Determination of the safety of Halomonas sp. KM-1-derived D-ß-hydroxybutyric acid and its fermentation-derived impurities in mice and Japanese adults.

The use of halophilic bacteria in industrial chemical and food production has received great interest because of the unique properties of these bacteria; however, their safety remains under investigation. Halomonas sp. KM-1 intracellularly stores poly-D-ß-hydroxybutyric acid under aerobic conditions and successively secretes D-ß-hydroxybutyric acid (D-BHB) under microaerobic conditions. Therefore, we tested the safety of Halomonas sp. KM-1-derived D-BHB and the impurities generated during D-BHB manufacturing at a 100-fold increased concentration in acute tests using mice and daily intake of 16.0 g D-BHB in Japanese adults for 12 weeks. In the mice test, there were no abnormalities in the body weights or health of mice fed the purified D-BHB or its impurities. In the Japanese adult test, blood parameters and body condition showed no medically problematic fluctuations. These findings indicate that Halomonas sp. KM-1 is safe and can be used for commercial production of D-BHB and its derivatives.

Dental Abnormalities in Pediatric Patients Receiving Chemotherapy.

Background: Chemotherapy is a common treatment for pediatric cancer. Although life prognosis is improving because of advances in medical science, it is important to deal with late effects such as dental abnormalities. We investigated the association between dental abnormalities and chemotherapy by age and tooth type. Methods: Among the 568 patients referred to the pediatric dentistry department of our hospital, we selected 32 patients (21 male and 11 female) who received chemotherapy between the ages of 0 and 6 and underwent panoramic examination after the age of 7. We recorded the age of chemotherapy commencement, diagnosis of systemic disease, and dental abnormalities such as congenital absence, microdonts, and short-rooted teeth. Results: Almost half of the patients had dental abnormalities such as congenital absence, microdonts, and short-rooted teeth, but there were no significant differences in the incidence of these abnormalities by age. When we analyzed the incidence of abnormal teeth by tooth type, the incidence of congenital absence was significantly higher in premolars (5.5%) and second molars (3.9%) than in incisor or canine or 1st molar (0.4%) (p < 0.01). The incidence of microdonts was significantly higher in premolars (3.9%) than in incisor or canine or 1st molar (0.2%) and second molars (0.0%) (p < 0.05). Conclusions: Patients who received chemotherapy had a high prevalence of dental abnormalities, and the incidence of abnormalities varied by tooth type. It is important to maintain long-term oral care for patients who have undergone chemotherapy even after the treatment is completed.

Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001).

OBJECTIVES: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery. MATERIALS AND METHODS: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate. RESULTS: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort. CONCLUSIONS: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted.

Effects of Extended Fixation on Advanced Gastric Cancer HER2 Status Assessment Using IHC and FISH.

BACKGROUND/AIM: In gastric cancer, accurate determination of human epidermal growth factor receptor type 2 (HER2) status is crucial for treatment decision-making. However, the optimal formalin fixation time of gastric cancer specimens for HER2 status determination remains unestablished. Here, we investigated real-world data on formalin overfixation and its effect on HER2 status determination in gastric cancer. PATIENTS AND METHODS: We comprehensively analyzed HER2 testing results in 228 gastric cancer specimens, including those subjected to formalin overfixation. Subsequently, we divided 52 resected specimens of advanced gastric cancer into three groups and studied the effects of short-term (6-72 h) and long-term (1 and 2 weeks) fixation on HER2 status determination using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: A total of 21.5% (49/228) of the specimens were HER2-positive, whereas 78.5% (179/228) were negative. Among the HER2-negative specimens, no biopsies were overfixed, whereas 12.5% (9/72) of the surgical resection specimens were overfixed. The HER2 status of the 6-72-h group was 82.7% and 76.9% identical to that of the 1- and 2-week groups, when determined using IHC, and 73.1% and 36.5%, when determined using FISH, respectively. However, HER2 determination was not feasible in 26.9% and 63.5% of the specimens in the 1- and 2-week groups, respectively. CONCLUSION: Formalin overfixation may hinder the determination of HER2 status and should be avoided in gastric cancer sample preparation.

Primary Pleural Angiosarcoma Treated with Nivolumab and Ipilimumab: A Case Report.

Primary pleural angiosarcoma (PPA) is a rare and clinically fatal pleural tumor originating from vascular endothelial cells. Herein, we presented the case of a 73-year-old man who was referred to our emergency room with complaints of right chest and back pain for a few days. Chest computed tomography revealed massive pleural effusion and a large mass in the right chest cavity. Thoracoscopic examination demonstrated a large hemorrhagic tumor on the parietal pleura whose pathological analysis indicated PPA. The patient received immunotherapy combined with nivolumab and ipilimumab. A cycle of nivolumab and ipilimumab improved his hemorrhagic anemia and reduced the pleural effusion and tumor size. This treatment outcome suggests that nivolumab and ipilimumab comprise a vital treatment option for PPA.

Fusion of a Tooth with a Supernumerary Tooth: A Case Report and Literature Review of 35 Cases.

Tooth fusion is a dental anomaly with a prevalence of 0.1% in permanent dentition. The aim of this paper is to present the occurrence, region of fusion, and prognosis of fused tooth which is a very rare case in the literature. The authors present a very rare case with a maxillary right lateral incisor fused to a supernumerary tooth on the palatal side. The eruption was delayed, but eruption occurred naturally at 9 years and 6 months. However, cone-beam computed tomography at 11 years and 6 months revealed it was diagnosed as a fused tooth. The authors undertook a literature review over the past 10 years and found 30 articles about fused teeth between permanent teeth and supernumerary teeth. It was more common in males than females and there were no differences depending on the occurrence. Mesiodistal fusion was more common in the incisor region, while labiopalatal fusion was more common in the molar region. Most cases required dental treatment with a surgical approach, root canal treatment, or orthodontic treatment. The present study highlights the importance of long-term follow-up and suggests the region of fusion and prognosis of the fused tooth may vary depending on the occurrence.

[A Case of Advanced Esophageal Cancer with pCR after Preoperative DCF Chemotherapy].

The patient is a man in his 60s. The patient was diagnosed with advanced esophageal cancer(cT3N0M0, cStage Ⅱ)and was treated with 2 courses of docetaxel/cisplatin/5-FU(DCF)combination as preoperative chemotherapy. On imaging, the tumor was markedly reduced. Adverse events were febrile neutropenia in the first course, neutropenia Grade 3 and vasculitis Grade 1 in the second course. We performed thoracoscopic subtotal esophagectomy and gastric tube reconstruction with lymphadenectomy. The histopathological findings showed no residual viable tumor cells. The pathological effect of chemotherapy was defined as Grade 3(pCR). Eight months post-operatively with no recurrence. Our case suggested that DCF chemotherapy is potentially a very effective treatment for advanced esophageal cancer.

Autoimmune pulmonary alveolar proteinosis with features similar to nonspecific interstitial pneumonia.

A 58-year-old woman with cough and dyspnea who was suspected of having idiopathic interstitial pneumonia had been treated with corticosteroids and cyclosporine, but the symptoms had worsened. There were no findings to suspect pulmonary alveolar proteinosis (PAP) in the bronchoalveolar lavage fluid, 17 months after the start of treatment. The transbronchial lung biopsy specimens showed eosinophilic bodies that strongly stained with periodic acid-Schiff staining. Anti-granulocyte macrophage colony-stimulating factor (anti-GM-CSF) antibodies were detected in her serum. We diagnosed the patient with autoimmune PAP. Thus, we present a rare case of PAP presenting atypical radiological images and bronchoalveolar lavage fluid findings.

Identification of New Halomonas Strains from Food-related Environments.

Halomonas species, which are aerobic, alkaliphilic, and moderately halophilic bacteria, produce diverse biochemicals. To identify food-related Halomonas strains for bioremediation and the industrial production of biochemicals, 20 strains were isolated from edible seashells, shrimp, and umeboshi (pickled Japanese plum) factory effluents. All isolates were phylogenetically classified into a large clade of Halomonas species. Most isolates, which grew in wide pH (6-13) and salt concentration (0-14%) ranges, exhibited the intracellular accumulation of poly(3-hydroxybutyrate) granules. The characteristics of these isolates varied. A020 isolated from umeboshi factory effluents exhibited enhanced stress tolerance and proliferation and comprised two plasmids. IMZ03 and A020 grew to more than 200 OD600, while IMZ03 produced 3.5% 3-hydroxybutyrate in inorganic medium supplemented with 10% sucrose. The mucus of TK1-1 cultured on agar medium comprised approximately 64| |mM of ectoine. Whole-genome sequencing of A020 was performed to elucidate its origin and genomic characteristics. The genome ana-lysis revealed a region exhibiting synteny with a large virus genome isolated from the ocean, but did not identify any predictable pathogenic genes. Therefore, saline foods and related materials may be suitable resources for isolating Halomonas strains exhibiting unique, useful, and innocuous features.

Vertical migration of cesium in weathered granite soil under flowing water condition depending on Cs concentration and states of dissolved organic matter.

After the accident at the Fukushima Daiichi nuclear power plant in Japan, the migration of radioactive cesium (Cs) in soils has become a crucial issue since this can negatively affect human health and the surrounding environment. Dissolved organic matter (DOM) may have different influences on Cs migration in soils depending on Cs adsorption sites with different selectivity. It is unclear how DOM affects the rapid migration of Cs in soils under flowing water conditions during rainfall events. This study evaluated the effects of DOM on Cs migration in weathered granite soil depending on Cs adsorption sites by conducting laboratory experiments under different DOM conditions and Cs concentrations in the liquid phase. Cs concentration can affect the fraction of Cs adsorbed onto differently selective sites, and DOM can have different influences on Cs migration in the soil accordingly. Under condition of high-Cs concentration, the DOM adsorbed on the soil reduced Cs migration due to increasing Cs electrostatic adsorption to less selective sites in the soil. Meanwhile, under low-Cs concentration, the DOM adsorbed on the soil enhanced Cs migration because the DOM on the soil decreased the Cs adsorption to highly selective sites. Furthermore, DOM in the liquid phase detached the Cs adsorbed on the less selective sites and enhanced Cs migration in the soil, regardless of the Cs concentration.

Multiple Cranial Neuropathies Similar to Orbital Apex Syndrome Associated with Pembrolizumab: A Case Report.

Neurotoxicity is one of the more serious immune-related adverse events (irAEs) linked to immune checkpoint inhibitors and calls for prompt diagnosis and treatment. We describe a case of posttreatment anti-programmed death-1 immune checkpoint inhibitor pembrolizumab-induced oculomotor, optic, and trigeminal neuropathy in an 84-year-old female patient with recurrent pulmonary adenocarcinoma. After she received 13 cycles of pembrolizumab, she experienced hyponatremia, anorexia, and right ptosis. There were signs of the suspected irAEs of pembrolizumab, including trigeminal neuropathy, optic neuropathy, and oculomotor neuropathy. Steroid pulse therapy had good results for her neurological findings. We reported this case despite reports of pembrolizumab-induced mononeuropathy of the oculomotor and optic nerves because multiple cranial neuropathies like orbital apex syndrome are thought to be uncommon.

[A Case of Multiple Liver Metastases of Mixed Adenonuroendocrine Carcinoma of the Ascending Colon with Poor Prognosis].

An 84-year-old woman presented with anorexia. CT showed ascending colon and multiple liver tumors, and a colonoscopy showed severe stenosis due to a tumor in the ascending colon. We diagnosed obstructive colon cancer with multiple liver metastases. It was difficult to approach this case with a colonic stent, and we suggested a colostomy, but the patient strongly objected and requested to undergo resection; thus, a laparoscopic right hemicolectomy was performed. Intraoperatively, there was no normal liver tissue, and liver metastases were diffuse. Histopathologically, neuroendocrine carcinoma and differentiated tubular adenocarcinoma were found; MANEC was diagnosed. Oral intake was started on the third postoperative day, but liver failure progressed gradually. Despite the best supportive care and medication, the patient died of liver failure 16 days after surgery. We report our experience of a MANEC case with a poor prognosis along with a literature review.

Inhibited nanobubble transport in a saturated porous medium: Effects of deposited colloidal particles.

Nanobubbles have recently attracted much interest for their practical use and potential applications in environmental issues. The pre-existence of deposited colloidal particles in porous media commonly occurs when nanobubbles applied to porous media interact with deposited colloidal particles. However, the current understanding of the effect of the interactions with pre-deposited colloidal particles on nanobubble transport in saturated porous media remains incomplete, and the effects are often overlooked. Therefore, we performed 1D column experiments with sequential injections of colloidal and nanobubble suspensions to study the effect of pre-deposited materials on the retention and release of colloids and nanobubbles in packed glass beads. In this study, we used resonant mass measurements to measure the number concentrations of colloids and nanobubbles during transport experiments for the first time to distinguish between coexisting solid colloidal particles and nanobubbles with different buoyancies in mixed effluent during transport. The nanobubble retention increased because of the pre-existence of deposited colloidal particles, indicating that the deposited colloidal particles act as additional deposition sites and physical obstacles for nanobubbles through physicochemical (including hydrophobic) interactions. This study also provides a future reference for the applicability of resonant mass measurement to cotransport experiments of different buoyant particles, including colloids, nanobubbles, and oil droplets.

[A Case of Gastric Perforation Due to an Unresectable Advanced Gastric Cancer That Achieved pCR after Conversion Surgery following SOX plus T-mab Therapy].

This case pertains to a 72-year-old man who visited the emergency department with a complaint of upper abdominal pain. On examination, we suspected gastric perforation due to gastric cancer and decided to perform emergency surgery. We performed laparoscopic omentoplasty and collected #4d lymph nodes that were enlarged on CT. The pathological diagnosis was lymph node metastasis. Based on CT findings, we determined it was Bulky N. For initial management, we performed 3 preoperative chemotherapy(SOX therapy)courses and staging laparoscopy. On surgery, extensive disseminated nodules on the abdominal wall, stomach wall, and liver surface were found, and ascites cytology revealed positive findings. Therefore, we did not perform primary lesion resection. Although the disseminated nodule did not pathologically show tumor cells, CY1 was found, resulting to a diagnosis of unresectable gastric cancer. Since the tumor was HER2 3+, we initiated SOX/trastuzumab therapy. After 16 courses, staging laparoscopy was performed as the lymph nodes had shrunk significantly. The results showed no tumor cells in ascites and the disseminated nodules, and laparoscopic total gastrectomy was subsequently performed. Pathological findings showed no tumor cells in the primary lesion or lymph nodes; therefore, a diagnosis of pathological complete response was made. Currently, the patient is alive without recurrence for 6 months after surgery.

[A Case Report of Recurrence on Umbilical Port Site and Ileum Close to Anastomotic Portion after Laparoscopic Ileocecal Resection for Cecal Cancer].

We report a case of recurrence on umbilical port site and ileum close to anastomotic portion after laparoscopic ileocecal resection for cecal cancer. A 62-year-old woman was diagnosed as cecal cancer and performed ileocecal resection with D3 lymphadenectomy. One year and half after surgery, recurrence on umbilical port site and ileum close to anastomotic portion was detected with computed tomography and positron emission tomography. Chemotherapy(CAPOX plus Bmab)was performed. As a result of partial response, we performed resection of umbilical portion and anastomotic portion. Adjuvant chemotherapy was not performed. Neither recurrence or metastasis have been detected until 10 months after surgery.

Rhizosphere modelling reveals spatiotemporal distribution of daidzein shaping soybean rhizosphere bacterial community.

Plant roots nurture a wide variety of microbes via exudation of metabolites, shaping the rhizosphere's microbial community. Despite the importance of plant specialized metabolites in the assemblage and function of microbial communities in the rhizosphere, little is known of how far the effects of these metabolites extend through the soil. We employed a fluid model to simulate the spatiotemporal distribution of daidzein, an isoflavone secreted from soybean roots, and validated using soybeans grown in a rhizobox. We then analysed how daidzein affects bacterial communities using soils artificially treated with daidzein. Simulation of daidzein distribution showed that it was only present within a few millimetres of root surfaces. After 14 days in a rhizobox, daidzein was only present within 2 mm of root surfaces. Soils with different concentrations of daidzein showed different community composition, with reduced α-diversity in daidzein-treated soils. Bacterial communities of daidzein-treated soils were closer to those of the soybean rhizosphere than those of bulk soils. This study highlighted the limited distribution of daidzein within a few millimetres of root surfaces and demonstrated a novel role of daidzein in assembling bacterial communities in the rhizosphere by acting as more of a repellant than an attractant.

Effects of the dissolved organic matter on Cs transport in the weathered granite soil.

It is important to understand the migration of Cesium (Cs) in soils, particularly after the nuclear power plant accident at Fukushima Dai-ichi, Japan. Dissolved organic matter (DOM) is one of factors affecting the migration of Cs in soils under flowing water conditions. We investigated the effect of DOM on the migration of Cs adsorbed to the clay planar site via laboratory column experiments. The sequence of DOM application had a significant influence on Cs transport in the soil. When DOM was applied concurrently with or prior to Cs application, the DOM adsorbed on to the clay planar site adsorbed onto the soil solid surface and enhanced Cs adsorption; consequently, it slowed Cs migration in the soil. In particular, in the case of DOM loaded prior to the application of Cs solution, a noticeable delay in Cs migration was observed. On the other hand, when DOM was applied to the soil where the Cs solution had been previously applied, the DOM desorbed Cs from the soil. DOM in liquid phase enhanced the migration of Cs through the formation of binding to organic matter. Majority of Cs affected by DOM was the exchangeable fraction that adsorbed to the clay planar site. In other words, DOM attached to the soil would adsorb Cs as a easily exchangeable form and depress migration of Cs. On the other hand, DOM in the soil solution may up take adsorbed Cs from the soil and enhanced the transport in the form of Cs bound to DOM.

Estimation of heat-related morbidity from weather data: A computational study in three prefectures of Japan over 2013-2018.

In recent years, the rates of heat-related morbidity and mortality have begun to increase with the increase in global warming; in this context, it is noteworthy that the number of patients transported by ambulance in heat-related cases in Japan reached 95,137 in 2018. The estimation of heat-related morbidity forms a key factor in proposing and implementing suitable intervention strategies and ambulance availability and arrangements. Heat-related morbidity is known to be fairly correlated to metrics related to ambient conditions, thus necessitating the exploration of new metrics to more accurately estimate morbidity. In this study, we use an integrated computational technique relating to thermodynamics and thermoregulation to estimate daily peak core temperature elevation and daily water loss, which are linked to heat-related illnesses, from weather data of three different prefectures in Japan (Tokyo, Osaka, and Aichi). The correlations of the computed core temperature elevation and water loss as well as conventional ambient conditions are investigated in terms of number of patients suffering from heat-related illnesses transported by ambulance from 2013 to 2018. The estimated water loss per the proposed computation yields better correlation with the number of patients transported by ambulance. In particular, the weight-sum daily water loss for two to three successive days is found to be an important metric for predicting the number of patients transported by ambulance. For the same ambient conditions, morbidity is found to decrease to 0.4 owing to heat adaption at the end of summer (60 days) as compared with that at the end of the rainy season. Thus, the weighted sum of water loss and daily average ambient temperature for successive days can be used as better metrics than conventional weather data for the application of intervention strategies and planning of ambulance arrangements for heat-related morbidity.

Nanobubble Retention in Saturated Porous Media under Repulsive van der Waals and Electrostatic Conditions.

An understanding of nanobubble (NB) migration in porous media is needed for potential environmental applications. The solution chemistry is well known to be a critical factor in determining interactions of other colloids and nanoparticles with surfaces. However, little quantitative research has examined the influence of solution chemistry on NB transport. One-dimensional column experiments were therefore conducted to investigate the transport, retention, and release of NBs in glass beads under different solution chemistry conditions. NB concentrations in the effluent were reduced with an increase in ionic strength (IS) or a decrease in pH due to a reduction in the repulsive force between the glass surface and NBs, especially when the solution contained Ca2+ as compared to Na+ and for larger NBs. This result was somewhat surprising because electrostatic and van der Waals interactions for NBs were both repulsive on a homogeneous glass bead surface. NB retention on the surface was explained by ubiquitous nanoscale roughness on the glass beads that significantly lowered the energy barrier and localized attractive charge heterogeneity and/or hydrophobic interactions. In contrast to Na+, adsorbed Ca2+ ions produced charge heterogeneity that enhanced NB retention and inhibited release with IS reduction.

Multicenter phase II study of biweekly CAPIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study).

BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. METHODS: Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). RESULTS: Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23-7.40 months], and median OS was 13.5 months (95% CI 11.57-20.23 months). The RR was 14.6% (95% CI 6.5-28.4%), and the DCR was 66.7% (95% CI 51.5-79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand-foot syndrome. CONCLUSIONS: In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.