Application of copper (I) selective ligands for PET imaging of reactive oxygen species through metabolic trapping.

INTRODUCTION: Reactive oxygen species (ROS) are attractive targets for clinical PET imaging. In this study, we hypothesized that PET imaging of ROS would be possible by using chelating ligands (L) that form stable complexes with copper (I) but not with copper (II), based on metabolic trapping. Namely, when [64Cu][CuI(L)2]+ is oxidized by ROS, the oxidized complex will release [64Cu]Cu2+. Then, the released [64Cu]Cu2+ will be trapped inside the cell, resulting in PET signal depending on the redox potential of ROS. To examine the potential of this novel molecular design for ROS imaging, we synthesized copper (I) complexes with bicinchoninic acid (BCA) disodium salt and bathocuproinedisulfonic acid (BCS) disodium salt and evaluated their reactivity with several kinds of ROS. In addition, the cellular uptake of [64Cu][CuI(BCS)2]3- and the stability of [64Cu][CuI(BCS)2]3- in a biological condition were also evaluated. METHODS: [64Cu]Cu2+ was reduced to [64Cu]Cu+ by ascorbic acid and coordinated with BCA and BCS in the acetate buffer to synthesize [64Cu][CuI(BCA)2]3- and [64Cu][CuI(BCS)2]3-. The radiochemical yields were determined by thin-layer chromatography (TLC). After [64Cu][CuI(BCS)2]3- was incubated with hydroxyl radical, lipid peroxide, superoxide, and hydrogen peroxide, the percentage of released [64Cu]Cu2+ from the parent complex was evaluated by TLC. HT-1080 human fibrosarcoma cells were treated with 0.1 % Dimethyl sulfoxide (control), imidazole ketone erastin (IKE), or IKE + ferrostatin-1 (Fer-1). Then, the uptake of [64Cu][CuI(BCS)2]3- to HT-1080 cells in each group was evaluated as %Dose/mg protein. Lastly, [64Cu][CuI(BCS)2]3- was incubated in human plasma, and its intact ratio was determined by TLC. RESULTS: The radiochemical yield of [64Cu][CuI(BCS)2]3- (86 ± 1 %) was higher than that of [64Cu][CuI(BCA)2]3- (44 ± 3 %). [64Cu][CuI(BCA)2]3- was unstable and partially decomposed on TLC. After [64Cu][CuI(BCS)2]3- was reacted with hydroxyl radical, lipid peroxide, and superoxide, 67 ± 2 %, 44 ± 13 %, and 22 ± 3 % of total radioactivity was detected as [64Cu]Cu2+, respectively. On the other hand, the reaction with hydrogen peroxide did not significantly increase the ratio of [64Cu]Cu2+ (4 ± 1 %). These results suggest that [64Cu][CuI(BCS)2]3- could be used for detecting high-redox-potential ROS such as hydroxyl radical and lipid peroxide with high selectivity. The cellular uptake values of [64Cu][CuI(BCS)2]3- in the control, IKE, and Fer-1 group were 42 ± 2, 54 ± 2, and 47 ± 5 %Dose/mg protein (n = 3), respectively, suggesting the ROS specific uptake of [64Cu][CuI(BCS)2]3-. On the other hand, the intact ratio after the incubation of [64Cu][CuI(BCS)2]3- in human plasma was 9 ± 5 %. CONCLUSION: PET imaging of ROS would be possible by using a copper (I) selective ligand, based on metabolic trapping. Although improvement of the membrane permeability and the stability of copper (I) complexes is required, the present results pave the way for the development of novel 64Cu-labeled complexes for PET imaging of ROS.

Feasibility study of multimodal imaging for redox status and glucose metabolism in tumor.

Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.

Asymptomatic Enteric Virus Infections and Association with the Gut Microbiome in Rural Residents of Northern Laos.

Viral gastrointestinal infections are an important public health concern, and the occurrence of asymptomatic enteric virus infections makes it difficult to prevent and control their spread. This study aimed to determine the prevalence of and factors associated with asymptomatic enteric virus infection in adults in northern Laos. Fecal samples were collected from apparently healthy participants who did not report diarrhea or high fever at the time of the survey in northern Laos, and enteric viruses were detected using polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. Individual characteristics, including the gut microbiome, were compared between asymptomatic carriers and noncarriers of each enteric virus. Of the participants (N = 255), 12 (4.7%) were positive for norovirus genogroup I (GI), 8 (3.1%) for human adenovirus, and 1 (0.4%) for norovirus GII; prevalence tended to be higher in less-modernized villages. Gut microbial diversity (evaluated by the number of operational taxonomic units) was higher in asymptomatic carriers of norovirus GI or human adenovirus than in their noncarriers. Gut microbiome compositions differed significantly between asymptomatic carriers and noncarriers of norovirus GI or human adenovirus (permutational analysis of variance, P <0.05). These findings imply an association between asymptomatic enteric virus infection and modernization and/or the gut microbiome in northern Laos.

Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 µg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.

Ruthenium Pyrazole Complexes: A Family of Highly Active Metallodrugs for Photoactivated Chemotherapy.

Ruthenium complexes bearing bis pyrazole (pzH) ligands, cis-[Ru(bpy)2(R-pzH)2]2+ (bpy = 2,2'-bipyridine, R = -H, -Cl), were examined as photoactivated anticancer prodrugs. A dicationic pyrazole complex deprotonated to give monocationic pyrazole-pyrazolate complexes, cis-[Ru(bpy)2(R-pz-)(R-pzH)]+, in an aqueous solution with pKa values of 9.5 and 7.2 for R = H and R = Cl, respectively. Upon deprotonation, relative quantum yields of photosubstitution decreased while lipophilicity of the complexes increased according to the measurements of water-octanol coefficients. The ruthenium complex with 4-chloropyrazole ligands displayed high cytotoxicity upon light irradiation (IC50 = 0.060 ± 0.016 µM) toward lung cancer cells, which was 7 times higher than that in the dark (IC50 = 0.44 ± 0.07 µM). Additional experiments for the ruthenium R-pyrazole complexes indicated that (1) selective photodissociation of the 4-chloropyrazole ligand occurs from cis-[Ru(bpy)2(4-Clpz-)(4-ClpzH)]+, (2) photoinduced ligand dissociation is dominant rather than photoinduced generation of singlet oxygen (1O2), and (3) induction of cell death occurs via the intrinsic pathway of apoptosis.

Transition to a market economy and chronic psychosocial stress in northern Laos: An exploratory study of urinary free cortisol in rural residents.

OBJECTIVES: The indigenous population in northern Laos has experienced a transition from self-sufficiency to a market-oriented economy, which may have brought about unprecedented chronic psychosocial stress. This study examined the association between the transition to a market economy and urinary free cortisol (UFC) concentration as a stress biomarker among rural residents of three villages with different degrees of integration into the market economy. METHODS: An interview survey and urine sample collection were conducted in August 2018 and March 2019. We measured the UFC concentration in spot urine samples collected in the morning from participants aged 20-60 years (n = 168) using an enzyme-linked immunosorbent assay. Multiple linear regression analysis was performed to examine differences in UFC concentrations among villages by sex, with time of arrival for the survey, age, and body mass index included as covariates. RESULTS: The UFC concentration was higher in men living in the village with the highest degree of integration into the market economy than in those in the two villages with a lower dependence on cash, possibly linking increased stress levels with a change in employment type. This trend was not observed in women. CONCLUSION: Socioeconomic changes incidental to a transition to a market economy may increase the stress levels of men in northern Laos.

Association between Sperm Mitochondrial DNA Copy Number and Concentrations of Urinary Cadmium and Selenium.

Elevated sperm mitochondrial DNA copy number (mtDNAcn) is associated with damage to sperm and poorer measures of semen quality. Exposure to cadmium (Cd) can increase oxidative stress and damage sperm mitochondria. The adverse effects of Cd can potentially be reduced by sufficient selenium (Se). The objective of this study was to examine the associations between sperm mtDNAcn and urinary concentrations of Cd and Se, as well as the Cd/Se molar ratio. Participants were recruited from patients who sought infertility treatment at two hospitals in Japan. Urine and semen specimens and self-administered questionnaires were collected on the day of recruitment. Sperm mtDNAcn was measured in extracted sperm DNA by multiplex real-time qPCR. Urinary Cd and Se concentrations were measured using inductively coupled plasma mass spectrometry, and their molar weights were calculated to obtain the Cd/Se molar ratio. Linear regression was used to estimate associations after adjusting for age, body mass index, smoking, drinking, exercise, varicocele, and hospital of recruitment. Sperm mtDNAcn showed statistically insignificant associations with creatinine-adjusted concentrations of urinary Cd (ß = 0.13, 95% CI -0.18, 0.44) and Se (ß = -0.09, 95% CI -0.54, 0.35), and Cd/Se molar ratio (ß = 0.12, 95% CI -0.13, 0.37). The current study found no evidence of an association between mtDNAcn and urinary concentrations of Cd or Se, or the Cd/Se molar ratio.

Efficacy of tolvaptan in an infant with syndrome of inappropriate antidiuretic hormone secretion associated with holoprosencephaly: A case report.

BACKGROUND: Holoprosencephaly (HPE) is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain. Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported, HPE with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare. Tolvaptan, a vasopressin V2 receptor antagonist, is effective in adults with SIADH. However, there is no report of its efficacy in infants with SIADH. The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration. CASE SUMMARY: A 2414-g female infant was born at 38 wk by normal vaginal delivery. Facial anomalies and head magnetic resonance imaging indicated semilobar HPE. After birth, she had hyponatremia due to SIADH and was treated using water and sodium restriction. However, she developed an exaggerated response to the fluid restrictions, resulting in large fluctuations in serum sodium levels. Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration. Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life. There were no side effects, such as hypernatremia or liver dysfunction, during the administration of tolvaptan. CONCLUSION: This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

Utility of an endoscopic image processing system for framing laparoscopic images using surgeon's gaze point and voice commands during laparoscopic percutaneous extraperitoneal closure of inguinal hernia in children.

Introduction: In laparoscopic surgery, it is the assistant who manipulates the laparoscope and manages the field of view. Aim: To develop an endoscopic image processing system that can adjust laparoscopic images as intended by the surgeon without interrupting the surgical procedure. Material and methods: We developed a touchless user interface that displays a magnified image of the endoscope using information of the surgeon's gaze point acquired by an eye-tracking device and the surgeon's voice commands, and evaluated its usefulness during laparoscopic percutaneous extraperitoneal closure (LPEC) of pediatric inguinal hernia. Results: LPEC was performed in 15 clinical cases of pediatric inguinal hernia using this system. In all cases, the internal inguinal ring could be ligated by digitally zooming and moving the endoscopic image by eye tracking and voice command while the scope was fixed. Conclusions: This new touchless user interface with eye tracking shows promise as a support system for laparoscopic surgery.

Peripherally inserted central catheters can be an alternative to tunneled central venous catheters in chemotherapy for hematological and oncological pediatric patients.

PURPOSE: Tunneled central venous catheters (TCVs) are commonly used for pediatric chemotherapy. Recently, peripherally inserted central catheters (PICCs) have been used instead. Although PICC has the advantages of simpler insertion and fewer severe complications, there is little information on the efficacy of PICC compared to TCV in pediatric chemotherapy. METHODS: Patients, aged younger than 18 years, with primary malignancy who received chemotherapy with PICC or TCV at our institution from December 2007 to August 2022 were included in the study. We retrospectively compared PICC and TCV using medical records. RESULTS: Within the observation period, 133 catheters (73 PICCs and 60 TCVs) were inserted. The median indwelling time was 99 days for PICCs and 182 days for TCVs, with TCVs being significantly longer (p < 0.001). There were no significant differences in the incidence of complications, such as infections, thrombosis, obstruction, or mechanical accidents. Comparing patients treated with PICC (PICC group) versus those with TCV (TCV group), the time from diagnosis to insertion was significantly shorter in the PICC group (p < 0.001). In the PICC group, none of the patients required general anesthesia, and chemotherapy was completed with PICC only. CONCLUSION: PICC can be an alternative to TCV in pediatric chemotherapy.

[New Methods of Evaluating Health Effects of Combined Exposures to Chemicals and Their Problems to Be Solved].

There are several basic prerequisites for the risk assessment of combined exposures to pesticides and dioxins using human health effects as the endpoint. First, all the target chemical substances exert the same toxicity to humans through the same mechanisms. Second, there is a linear dose-response relationship between the toxicity and effects of individual chemicals. With these two prerequisites, the effects of combined exposures are estimated as the sum of the toxicities of individual chemicals. For example, the toxicities of dioxins are calculated using their toxic equivalent quantities (TEQ) by considering the assigned toxic equivalent factor (TEF) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) set individually from their isomers and homologs. In conventional epidemiological studies, when the impact of each of multiple chemical substances is examined, methods such as multiple regression analysis or using a generalized linear model (GLM) have been used on the basis of the same prerequisites. However, in practice, some of the chemicals exhibit collinearity in their effects or do not show a linear dose-response relationship. In recent years, there have been several methods developed in the field of machine learning being applied to epidemiological research. Typical examples were methods using Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS), and the shrinkage method, i.e., using the least absolute shrinkage and selection operator (Lasso) and elastic network model (ENM). In the future, while taking into account the findings of experimental studies in biology, epidemiology, and other fields, it is expected that various methods will be applied and selected.

Impact of modernization on oxidative stress among indigenous populations in northern Laos.

OBJECTIVES: To explore the impact of modernization on oxidative stress during a momentous health transition process, we investigated differences in oxidative stress among the indigenous populations of villages in northern Laos with different levels of modernization. METHODS: We conducted a cross-sectional study of 380 adults in three villages with different levels of modernization. Three biomarkers related to oxidative stress were measured: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations (both measured by liquid chromatography-tandem mass spectrometry), and blood telomere length (measured with qPCR). We examined associations between village-level modernization and oxidative stress-related biomarkers in a multilevel analysis including a random effect and covariates. RESULTS: The geometric means of urinary 8-OHdG and 8-isoprostane concentrations were 2.92 and 0.700 µg/g creatinine, respectively, in our study population. Higher urinary 8-OHdG concentrations and shorter telomeres were observed in participants from the more modernized villages, whereas urinary 8-isoprostane concentrations did not differ significantly among villages. CONCLUSIONS: Our findings imply that modernization-induced changes in lifestyle may increase oxidative DNA damage. Baseline levels of oxidative lipid damage are expected to be high in the indigenous populations of northern Laos. Assessments of oxidative stress may provide valuable insights into the mechanisms of health transition in specific populations.

Determinants of oxidative stress among indigenous populations in Northern Laos: Trace element exposures and dietary patterns.

OBJECTIVES: To investigate determinants of oxidative stress in an indigenous population, we examined associations of trace element exposures and dietary patterns with three oxidative stress-related biomarkers among indigenous populations in Northern Laos. METHODS: This cross-sectional study included 341 adults from three villages with different levels of modernization. We used three oxidative stress-related biomarkers: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations, which were measured using liquid chromatography-tandem mass spectrometry, and blood telomere lengths, which were measured using a quantitative polymerase chain reaction method. We used multilevel analysis to examine associations of urinary arsenic, cadmium, and selenium concentrations, their interaction terms, and wild-plant-food scores (principal component scores calculated from food consumption frequencies) with oxidative stress-related biomarkers. RESULTS: Urinary arsenic and cadmium concentrations were positively associated with urinary 8-isoprostane concentrations. Urinary selenium concentrations were positively associated with urinary 8-OHdG concentrations. Interaction terms ([arsenic or cadmium] × selenium) showed negative associations with urinary 8-OHdG and 8-isoprostane concentrations, respectively. Urinary cadmium concentrations were negatively associated with telomere lengths. Wild-plant-food scores did not exhibit associations with oxidative stress-related biomarkers. CONCLUSION: Our findings imply that exposure to arsenic and cadmium is associated with greater oxidative lipid damage, whereas selenium may attenuate arsenic-induced oxidative DNA damage and cadmium-induced oxidative lipid damage. Cadmium exposure may accelerate telomere attrition. Trace element exposure may be a determinant of oxidative stress among indigenous populations in Northern Laos.

Stop posterior wall puncture of the arteriovenous graft (AVG). New findings of cannulation techniques from a prospective observational study with an AVG model and plastic cannula for dialysis.

BACKGROUND: Posterior wall puncture of the AVG causes serious vascular access complications, but there is no concrete technical recommendation for AVG cannulation with plastic cannula. The purpose of this study is to identify cannulation techniques to reduce posterior wall puncture of the AVG using plastic cannula. METHODS: Sixty-three hemodialysis nurses' cannulations on experimental models were recorded and included in this study. Cannulations were conducted on AVG and AVF models with a plastic cannulation needle. We analyzed the angle of the needle, the motion of the needle, and the location of the needle in the graft lumen. RESULTS: The occurrence of posterior wall puncture of the AVG model was 22.2%. The cannulation angles in the AVG model were greater than those in the AVF model (p < 0.05). In the posterior wall puncture group of the AVG model, after the tip of the needle had reached into the graft lumen, the angle of the needle was not flattened (p < 0.05) and the outer sleeve of the needle was not inserted into the graft (p < 0.05). Furthermore, posterior wall puncture of the AVG model were observed in the group with less than 5 years of dialysis nursing experience (p < 0.05). CONCLUSIONS: From this study, after the tip of the needle had reached into the graft lumen, flattening the angle of the needle and inserting the outer sleeve of the needle into the graft were suggested as specific cannulation techniques to reduce posterior wall puncture of the AVG. Furthermore, this study also suggests the importance of cannulation technique education for new dialysis nurses to reduce cannulation-caused complications.

Treatment Strategy for Currarino Syndrome Complicated With Anorectal Stenosis.

PURPOSE: The present study aimed to review the treatment experience and outcomes of Currarino syndrome (CS) complicated with anorectal stenosis to evaluate the current treatment strategies. METHODS: Seven cases of CS complicated with anorectal stenosis, treated at our hospital between 1998 and 2021, were retrospectively investigated. This is a case series article from a single institution. RESULTS: In six and three cases and one case, the presacral mass was a mature teratoma, meningocele, and lipoma, respectively. Resection of the lesion was performed in all six cases of mature teratoma, and duraplasty was performed before resection in all three cases of meningocele. Moreover, surgery for anorectal stenosis was performed simultaneously in four patients. Surgery was performed for six cases of anorectal stenosis, with the remaining case relieved by dilation using a metal bougie. The surgical methods used were a partial resection with end-to-end anastomosis, anorectal strictureplasty, pull-through, posterior sagittal anorectoplasty, and cutback after mass resection. Pathological analysis of the anorectal stenoses revealed disorganized and rough smooth muscle fibers and the replacement of the stroma by an increased quantity of collagen fibers. CONCLUSIONS: The clinical outcomes of CS can be improved by establishing a treatment flow chart and understanding the complicated pathophysiology of the disease.

Case report: HLA-haploidentical hematopoietic cell transplant with posttransplant cyclophosphamide in a patient with leukocyte adhesion deficiency type I.

Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive inborn error of immunity (IEI) caused by the defects in CD18, encoded by the ITGB2 gene. LAD-I is characterized by defective leukocyte adhesion to the vascular endothelium and impaired migration of leukocytes. Allogeneic hematopoietic cell transplant (HCT) is the only curative treatment for LAD-I. In an absence of ideal donor for HCT, human leukocyte antigen (HLA)-haploidentical HCT is performed. Posttransplant cyclophosphamide (PT-CY) is a relatively new graft-versus-host disease (GVHD) prophylactic measure and has been increasingly used in HLA-haploidentical HCT for malignant and nonmalignant diseases. However, experience in using PT-CY for rare IEIs, such as LAD-I, is very limited. We report a case of LAD-I successfully treated with HLA-haploidentical HCT with PT-CY. Complete chimerism was achieved, and the patient was cured. Her transplant course was complicated by mild GVHD, cytomegalovirus reactivation and veno-occlusive disease/sinusoidal obstruction syndrome, which were successfully treated. HLA-haploidentical HCT with PT-CY is a safe and effective option for patients with LAD-I when HLA-matched donors are unavailable.

Pre-Conceptional Anti-Thyroid Antibodies and Thyroid Function in Association with Natural Conception Rates.

Thyroid functioning is an integral part of the endocrine system that supports conception and pregnancy. Frequent consumption of seafood and iodine by Japanese people may adversely affect their thyroid function. Thus, in this study, we aimed to analyze the associations between iodine intake, thyroid hormones, autoimmunity, and natural conception rates in Japanese women trying to conceive their first child. A prospective study of 24 weeks targeted 80 women with no history of infertility, who did not plan to undergo fertility treatment. Concentrations of urinary iodine concentration and thyroid biomarkers in the serum at enrollment were measured. Thirty-five women naturally conceived during the follow-up. The median (inter-quartile range) urinary concentration of iodine was 297 (165, 500) µg/L. Free triiodothyronine (T3) and free thyroxin (T4) negatively correlated with urinary iodine concentrations. Women with anti-thyroid peroxidase (anti-TPO) ≥ 16 IU/mL had lower conception rates (hazard ratio: 0.28, 95% confidence interval, 0.08-0.92) compared with those with anti-TPO < 16 IU/mL, after adjusting for age and coital frequency. None of anti-thyroglobulin antibody, free T3, free T4, or thyroid-stimulating hormone showed significant associations with conception rate after adjusting for age and coital frequency. The negative association between thyroid autoimmunity and natural conception rates warrants further investigation.

Hyperglycemia and Lactic Acidosis Associated with Linezolid Therapy in an Extremely Premature Infant.

The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.

Intracerebral Transplantation of Mesenchymal Stromal Cell Compounded with Recombinant Peptide Scaffold against Chronic Intracerebral Hemorrhage Model.

Background: Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model. Methods: Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action. Results: rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization. Conclusion: Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.

Posterior pharyngeal wall augmentation using autologous tiered costal cartilage for velopharyngeal insufficiency.

The aim of this study was to retrospectively estimate intervention outcomes and to establish suitable indications for autogenous tiered cartilage augmentation (ATCA) of the posterior pharyngeal wall for velopharyngeal insufficiency (VPI). The sample cohort comprised 17 consecutive patients with VPI (10 boys, 7 girls), excluding syndromic cases. Pre- and postoperative findings were comprehensively evaluated using a combination of speech assessment and lateral pharyngography (LPG). Hypernasality and consonant distortion were scored (normal: 0; mild: 1; moderate: 2; severe: 3). Velopharyngeal gap size at rest (AC) and at maximum closure (BC) were measured on LPG. All patients displayed improvements in velopharyngeal function and speech score, and no patients required re-operation. Pre- and postoperative hypernasality scores were 1.9 ± 0.5 and 0.6 ± 0.5, respectively (P < .001). Pre- and postoperative consonant distortion scores were 1.9 ± 0.6 and 0.6 ± 0.5, respectively (P < .001). Pre- and postoperative AC distances were 8.2 ± 3.4 mm and 5.9 ± 2.6 mm, respectively (P < .001). Pre- and postoperative BC distances were 3.9 ± 2.4 mm and 0.3 ± 0.8 mm, respectively (P < .001). Conclusions: ATCA appears effective for surgical treatment of VPI patients with a gap less than 10 mm.