Marine Envenomation in Okinawa: Overview and Treatment Concept.

Okinawa prefecture is a popular tourist destination due to its beaches and reefs. The reefs host a large variety of animals, including a number of venomous species. Because of the popularity of the reefs and marine activities, people are frequently in close contact with dangerous venomous species and, thus, are exposed to potential envenomation. Commonly encountered venomous animals throughout Okinawa include the invertebrate cone snail, sea urchin, crown-of-thorns starfish, blue-ringed octopus, box jellyfish, and fire coral. The vertebrates include the stonefish, lionfish, sea snake, and moray eel. Treatment for marine envenomation can involve first aid, hot water immersion, antivenom, supportive care, regional anesthesia, and pharmaceutical administration. Information on venomous animals, their toxins, and treatment should be well understood by prehospital care providers and physicians practicing in the prefecture.

Nivolumab Therapy in Lung Cancer Associated with IgG4-related Disease.

A 75-year-old man with severe bilateral pleural thickening and dense soft tissue masses surrounding the abdominal aorta on computed tomography was diagnosed with IgG4-related disease (IgG4-RD) as a complication of lung cancer. He was started on nivolumab as second-line therapy along with low-dose prednisolone. Nivolumab was administered for 15 months until disease progression, during which time IgG4-RD did not relapse, and no problematic immune-related adverse events occurred. These results suggest that anti-programmed cell death protein-1 antibody may be used safely in lung cancer associated with IgG4-RD concomitantly with low-dose steroids.

Polyclonal Hyperglobulinemia with Multiple Pulmonary Cysts and Nodules: Concerning the Mechanism Underlying Cyst Formation.

We herein report a case of polyclonal hyperglobulinemia with multiple pulmonary cysts and nodules. The histopathological findings allowed us to speculate about the mechanism underlying cyst formation in these pathological conditions, which has not yet been thoroughly elucidated. The patient was a 49-year-old woman who presented with multiple pulmonary multilocular cysts and nodules. A lung biopsy revealed features of nodular lymphoid hyperplasia. Notably, lung structure fragmentation was evident, suggesting that structural destruction may have accompanied the disease during its course. The cysts were considered to have formed due to destruction of the lung structures.

Pet Animals Were Infected with SARS-CoV-2 from Their Owners Who Developed COVID-19: Case Series Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pets owned by coronavirus disease 2019 (COVID-19) patients has been reported around the world. However, how often the animals are exposed to SARS-CoV-2 by their owners is still unclear. We have collected swab samples from COVID-19 patients' pets and performed real-time RT-PCR to detect the viral genome. In total, 8 of 53 dogs (15.1%) and 5 of 34 cats (14.7%) tested positive for the SARS-CoV-2 N gene. The result of a virus neutralization (VN) test also showed VN antibodies in four cats and six dogs. Our results indicate that the virus often passed from infected owners to their pets, which then excreted the virus despite having no or mild clinical signs.

Celecoxib-Loaded Self-micellizing Solid Dispersion Suppresses Its Delayed Absorption in Rats with Impaired Gastrointestinal Motility.

The aim of this study was to develop a self-micellizing solid dispersion of celecoxib (SMSD/CEL) with enhanced dissolution to suppress a delay in absorption under impairment of gastrointestinal (GI) secretion and motility induced by severe pain. Soluplus®-based SMSD/CEL was prepared by lyophilization and physiochemically characterized. A pharmacokinetic study of orally-dosed CEL samples was carried out in rats with propantheline (PPT)-induced the impairment of GI secretion and motility. SMSD/CEL was micellized in aqueous media with a mean diameter of 153 nm, and it showed improved dissolution behavior of CEL under acidic conditions with 2.1-fold higher dissolved CEL at 120 min than crystalline CEL. SMSD/CEL was found to be in an amorphous state, and there was no significant crystallization even after storage under accelerated conditions for 8 weeks, indicating relatively high storage stability of the amorphous form. Orally-dosed crystalline CEL in PPT-treated rats showed a delayed mean absorption time (MAT) and area under the curve of plasma concentration versus time from 0 to 4 h (AUC0-4) was reduced to 12% compared with that in normal rats, whereas SMSD/CEL suppressed the delay and decrease of absorption in PPT-treated rats. From these findings, SMSD/CEL might be efficacious to suppress poor and delayed absorption of CEL for better pain medication in the presence of impaired GI secretion and motility associated with severe pain.

Capillary responses to functional and pathological activations rely on the capillary states at rest.

Brain capillaries play a crucial role in maintaining cellular viability and thus preventing neurodegeneration. The aim of this study was to characterize the brain capillary morphology at rest and during neural activation based on a big data analysis from three-dimensional microangiography. Neurovascular responses were measured using a genetic calcium sensor expressed in neurons and microangiography with two-photon microscopy, while neural acivity was modulated by stimulation of contralateral whiskers or by a seizure evoked by kainic acid. For whisker stimulation, 84% of the capillary sites showed no detectable diameter change. The remaining 10% and 6% were dilated and constricted, respectively. Significant differences were observed for capillaries in the diameter at rest between the locations of dilation and constriction. Even the seizures resulted in 44% of the capillaries having no detectable change in diameter, while 56% of the capillaries dilated. The extent of dilation was dependent on the diameter at rest. In conclusion, big data analysis on brain capillary morphology has identified at least two types of capillary states: capillaries with diameters that are relatively large at rest and stable over time regardless of neural activity and capillaries whose diameters are relatively small at rest and vary according to neural activity.

Transbronchial cryobiopsy using an ultrathin cryoprobe with a guide sheath for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is difficult to diagnose and relatively rare. Tissue sampling through transbronchial biopsy is often inadequate, necessitating surgical lung biopsy. However, a recently developed technique, transbronchial lung cryobiopsy (TBLC), has shown promise for obtaining larger specimens. A 1.1 mm cryoprobe has recently become available, and its usefulness has been increasingly reported. Use of a conventional cryoprobe for TBLC in diagnosing pulmonary MALT lymphoma has been previously reported; however, there are no reports on the use of a 1.1 mm ultrathin cryoprobe and guide sheath (GS). We aimed to assess the effectiveness and safety of using a 1.1 mm ultrathin cryoprobe in combination with a GS for diagnosing pulmonary MALT lymphoma using a simpler and safer method. We retrospectively analyzed the findings for four patients showing characteristic computed tomography (CT) findings of MALT lymphoma, including peripheral pulmonary lesions, air bronchogram nodules, and bronchiectasis, at our hospital. Each patient underwent endobronchial ultrasound (EBUS) with a GS, followed by TBLC using a 1.1 mm cryoprobe. Morphological diagnosis, immunohistochemical examination, and molecular testing were performed on the biopsy specimens to establish the diagnosis. Complications during the procedure were also monitored. We obtained 8-16 biopsy specimens in all four cases using a cryoprobe. Histopathological analysis of two cases revealed the infiltration of small lymphocytes with numerous lymphoepithelial lesions, confirming MALT lymphoma. Immunohistochemical examination further demonstrated B-cell lymphocyte proliferation and light-chain restriction, confirming monoclonality and providing a definitive diagnosis. In the remaining two cases, histopathological evidence of pulmonary MALT lymphoma was lacking. However, molecular testing using polymerase chain reaction to analyze immunoglobulin gene rearrangements revealed B-cell clonality, which supported the diagnosis. Molecular testing proved particularly useful when histopathological diagnosis alone was inconclusive. No complications such as pneumothorax or hemorrhage occurred during the procedure. The combination of a GS and EBUS facilitated specimen collection at the same location as EBUS, with the GS providing compression hemostasis and eliminating the need for an additional hemostatic device. Therefore, TBLC with a GS is a useful and safe method for diagnosing pulmonary MALT lymphomas and reproducibly yielded sufficient quantities of good-quality biopsy specimens.

[Growing Mixed Squamous Cell and Glandular Papilloma Difficult to Differentiate from Primary Lung Cancer:Report of a Case].

A 76-year-old woman was referred to our hospital due to abnormal chest radiography findings. Chest computed tomography (CT) revealed a nodule in the right lower lobe. Fluorodeoxyglucose-positronemission tomography (FDG-PET) showed abnormal accumulation in the nodule. Bronchoscopy did not provide a definitive diagnosis. Since the nodule tended to increase in size, primary lung cancer was suspected and surgery was performed. During the surgery, pathological diagnosis of squamous cell carcinoma was made, and a right lower lobectomy was performed. Subsequently, a pathological diagnosis of mixed squamous cell and glandular papilloma (mixed papilloma) was made. She has had no sign of recurrence for approximately four years since the surgery.

[Hemobilia due to ruptured superior pancreaticoduodenal pseudoaneurysm after chemoradiotherapy for pancreatic head cancer: an autopsy case report].

A 78-year-old man came to our department because of obstructive jaundice, and was diagnosed as pancreatic head cancer. He underwent chemoradiation therapy. A metal stent was inserted into the common bile duct and the patient was followed up on an outpatient basis. The patient visited our emergency department 46 days after stent insertion due to abdominal pain. The patient was diagnosed with ruptured pseudoaneurysm of the superior pancreaticoduodenal artery by angiography and treated with coil embolization. He died due to sudden deterioration the next day. Pathological autopsy revealed that the cause of the ruptured pseudoaneurysm appeared to be vasculopathy due to radiation therapy.

MicroRNAs secreted by human preimplantation embryos and IVF outcome.

OBJECTIVE: To generate an effective embryo prediction model and identify a non-invasive evaluation method by analyzing microRNAs (miRNAs) in embryo culture medium. DESIGN: Analysis of microRNA profiles from spent culture medium of blastocysts with good morphology that did or did not result in pregnancy. SETTING: Clinical and experimental research. PATIENTS: Sixty patients who underwent thawed embryo transfer of blastocysts after intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association of miRNA abundance levels secreted by blastocysts in culture medium and implantation success. RESULTS: Our RNA sequencing analysis found a total of 53 differentially expressed miRNAs in the culture media of pregnancy and non-pregnancy groups. Twenty-one miRNAs were analyzed for their potential to predict implantation success. Eight miRNAs (hsa-miR-191-5p, hsa-miR-320a, hsa-miR-92a-3p, hsa-miR-509-3p, hsa-miR-378a-3p, hsa-miR-28-3p, hsa-miR-512-5p, and hsa-miR-181a-5p) were further extracted from the results of a logistic regression analysis of qPCR Ct values. A prediction model for high-quality blastocysts was generated using the eight miRNAs, with an average accuracy of 0.82 by 5-fold cross validation. CONCLUSION: We isolated blastocyst miRNAs that may predict implantation success and created a model to predict viable embryos. Increasing the number of investigated cases and further studying the effect of each miRNA on embryonic development is needed to refine the miRNA-based predictive model.

[Diffuse Pulmonary Meningotheliomatosis Needed to be Differentiate from Metastatic Lung Tumor:Report of a Case].

A 77-year-old woman was found to have multiple granular shadows in the bilateral lungs and a right mammary mass on chest computed tomography (CT) scan for preoperative check of colorectal cancer. The right mammary mass was diagnosed as breast cancer as a result of vacuum-assisted breast biopsy. Fluorodeoxyglucose-positron emission tomography( FDG-PET) showed no abnormal uptake in the lung fields. Since a transbronchial lung biopsy did not establish a diagnosis, an incisional biopsy was performed via a thoracoscopic approach. The histology of the pulmonary nodules revealed minute pulmonary meningothelial-like nodules (MPMNs) and the patient was diagnosed with diffuse pulmonary meningotheliomatosis (DPM). When multiple pulmonary nodules are found in patients with coexisting malignancy, DPM should be considered in addition to metastatic lung tumors.

Masticatory performance and other oral functions in community-dwelling elderly patients without posterior occlusal support by natural teeth.

PURPOSE: To evaluate masticatory performance (MP), maximum occlusal force (MOF), maximum tongue pressure (MTP) and oral diadochokinesis (ODK) among community-dwelling elderly patients without posterior occlusal support. METHODS: This study enrolled community-dwelling elderly patients (≥65 years old) who belonged to Eichner A, B4, C1, C2, and C3. Each oral function was statistically compared among groups. Correlations between MP and other variables were examined in Eichner B4 and C patients. RESULTS: MP and MOF values in Eichner B4 and C patients were significantly lower than in Eichner A patients. There were significant differences in MTP values between Eichner "A and C2, C3", and "B4 and C2, C3". ODK in Eichner C patients showed significantly lower values compared to Eichner A patients in general. Although there were statistically significant correlations of MP with age, the number of remaining teeth and all oral functions were identified, and multiple regression analysis indicated that MOF and MTP were independently related to MP. CONCLUSION: Oral functions in Eichner B4 and C patients were lower compared to Eichner A patients. MP was significantly correlated with MOF and MTP in elderly patients without posterior occlusal support, suggesting the importance of rehabilitation of MOF and MTP in MP.

Long Carbon-Carbon Bonding beyond 2 Å in Tris(9-fluorenylidene)methane.

We report on our investigation of C-C bonding longer than 2.0 Å, which can be realized by perpendicularly facing two fluorenyl rings in the title compound. A small orbital overlap between the distantly positioned carbon atoms is observed as a small concentration of electrons on the X-ray electron density map. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the compound originate from the in-phase and out-of-phase interactions of the overlapping orbitals, respectively, with a gap of 2.39 eV. Solid-state 13C NMR spectroscopy shows a sharp peak at 82.9 ppm for the long-bonded carbons, and a CASSCF(6,6) calculation indicates small diradical character. The experimental and theoretical analyses reveal sufficient covalent-bonding interaction in the long-bonded carbon pair.

Analyses of Swallowing Function and Its Related Factors in Community-Dwelling Elderly Patients: A Case-Control Study.

This retrospective case-control study evaluated the prevalence of declined swallowing function and the association with oral functions and gender in community-dwelling elderly patients. Their profiles, the results of swallowing function (Eating Assessment Tool: EAT-10) and other oral functions (oral dryness, maximum occlusal force (MOF), tongue-lip motor function (oral diadochokinesis: ODK), maximum tongue pressure (MTP) and masticatory performance (MP)) were extracted for analyses. The patients were categorized into three groups according to EAT-10 score (Group 1: 0, Group 2: 1 and 2, Group 3: ≥3). In total, 242 patients were enrolled and 46 of them (19.0%) were categorized into declined swallowing function (Group 3). In two-group comparisons (Group 1, 2 versus Group 3), significant differences were identified in age and the number of remaining teeth, but they were not identified in three-group comparisons. The patients with declined swallowing function (Group 3) had significantly lower function in ODK and MTP. Multiple logistic regression analyses identified that declined swallowing function was independently associated with declined functions in ODK /ka/ (OR: 5.31, 95% CI: 1.03-27.23, p = 0.04) and in MTP (OR: 2.74, 95% CI: 1.12-6.66, p = 0.03). This study could confirm the critical role of tongue functions in swallowing in community-dwelling elderly patients.

Error Evaluation for Automated Diameter Measurements of Cerebral Capillaries Captured with Two-Photon Laser Scanning Fluorescence Microscopy.

Cerebral capillaries respond to changes in neural activity to maintain regional balances between energy demand and supply. However, the quantitative aspects of the capillary diameter responses and their contribution to oxygen supply to tissue remain incompletely understood. The purpose of the present study is to check if the diameters measured from large-scale angiographic image data of two-photon laser scanning fluorescent microscopy (2PLSM) are correctly determined with a custom-written MATLAB software and to investigate how the measurement errors can be reduced, such as at the junction areas of capillaries. As a result, nearly 17% of the measured locations appeared to be outliers of the automated diameter measurements, in particular arising from the junction areas where three capillary segments merged. We observed that about two-thirds of the outliers originated from the measured locations within 6 µm from the branching point. The results indicate that the capillary locations in the junction areas cause non-negligible errors in the automated diameter measurements. Considering the common site of the outliers, the present study identified that the areas within 6 µm from the branch point could be separately measured from the diameter analysis, and careful manual inspection with reference to the original images for these transition areas around the branch point is further recommended.

Time Series Tracking of Cerebral Microvascular Adaptation to Hypoxia and Hyperoxia Imaged with Repeated In Vivo Two-Photon Microscopy.

The present study describes methodological aspects of image analysis for angiographic image data with long-term two-photon microscopy acquired for the investigation of dynamic changes in the three-dimensional (3D) network structure of the capillaries (less than 8 µm in diameter) in the mouse cerebral cortex. Volume images of the identical capillaries over different periods of days up to 32 days were compared for adaptation under either chronic hypoxia (8-9% O2) or hyperoxia (40-50% O2). We observed that the median diameters of measured capillaries were 5.8, 8.4, 9.0, and 8.4 µm at 0, 1, 2, and 3 weeks during exposure to hypoxia, respectively (N = 1, n = 2193 pairs at day 0), and 5.4, 5.7, 5.4, 6.0, and 6.1 µm measured weekly up to 32 days under hyperoxia (N = 1, n = 1025 pairs at day 0). In accordance with these changes in capillary diameters, tissue space was also observed to change in a depth-dependent manner under hypoxia, but not hyperoxia. The present methods provide us with a method to quantitatively determine three-dimensional vascular and tissue morphology with the aid of a computer-assisted graphical user interface, which facilitates morphometric analysis of the cerebral microvasculature and its correlation with the adaptation of brain cells imaged simultaneously with the microvasculature.

Glucose transporter Glut1 controls diffuse invasion phenotype with perineuronal satellitosis in diffuse glioma microenvironment.

BACKGROUND: Gliomas typically escape surgical resection and recur due to their "diffuse invasion" phenotype, enabling them to infiltrate diffusely into the normal brain parenchyma. Over the past 80 years, studies have revealed 2 key features of the "diffuse invasion" phenotype, designated the Scherer's secondary structure, and include perineuronal satellitosis (PS) and perivascular satellitosis (PVS). However, the mechanisms are still unknown. METHODS: We established a mouse glioma cell line (IG27) by manipulating the histone H3K27M mutation, frequently harboring in diffuse intrinsic pontine gliomas, that reproduced the diffuse invasion phenotype, PS and PVS, following intracranial transplantation in the mouse brain. Further, to broadly apply the results in this mouse model to human gliomas, we analyzed data from 66 glioma patients. RESULTS: Increased H3K27 acetylation in IG27 cells activated glucose transporter 1 (Glut1) expression and induced aerobic glycolysis and TCA cycle activation, leading to lactate, acetyl-CoA, and oncometabolite production irrespective of oxygen and glucose levels. Gain- and loss-of-function in vivo experiments demonstrated that Glut1 controls the PS of glioma cells, that is, attachment to and contact with neurons. GLUT1 is also associated with early progression in glioma patients. CONCLUSIONS: Targeting the transporter Glut1 suppresses the unique phenotype, "diffuse invasion" in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.

An unusual case of eosinophilic lung disease with multiple cyst formation.

We report here an unusual case of eosinophilic necrotizing inflammation of the lung that mimicked chronic eosinophilic pneumonia. A 71-year-old man who lived in an unsanitary environment and was referred to our hospital with suspected pneumonia. Peripheral blood eosinophilia was observed, and computed tomography indicated extensive consolidation with multiple cystic lesions, mainly in the left lung. A histological analysis using video-assisted thoracic surgery revealed diffuse infiltration of inflammatory cells into the alveolar wall and massive accumulation of macrophages and eosinophils in the airspace. Many tiny eosinophilic abscesses were scattered through the tissue. These findings were more severe than those associated with chronic eosinophilic pneumonia. Immunostaining revealed the deposition of eosinophil granular protein and the presence of extracellular traps and Charcot-Leyden crystals, which suggested excessive eosinophil activation. Interestingly, the patient's symptoms and clinical findings gradually improved without treatment after admission. He was discharged to a clean residence and did not have a recurrence for 19 months. The observations suggest a hypersensitivity reaction to an environmental allergen and consequent multiple cyst formation in association with eosinophilic necrotizing inflammation, although further studies are warranted.

Relationship between Maximum Tongue Pressure Value and Age, Occlusal Status, or Body Mass Index among the Community-Dwelling Elderly.

Background and objectives: In an aging society, the maintenance of the oral function of the elderly is of importance for the delay or prevention of frailty and long-term care. In the present study, we focused on the maximum tongue pressure (MTP) value and analyzed the relationship between MTP and age, occlusal status, or body mass index (BMI). Materials and Methods: This one-center observatory study was conducted using a cohort consisting of 205 community-dwelling outpatients over 65 years old. The MTP values of all subjects were measured using a commercially available tongue pressure measurement device and statistically analyzed. In addition, the correlation between MTP value and BMI was analyzed. Results: The MTP value decreased with age, especially in subjects classified as Eichner B and C. The difference in occlusal status did not show any statistically significant influence on MTP value. The correlation between BMI and MTP value was indicated in the tested groups other than an age of 65-74 and Eichner A groups. Conclusions: Although MTP value decreased with age, the difference in occlusal status did not have an impact on MTP value. The correlation between BMI and MTP value was not shown in the youngest group or a group with sufficient occlusal units. The results presented in the present study may imply that, even if MTP is low, younger age and/or better occlusal status compensate for the inferior MTP value in the cohort studied.

Self-Emulsifying Drug Delivery System of Celecoxib for Avoiding Delayed Oral Absorption in Rats with Impaired Gastric Motility.

This study aimed to develop a self-emulsifying drug delivery system (SEDDS) of celecoxib (CEL) for suppressed delay in oral absorption under impaired gastric motility. A pseudo-ternary phase diagram was constructed for the determination of the optimal component ratio in SEDDS of CEL (SEDDS/CEL), and the SEDDS/CEL was physicochemically characterized. A pharmacokinetic study on orally dosed CEL samples (5-mg CEL/kg) was carried out in normal and propantheline (PPT)-treated rats to mimic impaired gastric motility. SEDDS/CEL rapidly formed a fine emulsion with a mean size of 147 nm in distilled water and significantly improved the dissolution behavior of CEL under pH 1.2 condition with a 20-fold higher dissolved amount than crystalline CEL. In normal rats, orally dosed SEDDS/CEL provided a 4.6-fold higher systemic exposure than that of crystalline CEL, due to the improved dissolution properties of CEL. Crystalline CEL showed delayed and decreased oral absorption of CEL in PPT-treated rats as evidenced by a 6.9-h-delayed mean absorption time and only 12% of the systemic exposure of CEL compared with those in normal rats. In contrast, SEDDS/CEL enhanced the oral absorption of CEL with a 14.6-fold higher systemic exposure with significant suppression of delay in absorption than crystalline CEL even in PPT-treated rats. SEDDS/CEL could be an efficacious option for suppressing delay in CEL absorption even under impairment of gastric motility, possibly leading to rapid and reproducible management of severe acute pain.