Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia

IntroductionL-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN.MethodsThe study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias.ResultsThe analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17–1.62) or the complete response rate (OR 0.86; 95% CI = 0.29–2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36–2.78 and OR 1.24; 95% CI, 0.50–3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups.ConclusionThere is no clear rationale for avoiding Asp-TPN in ASNase-treated patients

Coupling characteristics of surface modes in truncated two-dimensional photonic crystals

On 1 February, 1994 the Republic of Austria concluded the Accession Treaty and on 1 January, 1995 became a full member of the European Union. Membership obliged Austrians to ‘provide’ the Community with appropriate personnel to take up different posts in various EU authorities, as well as in the European Parliament. The most important issue was to alter particular statutory regulations and the Austrian Constitution to adjust to the new situation.The paper aims at presenting the Austrian solutions in this matter in the context of European Union law, with particular emphasis on regulations which are uncommon or specific to the Republic of Austria. The matter of interest is the constitutional practice of EU member states and the reader’s perspective is taken into account. The latter approach not only evaluates the Austrian solutions in the context of the electoral law to the European Parliament contained in the Election Code, but could also suggest some ideas in regard to prospective amendments. The authors would, in particular, like to pay attention to two issues: the lowering of the voting age, and the single constituency electoral system. The Austrian solutions might be valuable to refer to in the countries where a system of correspondence voting is just being introduced. These resolutions are particularly interesting taking into consideration prospective, possible amendments to the electoral laws of the EU member states.Republika Austrii, 1 lutego 1994 r. podpisała traktat akcesyjny i z dniem 1 stycznia 1995 r. stała się pełnoprawnym członkiem Unii Europejskiej. Członkostwo zobowiązało Austriaków do “dostarczenia” Wspólnocie odpowiednich osób do objęcia różnych stanowisk w różnych unijnych organach. Nie inaczej było także w przypadku Parlamentu Europejskiego. Ważnym aspektem stało się dostosowanie poszczególnych norm ustawowych i własnej konstytucji do nowych rozwiązań. Celem niniejszego opracowania jest właśnie przedstawianie austriackich rozwiązań w tym temacie na tle rozwiązań europejskich, ze szczególnym uwzględnieniem unormowań rzadko spotykanych lub wręcz odrębności sytemu Republiki Austrii. Rzecz wydaje się być interesująca zarówno z punktu widzenia praktyki ustrojowej państw członkowskich Unii Europejskiej, jak i z punktu widzenia czytelnika. To drugie podejście pozwoli na ocenę austriackich rozwiązań na tle niedawno wprowadzonej ordynacji wyborczej do PE zawartej w Kodeksie Wyborczym, ale również może podsunąć pewne pomysły, co do przyszłych nowelizacji. Autorzy zwrócili szczególną uwagę na dwa rozwiązania: obniżenie cenzusu wieku czynnego prawa wyborczego oraz jednookręgowy system wyborczy. Austriackie doświadczenia mogą być również pomocne państwom, które wprowadzają możliwość głosowania korespondencyjnego. Są to propozycje szczególnie interesujące z punktu widzenia przyszłych, możliwych nowelizacji systemów wyborczych państw członkowskich

Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial.

Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy

Patterns of Using Complementary and Alternative Medicine by Stroke Patients at Two University Hospitals in Korea

This study measured the prevalence of complementary and alternative medicine (CAM) use among Korean stroke patients. Questionnaire-based 20-min interviews were conducted at the hospitals by a trained nurse after an outpatient visit. It included questions on demographic information, clinical information and the utilization of CAM. Of 304 stroke-patient respondents, 164 (54%) had used CAM, of which 66% had started taking CAM products following suggestions from family members and other relatives. Of the 57% of users who felt that CAM was effective, 84% considered that it improved the symptoms of stroke and 16% felt it was effective in achieving psychological relaxation. Of the eight CAM categories used by respondents, 92% used traditional Oriental medical treatments, 36% used plant- and animal-derived over-the-counter health care products, 24% used minerals and vitamins, and 11% used manual therapies. The majority of stroke patients (68%) were trying a new type of CAM, and half of the respondents (45%) relied on the knowledge of their general practitioner about CAMs when deciding whether to use them. Most of the stroke patients in this study used CAM, and a half of them reported beneficial effects. Despite the presence of adverse side effects, they tended to be used without discussion with chief physicians, and hence physicians should be actively involved in the usage of CAM

Kdm3b haploinsufficiency impairs the consolidation of cerebellum-dependent motor memory in mice

Histone modifications are a key mechanism underlying the epigenetic regulation of gene expression, which is critically involved in the consolidation of multiple forms of memory. However, the roles of histone modifications in cerebellum-dependent motor learning and memory are not well understood. To test whether changes in histone methylation are involved in cerebellar learning, we used heterozygous Kdm3b knockout (Kdm3b+/−) mice, which show reduced lysine 9 on histone 3 (H3K9) demethylase activity. H3K9 di-methylation is significantly increased selectively in the granule cell layer of the cerebellum of Kdm3b+/− mice. In the cerebellum-dependent optokinetic response (OKR) learning, Kdm3b+/− mice show deficits in memory consolidation, whereas they are normal in basal oculomotor performance and OKR acquisition. In addition, RNA-seq analyses revealed that the expression levels of several plasticity-related genes were altered in the mutant cerebellum. Our study suggests that active regulation of histone methylation is critical for the consolidation of cerebellar motor memory.This work was supported by grants to S.B.S. and Y.-S.L. (NRF2019R1A4A2001609), Y.-S.L. (NRF-2017M3C7A1026959), and S.J.K. (NRF2018R1A5A2025964) from the National Research Foundation of Korea

The effect of probiotic supplementation on systemic inflammation in dialysis patients

Background Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients. Methods Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation. Results Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/mm2 vs. 194/mm2, p < 0.05). Conclusion Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients

Body mass index affecting ticagrelor monotherapy vs. ticagrelor with aspirin in patients with acute coronary syndrome: A pre-specified sub-analysis of the TICO randomized trial

BackgroundAlthough ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) results in a significantly greater net clinical benefit over that with ticagrelor-based 12-month DAPT in patients with acute coronary syndrome (ACS), it remains uncertain whether this effect is dependent on body mass index (BMI). We aimed to evaluate the BMI-dependent effect of these treatment strategies on clinical outcomes.MethodsThis was a pre-specified subgroup analysis from the TICO trial (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome), evaluating the interaction between BMI and treatment strategies for the primary outcome [composite of major bleeding and adverse cardiac and cerebrovascular events (MACCE): death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization]. The secondary outcomes were major bleeding and MACCE.ResultsBased on a pre-specified BMI threshold of 25 kg/m2, 3,056 patients were stratified. Patients with BMI &lt;25 kg/m2 had a higher risk of primary and secondary outcomes than those with BMI ≥25 kg/m2. Regardless of the BMI subgroup, the effects of ticagrelor monotherapy after 3-month DAPT on the primary outcome (pint = 0.61), major bleeding (pint = 0.76), and MACCE (pint = 0.80) were consistent without significant interaction compared with ticagrelor-based 12-month DAPT. The treatment effects according to the BMI quartiles and age, sex, and diabetic status were also consistent without significant interaction.ConclusionThe BMI-dependent impact of ticagrelor monotherapy after 3-month DAPT compared with 12-month DAPT on clinical outcomes was not heterogeneous in patients with ACS.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02494895]

Wild and Hatchery Populations of Korean Starry Flounder (Platichthys stellatus) Compared Using Microsatellite DNA Markers

Starry flounder (Platichthys stellatus) is an important sport and food fish found around the margins of the North Pacific. Aquaculture production of this species in Korea has increased because of its commercial value. Microsatellite DNA markers are a useful DNA-based tool for monitoring the genetic variation of starry flounder populations. In this study, 12 polymorphic microsatellite DNA markers were identified from a partial genomic starry flounder DNA library enriched in CA repeats, and used to compare allelic variation between wild and hatchery starry flounder populations in Korea. All loci were readily amplified and demonstrated high allelic diversity, with the number of alleles ranging from 6 to 18 in the wild population and from 2 to 12 in the farmed population. A total of 136 alleles were detected at the 12 microsatellite loci in the two populations. The mean observed and expected heterozygosities were 0.62 and 0.68, respectively, in the hatchery samples and 0.67 and 0.75, respectively, in the wild samples. These results indicate lower genetic variability in the hatchery population as compared to the wild population. Significant shifts in allelic frequencies were detected at eight loci, which resulted in a small but significant genetic differences between the wild and hatchery populations (FST = 0.043, P < 0.05). Further studies with additional starry flounder sample collections are needed for comprehensive determinations of the genetic varieties between the wild and hatchery populations. These microsatellite loci may be valuable for future population genetic studies, monitoring the genetic variation for successful aquaculture management and the preservation of aquatic biodiversity

Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect

Background A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury