Morphological and antioxidant responses of Nopalea cochenillifera cv. Maya (edible Opuntia sp. "Kasugai Saboten") to chilling acclimatization.

To clarify the wintering ability of the cactus Nopalea cochenillifera cv. Maya (edible Opuntia sp., common name "Kasugai Saboten"), we investigated the effects of temperature and antioxidant capacity on chilling acclimatization. We analyzed the anatomy of cladode chlorenchyma tissue of plants exposed to light under chilling. We found that chilling acclimatization can be achieved by exposure to approximately 15 °C for 2 weeks and suggest that it is affected by whether or not antioxidant capacity can recover. The overwintering cacti had the thinnest cuticle but firm cuticular wax, which is important in the acquisition of low temperature tolerance under strong light. In cacti with severe chilling injury, round swollen nuclei with clumping chloroplasts were localized in the upper part (axial side) of the cell, as though pushed up by large vacuoles in the lower part. In overwintering cacti, chloroplasts were arranged on the lateral side of the cell as in control plants, but they formed pockets: invaginations with a thin layer of chloroplast stroma that surrounded mitochondria and peroxisomes. Specific cellular structural changes depended on the degree of chilling stress and provide useful insights linking chloroplast behavior and structural changes to the environmental stress response.

[A Case of Diffuse Large B Cell Lymphoma of the Extrahepatic Bile Duct Cholangiocarcinoma].

The patient was an 81-year-old man who was hospitalized with poor appetite and obstructive jaundice. An abdominal CT scan showed remarkable thickening of the wall from the cystic duct to extrahepatic bile duct. Endoscopic retrograde cholangiopancreatography( ERCP)revealed stricture at the extrahepatic bile duct. Cholangiocarcinoma was diagnosed and pancreaticoduodenectomy was performed. The histopathological diagnosis was diffuse large B cell lymphoma (DLBCL). The patient was stable after the operation. We present a case report describing the resection of DLBCL of the extrahepatic bile duct along with a review of the literature.

[A Case of Gastric Endocrine Carcinoma].

The patient was an 80-year-old man, hospitalized with poor appetite, light-headedness, and black stool. Esophagogastroduodenoscopy showed an ulcerative lesion in cardia, and the tumor was diagnosed as gastric cancer using the biopsy specimens. The patient underwent a gastrectomy with D1-node dissection. Pathologically, the small tumor cells infiltrated the muscularis propria of the gastric wall, and these tumor cells immunohistochemically showed a positive reaction for synaptophysin. Therefore, the tumor was diagnosed as small cell-neuroendocrine carcinoma of the stomach. Metastasis was not observed in regional lymph nodes, and the TNM classification was defined as pStage ⅠB. After surgery, adjuvant chemotherapy was not performed. The patient is well without recurrence for more than 7 months after the surgery. We experienced and report a case of gastric endocrine cell carcinoma that underwent resection and provide a review of the literature.

Breeding and characterization of the high cadmium-accumulating rice line 'Akita 119'.

Cadmium (Cd) is a toxic heavy metal that is mainly accumulated through the consumption of foods produced in Cd-contaminated fields. Phytoremediation is one of the most effective methods to reduce the soil Cd concentration. In this study, we bred a new rice line, 'Akita 119', for Cd phytoremediation. 'Akita 119' was obtained by a soft X-ray mutation of 'Cho-ko-koku', a naturally high-Cd-accumulating rice cultivar. The heading date of 'Akita 119' was about 2 weeks later than that of 'Akitakomachi', which is the leading cultivar in Akita Prefecture, Japan. 'Akita 119' has a short culm length and many panicles. The shattering resistance and lodging resistance of 'Akita 119' were improved compared to 'Cho-ko-koku'. The thousand-grain weight of 'Akita 119' was much smaller than that of 'Akitakomachi', and grains of 'Akita 119' could be easily distinguished from general japonica cultivars. When 'Akita 119' was grown in Cd-contaminated fields, the shoot dry weight and Cd concentration were similar to those of 'Cho-ko-koku'. These results demonstrate that 'Akita 119' has improved agronomic characteristics compared to 'Cho-ko-koku' while retaining the ability to extract Cd. Therefore, it should be considered a promising candidate for Cd phytoremediation in paddy fields in northern parts of Japan.

Low- and high-dose aripiprazole augmentation and plasma levels of homovanillic acid in major depressive disorder: A randomized, open-label study.

OBJECTIVE: This randomized controlled study evaluated the efficacy of low-dose (LD) and high-dose (HD) aripiprazole augmentation in major depressive disorder. Additionally, we examined the relationship between clinical response and changes in plasma homovanillic acid (pHVA) levels during aripiprazole augmentation. METHODS: Thirty-one patients with inadequate response to antidepressants were randomized to receive adjunctive treatment with LD (3 mg/day, n = 17) or HD (up to 12 mg/day, n = 14) aripiprazole for 6 weeks. We evaluated the Montgomery-Åsberg Depression Rating Scale (MADRS) and measured pHVA at baseline, Week 2, and end point. RESULTS: Both LD and HD aripiprazole significantly decreased MADRS score after 6 weeks, and the response rate was higher in HD aripiprazole group at end point. HD aripiprazole significantly decreased MADRS score at Week 2 compared with LD aripiprazole (p = .015). There was a significant difference in changes in pHVA between responders and nonresponders, showing pHVA decreased significantly in responders at Week 2 (p = .044). CONCLUSIONS: Increasing aripiprazole from the early period appeared useful for immediate response, although caution is needed when increasing the dose >6 mg/day. pHVA may be a possible indicator of the response to aripiprazole augmentation. Caution is needed in interpreting these findings because of the small sample size.

Non-invasive estimation of 10 B-4-borono-L-phenylalanine-derived boron concentration in tumors by PET using 4-borono-2-18 F-fluoro-phenylalanine.

In boron neutron capture therapy (BNCT), 10 B-4-borono-L-phenylalanine (BPA) is commonly used as a 10 B carrier. PET using 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18 F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18 F-FBPA and BPA, and evaluated the utility of 18 F-FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid, an inhibitor of the L-type amino acid transporter, significantly inhibited 18 F-FBPA and 14 C-4-borono-L-phenylalanine (14 C-BPA) uptake in FaDu and LN-229 human cancer cells. 18 F-FBPA uptake strongly correlated with 14 C-BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18 F-FBPA was independent of the administration method, and uptake of 18 F-FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18 F-FBPA by PET was useful for estimating 10 B concentration in tumors.

Association between CYP2C19 genotype and the additional effect of cilostazol to clopidogrel resistance in neuroendovascular therapy.

We investigated the association between CYP2C19 genotype and additional effect of cilostazol on clopidogrel resistance (CR) in neuroendovascular therapy. Between January 2012 and January 2016, 447 consecutive patients were administered with 75-mg cilostazol/day. The VerifyNow System was used for evaluating P2Y12 reaction units (PRU) > 230 and/or percentage inhibition of platelet function (% Inhibition) ≤ 20 as CR. Among 158 patients with CR, 31 were administered with additional 100- or 200-mg cilostazol/day and their platelet function was evaluated. According to CYP2C19 genotypes revealed using the Spartan RX and DNeasy Blood & Tissue Kit, patients were classified into three phenotypic groups: extensive metabolizer (EM, three patients), intermediate metabolizer (IM, 12 patients), and poor metabolizer (PM, 16 patients). Administration of additional cilostazol decreased PRU (EM group: 160.7 ± 85.2 after vs 278.3 ± 40.1 before, P = 0.15; IM group: 205.6 ± 74.0 vs 254.3 ± 35.0, P = 0.02; and PM group: 227.8 ± 52.2 vs 282.1 ± 30.4, P = 0.003), and increased % Inhibition (EM group: 40.0 ± 27.9 vs 9.3 ± 3.8, P = 0.25; IM group: 31.4 ± 18.0 vs 11.8 ± 8.2, P = 0.001; and PM group: 24.6 ± 15.0 vs 10.4 ± 9.3, P = 0.001). However, the rate of normalized-clopidogrel response, thromboembolic lesions, and bleeding complications were not significantly different among the three groups. Thus, the addition of cilostazol was effective on CR in terms of PRU, % Inhibition, rate of change of normalized-clopidogrel response, thromboembolic events, and bleeding complications irrespective of phenotype.

[A Case of Fatal Interstitial Pneumonia during FOLFIRI plus Cetuximab Therapy for Liver Metastasis of Colon Cancer].

The patient was a 76-year-old woman who underwent sigmoidectomy in April 2011 for sigmoid colon cancer with multiple concurrent liver metastases. She was treated postoperatively with mFOLFOX6 plus cetuximab but was diagnosed with the progressive disease at the end of course 14. The patient started receiving FOLFIRI plus cetuximab therapy in May 2012. Later in August 2012, she was examined for respiratory distress on the scheduled date of receiving course 7 and was diagnosed with drug-induced interstitial pneumonia resulting from systemic chemotherapy. The patient was administered oxygen, and her symptoms improved temporarily with steroid half-pulse and endotoxin adsorption therapy, but on inpatient day 10, her respiratory condition deteriorated. She was treated with steroid pulse therapy, but died of respiratory failure on inpatient day 17. The main adverse events associated with FOLFIRI plus cetuximab therapy are gastrointestinal symptoms, hematotoxicity, peripheral nerve damage, and dermatological symptoms. However, reports of respiratory conditions such as interstitial pneumonia are rare. Although the incidence is low, interstitial pneumonia can be severe and fatal and therefore requires close attention.

Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system.

This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.

Isolation and Structure Elucidation of Cytotoxic Saccharothriolides D to F from a Rare Actinomycete Saccharothrix sp. and Their Structure-Activity Relationship.

Three new 10-membered macrolides, saccharothriolides D-F (1-3), were isolated from a rare actinomycete, Saccharothrix sp. A1506. The planar structures were determined from analysis of extensive NMR and HR-ESI-MS data, and the absolute configurations were established by ECD spectroscopy analysis. Saccharothriolides D (1) and E (2) were determined to be C-2 epimers of saccharothriolides A (4) and B (5), respectively. Saccharothriolide F (3) was identified to be a demethylated congener of saccharothriolides D (1) and A (4) at the C-2 position. The availability of compounds 1-6 enabled a structure-activity relationship study that revealed the importance of the phenolic hydroxy group at C-2″ and the stereochemistry of C-2 for the inhibition of human fibrosarcoma HT1080 cell growth.

[A Case of Stage â £ Rectal Cancer with No Evidence of Disease after Neoadjuvant Chemotherapy and Surgery].

A 46-year-old man presented with hematochezia in October 2012. A circumferential type 2 rectal cancer was detected with colonoscopy. Contrast-enhanced CT showed multiple liver and lung metastases. Chemotherapy was administered after the diagnosis of cStage Ⅳ rectal cancer. After 1 course of XELOX plus Bmab, the treatment was changed to XELOX plus Cmab for 21 courses. An infusion reaction occurred during the 21st course. Because a complete response of the liver metastases and a reduction in size of the primary tumor had been achieved, we performed a low anterior resection in April 2014. The final pathological diagnosis was type 2, 10×25 mm, tub1, pMP, int, INF b, pN1 (251). There was no evidence of disease (NED) after the surgery. We are closely following up this patient with no postoperative chemotherapy, and as of July 2015, there is no sign of recurrence. We describe a case of a Stage Ⅳ rectal cancer that was resected with radical surgery after neoadjuvant chemotherapy. We also include a brief review of the literature.

Impact of primary ciliary dyskinesia: Beyond sinobronchial syndrome in Japan.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by impaired motile cilia function, particularly in the upper and lower airways. To date, more than 50 causative genes related to the movement, development, and maintenance of cilia have been identified. PCD mostly follows an autosomal recessive inheritance pattern, in which PCD symptoms manifest only in the presence of pathogenic variants in both alleles. Several genes causing PCD have been recently identified that neither lead to situs inversus nor cause definitive abnormalities in ciliary ultrastructure. Importantly, the distribution of disease-causing genes and pathogenic variants varies depending on ethnicity. In Japan, homozygosity for a ∼27.7-kb deletion of DRC1 is estimated to be the most common cause of PCD, presumably as a founder mutation. The clinical picture of PCD is similar to that of sinobronchial syndrome, thus making its differentiation from diffuse panbronchiolitis and other related disorders difficult. Given the diagnostic challenges, many cases remain undiagnosed or misdiagnosed, particularly in adults. While no fundamental cure is currently available, lifelong medical subsidies are provided in Japan, and proper respiratory management, along with continued prevention and treatment of infections, is believed to mitigate the decline in respiratory function. Timely action will be necessary when specific treatments for PCD become available in the future. This narrative review focuses on variations in the disease status of PCD in a non-Western country.

Primary Ciliary Dyskinesia Due to Compound Heterozygous Variants in CFAP221 with Obstructive Azoospermia: Young's Syndrome May Be a Phenotype of Primary Ciliary Dyskinesia.

We report the case of a 42-year-old man with bronchiectasis who had a history of infertility treatment for obstructive azoospermia. Young's syndrome was suspected based on the triad of obstructive azoospermia, sinusitis, and bronchiectasis. He had normal electron microscopy findings, normal nasal nitric oxide levels (116 nL/min), and no situs inversus. However, we found compound heterozygous variants in CFAP221. This led to a diagnosis of primary ciliary dyskinesia (PCD). Distinguishing PCD from Young's syndrome in patients with the triad of obstructive azoospermia, sinusitis, and bronchiectasis is challenging. Young's syndrome may be a phenotype of PCD.

Time course of tumorigenesis of a newly developed sporadic hemangioblastoma in an elderly patient: illustrative case.

BACKGROUND: von Hippel-Lindau disease-associated hemangioblastomas (HBs) account for 20%-30% of all HB cases, with the appearance of new lesions often observed in the natural course of the disease. By comparison, the development of new lesions is rare in patients with sporadic HB. OBSERVATIONS: A 65-year-old man underwent clipping for an unruptured aneurysm of the anterior communicating artery. Fourteen years later, follow-up magnetic resonance imaging (MRI) revealed a strongly enhanced mass in the right cerebellar hemisphere, diagnosed as a sporadic HB. A retrospective review of MRI studies obtained over the follow-up period revealed the gradual development of peritumoral edema and vascularization before mass formation. LESSONS: Newly appearing high-intensity T2 lesions in the cerebellum may represent a preliminary stage of tumorigenesis. Careful monitoring of these patients would be indicated, which could provide options for early treatment to improve patient outcomes.

Dapagliflozin induced hypernatremia via osmotic diuresis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used. They inhibit proximal tubular glucose reabsorption, resulting in glycosuria. Herein, we report the case of a 65-year-old woman who presented with hypernatremia during the perioperative period of a subarachnoid hemorrhage. The patient continued to take dapagliflozin postoperatively and subsequently developed severe hypernatremia. Based on the urinalysis findings, we diagnosed osmotic diuresis due to glycosuria as contributing to hypernatremia. Hypernatremia improved with the discontinuation of dapagliflozin and the administration of a hypotonic infusion. In the perioperative period, physicians should discontinue SGLT2 inhibitors owing to concerns about the development of hypernatremia.

Primary Ciliary Dyskinesia Caused by Homozygous DNAAF1 Mutations Resulting from a Consanguineous Marriage: A Case Report from Japan.

We present the case of a 58-year-old female patient with primary ciliary dyskinesia (PCD). She was born to parents with a consanguineous marriage. Chest computed tomography conducted at age 41 years indicated no situs inversus, and findings of bronchiectasis were limited to the middle and lingular lobes. Despite long-term macrolide therapy, bronchiectasis exacerbations frequently occurred. PCD was suspected because of the low nasal nitric oxide level (20.7 nL/min). Electron microscopy revealed outer and inner dynein arm defects, and a genetic analysis identified a homozygous single-nucleotide deletion in the DNAAF1 gene. Based on these results, the patient was diagnosed with PCD due to a biallelic DNAAF1 mutation.

Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment.

BACKGROUND: Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD. METHODS: This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included. RESULTS: The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9-25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3-38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study. CONCLUSION: CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Highly Permeable and Regenerative Microhoneycomb Filters.

Allergic reactions can profoundly influence the quality of life. To address the health risks posed by allergens and overcome the permeability limitations of the current filter materials, this work introduces a novel microhoneycomb (MH) material for practical filter applications such as masks. Through a synthesis process integrating ice-templating and a gas-phase post-treatment with silane, MH achieves unprecedented levels of moisture resistance and mechanical stability while preserving the highly permeable microchannels. Notably, MH is extremely elastic, with a 92% recovery rate after being compressed to 80% deformation. The filtration efficiency surpasses 98.1% against pollutant particles that simulate airborne pollens, outperforming commercial counterparts with fifth-fold greater air permeability while ensuring unparalleled user comfort. Moreover, MH offers a sustainable solution, being easily regenerated through back-flow blowing, distinguishing it from conventional nonwoven fabrics. Finally, a prototype mask incorporating MH is presented, demonstrating its immense potential as a high-performance filtration material, effectively addressing health risks posed by allergens and other harmful particles.

Beyond Symptoms: Radiologic identification of asymptomatic Mycobacterium avium complex pulmonary infections.

BACKGROUND: Although international nontuberculous mycobacterial pulmonary disease (NTM-PD) guidelines highlight symptom presence at diagnosis, the clinical characteristics of asymptomatic Mycobacterium avium complex pulmonary infection (MAC-PI) patients remain understudied. We clarified the clinical characteristics and course of asymptomatic MAC-PI patients. METHODS: We retrospectively analyzed 200 consecutive patients with MAC-PIs and adequate available data who newly met the microbiological and radiological criteria for NTM-PD at Fukujuji Hospital from January 2018 to June 2020. We compared the clinical characteristics and course of asymptomatic patients with symptomatic patients and evaluated factors influencing treatment initiation through multivariate analysis. RESULTS: 111 patients were symptomatic and 89 were asymptomatic at diagnosis. While the proportion was significantly lower than that in the symptomatic group (28.8 %), 15.7 % of asymptomatic group patients had cavitary lesions (P = 0.042). In the asymptomatic group, treatments were initiated in 38 (42.7 %) patients, and cavitary lesions, a positive acid-fast bacilli smear, and younger age were independent risk factors for treatment initiation. Among 22 (57.9 %) patients who experienced disease progression necessitating treatment during follow-up, 13 (34.2 %) displayed radiological progression without any worsening of symptoms. Agents used for treatment were consistent across the groups, with no significant differences in culture conversion, microbiological recurrence rates, or spontaneous culture conversion rates. CONCLUSION: Routine health checkups and radiological examinations can detect clinically important MAC-PIs even in the absence of symptoms. Considering that the clinical course of asymptomatic MAC-PI patients is largely similar to that of symptomatic patients, timely and appropriate management and intervention are essential for all MAC-PI patients.