The sexual plasticity of the gonads is not retained after the completion of sex differentiation in vertebrates, except in some hermaphroditic species. Here, we report that the depletion of ...estradiol-17β (E2) by aromatase inhibitors (AI) for up to six months resulted in a functional female-to-male sex reversal in sexually-mature adults of two gonochoristic fish species, Nile tilapia and medaka. The sex-reversed fish showed a typical male pattern of E2 and androgen levels, secondary sexual characteristics, and male-like sex behavior, producing fertile sperm. Conversely, co-treatment of E2 inhibited AI-induced sex reversal. In situ hybridization of medaka gonads during AI-induced sex reversal indicated that cysts on the dorsal side of the adult ovaries are the origin of germ cells and Sertoli cells in the newly formed testicular tissue. Gonochoristic fish maintain their sexual plasticity until adulthood and E2 plays a critical role in maintaining the female phenotype.
This paper deals with the maximal
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regularity theorem for the linearized electro-magnetic field equations with interface conditions and perfect wall condition. This problem is motivated by ...linearization of the coupled magnetohydrodynamics system which generates two separate problems. The first problem is associated with well studied Stokes system. Another problem related to the magnetic field is studied in this paper. The maximal
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regularity theorem for the Stokes equations with interface and nonslip boundary conditions has been proved by Pruess and Simonett (2016), and Maryani and Saito (2017). Combination of these results and the result obtained in the present paper yields local well-posedness for the MHD problem in the case of two incompressible liquids separated by a closed interface. It is planned to prove it in a forthcoming paper.
The main part of the present paper is devoted to proving the existence of
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-bounded solution operators associated with generalized resolvent problem. The maximal
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regularity is established by applying the Weis operator-valued Fourier multiplier theorem.
In Lindsley's thermometry, a revised sequence of calculation of components is proposed for clinopyroxene, in which kosmochlor component is added. Temperatures obtained for the components calculated ...by the revised method are about 50 °C lower than those obtained for the components calculated by the Lindsley's original method and agree well with temperatures obtained from orthopyroxenes. Ca‐partitioning between clino‐ and orthopyroxenes is then thought to be equilibrated in types 5 to 7 ordinary chondrites. The temperatures for Tuxtuac (LL5), Dhurmsala (LL6), NWA 2092 (LL6/7), and Dho 011 (LL7) are 767–793°, 818–835°, 872–892°, and 917–936°C, respectively, suggesting that chondrites of higher petrographic types show higher equilibrium temperatures of pyroxenes. The regression equations which relate temperature and Wo and Fs contents in the temperature‐contoured pyroxene quadrilateral of 1 atm of Lindsley (1983) are also determined by the least squares method. It is possible to reproduce temperatures with an error less than 20 °C (2SE) using the regression equations.
We assessed S-268019-b, a recombinant spike protein vaccine with a squalene-based adjuvant, for superiority in its immunogenicity over ChAdOx1 nCoV-19 vaccine among adults in Japan. In this ...multicenter, randomized, observer-blinded, phase 3 study, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naïve participants (aged ≥ 18 years, without prior infection or vaccination against SARS-CoV-2) were randomized (1:1) to receive either S-268019-b or ChAdOx1 nCoV-19 as two intramuscular injections given 28 days apart. Participants who provided consent for a booster administration received S-268019-b at Day 211. The primary endpoint was SARS-CoV-2 neutralizing antibody (NAb) titer on Day 57; the key secondary endpoint was the seroconversion rate for SARS-CoV-2 NAb titer on Day 57. Other endpoints included anti-SARS-CoV-2 S-protein immunoglobulin (Ig)G antibody titer and safety. The demographic and baseline characteristics were generally comparable between S-268019-b (n = 611) and ChAdOx1 nCoV-19 (n = 610) groups. S-268019-b showed superior immunogenicity over ChAdOx1 nCoV-19, based on their geometric mean titers (GMTs) and GMT ratios of SARS-CoV-2 NAb on Day 57 by cytopathic effect assay (GMT 95% confidence interval {CI} 19.92 18.68, 21.23 versus 3.63 3.41, 3.87; GMT ratio 95% CI 5.48 5.01, 6.00, respectively; two-sided p-values < 0.0001). Additionally, NAb measured using a cell viability assay also showed similar results (GMT 95% CI 183.25 168.04, 199.84 versus 24.79 22.77, 27.00; GMT ratio 95% CI 7.39 6.55, 8.35 for S-268019-b versus ChAdOx1 nCoV-19, respectively; p < 0.0001). The GMT of anti-SARS-CoV-2 S-protein IgG antibody was 370.05 for S-268019-b versus 77.92 for ChAdOx1 nCoV-19 on Day 57 (GMT ratio 95% CI 4.75 4.34, 5.20). Notably, immune responses were durable through the end of the study. S-268019-b elicited T-helper 1 skewed T-cell response, comparable to that of ChAdOx1 nCoV-19. After the first dose, the incidence of solicited systemic treatment-related adverse events (TRAEs) was higher in the ChAdOx1 nCoV-19 group, but after the second dose, the incidence was higher in the S-268019-b group. Headache, fatigue, and myalgia were the most commonly reported solicited systemic TRAEs, while pain at the injection site was the most frequently reported solicited local TRAE following both doses in both groups. No serious treatment-related adverse serious TRAEs events were reported in the two groups. S-268019-b was more immunogenic than ChAdOx1 nCoV-19 vaccine and was well tolerated (jRCT2051210151).
Summary
Thoracic interfascial plane blocks are effective for post‐mastectomy acute analgesia. However, their effects on chronic pain are uncertain. We randomly allocated 80 women equally to pectoral ...nerve‐2 (PECS 2) block or serratus plane block. The pectoral nerve‐2 block reduced the rate of moderate or severe chronic pain from 13/40 (33%) with the serratus plane block to 4/40 (10%), p = 0.03, adjusted odds ratio (95%CI) 0.23 (0.07–0.80), p = 0.02. The rates of pain‐free women at six postoperative months were indeterminate, 10/40 (25%) after serratus plane block vs. 19/40 (48%) after pectoral nerve‐2 block, p = 0.06, adjusted odds ratio (95%CI) 2.9 (1.1–7.5), p = 0.03. Health‐related quality of life at six postoperative months was similar after serratus plane and pectoral nerve‐2 blocks, mean (SD) EQ‐5D‐3L scores 0.87 (0.15) vs. 0.91 (0.14), respectively, p = 0.21. The pectoral nerve‐2 block reduced median (IQR range) morphine consumption in the first 24 postoperative hours from 6 (3–9 1–25) mg to 4 (2–7 0–37) mg, p = 0.04. However, acute pain scores after serratus plane and pectoral nerve‐2 blocks were similar, median (IQR range) 23 (11–35 0–70) mm vs. 18 (11–27 0–61) mm, respectively, p = 0.44. Pectoral nerve‐2 block reduced chronic pain 6 months after mastectomy compared with serratus plane block.
FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab.
WJOG4407G was a randomized, ...open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396.
Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively HR, 0.905; 95% confidence interval (CI) 0.723–1.133; P = 0.003 for non-inferiority. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785–1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months.
FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC.
UMIN000001396.
Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine ...cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of
based on their growth rate.
Objective
Oral fungal infection is generally associated with dysbiosis related to antibiotic use, immunodeficiency, or frailty. However, fungal colonization in a typical population without apparent ...symptoms and its associated conditions are poorly understood. In this study, oral fungal colonization in community‐dwelling and independently living elderly populations was evaluated and factors affecting fungal colonization were analyzed.
Subjects and Methods
The subjects (410; 181 males and 229 females) were 75–99 years of age; those under prior antibiotic use were excluded. Fungal populations in the saliva were evaluated by PCR‐based molecular techniques. Body mass index (BMI), smoking habits, and oral health conditions were examined.
Results
Salivary fungal amounts exceeded 104 CFU/ml in 63 (15.4%) of 410 subjects. Candida albicans was most frequently detected (98.4%), followed by Candida glabrata (54.0%), and Candida dubliniensis (38.1%) in those subjects with fungi at 104 CFU/ml or over. Fungi at 104 CFU/ml or over in the presence of C. glabrata or C. dubliniensis was significantly associated with low BMI.
Conclusions
Candida albicans, C. glabrata, and C. dubliniensis dominated the oral mycobiome in Japanese community‐dwelling elderly. Lower BMI might signify compromised health status and thus could result in susceptibility to specific candidiasis by C. glabrata and C. dubliniensis.
Aim
To characterize the microbial composition of persistent periapical lesions of root filled teeth using a molecular genetics approach.
Methodology
Apical lesion samples were collected from 12 ...patients (23–80 years old) who visited the Kyushu University Hospital for apicectomy with persistent periapical lesions associated with root filled teeth. DNA was directly extracted from each sample and the microbial composition was comprehensively analysed using clone library analysis of the 16S rRNA gene. Enterococcus faecalis, Candida albicans and specific fimA genotypes of Porphyromonas gingivalis were confirmed using polymerase chain reaction (PCR) analysis with specific primers.
Results
Bacteria were detected in all samples, and the dominant findings were P. gingivalis (19.9%), Fusobacterium nucleatum (11.2%) and Propionibacterium acnes (9%). Bacterial diversity was greater in symptomatic lesions than in asymptomatic ones. In addition, the following bacteria or bacterial combinations were characteristic to symptomatic lesions: Prevotella spp., Treponema spp., Peptostreptococcaceae sp. HOT‐113, Olsenella uli, Slackia exigua, Selemonas infelix, P. gingivalis with type IV fimA, and a combination of P. gingivalis, F. nucleatum, and Peptostreptococcaceae sp. HOT‐113 and predominance of Streptococcus spp. On the other hand, neither Enterococcus faecalis nor C. albicans were detected in any of the samples.
Conclusion
Whilst a diverse bacterial species were observed in the persistent apical lesions, some characteristic patterns of bacterial community were found in the symptomatic lesions. The diverse variation of community indicates that bacterial combinations as a community may cause persistent inflammation in periapical tissues rather than specific bacterial species.
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