />low land latosol soil, Cileungsi, Bogor, West Java. Experiment was carried<br />out from October 2003 – August 2004 and arranged in randomized block<br />in factorial design, with two replications. First factor is the promising lines<br />(V1, V2, V3, V4 and V5); factor II is fertilization packages (6 packages).<br />Plot size of 4 x 1.2 m and plant spacing of 20 x 20 cm, were applied. The<br />results showed that four of five tested promising lines yielded the same<br />results of fresh and dry weight of rhizomes ranged from 62.27-70.22<br />g/plant, and the dry weight was 16.95-19.33 g/plant respectively.<br />Fertilization packages of dung manure 20 t/ha + urea 250 kg/ha + SP36<br />200 kg/ha + KCl 200 kg/ha, or organic fertilizer by using dung manure 40<br />ton/ha, are recommended. Application of fertilization package resulted in<br />different response to the plant for their qualities. The essential oil content<br />of promising lines V3 belongs to the first grade of quality (2.03%), while<br />the others are the second one (1.08-1.97%), with the yield of essential oil<br />ranged from 0.325 – 0.466 ml/plant. The nutrients uptake of the promising<br />lines to the applied technology package were 149.60 – 415.60 mg/plant of<br />N, 41.50 – 112.50 mg/plant of P, and 236.10 – 571.70 mg/plant of K<br />nutrients.<br />Key words: Kaempferia galanga , superior variety, fertilization, nutrient<br />up take, yield, quality</p>
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R.K. PAIKARAY and K.N. MISHRA. "Productivity and water use efficiency of niger (Guizotia abyssinica) genotypes under different dates of sowing." Indian Journal of Agronomy 44, no. 3 (October 10, 2001). http://dx.doi.org/10.59797/ija.v44i3.3564.
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4 A field experiment was conducted for 3 consecutive years from 1989 to 1991 to find out the effect of sowing time on productivity and water use efficiency of niger (Guizotia abyssinica Coss.) genotypes. GA 10 produced the highest seed yield of 497.4 kglha which was 3.8 and 21.3% more over IGP 76 and UN 4, respectively. The crop sown on 20 August recorded higher yield (571.9 kg seed/ ha) than earlier or later sown crops. The moisture use efficiency was maximum for GA 10 (16.08 kg seed/ha/mm and 98.5 kg total yield/ha/mm. Sowing of the crop on 20 August proved efficient in utilizing soil moisture towards seed yield (19.78 kglhalmm) while 21 July sown crop resulted in the highest water use proved efficiency for total biomass yield (117.27 kglhdmm). GA 10 showed the maximum moisture use efficiency for its seed yield when sown on 20 August. .+-
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AlSumadi, Mutaz, Aatif Mahmood, David Whittam, Lara Kharma, Rami Ashour, and Ronan Banim. "Efficacy and safety of tranexamic acid in hip fracture surgery: A comparative study of 613 patients." Journal of Perioperative Practice, July 1, 2021, 175045892110020. http://dx.doi.org/10.1177/17504589211002090.
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Background Blood loss is a major concern in the frail elderly patient undergoing hip fracture surgery. The objective of this study was to investigate the efficacy of tranexamic acid in reducing blood loss and allogenic blood transfusions. The study also investigated the safety profile by comparing rates of thromboembolic events, Methods A total of 613 patients with hip fractures were included in the study. Patients received 1g of tranexamic acid on induction of anaesthesia. Postoperative haemoglobin was measured on day one. Blood loss was calculated, and blood transfusion was recorded. Results Tranexamic acid use resulted in a higher mean postoperative haemoglobin (110.3 ± 15.9 vs 106.8 ± 16.2; p = 0.023) and reduced mean estimated blood loss (571.3 ± 150.4 vs 678.3 ± 201.2; p = 0.001). There was also a significantly reduced number of transfusions in tranexamic acid group (13% vs 28%; p = 0.002). There was no difference in rates of deep vein thrombosis (4 vs 3; p = 0.98) or pulmonary embolism (2 vs 2; p = 1). Conclusion The use of tranexamic acid is effective in reduction of blood loss and rates of blood transfusion, without an apparent increase in adverse thromboembolic events.
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Tulukcu, Eray. "Effect of Planting Density on Yield Components of False Flax." Asian Plant Research Journal, February 1, 2021, 10–15. http://dx.doi.org/10.9734/aprj/2021/v7i130144.
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This research was carried out to determine the effect of population density on the performance components of false flax (Camelina sativa (L.) Crantz). This would allow to determine the effect of increasing the number of seeds of the false flaxon the yield and also the appropriate sowing distance under Konya conditions. The research was developed in the experimental field of Çumra Vocational School, Konya, Turkey. The experimental design was randomized complete blocks designwith three repetitions. Analyzes were made using the Jump statistics program.A thousand seeds were weighed and 4 different planting population densities were used: 500, 750, 1000 and 1250 seeds per square meter.On May 2, 2014 it was sown and on August 10, 2014 it was harvested. Plant height, number of plants per m2, biomass, root length, number of capsules, number of seeds per capsules, weight of a thousand seeds and other yield values were evaluated. The vegetative period of false flax under Konya ecological conditions was 100 days. The thousand-grain weight was 1.4 g (500) to 2 g (1000), plant height 58.3 cm (500) to 74 cm (750) and root length 9.6 cm (1000) to 16.3 cm (750). The number of capsules per plant and of seeds per capsule ranged from 152.6 (750) to 571.6 (500) and from 11 (1000) to 19.6 (500). In this study, It was found that applications of 1250 seeds per m2 were the most suitable sowing density for yield
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Menendez, Mariano E., Suleiman Y. Sudah, Matthew R. Cohn, Pablo Narbona, Alexandre Lädermann, Johannes Barth, and Patrick J. Denard. "Defining Minimal Clinically Important Difference and Patient Acceptable Symptom State After the Latarjet Procedure." American Journal of Sports Medicine, July 18, 2022, 036354652211079. http://dx.doi.org/10.1177/03635465221107939.
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Background: The Latarjet procedure is one of the most well-established treatment options for anterior shoulder instability. However, meaningful clinical outcomes after this surgery have not been defined. Purpose: This study aimed to establish the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) for commonly used outcome measures in patients undergoing the Latarjet procedure and determine correlations between preoperative patient characteristics and achievement of MCID or PASS. Study Design: Case series; Level of evidence, 4. Methods: A multicenter retrospective review at 4 institutions was performed to identify patients undergoing primary open Latarjet procedure with minimum 2-year follow-up. Data collected included patient characteristics (age, sex, sports participation), radiological parameters (glenoid bone loss, off-track Hill-Sachs lesion), and 4 patient-reported outcome measures (collected preoperatively and 2 years postoperatively): the American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), the visual analog scale (VAS) for pain, and the Western Ontario Shoulder Instability Index (WOSI). The MCID and PASS for each outcome measure were calculated, and Pearson and Spearman coefficient analyses were used to identify correlations between MCID or PASS and preoperative variables (age, sex, sports participation, glenoid bone loss, off-track Hill-Sachs lesion). Results: A total of 156 patients were included in the study. The MCID values for ASES, SANE, VAS pain, and WOSI were calculated to be 9.6, 12.4, 1.7, and 254.9, respectively. The PASS values for ASES, SANE, VAS pain, and WOSI were 86.0, 82.5, 2.5, and 571.0, respectively. The rates of patients achieving MCID were 61.1% for VAS pain, 71.6% for ASES, 74.1% for SANE, and 84.2% for WOSI. The rates of achieving PASS ranged from 78.4% for WOSI to 84.0% for VAS pain. There was no correlation between any of the studied preoperative variables and the likelihood of achieving MCID or PASS. Conclusion: This study defined MCID and PASS values for 4 commonly used outcome measures in patients undergoing the Latarjet procedure. These findings are essential for incorporating patient perspectives into the clinical effectiveness of the Latarjet procedure and provide valuable parameters for the design and interpretation of future clinical trials.
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El-Beltagi, Hossam S., Asmaa A. Halema, Zainab M. Almutairi, Hayfa Habes Almutairi, Nagwa I. Elarabi, Abdelhadi A. Abdelhadi, Ahmed R. Henawy, and Heba A. R. Abdelhaleem. "Draft genome analysis for Enterobacter kobei, a promising lead bioremediation bacterium." Frontiers in Bioengineering and Biotechnology 11 (January 8, 2024). http://dx.doi.org/10.3389/fbioe.2023.1335854.
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Lead pollution of the environment poses a major global threat to the ecosystem. Bacterial bioremediation offers a promising alternative to traditional methods for removing these pollutants, that are often hindered by various limitations. Our research focused on isolating lead-resistant bacteria from industrial wastewater generated by heavily lead-containing industries. Eight lead-resistant strains were successfully isolated, and subsequently identified through molecular analysis. Among these, Enterobacter kobei FACU6 emerged as a particularly promising candidate, demonstrating an efficient lead removal rate of 83.4% and a remarkable lead absorption capacity of 571.9 mg/g dry weight. Furthermore, E. kobei FACU6 displayed a remarkable a maximum tolerance concentration (MTC) for lead reaching 3,000 mg/L. To further investigate the morphological changes in E. kobei FACU6 in response to lead exposure, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed. These analyses revealed significant lead adsorption and intracellular accumulation in treated bacteria in contrast to the control bacterium. Whole-genome sequencing was performed to gain deeper insights into E. kobei’s lead resistance mechanisms. Structural annotation revealed a genome size of 4,856,454 bp, with a G + C content of 55.06%. The genome encodes 4,655 coding sequences (CDS), 75 tRNA genes, and 4 rRNA genes. Notably, genes associated with heavy metal resistance and their corresponding regulatory elements were identified within the genome. Furthermore, the expression levels of four specific heavy metal resistance genes were evaluated. Our findings revealed a statistically significant upregulation in gene expression under specific environmental conditions, including pH 7, temperature of 30°C, and high concentrations of heavy metals. The outstanding potential of E. kobei FACU6 as a source of diverse genes related to heavy metal resistance and plant growth promotion makes it a valuable candidate for developing safe and effective strategies for heavy metal disposal.
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El-Sayed, Saber A. M., Yasser F. Ali, Mostafa M. Ahmady, Salah F. Alsayed, and Ahmed M. Baraka. "Outcome and Clinical Spectrum of Post-streptococcal Glomerulonephritis in Children in Developing Countries." Asian Journal of Applied Sciences 5, no. 2 (April 22, 2017). http://dx.doi.org/10.24203/ajas.v5i2.4689.
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Background: Post streptococcal glomerulonephritis with crescentic glomerulonephritis is an uncommon outcome in children. This study was done to evaluate the clinical spectrum and outcome in children with crescentic glomerulonephritis following acute post-streptococal glomerulonephritis. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received treatment in the form of intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide .Objective: to evaluate the clinical spectrum and outcome of the pediatric patients with post-streptococal crescentic glomerulonephritis admitted or referred in Zagazig general hospital in nephrology unit. Study design: The study included ( 20 ) children patients with biopsy proven crescentic golmerulonephritis following APSGN admitted or referred from other hospitals to the nephrology unit in Zagazig general hospital between Marsh 2010 to May 2016 These patients were subjected to detailed clinical and biochemical examinations including urine analysis ,U&E ,serum albumin, ASOT ,anti- DNase-B test, complements ( C3 and C4), ANA, ANCAs ,anti- DNA antibodies; anti-(GBM) antibodies . The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology by light immunofluorescence and electron microscopy and all patients were taken immunosuppressive treatment.Results: 20 patients with poststreptococcal crescentic glomerulonephritis (12 males and 8 females). The mean age of patients at the time of presentation was (7.5) years with range of 5 to 12 years. All were having gross hematuria ,progressive rise of serum creatinine, mean creatinine was 571.5 umol/l with range of (413umol/- 822umol/1) ,low complement C3, 16 patients were having hypertension (80%),10 patients (50%) had nephrotic range of proteinuria and remaining were having moderate range. Renal biopsy which revealed more than 50% crescents in all biopsies with mean of 62.5% and ranging between 50-90%. 4 patients had fibrocellular crescents (20%) and 16 had cellular crescents (80%). the mean follow up duration in months was 25 mo ranging between 22-28 months after immunosuppression,16 patients regained their normal kidney functions (80%) with mean creatinine 47 umol/l ranging between (40-68) P-value <0.001**.4 patients (20%) had residual renal impairment, these 4 patients had fibro cellular crescents in renal biopsy. 8 patients regained their normal blood pressure at last follow up (80%) P-value <0.001**.Conclusion: the overall outcome of 20 patients with post streptococcal crescentic glomerulonephritis was accepted & excellent, 16 patients out of 20 (80%) regained their normal kidney functions. Due to the limited number of our patients , large multi-center study is needed to prove this result.
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Sedova, K., J. Azarov, P. Van Dam, and J. Kautzner. "CineECG repolarization gradients predict acute hemodynamical response in CRT patients." European Heart Journal 44, Supplement_2 (November 2023). http://dx.doi.org/10.1093/eurheartj/ehad655.1024.
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Abstract Background Cardiac resynchronization therapy (CRT) is widely used for patients with conduction disorders and heart failure. The proportion of the CRT-non-responders can exceed 30%, which warrants search for new approaches to optimize the CRT device implantation and follow-up. CineECG is a novel cardiac anatomy-based ECG modality proposed for better visualization of the myocardial depolarization and repolarization processes. This method yielded promising results in patients with sinus rhythm but has not been tested in ventricular pacing. Purpose The aim of the present study was to evaluate CineECG-derived mean temporo-spatial isochrone (TSI) trajectory in different pacing protocols and test its association with acute hemodynamical responses in CRT patients. Methods CineECG uses a generic heart/torso model to construct the average electrical pathway within the cardiac anatomy from the 12 lead ECG. CineECG and invasive hemodynamical parameters were tested in 15 patients undergoing multisite CRT system implantation. ECG recording and hemodynamical measurements were performed simultaneously, while the patients were undergoing 4-6 biventricular pacing protocols with the same interventricular pacing delay (30 ms) and different left ventricular (LV) lead localizations (apical, basal, multisite). LV dP/dt max was tested for association with the parameters of standard ECG (QRS duration, QT duration, Tpeak-Tend duration) and CineECG pathway parameters. The latter pathway directions were computed for QRS and ST-T intervals for anteroposterior (X), left-to-right (Y), and apicobasal (Z) directions. Results Biventricular protocols did not differ between each other in LV dP/dt. In univariate linear regression analysis, LV dP/dt max was associated with QRS and ST-T pathway directions (Figure 1 - table). The left-to-right (Y) and apicobasal (Z) ST-T pathway directions remained independent predictors of LV dP/dt max in multivariate linear regression analysis with the adjustment for a pacing protocol [regression coefficient 571.6 (319.3 – 823.8), p<0.001; regression coefficient -406.9 (-636.7 – -177.2), p=0.001, respectively]. Optimal repolarization sequences associated with better acute hemodynamic responses assessed by LV dP/dt max were from right to left and from base to apex (Figure 2). Conclusion CineECG repolarization pathway gradients in the left-to-right and apicobasal directions outperform temporal ECG parameters and predict the acute hemodynamical response in biventricular pacing protocols in CRT patients.
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Marques Da Silva, Bernardo, José Charreu, Inês Duarte, Cristina Outerelo, José António Lopes, and Joana Gameiro. "MO483: Validation of The Kidney Failure Risk Equation in a Portuguese Cohort." Nephrology Dialysis Transplantation 37, Supplement_3 (May 2022). http://dx.doi.org/10.1093/ndt/gfac071.014.
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Abstract BACKGROUND AND AIMS In chronic kidney disease (CKD) patients, the risk of kidney replacement therapy (KRT) is highly variable. In 2011, Tangri et al. developed the kidney failure risk equations (KFRE) to predict the 2- and 5-year probability of requiring kidney replacement therapy (KRT). The KFRE is an easily calculated 4-variable equation that has been extensively validated in multiple cohorts. The aim of this study was to validate this risk score in a Portuguese cohort. METHOD We conducted a retrospective analysis of CKD patients stage 3–5 referred for nephrology consult at Centro Hospitalar Universitário Lisboa Norte during the first 6 months of 2018. Age, gender, estimated glomerular filtration rate (eGFR) and albuminuria were assessed. The four-variable Kidney Failure Risk Equation (KFRE) calibrated for a non-North American population was calculated. Requirement for KRT was assessed in a 2-year follow-up. We assessed the Cox logistic regression method of the KFRE to predict KRT requirement, and the discriminatory ability was determined using the receiver operating characteristic (ROC) curve. A cut-off value was defined as that with the highest validity. RESULTS A total of 360 patients were included, and 54.4% were male. The mean age was 74.9 ± 12.2 years, serum creatinine was 1.97 ± 0.84 mg/dL, eGFR was 33.4 ± 12.13 mL/min/1.73 m2 and albuminuria was 571.1 ± 848.3 mg/g. The mean calculated risk score was 6.2 ± 11.2%. A total of 23 patients required KRT (6.4%) in the 2-year follow-up. The hazard ratio was 1.1 [95% confidence interval (95% CI) 1.06–1.12; P < .001] for the 2-year risk of KRT. The KFRE predicted progression to KRT requirement with an auROC of 0.903, (95% CI 0.86–0.95; P < 0.001), with a sensitivity of 91.3% and specificity of 71.8%. The optimal KFRE cut-off was >4.5% for 2-year nephrologist referral, with a hazard ratio of HR 26.7 [95% CI 6.15–116.3; P < .001] for 2-year risk of KRT. requirement. CONCLUSION We have independently externally validated the 2-year KFRE and shown that it has excellent discrimination. The KFRE should be incorporated into the clinical care of patients with CKD to improve patient-clinician dialogue and provide guidance on the timing of referral for nephrology evaluation and planning for dialysis access.
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Metry, S., T. Suvorava, and G. Kojda. "Bradycardic effect of endothelial-specific bradykinin type-II receptors overexpression in mice: impact on blood pressure." European Heart Journal 44, Supplement_2 (November 2023). http://dx.doi.org/10.1093/eurheartj/ehad655.3222.
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Abstract Background/Introduction Polymorphisms of the gene encoding for the bradykinin type-II receptors (B2R) has been shown to decrease the expression of B2R and increased vascular resistance and blood pressure in humans. Purpose We aimed to study the role of endothelial B2R on systolic blood pressure (SBP) and heart rate (HR) using a novel mice model with endothelial-specific B2R overexpression (B2tg) as compared with transgene negative littermates (B2n) and on differential expression of proteins potentially relevant to vascular tension. Methods Human and murine B2R expression levels were quantified by rtPCR. Thoracic aortic tissues were used for vascular reactivity studies and proteomic analysis. SBP and HR were measured by the tail-cuff method at baseline, after administration of the COX inhibitor diclofenac (10 mg/kg/day), B2R antagonist icatibant (1 mg/kg) or NOS inhibitor L-NAME (100 mg/kg/day). Results In aortic tissues of B2tg human B2R were exclusively expressed (n=6, P=0.0005), while murine B2R expression levels remained unchanged. Similar results were found in skeletal muscle tissues used as an estimate for resistance vessels. Aortic ring studies revealed a concentration-dependent constriction to bradykinin in wild-type mice (maximal vasoconstriction 9.6±3.0%, n=5) whereas aortic rings of B2tg showed concentration-dependent relaxation (-27.4±4.1%, n=12). SBP was significantly lower in B2tg (125.0 ±1.6 mmHg) as compared to B2n (129.9±1.1 mmHg, n=9, P=0.03). Diclofenac treatment slightly but not significantly reduced SBP in B2n (to 125.5±2.4 mmHg, P=0.09) and in B2tg (to 119.8±2.8 mmHg, n=9, P=0.12), however the difference in SBP remained (P=0.03). In a pilot study, L-NAME administration did also not change the SBP difference between B2n and B2tg (9.9±10.3 mmHg, n=3-4). In contrast, icatibant administration abolished the difference between the groups (B2n 128.6±4.6 vs B2tg 128.3±2.0 mmHg, n=8, P=ns) suggesting the involvement of endothelial B2R in SBP reduction. Interestingly, in the same mice, HR was significantly lower in B2tg (571.4±20.8 bpm) as compared to B2n (626.7±13.7 bpm, P=0.02). While diclofenac didn’t affect HR, icatibant significantly increased HR to (630.8±21.8 bpm in B2tg and 685.5±16.4 bpm in B2n, n=8, P=0.01). Only in B2tg, there was a significant strong correlation between SBP and HR (r=0.76, P=0.016). Analysis of proteomic data revealed differential upregulation of proteins related to cell adhesion (CD44), extracellular matrix (hyaluronidase), and differential downregulation of proteins related to oxidative stress (superoxide dismutase) in B2tg. Conclusion Endothelial B2R overexpression reduces SBP and HR. SBP reduction is not dependent on two major vascular pathways stimulated by products of NOS and COX but appears to be related to endothelial B2R-dependent HR reduction. Hence, agonism at B2R could be a valuable target for development of new cardiovascular drugs.
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Seo, Young Ah, and Marianne Wessling‐Resnick. "Trace Element Distribution in Flatiron Mice, a Genetic Model of Human Ferroportin Disease." FASEB Journal 30, S1 (April 2016). http://dx.doi.org/10.1096/fasebj.30.1_supplement.292.7.
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Ferroportin (Fpn; SLC40A1) is a metal exporter involved in the assimilation of dietary iron (Fe) and manganese (Mn). Accumulating evidence suggest it also may function in the transport of additional metals, including copper (Cu) and zinc (Zn). Patients with mutations in the Fpn gene develop hereditary hemochromatosis (HH) type 4, also called “ferroportin disease”, which is associated with Fe‐loading and restricted erythropoiesis. Flatiron (ffe) mice have deficiency in Fpn and provide the first genetic model that fully recapitulates human ferroportin disease. While the role of Fpn in Fe metabolism has been established and its influence on Mn homeostasis begins to be appreciated, relatively little is known about the potential impact of Fpn on the distribution of other metals or how ferroportin disease might alter trace element metabolism. Therefore, we characterized the distribution of Mn, Fe, Zn, and Cu in flatiron mice. Tissues, erythrocytes, and plasma from flatiron mice and wild‐type control (+/+) mice at 15 weeks of age were analyzed for trace element by inductively coupled plasma mass spectrometry (ICP‐MS). Ffe/+ mice had reduced hematocrit values (47.2 vs. 49.80 %; P=0.01) and higher non‐heme Fe levels in both liver (151.9 vs. 112.9 μg/mL; P=0.025) and spleen (587.0 vs. 571.6 μg/mL; P=0.0002) compared to +/+ mice. These data confirm the Fe deficiency and Fe loading phenotype of flatiron mouse associated with ferroportin disease. Mn associated with red blood cells was significantly reduced in ffe/+ mice compared to +/+ mice (2.5 vs. 2.9 μg/L, P=0.011). Mn (0.596 vs. 0.788 mg/kg; P=0.002), Zn (61.079 vs. 77.840 mg/kg; P=0.008), and Cu (0.716 vs. 0.941 mg/kg; P=0.008) levels were reduced in femurs from ffe/+ mice compared to +/+ mice. Because bone deposits reflect metal accumulation, these data indicate that Mn, Zn and Cu metabolism are altered by Fpn deficiency. Lung Mn (0.153 vs. 0.180 mg/kg; P=0.01), and kidney Cu (24.0 vs. 48.0 mg/kg; P=0.002) and kidney Zn (7.5 vs. 10.5 mg/kg; P=0.018) were reduced in ffe/+ mice compared to +/+ mice. Interestingly, Mn and Fe levels were higher in olfactory bulbs of ffe/+ mice compared to +/+ controls (0.650 vs. 0.162; P=0.0006 and 20.4 vs. 7.58 mg/kg; P=0.05 respectively). To further study brain metal distribution, 54MnCl2 was administered by intravenous injection and total brain 54Mn was measured over time. By 72 h post‐intravenous injection, brain 54Mn was increased in ffe/+ mice compared to +/+ mice (0.809 vs. 0.502 % dose; P=0.04), but blood 54Mn was reduced to the same level at 24 and 72 h in both groups of mice. Taken together, these results indicate that Fpn deficiency alters body Fe, Mn, Zn and Cu levels, decreases Mn trafficking out of the brain, and promotes brain metal accumulation in the flatiron mouse model of “ferroportin disease”. These findings highlight the importance of Fpn function in trace element homeostasis, and implicate metal dyshomeostasis in patients with ferroportin disease.Support or Funding InformationThis work was supported by grants from the U.S. National Institute of Health (NIH) to Y.A.S (K99ES024340) and M.W.R (R01ES0146380). This study was supported in part by funding from the HSPH‐NIEHS Center for Environmental Health (ES000002).