High oxygen exposure's impact on newborn mice: Temporal changes observed via micro-computed tomography.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) impacts life expectancy and long-term quality of life. Currently, BPD mouse models exposed to high oxygen are frequently used, but to reevaluate their relevance to human BPD, we attempted an assessment using micro-computed tomography (µCT). METHODS: Newborn wildtype male mice underwent either 21% or 95% oxygen exposure for 4 days, followed until 8 wk. Weekly µCT scans and lung histological evaluations were performed independently. RESULTS: Neonatal hyperoxia for 4 days hindered lung development, causing alveolar expansion and simplification. Histologically, during the first postnatal week, the exposed group showed a longer mean linear intercept, enlarged alveolar area, and a decrease in alveolar number, diminishing by week 4. Weekly µCT scans supported these findings, revealing initially lower lung density in newborn mice, increasing with age. However, the high-oxygen group displayed higher lung density initially. This difference diminished over time, with no significant contrast to controls at 3 wk. Although no significant difference in total lung volume was observed at week 1, the high-oxygen group exhibited a decrease by week 2, persisting until 8 wk. CONCLUSION: This study highlights µCT-detected changes in mice exposed to high oxygen. BPD mouse models might follow a different recovery trajectory than humans, suggesting the need for further optimization.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Detection of Pathologic Heart Murmurs Using a Piezoelectric Sensor.

This study aimed to evaluate the capability of a piezoelectric sensor to detect a heart murmur in patients with congenital heart defects. Heart sounds and murmurs were recorded using a piezoelectric sensor and an electronic stethoscope in healthy neonates (n = 9) and in neonates with systolic murmurs caused by congenital heart defects (n = 9) who were born at a hospital. Signal data were digitally filtered by high-pass filtering, and the envelope of the processed signals was calculated. The amplitudes of systolic murmurs were evaluated using the signal-to-noise ratio and compared between healthy neonates and those with congenital heart defects. In addition, the correlation between the amplitudes of systolic murmurs recorded by the piezoelectric sensor and electronic stethoscope was determined. The amplitudes of systolic murmurs detected by the piezoelectric sensor were significantly higher in neonates with congenital heart defects than in healthy neonates (p < 0.01). Systolic murmurs recorded by the piezoelectric sensor had a strong correlation with those recorded by the electronic stethoscope (ρ = 0.899 and p < 0.01, respectively). The piezoelectric sensor can detect heart murmurs objectively. Mechanical improvement and automatic analysis algorithms are expected to improve recording in the future.

Sox2 induces tumorigenesis and angiogenesis of early-stage esophageal squamous cell carcinoma through secretion of Suprabasin.

Early stage of esophageal squamous cell carcinoma (ESCC) is known to be accompanied by angiogenesis and morphological changes of microvessels. Transcription factor Sox2 is amplified in various cancers including ESCC, but the role of Sox2 in the carcinogenesis and angiogenesis has not been determined. Hence, we aimed to investigate the role of Sox2 in the early stage of ESCC. We found that the expression of Sox2 was significantly higher in early-stage ESCC tissues than that in their adjacent normal tissues. We then established Sox2-inducible normal human esophageal squamous cell line (HetSox2) to investigate the role of Sox2 in esophageal carcinogenesis and angiogenesis in vitro. Sox2 overexpression led to increased cell proliferation and spheroid formation. The culture supernatant of Sox2-overexpressing HetSox2 induced migration and sprouting of endothelial cell line HUVEC (human umbilical vein endothelial cell). As for the mechanism, we found that the expression of secreted protein Suprabasin was directly induced by Sox2. Suprabasin enhanced proliferation of normal human esophageal squamous cells when added to the culture. Moreover, Suprabasin enhanced migration and sprouting of HUVEC cells, which were observed with the culture supernatant of Sox2-overexpressing HetSox2. This angiogenic effect of Suprabasin was abolished by inhibiting AKT phosphorylation, which suggested its dependence on AKT signaling. Finally, we showed that Suprabasin expression and the density of microvessels were significantly higher in ESCC tissues with high Sox2 expression. Our study suggested that increased Sox2 expression in esophageal squamous cells induced Suprabasin expression, and as a result initiated the carcinogenesis via increased cell proliferation and angiogenesis.

Saline Solution Irrigation of the Bile Duct after Stone Removal Reduces the Recurrence of Common Bile Duct Stones.

Common bile duct (CBD) stone is a relatively common but potentially life-threatening disease. Endoscopic sphincterotomy (EST) has been performed as standard therapy for CBD stones, but the rate of recurrence of CBD stones is high. Risk factors have been poorly defined, and no effective means for the prevention of the recurrence of CBD stones have been established so far. We aimed to identify significant risk factors for the recurrence of bile duct stones. This study included 477 patients (231 women; mean age, 80.5 years) who underwent EST and cleared CBD stones on cholangiography. A retrospective analysis was performed for the consecutively collected data. During the follow-up period of 6-75 months, the recurrence of CBD stones was observed in 99 patients (20.8%). The median time to the recurrence was 19.0 months (range 4-72 months). Multivariate analysis identified the need for mechanical lithotripsy, which was used for stone fragmentation, as a risk factor. Mechanical lithotripsy caused cholangiography-negative small residua. Notably, saline solution irrigation of the bile duct reduced the recurrence of CBD stones. These results demonstrate that subsequent biliary irrigation after stone removal may prevent the recurrence of CBD stones by clearing small residual fragments.

Speed ratio but cabin temperature positively correlated with increased heart rates among professional drivers during car races.

OBJECTIVES: The present study measures heart rate (HR) on a number of professional race-car drivers during actual car races through annual seasons to test hypotheses that faster relative speed and higher cabin temperature would induce higher HR. METHODS: Heart rates in fifteen male drivers (31.2 ± 5.5 years old) were obtained by chest-strap sensors during official-professional 13 races. Average HR was calculated while the driver was racing from the start to the end of each race. RESULTS: The average HR during races was 164.5 ± 15.1 beats min-1 and the average amount of time each driver spent driving per race was 54.2 ± 13.7 min. Average HR significantly and positively correlated with mean speed ratio (P < 0.001), but not with the average cabin temperatures (P = 0.533, range 25.6-41.8 °C) by the multiple linear regression analysis. Both average HR and mean speed ratio were significantly lower under wet, than dry conditions (151.9 ± 16.5 vs. 168.3 ± 12.5 beats min-1, 86.9 ± 4.4 vs. 93.4 ± 1.5 %). CONCLUSIONS: The cardiovascular system of drivers is considerably stressed at extremely high HR. This high average HR positively correlated with mean speed ratio, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. However, contrary to our hypothesis, cabin temperature was not significantly correlated with average HR. It is speculated that direct body cooling systems used in this professional race category work well against increases in HR by thermal stress under the temperature range found herein.

A novel method to detect heat illness under severe conditions by monitoring tympanic temperature.

INTRODUCTION: We report a new methodology for detecting heat illness based on continuous tympanic temperature monitoring. This is relevant to industrial workers, astronauts, and pilots, as well as athletes. Here we evaluate the method in Grand Touring (GT) car racers in the closed-cockpit category who can face life-threatening hyperthermia. METHODS: The system comprises an earpiece containing an infrared-radiation-type tympanic thermometer and a microspeaker. In 10 healthy subjects, using a temperature-controlled water bath in the laboratory, we determined the differences in measurements taken from an infrared thermometer in one ear canal and from a thermistor probe in the other ear canal for direct tympanic temperature measurement. We employed an ingestible telemetry pill for gastrointestinal temperature measurement as a reference of core temperature. Then we assessed the usefulness of the system under real racing conditions with two professional drivers in the 2010 Super GT International Series held at the Twin Ring Motegi in Japan. RESULTS: The results showed a good correlation between the infrared tympanic temperature and both the direct one (r = 0.985) and the gastrointestinal temperature (r = 0.932). The mean difference between these temperatures was +0.01 degree C and +0.27 degrees C, with 95% confidence intervals (equal to 1.96 SD) of 0.30 degrees C and 0.58 degrees C, respectively. As for the field test, the system functioned well during real competitive and extremely severe race conditions on the racing circuit. CONCLUSIONS: The new method was found to perform well in an extreme car racing setting. It has the potential to be used in other applications, including the industrial and aerospace sectors.

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

E44Q mutation in NaV1.7 in a patient with infantile paroxysmal knee pain: electrophysiological analysis of voltage-dependent sodium current.

Gain-of-function mutations in voltage-gated sodium channels (NaV1.7, NaV1.8, and NaV1.9) are known causes of inherited pain disorders. Identification and functional assessment of new NaV1.7 mutations could help elucidate the phenotypic spectrum of NaV1.7 channelopathies. We identified a novel NaV1.7 mutation (E44Q in exon 2) that substitutes a glutamic acid residue for glutamine in the cytoplasmic N-terminus of NaV1.7 in a patient with paroxysmal pain attacks during childhood and his family who experienced similar pain episodes. To study the sodium channel's function, we performed electrophysiological recordings. Voltage-clamp recordings revealed that the mutation increased the amplitude of the non-inactivating component of the sodium current, which might facilitate channel opening. These data demonstrate that E44Q is a gain-of-function mutation in NaV1.7, which is consistent with our patient's pain phenotype.

A Japanese Patient with Genitopatellar Syndrome Transiently Presenting with Cardiac Intramural Cavity during the Neonatal Period.

Genitopatellar syndrome (GPS) is a rare autosomal dominant disorder caused by de novo pathogenic variants in the KAT6B gene. It is characterized by genital abnormalities, patellar hypoplasia/agenesis, flexion contractures of the hips and knees, corpus callosum agenesis with microcephaly, and hydronephrosis and/or multiple renal cysts. More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus. We report a case of a Japanese neonate with a de novo heterozygous c.3769_3772delTCTA pathogenic variant in the KAT6B gene who presented with a cardiac intramural cavity of the ventricular septum at birth. The cavity unexpectedly disappeared at 1 month of age, but trabecular septal thinning and flash remained. The features of the cavity were not consistent with those of congenital ventricular diverticulum or aneurysm, and its identity and prognosis are still unclear. Because patients with GPS may exhibit various forms of cardiac malformation, careful cardiac examination and follow-up are required from birth in cases of suspected GPS.

The slow progressive nature of duodenal neuroendocrine tumor: a case report of long-term observation over 14 years.

The number of duodenal neuroendocrine tumors has recently increased, but their natural history has not been well characterized. Here we report the case of a 59-year-old female undergoing complete resection by endoscopic mucosal resection after monitoring endoscopic morphologic changes and the size increment of a duodenal neuroendocrine tumor over the longest follow-up duration. An elevated lesion was initially detected on the duodenal bulb. Endoscopic biopsy from this lesion was performed three times during the follow-up, but all of the specimens simply demonstrated the presence of gastric metaplasia. Thereafter, in the esophagogastroduodenoscopy performed 14 years after the initial examination, a slight depression was detected in the center of the lesion together with an incremental change of its size. The histopathologic diagnosis of neuroendocrine tumor was made by deeper tissue sampling, and the patient subsequently underwent endoscopic mucosal resection for this tumor and was finally diagnosed with a G1 duodenal neuroendocrine tumor with pT2 cN0, cM0, stage IIa in the TNM classification. This is the first case demonstrating the slowly progressive nature of such a tumor with the longest follow-up of a duodenal neuroendocrine tumor ever reported, which could provide important information regarding the natural history and management of such tumors.