Controlling Nutritional Status Score Predicts 1-Year Outcomes in Chronic Thromboembolic Pulmonary Hypertension.

Background: The prognosis for patients with chronic thromboembolic pulmonary hypertension (CTEPH) using their nutritional status has not been established. We investigated the relationship between the prognosis of patients with CTEPH and the Controlling Nutritional Status (CONUT) score, which is a nutritional assessment tool. Methods and Results: A total of 157 patients with CTEPH was enrolled in the study. The primary outcome was defined as the composite outcome of all-cause mortality and non-elective hospitalization due to heart failure. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff CONUT score for predicting the 1-year rate of the primary outcome. Patients were divided into 2 groups according to the significant cutoff value and compared. Undernutrition was observed in 51.6% of patients. ROC analysis revealed a significant cutoff CONUT score of 3.5 (area under the curve=0.789). The incidence rate of the primary composite outcome was higher in the high CONUT group (score ≥4) than in the low CONUT group (score ≤3; 20% vs. 2.2%; P<0.001). Cox analysis revealed the CONUT score per point increase was an independent risk factor for the primary composite outcomes (hazard ratio 2.301; 95% confidence interval 1.081-4.895; P=0.031). Conclusions: The CONUT score can predict the 1-year rate of all-cause death and non-elective hospitalization in patients with CTEPH.

Dedifferentiation- and aging-induced loss of mechanical contractility and polarity in vascular smooth muscle cells: Heterogeneous changes in macroscopic and microscopic behavior of cells in serial passage culture.

Dedifferentiation and aging of vascular smooth muscle cells (VSMCs) are associated with serious vascular diseases, such as arteriosclerosis and aneurysm. However, how cell dedifferentiation and aging affect cellular mechanical behaviors at the single-cell and intracellular structure levels remains unclear. An in-depth understanding of these interactions is extremely important for understanding the mechanism underlying VSMC mechanical integrity and homeostatic regulation of vascular walls. Herein, we systematically investigated changes in VSMC morphology, structure, contractility, and motility during dedifferentiation and aging induced by serial passage culture using traction force microscopy with elastic micropillar substrates, laser nanodissection of cytoskeletons, confocal fluorescence microscopy, and atomic force microscopy. We found that VSMC dedifferentiation started in the middle stage of serial passage culture, accompanied by a transient cell spreading in the cell width and decrease in contractile protein expression. Dedifferentiated VSMCs showed a significant decrease in the contraction and stiffness of individual actin stress fibers; however, their overall cell traction forces were maintained. Simultaneously, a significant increase in cell motility and the number of actin fibers was observed in dedifferentiated VSMCs, which may be associated with the enhancement of cell migration and disruption of cell/tissue integrity during the early stage of vascular diseases. As cell senescence progressed in the later stage of serial passage culture, VSMCs displayed reduced cell spreading and migration with decrease in the overall cell traction forces and drastic reduction in mechanical polarity of cell structures and forces. These results suggested that cell senescence causes loss of mechanical contractility and polarity in VSMCs, which may be an important factor in vascular disease progression. The experimental systems established in this study can be powerful tools for understanding the mechanisms underlying cellular dedifferentiation and aging from a biomechanical perspective.

Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo.

Extracellular hydrolysis of the phosphate esters of B vitamins (B1, B2, and B6) is crucial for their cellular uptake and metabolism. Although a few zinc-dependent enzymes have been implicated in these processes, their exact mechanisms of action remain largely unknown. This study investigated the potential involvement of phosphate group hydrolyzing enzymes in the hydrolysis of B vitamin phosphate esters. We evaluated enzyme activity in membrane lysates prepared from cells transiently transfected with these enzymes or those endogenously expressing them. Specifically, we investigated how zinc deficiency affects the rate of hydrolysis of B vitamin phosphate esters in cellular lysates. Assessment of the activities of zinc-dependent ectoenzymes in the lysates prepared from cells cultured in zinc-deficient conditions and in the serum of rats fed zinc-deficient diets revealed that zinc deficiency reduced the extracellular hydrolysis activity of B vitamin phosphate esters. Furthermore, our findings explain the similarities between several symptoms of B vitamin and zinc deficiencies. Collectively, this study provides novel insights into the diverse symptoms of zinc deficiency and could guide the development of appropriate clinical strategies.

Factors encouraging participation in social activities after hospital discharge in people with severe mental illness who received occupational therapy.

Introduction: Occupational therapy (OT), a vital part of psychiatric rehabilitation, encourages participation in social activities, which is critical for the recovery of people with severe mental illnesses (SMI). However, the effects of OT on the subsequent social activities of patients with SMI have not been fully clarified. We aimed to identify the factors that encourage post-discharge social activity participation among patients with SMI who received OT. Method: Patients who underwent OT at the Kyorin University Hospital between April 2016 and March 2020 were retrospectively examined for baseline data during hospitalization and social activity status 1 year after discharge. Occupational support, group adaptation, artistic activities, and exercise programs were considered. Activities requiring social interaction were defined as social activities, including employment, schooling, sheltered work, and volunteer work. Multiple logistic regression analyses using demographic and medical data, prehospitalization social activity status, and OT participation rates as independent variables were used to examine the factors encouraging social activity participation after discharge. Decision tree analysis was conducted to identify patients who specifically needed to increase OT participation. Results: Of 524 eligible patients, 247 were included in the study. The number of patients who were socially active at admission and after discharge was 116 and 188, respectively. Multiple logistic regression analyses revealed that the following factors were likely to encourage social activity participation after discharge: higher rates of OT participation to facilitate group adaptation (OR = 1.015, 95% CI 1.003-1.027), being socially active at admission (OR = 4.557, 95% CI 2.155-9.637), and no marital history (OR = 0.293, 95% CI 0.130-0.661). Decision tree analysis showed that for patients who were socially inactive at admission and had a history of marriage, increasing OT participation to 52.6% or higher may ensure social activity participation after discharge. Conclusions: This study identified patients whose social participation after discharge could be boosted by OT that facilitates group adaptation. Our findings would facilitate the development of individualized add-on rehabilitation based on the effects of real-world OT practices.

Evaluation of reflective fiber-optic surface plasmon resonance sensor for monitoring scale deposition.

A reflective surface plasmon resonance (SPR) sensor was evaluated for real-time monitoring of scale deposition. The sensor consists of an optical fiber, only 5 mm at the gold-coated tip of the sensing area. The effect of silica growth on the sensor response was evaluated using a Na2SiO3 solution. The sensitivity of the sensor to silica was 1.6 ± 0.3 nm per one immersion in the solution of 1000 mg/L (as SiO2) at 85 °C and subsequnt air drying, as indicated by the SPR peak shift. The amount of silica deposited on the gold surface was measured by the quartz crystal microbalance method, and the SPR sensitivity of 0.089 nm/ng to silica mass was obtained. The detection limit (3σ) of the SPR sensor was 17 ng, corresponding to a thickness of 2.5 nm for amorphous silica. The SPR sensor was tested in geothermal brine sampled at the Sumikawa Geothermal Power Plant, where a clear SPR shift was observed, suggesting the effectiveness of the SPR sensor for scale monitoring.

Climate Change Projections for Stroke Incidence in Taiwan: Impact of 2 °C and 4 °C Global Warming Level.

OBJECTIVES: This study aimed to establish the exposure-lag-response effect between daily maximum temperature and stroke-related emergency department visits and to project heat-induced stroke impacts under global warming levels (GWL) of 2 °C and 4 °C. METHODS: Stroke-related emergency department visits in Taiwan from 2001 to 2020 were identified using the National Health Insurance Research Database (NHIRD). The study population consisted of 1,100,074 initial stroke cases matched with 2,200,148 non-stroke controls. We employed Distributed Lag Nonlinear Models (DLNM) in a case-crossover study to investigate the association between temperature and stroke. Generalized Estimating Equations (GEE) models with a Poisson function were used to correlate high-temperature exposure with annual stroke incidence rates. Projections were made under two global warming scenarios, GWL 2.0 °C and 4.0 °C, using Coupled General Circulation Model (GCMs). Baseline data from 1995 to 2014 were transformed for spatial distribution at the township level. Geographic Information System (GIS) spatial analysis was performed using Quantum GIS 3.2.0 software. RESULTS: DLNM exposure-lag-response effect revealed that daily maximum temperature exceeding 34 °C significantly increased the risk of stroke-related emergency department visits, particularly for ischemic stroke. Under the 2 °C GWL scenario, the frequency of days with temperatures surpassing 34 °C is projected to rise substantially by the median year of 2042, with a further increase to 92.6 ± 18.0 days/year by 2065 under the 4 °C GWL scenario. Ischemic stroke showed the highest increase in temperature-related incidence rates, notably rising from 7.80% under the GWL 2 °C to 36.06% under the GWL 4 °C. Specifically, the annual temperature-related incidence rate for ischemic stroke is expected to increase significantly by 2065. Regions such as Taichung, Hsinchu, Yilan, and Taitung demonstrated pronounced changes in heat-related ischemic stroke incidence under the GWL 4 °C. CONCLUSIONS: The findings emphasize the importance of addressing temperature-related stroke risks, particularly in regions projected to experience significant temperature increases. Effective mitigation strategies are crucial to reduce the impact of rising temperatures on stroke incidence and safeguard public health.

Sporangimicins A-D, acylated maltose derivatives from a rare actinomycete of the genus Pseudosporangium.

Sporangimicins A-D (1-4), four anomeric pairs of diacyl disaccharides that represent a new metabolite class, were discovered from the culture extract of an actinomycete Pseudosporangium sp. RD061809. Compounds 1-4 caused peak separation in the HPLC chromatogram and partial duplication of the NMR resonances by anomeric interconversion of a maltose core modified at the two sugar 6-positions with an isobutanoyl and a methyl-branched long-chain dienoyl groups. A highlight of the structure elucidation was application of Ohrui-Akasaka's method to a chromatographically inseparable mixture of 3 and 4, which proved the composition ratio of 3 and 4 to be 82:18 and the R/S ratio at the anteiso-methyl bearing chiral center in 3 to be 66:34. Compounds 1-4 showed antimicrobial activity against Gram-positive bacteria and modest cytotoxicity toward P388 murine leukemia cells.

Shorter Drainage Tube to the Pancreatic Stump Reduces Pancreatic Fistula After Distal Pancreatectomy.

BACKGROUND: We investigated the relationship between the length of a prophylactic closed-suction drainage tube and clinically relevant postoperative pancreatic fistula (CR-POPF) in distal pancreatectomy (DP). MATERIALS AND METHODS: The clinical data of 76 patients who underwent DP using a reinforced stapler for the division of the pancreas at Ehime University Hospital between December 2017 and May 2023 were retrospectively analyzed. Laparoscopic DP was performed in 41 patients (53.9%). Closed-suction drainage was performed using a 19 Fr ExuFlow Round Drain with a vacuum bulb. The drainage tube length was defined as the distance between the peripancreatic stump site and the abdominal wall insertion site using abdominal radiography. RESULTS: CR-POPF was observed in 12 patients (15.8%). Univariate analyses demonstrated that male sex (P=0.020), American Society of Anesthesiologists Physical Status (P=0.017), current smoking (P=0.005), and drainage tube length (P<0.001) were significantly associated with CR-POPF. The optimal cut-off value of drainage tube length for CR-POPF was 220 mm (area under the receiver operating characteristic curve=0.80). In multivariate analyses, drainage tube length (≥220 mm) was the sole independent predictor for CR-POPF (odds ratio, 6.59; P=0.023). According to computed tomography performed ∼1 week after surgery, the median volume of peripancreatic fluid collection was significantly higher in the long drainage tube group than in the short drainage tube group (P<0.001). CONCLUSION: A drainage tube inserted at a shorter distance to the pancreatic stump may reduce the incidence of CR-POPF after DP.

Central δ/κ opioid receptor signaling pathways mediate chronic and/or acute suckling-induced LH suppression in rats during late lactation.

In mammals, secretion of tonic (pulsatile) gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) is often suppressed during lactation. Suppression of GnRH/LH pulses in lactating dams is assumed to be caused by suckling stimuli and a chronic negative energy balance due to milk production. The present study aimed to investigate whether the central enkephalin-δ opioid receptor (DOR) signaling mediated the suppression of LH secretion by acute suckling stimuli and/or chronic negative energy balance due to milk production in rats during late lactation when dams were under a heavy energy demand. On postpartum day 16, the number of Penk (enkephalin mRNA)-expressing cells in the arcuate nucleus was significantly higher in lactating rats than in non-lactating control rats. Pulsatile LH secretion was suppressed in rats with chronic suckling or acute 1-h suckling stimuli 6 h after pup removal on day 16 of lactation. Central DOR antagonism significantly increased the mean LH concentrations and the baseline of LH pulses in rats with chronic suckling but not with acute suckling stimuli on day 16 of lactation. Besides, central κ opioid receptor (KOR) antagonism increased the amplitude of LH pulses in rats with the acute suckling stimuli on day 16 of lactation. These results suggest that central DOR signaling mediates the suppression of LH secretion caused by a negative energy balance in rats receiving chronic suckling during late lactation. On the other hand, central KOR signaling likely mediates acute suckling stimuli-induced suppression of LH secretion in rats during late lactation.

Environmental and host factors underlying tick infestation in invasive raccoons (Procyon lotor) in Hokkaido, Japan.

Revealing interactions between ticks and wild animals is vital for gaining insights into the dynamics of tick-borne pathogens in the natural environment. We aimed to elucidate the factors that determine tick infestation in wild animals by investigating ticks on invasive raccoons (Procyon lotor) in Hokkaido, Japan. We first examined the composition, intensity, and seasonal variation of ticks infesting raccoons in six study areas in Hokkaido from March 2022 to August 2023. In one study area, ticks infesting tanukis (raccoon dog, Nyctereutes procyonoides albus) were collected in May to July in both 2022 and 2023, and questing ticks were collected from the vegetation by flagging every other week in the same period. Next, we screened 17 environmental and host variables to determine factors that affect the number of ticks infesting raccoons using generalized linear (mixed) models. From 245 raccoons, we identified a total of 3,917 ticks belonging to eight species of two genera: the most prominent species were Ixodes ovatus (52.9 %), followed by Haemaphysalis megaspinosa (14.4 %), Ixodes tanuki (10.6 %), and Ixodes persulcatus (9.5 %). Ixodes ovatus was also predominant among questing ticks and ticks infesting tanukis. Although I. tanuki was frequently collected from raccoons and tanukis, it was rarely collected in the field. The variables that significantly affected the infestation on raccoons differed by genus, species and developmental stage of the tick. For instance, the infestation of adult I. ovatus was significantly affected by four variables: night-time temperature during nine days before capturing the raccoon, the size of forest area around the capture site, sex of the raccoon, and sampling season. The first two variables were also responsible for the infestation on raccoons of almost all species and stages of ticks. Our study revealed that the number and composition of ticks infesting raccoons can be affected not only by landscape of their habitats but also by weather conditions in several days before capturing.

Francisella sciaenopsi sp. nov. isolated from diseased red drum Sciaenops ocellatus in Florida, USA.

Piscine francisellosis is one of the most important bacterial diseases affecting various fish species worldwide. Francisella orientalis, F. noatunensis, and F. salimarina (F. marina) have been reported as etiological agents of disease in fish. A Francisella sp. was isolated from several diseased red drum Sciaenops ocellatus experiencing morbidity in Florida, USA, in 2008. In this study, molecular and phenotypic characterization of the recovered isolate was conducted. Phenotypically, the isolate showed a biochemical reaction profile distinct from that of F. orientalis and F. salimarina. Although the 16S rRNA sequence of this isolate shared 99.61% identity to the type strain of F. philomiragia O#319LT, whole genome analysis (average nucleotide identity <95%; digital DNA-DNA hybridization <70%) and a multilocus sequence analysis of 8 concatenated housekeeping genes in comparison with other Francisella spp. indicated that this isolate was a novel Francisella species, more closely related to F. orientalis. Immersion, intracoelomic injection, and co-habitation challenges using a Nile tilapia Oreochromis niloticus fingerling model of infection were done to investigate virulence in a piscine model. Variably pigmented granulomas and pigmented macrophage aggregates were observed in the kidneys and spleens of the challenged fish, but no mortality was recorded during the 15 d challenge period, suggesting that this novel Francisella sp. might be an opportunistic pathogen of fish. Based on the phenotypic and genotypic differences from other Francisella spp. observed in this study, we propose the name Francisella sciaenopsi sp. nov. for this novel isolate.

Haematopoietic regeneration by HLA-A*0206-deficient clones in severe aplastic anaemia without definitive immunosuppressive treatment.

We describe the case of a 74-year-old man with severe aplastic anaemia who experienced persistent remission attributed to proliferation of HLA allele-deficient clones. Despite an initial worsening of pancytopenia with eltrombopag and ciclosporin treatment, gradual trilineage haematopoietic recovery occurred, with blood counts normalizing over 3 years. Flow cytometry and deep nucleotide sequencing revealed that haematopoiesis was primarily supported by several clones with somatic mutations that inactivated antigen presentation via HLA-A*0206. This suggests that monitoring haematopoietic regeneration by immune escape clones could be an alternative approach for immune aplastic anaemia patients who possess HLA allele-deficient clones and cannot tolerate standard therapy.

The effects of telepresence with real-time video and audio communication on parent-infant interaction and staff experience in neonatal intensive care unit.

Objective: We implemented an online visitation system named "telepresence" in the neonatal intensive care unit (NICU) for family members at home to communicate with their babies in real-time using video and audio. This study evaluated the impact of this system on families and medical staff. Methods: Nineteen families of babies admitted to the NICU between 2022 and 2023 and 65 medical staff participated. Each family experienced two weeks of virtual visits. Changes in parental depression and attachment were assessed. Result: Before and after telepresence, the median Edinburgh Postnatal Depression Scale score reduced from 6 to 4 (p = 0.026), and the Mother-to-Infant Bonding Scale score showed a decreasing trend, with both medians at 2 (p = 0.057). Eighty-nine percent of the parents and 97% of staff reported that telepresence did not increase parental stress, and 88% of parents felt positive changes in their baby's siblings. All parents wanted to visit their babies in person after seeing them on camera. Conclusion: Telepresence improved parental mental health, reduced family distress, and supported connection with their infants, making them eager to visit in person. Innovations: This technology potentially make parents want to visit more by helping them feel more connected to their infants.

Low pH modulates lipopolysaccharide-induced tumor necrosis factor-alpha expression and macropinocytotic activity in RAW264.7 cells.

Inflammation triggers various types of diseases that need to be addressed. Macrophages play important roles in the inflammatory responses. As atherosclerosis progresses, macrophages transform into foam cells. Extracellular acidification is observed at and around bacterial infection and atherosclerotic sites. However, the effects of acidification on the inflammatory response of macrophages and the progression of atherosclerosis have not been fully understood. This study investigates the impact of extracellular acidification on lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) expression and macropinocytotic activity in RAW264.7 cells. TNF-α expression is measured by real-time polymerase chain reaction (relative value to glyceraldehyde-3-phosphate dehydrogenase expression). Macropinocytotic activity is measured by neutral red uptake (absorbance at 540 nm). Results show that TNF-α expression increased with decreasing extracellular pH in both un-foamed and foamed cells. Macropinocytotic activity was upregulated at pH 6.8 in un-foamed cells, but downregulated in foamed cells stimulated at low pH. Proton-sensing G protein-coupled receptors (GPCRs) were involved in the expression of TNF-α and in the macropinocytotic activity of foamed cells. In conclusion, this study reveals that extracellular acidification differently affect various inflammatory responses such as LPS-induced TNF-α expression and macropinocytotic activity of RAW264.7 cells and different proton-sensing GPCRs are involved in the different inflammatory responses.

Surgical and irradiated case of early breast cancer in a patient with Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disease characterized by hyperextensibility of the skin and joints and tissue fragility of the skin and blood vessels, Vascular EDS is the most severe form of EDS, with abnormal arterial fragility. There have been no reports of breast cancer occurring in patients with vascular EDS. Here, we report here a very rare case of breast cancer in a patient with vascular EDS. CASE PRESENTATION: A 46-year-old woman with vascular EDS underwent partial left mastectomy and sentinel lymph node biopsy for left breast cancer (cStage 0) detected by medical examination. The final pathological diagnosis was invasive ductal carcinoma of the breast (pStage IA) [hormone receptor-positive, HER2 score 2 equivocal (FISH-positive), Ki-67LI 18%, luminal-HER2 type]. BluePrint was submitted as an aid in determining the postoperative treatment strategy, BluePrint Molecular Subtype HER2-type. However, the 10-year breast cancer mortality risk using Predict was low (5%). After consultation with the patient, the decision was made to administer postoperative radiation to the preserved breast along with hormone therapy only. There was no delay in postoperative wound healing, and the patient was free of metastatic recurrence for 9 months after surgery. CONCLUSION: We performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications.

Association Between Self-Direction and Personal Care Aide Wages.

The supply of personal care aides (PCAs), who assist people receiving home care, is a growing concern. PCA shortages result, in part, from the low wages earned by these workers. State policies have had some effect on wages. Self-direction (SD) may be associated with wages because SD allows home care recipients to hire and manage workers, including setting wages in most states. We used wage data from the Bureau of Labor Statistics to examine the association between SD and the wages of PCAs. We found implementation of SD did not have a consistent association with PCA wages, with wages improving in some states and worsening in others. We also found little difference in PCA wages between states that allow participants to set worker wages and those that do not. SD does not seem to improve PCA wages in states, so other policy strategies will be needed.

Comparative analyses of immune cells and alpha-smooth muscle actin-positive cells under the immunological microenvironment between with and without dense fibrosis in primary central nervous system lymphoma.

Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients.

Effect of the 2024 Noto Peninsula earthquake on outpatient chemotherapy among cancer survivors in Japan: a retrospective study.

BACKGROUND: The study aim was to elucidate the effect of the 2024 Noto Peninsula earthquake on outpatient chemotherapy treatment of cancer survivors at Kanazawa Medical University Hospital (KMUH), Japan. METHODS: Medical and nursing records for January 4-31, 2024, from KMUH were retrospectively collected, and data for 286 participants were analyzed. RESULTS: Of the 286 participants, 95.1% were able to attend their first scheduled appointment. Of the 12 (4.2%) who could not attend because of the earthquake, 7 (58.3%) rescheduled their appointments. A total of 8 participants (2.8%) were unable to attend their second scheduled appointment in January, despite being able to attend their first appointment; 3 (37.5%) of these participants reported that they were unable to attend their appointments because of the effect of the earthquake. Chemotherapy was not administered to 53 (18.5%) participants who did attend, mainly owing to neutropenia, progressive disease, rash, and anemia. Evacuation information was available for 25 participants (8.7%); of these, 8 (28.6%) evacuated to their homes, 7 (25.0%) to public shelters, and 4 (14.3%) to apartments near the hospital. Disaster status information was obtained from 62 participants (21.7%), and indicated experiences such as home damage, water outages, and relying on transportation assistance from family to attend appointments. CONCLUSIONS: Most cancer survivors receiving chemotherapy at KMUH were able to maintain outpatient visits. However, a few could not attend because of the earthquake. Further studies are needed to provide more detailed information on the effect of disasters on cancer survivors and the potential factors underlying non-attendance at medical appointments.

Overdose of angiotensin II receptor blocker in the third trimester of pregnancy: A case report.

Angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy because of fetal toxicity. All previous reports on adverse fetal outcomes involved women who continued to take low-dose ARBs for hypertension and were unaware of the adverse effects. Herein, we report the case of a 23-year-old pregnant woman in her third trimester who experienced an ARB overdose after an argument with her partner. Pregnancy was complicated by transient oligohydramnios, and fetal magnetic resonance imaging suggested renal failure. Despite these concerns, the newborn had no morphological abnormalities or abnormal neurological findings. Renal impairment improved over time, and the infant grew well. A single overdose of ARBs in the third trimester can lead to fetal renal failure, similar to long-term low-dose ARB administration; however, favorable outcomes are possible. An overdose of ARBs may transiently cause renal failure, which may improve. The study findings may inform counseling for women who are unexpectedly exposed to an overdose of ARBs.

Effects of phospholipid type and particle size on lipid nanoparticle distribution in vivo and in pancreatic islets.

Lipid nanoparticles (LNPs) have recently been used as nanocarriers in drug delivery systems for nucleic acid drugs. Their practical applications are currently primarily limited to the liver and specific organs. However, altering the type and composition ratio of phospholipids improves their distribution in organs other than the liver, such as the spleen and lungs. This study aimed to elucidate the effects of LNP components and particle size on in vivo distribution through systemic circulation to pancreatic islets to achieve better targeting of islets, which are a fundamental therapeutic target for diabetes. Fluorescence-labeled LNPs were prepared using three phospholipids: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), with particle sizes of 30-160 nm (diameter) using a microfluidic device. Baffled-structured iLiNP devices with adjusted flow-rate ratios and total flow rates were used. After the intravenous administration of LNPs to C57BL/6 J mice, the distribution of each LNP type to the major organs, including the pancreas and pancreatic islets, was compared using ex vivo fluorescence imaging and observation of pancreatic tissue sections. DSPC-LNPs- and DOPE-LNPs showed the highest distribution in the spleen and liver, respectively. In contrast, the DOPC-LNPs showed the highest distribution in the pancreas and the lowest distribution in the liver and spleen. In addition, smaller particles showed better distribution throughout the pancreas. The most significant LNP distribution in the islets was observed for DOPC-LNPs with a particle size of 160 nm. Furthermore, larger LNPs tended to be distributed in the islets, whereas smaller LNPs tended to be distributed in the exocrine glands. DOPC-LNPs were distributed in the islets at all cholesterol concentrations, with a high distribution observed at >40% cholesterol and > 3% PEG and the distribution was higher at 24 h than at 4 h. Thus, LNP composition and particle size significantly affected islet distribution characteristics, indicating that DOPC-LNPs may be a drug delivery system for effectively targeting the pancreas and islets.