Acute Kidney Injury (AKI)

Acute kidney injury (AKI) is a serious public health issue, with an increasing incidence and significant associated deleterious effects. Several studies have reported the consequences of AKI, including prolonged hospital stay, increased healthcare costs, morbidity, and mortality. Many factors are known to affect AKI development. Kidney is exposed to a larger proportion and a higher concentration of drugs and toxins than other organs through the secretion of ionic drugs by tubular organic ion transporters across the luminal membranes of renal tubular epithelial cells and through reabsorption of filtered toxins into the lumen of the tubule; these cells are at a greater risk for injury. This section gives an overview of AKI including the definition, causes, and prognosis

Effect of triclocarban on membrane potential of rat thymocytes : Assessment with bis-(1,3-dibutylbarbituric acid)trimethine oxonol

The effect of triclocarban (TCC), an　environmental pollutant from household items and health care products, on membrane potential of rat thymocytes was examined by a flow cytometry with a fluorescent probe sensitive to membrane potential, bis-(1,3-dibutylbarbituric acid)trimethine oxonol, because TCC changes intracellular ionic circumstance that may affect the membrane potential. TCC at 0.3 μM or more (up to 3 μM) depolarized the membranes. This TCC-induced phenomenon was against our prediction because TCC increases intracellular Ca2+ concentration that activates Ca2+-dependent K+ channels, resulting in a hyperpolarization. The depolarization was still observed under Ca2+-free condition, but not under Na+-free condition. Furthermore, TCC hyperpolarized the membranes under Ca2+- and Na+-free condition. To see if TCC inhibits Ca2+-dependent hyperpolarization, the effect of A23187, a calcium ionophore, on the membrane potential was examined in the cells treated with TCC. A23187 induced large depolarization in the cells treated with 0.3–3 μM TCC. The A23187-induced depolarization in the presence of TCC was greatly attenuated under Na+-free or Ca2+-free condition whereas A23187 elicited hyperpolarization in the cells treated with 0.3–3 μM TCC under Ca2+- and Na+-free condition. Results suggest that 0.3–3 μM TCC increases membrane permeability of Na+ and Ca2+, resulting in the depolarization. Large depolarization induced by TCC in the presence of external Ca2+ and Na+ may mask the hyperpolarization elicited via the increase in intracellular Ca2+ concentration by TCC. Thus, there is a possibility that TCC depolarizes membranes of lymphocytes, resulting in alteration of cellular functions of lymphocytes

Correlation between length of stay in acute stroke wards and the functional prognosis after comprehensive rehabilitation

　脳卒中発症後の機能予後改善には回復期リハビリテーションが有効である．急性期病棟から回復期リハビリテーション病棟に早期に移ることが，機能予後改善につながる可能性がある．本研究では，急性期病棟の在院期間と長期予後改善効果の関連性を検討することを目的とした．2018年１月1日から2018年12月31日までに川崎医科大学附属病院脳卒中科に入院した急性期脳卒中症例のうち，回復期リハビリテーション病棟に転棟・転院した症例を対象とした．脳卒中科退院時に比し，一年後に modified Rankin scale が１以上改善した症例を改善有と定義した．改善有と関連する患者背景因子，入院中の診療データについて検討を行った．関連性はカイ二乗検定を用いて評価し，有意な関連性を示した因子についてはロジスティック回帰分析を用いて解析した．対象期間に入院した急性期脳卒中408例中，回復期リハビリテーション病棟に転棟・転院したのは142例であった（男性90人，中央値76.0歳）．改善有は57例であり，在院期間の第一四分位である17日未満で回復期病棟に移った群で改善有が有意に多かった（P < 0.01）．ロジスティック回帰分析でも急性期病棟の在院期間が短い（17日未満）ことが改善有と独立して関連した．急性期脳卒中患者の急性期病棟在院期間を短縮することが機能予後改善につながることが示唆された．　Neurological symptoms and functional disability of stroke survivors can be improved through comprehensive rehabilitation in the post-acute phase. Early transfer from the stroke unit to the rehabilitation ward possibly leads to an improvement of functional prognosis. The purpose of this study was to investigate the relationship between the length of stay in the stroke unit and the long-term prognosis improvement. The study involved acute stroke patients admitted to the Department of Stroke, Kawasaki Medical School Hospital between January 1, 2018 and December 31, 2018. Specifically, those selected and included in the study were patients eventually transferred to a rehabilitation department or hospital. Improvement of functional prognosis was defined as a 1-point decrease on the modified Rankin scale at 1 year compared with that at the time of discharge from the stroke department. Factors associated with the improvement group were evaluated using the chi-square test and then logistic regression analysis. Of the 408 patients with acute stroke admitted during the study period, 142 were transferred to rehabilitation centers (90 men, median age: 76.0 years). Fifty-seven patients had improvement. The rate of improvement was significantly higher in the group transferred to the rehabilitation ward by day 17, the first quartile of time in the stroke unit (p < 0.01). Logistic regression analysis also showed that a shorter length of stay (< 17 days) in the stroke unit was independently associated with improvement. The results suggest that early initiation of comprehensive rehabilitation in the post-acute phase leads to improved functional outcomes of patients with acute stroke

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron

Stereocomplex Poly(lactic acid) Alloys with Superb Heat Resistance and Toughness

Biobased, biocompatible, and biodegradable poly­(lactic acid), PLA, possesses unique properties that give it high potential for a wide range of applications. However, its low thermal stability and brittleness are major obstacles for its use. In this study, both the thermal stability and toughness of PLA were simultaneously improved via stereocomplexation and reactive blending, by generating alloys composed of two PLA enantiomers, PLLA and PDLA, together with poly­(ethylene-<i>ran</i>-methylacrylate–<i>ran</i>-glycidyl methacrylate), EMA-GMA. It was found that reactive blending at 200 °C was very effective in generating alloys with high degrees of stereocomplex (sc) crystallinity and that the interfacial reaction between PLA and EMA-GMA contributed to a significant improvement in toughness. Most importantly, a (40/40/20)­PLLA/PDLA/EMA-GMA film with high sc crystallinity exhibited both much higher tensile impact strength and thermal stability than neat PLLA, retaining high storage modulus up to 210 °C. The scPLA alloys also exhibited superior chemical resistance to neat PLA. Thus, it was demonstrated that simultaneous complexation and the interfacial reaction transform PLA to the level of high performance materials

Effect of Pre-Surgical Orthopedic Treatment on Hard and Soft Tissue Morphology in Infants with Cleft Lip and Palate

The frequency of cleft lip and palate births in Japan is approximately 0.146%. The study aimed to compare the effects of NAM on restoring nasal morphology and improving extraoral nasal morphology in children with cleft lip and palate in the first stage of treatment using 3D imaging and oral model analysis. The subjects were five infants (37.6 ± 14.4 days old) with unilateral cleft lip and palate. The images taken with the 3D analyzer and oral model used for constructing the NAM at the first examination (baseline) and at the completion of the pre-surgical orthodontic treatment (157.8 ± 37.8 days old) were analyzed. The cleft distance was measured at the upper, middle, and lower points on the 3D images. On the model, the cleft jaw width at the maximum protrusion of the healthy and affected sides of the alveolar bone was measured. After the pre-surgical orthopedic treatment, the measured value on the model decreased significantly by a mean of 8.3 mm from baseline, and the cleft lip width narrowed by an average of 2.8 ± 2.2, 4.3 ± 2.3, and 3.0 ± 2.8 mm at the upper, middle, and lower points of the cleft, respectively. Pre-surgical orthopedic treatment using NAM can help narrow the width of the cleft jaw and lip. The sample size is stated at the study limit in the paper

Novel variants in outer protein surface of flavin-containing monooxygenase 3 found in an Argentinian case with impaired capacity for trimethylamine N-oxygenation

Flavin-containing monooxygenase 3 (FMO3) is a polymorphic drug metabolizing enzyme associated with the genetic disorder trimethylaminuria. We phenotyped a white Argentinian 11-year-old girl by medical sensory evaluation. After pedigree analysis with her brother and parents, this proband showed to harbor a new allele p.(P73L; E158K; E308G) FMO3 in trans configuration with the second new one p.(F140S) FMO3. Recombinant FMO3 proteins of the wild-type and the novel two variants underwent kinetic analyses of their trimethylamine N-oxygenation activities. P73L; E158K; E308G and F140S FMO3 proteins exhibited moderately and severely decreased trimethylamine N-oxygenation capacities (∼50% and ∼10% of wild-type FMO3, respectively). Amino acids P73 and F140 were located on the outer surface region in a crystallographic structure recently reported of a FMO3 analog. Changes in these positions would indirectly impact on key FAD-binding residues. This is the first report and characterization of a patient of fish odor syndrome caused by genetic aberrations leading to impaired FMO3-dependent N-oxygenation of trimethylamine found in the Argentinian population. We found novel structural determinants of FAD-binding domains, expanding the list of known disease-causing mutations of FMO3. Our results suggest that individuals homozygous for any of these new variants would develop a severe form of this disorder.Fil: Dionisio, Leonardo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Shimizu, Makiko. Showa Pharmaceutical University; JapónFil: Stupniki, Sofia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Oyama, Saki. Showa Pharmaceutical University; JapónFil: Aztiria, Eugenio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Alda, Maximiliano. Instituto de Diagnóstico Infantil; ArgentinaFil: Yamazaki, Hiroshi. Showa Pharmaceutical University; JapónFil: Spitzmaul, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Cluster analysis of patients with cough, mainly cough variant asthma, showing a good response to asthma therapy

Introduction: Cough variant asthma (CVA) and asthma account for a large proportion of patients with chronic cough. We used hierarchical cluster analysis (HCA) to characterize the phenotypes of patients with cough, mainly those with CVA, who showed a rapid response to asthma therapy, and sought to identify simple diagnostic markers. Methods: Patients who initially presented with cough as the main symptom were retrospectively enrolled. Those who were clinically diagnosed with asthma/CVA were selected and analyzed. HCA was performed and the patients were classified by phenotype. Results: HCA identified the five following phenotypes among the 221 participants: highly eosinophilic bronchitis [high fractional exhaled nitric oxide (FeNO) , n = 28]; atopic [high total serum IgE , n = 23]; non-atopic and non-eosinophilic [n = 104]; distal airway narrowing [low FEF75 (V ₂₅), n = 21] and severely atopic [extremely high total serum IgE and/or extreme high FeNO, n = 45]. No significant differences in long-term prognosis were found among the phenotypes. Discussion: Five phenotypes were identified among patients with cough who showed a rapid response to asthma treatment. Wheezing was observed in about 24% of patients, and abnormal FeNO or V₂₅ levels in about 30%