Effect of postbiotic Lactiplantibacillus plantarum LRCC5314 supplemented in powdered milk on type 2 diabetes in mice.

Type 2 diabetes (T2D) is a chronic multifactorial disease characterized by a combination of insulin resistance and impaired glucose regulation. The alleviative effects of probiotics on T2D have been widely studied. However, studies on the effects of postbiotics, known as inactivated probiotics, on dairy products are limited. This study aimed to evaluate the effectiveness of postbiotic Lactiplantibacillus plantarum LRCC5314 in milk powder (MP-LRCC5314) in a stress-T2D mouse model. Compared with probiotic MP-LRCC5314, postbiotic MP-LRCC5314 significantly influenced stress-T2D-related factors. The administration of heat-killed MP-LRCC5314 reduced corticosterone levels, increased short-chain fatty acid production by modulating gut microbiota, and regulated immune response, glucose metabolism, stress-T2D-related biomarkers in the brain, gut, and adipose tissues, as well as glucose and insulin sensitivity. Additionally, heat-killed MP-LRCC5314 treatment led to a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels. Overall, these findings suggest that adding postbiotic MP-LRCC5314 to milk powder could serve as a potential supplement for stress-T2D mitigation.

Different tumor growth pattern of clinically nonfunctioning pituitary neuroendocrine tumor according to sex and age: a longitudinal study.

PURPOSE: Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. METHODS: In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66 months. RESULTS: The median age of the patients was 53.0 years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51 years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50 years showed significantly lower annual tumor volume change than those aged > 50 years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50 years (0.01 vs. 0.15 cm3/year, P < 0.001). CONCLUSIONS: Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50 years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.

Development of machine learning models for the surveillance of colon surgical site infections.

BACKGROUND: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency. METHODS: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method. RESULTS: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method. CONCLUSION: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV.

An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

A RARE CASE OF GRAVES' THYROTOXICOSIS WITH CONCOMITANT PULMONARY ALVEOLAR PROTEINOSIS.

Background: Graves' disease results in various clinical cardio-pulmonary manifestations such as tachycardia, atrial fibrillation, and pulmonary edema. Clinical Case: A 62-year-old woman presented with palpitations and dyspnea. Laboratory and radiologic examination revealed markedly elevated free T4 (4.79 ng/dL), T3 (4.42 ng/mL), lowered TSH (0.01 uIU/mL), atrial fibrillation and multifocal lung haziness. She was initially diagnosed with atrial fibrillation with pulmonary edema, which subsequently changed to pulmonary alveolar proteinosis by further evaluations such as computed tomography and bronchoscopic biopsy. Conclusion: Pulmonary alveolar proteinosis is a rare lung disease. Clinicians should carefully assess lung lesions in thyrotoxicosis patients as they can be easily mistaken for pulmonary edema in clinical practice.

Electron Temperature Measurements Using a Two-Filter Soft X-ray Array in VEST.

A multichannel soft X-ray (SXR) array has been developed to measure the electron temperature in the Versatile Experiment Spherical Torus (VEST). To estimate electron temperature using the two-filter method applied to SXR intensity, we designed a pinhole camera that has two photodiode arrays with different metallic filters. We also adopted a filter wheel and tested various filter parameters to find the optimal filter set. Through tests, the combination of aluminum and beryllium was found to be the most suitable for the current experimental conditions in VEST. The filtered SXR signals were acquired with a low-noise preamplifier, exhibiting sufficient signal-to-noise ratios for electron temperature estimation based on the intensity ratio of two signals obtained with different filters. The estimated electron temperature from the developed two-filter SXR array showed reasonably matched levels and consistent trends with Thomson scattering measurements. Error contribution from impurity line emission is also discussed.

Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: a single-centre, retrospective, cohort study.

BACKGROUND: Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are among the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO). BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. AIM: To analyse whether body mass index (BMI) is associated with BSI during ECMO or with in-hospital mortality. METHODS: All adult patients who had received ECMO support for >48 h were included in the analysis. The analysis of total duration of ECMO support, in-hospital mortality and BSI was stratified by BMI category. The Cox proportional hazards model was used to compare the risk of BSI among BMI categories. FINDINGS: In total, 473 patients were enrolled in the study. The average age was 56.5 years and 65.3% were men. The total duration of ECMO was approximately 11.8 days, with a mortality rate of 47.1%. The incidence rates of BSI and candidaemia were 20.5% and 5.5%, respectively. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required ECMO for cardiogenic support (P<0.0001). No significant difference in BSI rate was found (P=0.784). However, after adjusting for clinical factors, patients in Group 4 (BMI 25.0-<30.0 kg/m2) exhibited lower mortality compared with patients in Group 2 (normal BMI) (P=0.004). CONCLUSION: BMI was not associated with risk of BSI, but patients with higher BMI showed lower in-hospital mortality associated with ECMO support.

Significance of photodocumentation-associated factors in colonoscopy on the detection rate of colorectal neoplasms.

OBJECTIVE: It is unclear whether photodocumentation is associated with colorectal neoplasm (CRN) detection at colonoscopy, despite its ability to take more images with the development of affordable digital imaging systems. This study aimed to investigate whether photodocumentation-related factors could affect the detection rate of CRNs in healthy subjects. PATIENTS AND METHODS: A total of 2,637 subjects undergoing screening colonoscopy in routine health check-ups at CHA Bundang Medical from January to September 2016 were enrolled in this study. Only the endoscopic image data for observation purposes during colonoscopy withdrawal was used in this analysis. The number of observation images, observation time and the speed of photodocumentation (SPD) defined as the number of observation images per minute were used as quantity measures of photodocumentation. The presence of documented anatomical landmarks such as appendix orifice (AO), ileocecal valve (ICV), anorectal junction was used as quality measures of photodocumentation. RESULTS: Among subject-related factors, the independent factors for CRN detection in the multivariate analysis were age, male sex, waist circumference, and family history of colorectal cancer. In photo-documentation-related factors, SPD [Odds ratio (OR) 0.800; 95% confidence interval (CI), 0.740 to 0.864], observation time over 6 min (OR 1.671; 95% CI, 1.145 to 2.439), clear documentation of appendix orifice (AO) (OR 5.976; 95% CI, 4.548 to 7.852) and ileocecal valve (ICV) (OR 3.826; 95% CI, 2.985 to 4.904), and endoscopists (p < 0.001) were independently significant factors. However, the number of observation images was not associated with the detection of CRNs. CONCLUSIONS: Lower SPD and clear documentation of cecal landmarks might be associated with an increased detection rate of CRNs.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.

Urine phthalate levels were associated with skin barrier dysfunction and atopic sensitization in children.

OBJECTIVE: Phthalates can cause immunological disorders and aggravate allergic diseases. Thus, we investigated the relationship between urinary phthalate, skin barrier function, and atopic sensitization in children. PATIENTS AND METHODS: In total, 448 school children [334 with severe allergic disease; and 123 with severe atopic dermatitis (AD)] aged 10-12 years were enrolled in this study between June and July 2017. Four high-molecular-weight phthalates (HMWP) [Σ4HMWP] and three low-molecular-weight phthalates (LMWP) [Σ3LMWP] metabolites in urine samples, specific immunoglobulin E (IgE), and total eosinophil count were measured. Four-part trans epidermal water loss (TEWL) (cheek, leg, and upper/lower arm; Σ4TEWL) was measured to evaluate the skin barrier function. RESULTS: After adjusting for confounding variables, Σ4TEWL was significantly associated with the quartiles of urinary Σ4HMWP [adjusted ß=7.897, 95% confidence interval (CI): 0.636-15.158, p=0.033] and Σ3LMWP (adjusted ß=9.670, 95% CI: 2.422-16.919, p=0.009). The adjusted analyses revealed that the quartiles of urinary Σ4HMWP and Σ3LMWP were not significantly associated with total eosinophil count, atopic sensitization, and severe AD (p>0.05). According to the quartiles of urinary Σ4HMWP and Σ3LMWP, there were significant differences in the TEWL of the lower arm and leg (p<0.05) but not in cheek and upper arm. CONCLUSIONS: Exposure to HMWPs and LMWPs was significantly associated with skin barrier dysfunction but not with atopic sensitization. These results suggest that children exposed to phthalates may be more susceptible to fragile skin barrier function.

Impact of tuberculosis on the incidence of osteoporosis and osteoporotic fractures: a nationwide population-based cohort study.

OBJECTIVES: Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures. STUDY DESIGN: This was a nationwide population-based cohort study. METHODS: This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated. RESULTS: A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio [aHR] 1.349, 95% confidence interval [CI] 1.302-1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357-1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612-1.798, P < 0.001). CONCLUSIONS: TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.

Fabrication of THz corrugated wakefield structure and its high power test.

We present overall process for developing terahertz (THz) corrugated structure and its beam-based measurement results. 0.2-THz corrugated structures were fabricated by die stamping method as the first step demonstration towards GW THz radiation source and GV/m THz wakefield accelerator. 150-[Formula: see text]m thick disks were produced from an OFHC (C10100) foil by stamping. Two types of disks were stacked alternately to form 46 mm structure with [Formula: see text] 170 corrugations. Custom assembly was designed to provide diffusion bonding with a high precision alignment of disks. The compliance of the fabricated structure have been verified through beam-based wakefield measurement at Argonne Wakefield Accelerator Facility. Both measured longitudinal and transverse wakefield showed good agreement with simulated wakefields. Measured peak gradients, 9.4 MV/m/nC for a long single bunch and 35.4 MV/m/nC for a four bunch trains, showed good agreement with the simulation.

Evaluation of the efficacy and safety of NVP-1203 and aceclofenac in patients with acute low back pain and muscle spasm: A randomized, double-blind, active-controlled, parallel, multicenter, phase 3 clinical trial.

OBJECTIVE: Acute low back pain (LBP) is a common condition that can be chronic if not properly treated. Aceclofenac and eperisone hydrochloride are commonly prescribed drugs for acute LBP and muscle spasms. Therefore, NVP-1203, a fixed-dose combination of 100 mg aceclofenac and 75 mg eperisone hydrochloride, is being developed. This study aimed to evaluate the efficacy and safety of NVP-1203 compared to those of a single administration of 100 mg aceclofenac in patients with acute LBP and muscle spasms. PATIENTS AND METHODS: Overall, 455 patients with acute LBP and muscle spasms were enrolled. The patients were assigned to NVP-1203 or Airtal group (aceclofenac 100 mg). The primary efficacy endpoint was the mean change in the 100 mm pain movement and resting visual analog scale (VAS) scores on treatment day 7. RESULTS: The mean change in the 100 mm pain movement/resting VAS scores from baseline to day 7 was -49.7 ± 21.5/-41.0 ± 19.4 mm and -38.8 ± 18.9/-33.8 ± 18.0 mm for the NVP-1203 and Airtal groups, respectively. The differences between the two groups were statistically significant (movement, p < 0.0001; resting, p = 0.0002). Differences in least-square (LS) mean change of the 100 mm pain movement/resting VAS score between the two groups using the analysis of covariance (ANCOVA) model was -10.2/-7.4 mm, and the upper limit of the 95% confidence interval was -6.44/-4.16 mm. CONCLUSIONS: NVP-1203 is more effective in reducing pain than the 100 mg aceclofenac alone. However, the two drugs have similar safety profiles in patients with acute LBP and muscle spasms.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review.

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

Transcriptomic analysis of the liver in aged laying hens with different eggshell strength.

Eggshell is composed of a very ordered and mineralized structure and is important for egg quality. Eggshell strength is particularly important because of its direct association with economic outcomes and egg safety. Various factors related to laying hens and their environment affects eggshell strength. However, the molecular mechanisms of liver functions related to decreased eggshell strength of aged laying hens are largely unknown. Therefore, this study aimed to identify potential factors affecting eggshell strength in aged laying hens at the hepatic transcriptomic level. A total of five hundred 92-wk-old Hy-line Brown laying hens were screened to select those exhibiting the greatest variation in eggshell strength. Based on the final eggshell strength, 12 hens producing eggs with strong eggshell strength (SES) and weak eggshell strength (WES) were finally selected (n = 6) for liver tissue sampling. The RNA-sequencing was performed to identify differentially expressed genes (DEGs) between the 2 groups. We identified a total of 2,084 DEGs, of which 1,358 genes were upregulated and 726 genes were downregulated in the WES group compared with SES group. According to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the DEGs indicated the mammalian target of rapamycin signaling pathway, the Janus kinase-signal transducer and activator of transcription pathway, the mitogen­activated protein kinase signaling pathway, and the insulin resistance pathways. Genes related to fatty liver disease were upregulated in WES group compared with SES group. In addition, expression of several genes associated with oxidative stress and bone resorption activity was altered in aged laying hens with different eggshell strength. Overall, these findings contribute to the identification of genes involved in different intensity of eggshell strength, enabling more understanding of the hepatic molecular mechanism underlying in decreased eggshell strength of aged laying hens.

Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Cavitation processes in a space filled with loose mesenchymal tissues: a comparison between the retrosternal space and the middle ear tympanic cavity in human fetuses.

BACKGROUND: During the expansion of the pleural cavity in early fetuses, a thick sheet of loose mesenchymal tissue (SLMT) appears between the lung bud and body wall. Subsequently, the growing lung bud invades into the SLMT and the latter becomes fragmented to disappear. To compare this with the tympanic cavity filled with loose mesenchymal tissues, the present study aimed to demonstrate the development, establishment, and breaking of the SLMT in the retrosternal space. MATERIALS AND METHODS: Although the retrosternal tissue was almost absent or very thin at 7 weeks, the SLMT appeared behind the manubrium sterni at 8 weeks. Accordingly, at 9-10 weeks, cavitation occurred in the SLMT to expand the pleural cavity. Therefore, the volume of SLMT was not determined by the adjacent structures such as the pericardium and sternum. Likewise, mesenchymal tissues filling the middle ear disappeared after 26 weeks. RESULTS: There were considerable individual variations in the timing of beginning and location of the tympanic cavitation. However, in contrast to the retrosternal SLMT, the volume of the future tympanic cavity is determined by the adjacent hard tissue and tympanic membrane much earlier than the cavitation. The mesenchymal tissue carried abundant vessels in the middle ear but none or few veins in the retrosternal SLMT. CONCLUSIONS: The concept that the lung bud invades into the splanchnic mesoderm to expand the pleural cavity seems oversimplified. Mechanical stresses from the pleural cavity might induce retrosternal cavitation, while a loss in blood supply might cause tympanic cavitation.