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Protecting the adjacent soft tissues using a channel retractor prevents complications, such as excessive bleeding, during sagittal split ramus osteotomy. However, the saucer-shaped blade of the conventional channel retractor fits poorly into the posterior border of the mandibular ramus during medial osteotomy, which is typically performed parallel to the occlusal plane. Therefore, a novel channel retractor was developed with an adjusted blade bending angle, based on cephalometric data. The lateral cephalograms of 339 Japanese patients with jaw deformities were collected. Cephalometric landmarks were identified based on the definitions of the Downs-Northwestern analysis, and the acute angle between the occlusal and ramus planes was calculated. Based on the consistent mean and median occlusal ramus angles obtained, the blade was bent at 70° in the sagittal plane to fabricate the angled channel retractor. The engagement at the posterior border of the mandibular ramus during medial osteotomy enhances its stability. Furthermore, owing to the bending direction, the angled channel retractor used for medial osteotomy on one side can be used as a channel retractor for lateral osteotomy on the other side. The proposed angled channel retractor offers both stability and versatility for osteotomy manoeuvres.
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The P of achieving pregnancy is an important trait of bull fertility in beef cattle and is defined as the bull conception rate (BCR). This study aimed to clarify and better understand the genetic architecture of the BCR calculated using artificial insemination and pregnancy diagnosis records from a progeny testing program in Japanese Black bulls. In this study, we estimated the genetic parameters of the BCR and their correlation with semen production traits. In addition, we assessed the correlated responses in BCR by considering the selection of semen production traits. Nine hundred and sixteen Japanese Black bulls were selected based on fertility, with 28 869 pregnancy diagnostic records from the progeny testing program. Our results showed that the heritability estimate was 0.04 in the BCR at the first service and 0.14 in BCR for the three services, and an increase in the inbreeding coefficient led to a significant decrease in BCR. The phenotypic trend of BCR remained almost constant over the years, whereas the genetic trend increased. In addition, the changes in the progeny testing year effect showed a similar tendency to the phenotypic trends, suggesting that the phenotypic trends could be mainly due to non-genetic effects, including progeny testing year effects. The estimated genetic correlation of BCR with sperm motility traits was favorably moderate to high (ranging from 0.49 to 0.97), and those with sperm quantity traits such as semen volume were favorably low to moderate (ranging from 0.23 to 0.51). In addition, the correlated responses in BCR at the first service by selection for sperm motility traits resulted in a higher genetic gain than direct selection. This study provides new insights into the genetic factors affecting BCR and the possibility of implementing genetic selection to improve BCR by selecting sperm motility traits in Japanese Black bulls.
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Fertilidade , Inseminação Artificial , Sêmen , Animais , Bovinos/genética , Bovinos/fisiologia , Masculino , Sêmen/fisiologia , Feminino , Inseminação Artificial/veterinária , Fertilidade/genética , Fertilização/genética , Gravidez , Motilidade dos Espermatozoides/genética , Fenótipo , Cruzamento , Análise do Sêmen/veterinária , EndogamiaRESUMO
Scientific exploration of phototrophic bacteria over nearly 200 years has revealed large phylogenetic gaps between known phototrophic groups that limit understanding of how phototrophy evolved and diversified1,2. Here, through Boreal Shield lake water incubations, we cultivated an anoxygenic phototrophic bacterium from a previously unknown order within the Chloroflexota phylum that represents a highly novel transition form in the evolution of photosynthesis. Unlike all other known phototrophs, this bacterium uses a type I reaction centre (RCI) for light energy conversion yet belongs to the same bacterial phylum as organisms that use a type II reaction centre (RCII) for phototrophy. Using physiological, phylogenomic and environmental metatranscriptomic data, we demonstrate active RCI-utilizing metabolism by the strain alongside usage of chlorosomes3 and bacteriochlorophylls4 related to those of RCII-utilizing Chloroflexota members. Despite using different reaction centres, our phylogenomic data provide strong evidence that RCI-utilizing and RCII-utilizing Chloroflexia members inherited phototrophy from a most recent common phototrophic ancestor. The Chloroflexota phylum preserves an evolutionary record of the use of contrasting phototrophic modes among genetically related bacteria, giving new context for exploring the diversification of phototrophy on Earth.
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Bactérias , Complexo de Proteína do Fotossistema I , Processos Fototróficos , Bactérias/química , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bacterioclorofilas/metabolismo , Lagos/microbiologia , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Filogenia , Anaerobiose , Complexo de Proteína do Fotossistema II/metabolismo , Perfilação da Expressão GênicaRESUMO
It is found that, in the studies of heavy ion transport with gyrokinetic simulations, the ion parallel drift frequency can reverse sign in velocity space when the amplitude variation of the electrostatic potential fluctuation is strong along the magnetic field line. As a result, the particle transport related to the parallel dynamics is strongly enhanced. It is noted that, while parallel gradient of the fluctuation amplitude can be instigated by a large magnetic shear or safety factor in a tokamak, the generic mechanism is independent of its cause, which suggests broader applications to kinetic plasma problems. Some relevant topics are briefly addressed in the end.
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Delivering piglets is one of the most energy-demanding activities sows undergo in their lifetime. Sows can have myometrial contractions from 2 to 12 h before the first piglet is expelled as well as a nest-building behavior. Thus, when the first piglet is delivered, the female has already used part of her energy supply. When the sow gets exhausted due to lack of energy, the farrowing process can be interrupted, causing damage to the viability and vitality of the piglets. In the present study, we evaluated the effects of feeding sows an energy supplement at the onset of farrowing on farrowing kinetics and piglet vitality. The energy supplement consisted of a blend of carbohydrates and glycerol which provides 439 kJ of metabolizable energy per kg of metabolic weight. A total of 180 sows were used. At the onset of farrowing, sows were assigned to one of the following treatments: sows that were not supplied energy at the onset of farrowing, serving as controls (CON, n = 85); sows fed the energy supplement at the onset of farrowing (ESP, n = 95). Farrowing kinetics, blood glucose concentration, and piglet vitality were recorded for each sow. Blood glucose concentration was assessed by puncturing the auricular vein and using a portable glucometer at four different time points: after the birth of the 1st piglet (T0), and at 20 (T20), 40 (T40), 80 (T80), and 180 (T180) min after the birth of the 1st piglet. The vitality of the 1st, 6th, 12th, 17th, and 20th piglet born was evaluated using the Apgar score. Piglet birth weight and average colostrum intake were measured. The farrowing duration was 20 min shorter (P < 0.05) for ESP sows in comparison with CON sows. Sows from ESP treatment had higher (P ≤ 0.05) blood glucose concentration at T20 and T40 compared to the CON sows. The inter-piglet birth interval was shortened (P < 0.05) by 14 min between the 1st and 2nd piglet for the ESP treatment. The 17th and 20th piglets born from ESP sows had higher (P < 0.05) Apgar score compared to piglets of the same birth order from CON sows. Colostrum intake was higher (P < 0.01) for piglets born from ESP sows. Litter growth performance did not differ (P > 0.05). In conclusion, feeding a blend of carbohydrates and glycerol as an energy supplement for farrowing sows improved farrowing kinetics and piglet vitality score.
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Glicerol , Lactação , Gravidez , Animais , Suínos , Feminino , Animais Recém-Nascidos , Glicerol/farmacologia , Glicerol/metabolismo , Glicemia/metabolismo , Colostro/metabolismoRESUMO
The objective of this study was to evaluate the effects of cashew nut shell extract (CNSE) and monensin on ruminal in vitro fermentation, CH4 production, and ruminal bacterial community structure. Treatments were as follows: control (CON, basal diet without additives); 2.5 µM monensin (MON); 0.1 mg CNSE granule/g DM (CNSE100); and 0.2 mg CNSE granule/g DM (CNSE200). Each treatment was incubated with 52 mL of buffered ruminal content and 500 mg of total mixed ration for 24 h using serum vials. The experiment was performed as a complete randomized block design with 3 runs. Run was used as a blocking factor. Each treatment had 5 replicates, in which 2 were used to determine nutrient degradability, and 3 were used to determine pH, NH3-N, volatile fatty acids, lactate, total gas, CH4 production, and bacterial community composition. Treatment responses for all data, excluding bacterial abundance, were analyzed with the GLIMMIX procedure of SAS v9.4. Treatment responses for bacterial community structure were analyzed with a PERMANOVA test run with the R package vegan. Orthogonal contrasts were used to test the effects of (1) additive inclusion (ADD: CON vs. MON, CNSE100, and CNSE200); (2) additive type (MCN: MON vs. CNSE100 and CNSE200); and (3) CNSE dose (DOS: CNSE100 vs. CNSE200). We observed that pH, acetate, and acetate:propionate ratio in the CNSE100 treatment were lower compared with CNSE200, and propionate in the CNSE100 treatment was greater compared with CNSE200. Compared with MON, CNSE treatments tended to decrease total lactate concentration. Total gas production of CON was greater by 2.63% compared with all treatments, and total CH4 production was reduced by 10.64% in both CNSE treatments compared with MON. Also, compared with MON, in vitro dry matter degradabilities in CNSE treatments were lower. No effects were observed for NH3-N or in vitro neutral detergent fiber degradability. Finally, the relative abundances of Prevotella, Treponema, and Schwartzia were lower, whereas the relative abundances of Butyrivibrio and Succinivibrio were greater in all treatments compared with CON. Overall, the inclusion of CNSE decreased CH4 production compared with MON, making CNSE a possible CH4 mitigation additive in dairy cattle diets.
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Anacardium , Monensin , Bovinos , Feminino , Animais , Monensin/farmacologia , Monensin/metabolismo , Lactação , Propionatos/metabolismo , Fermentação , Nozes , Digestão , Dieta/veterinária , Bactérias , Acetatos/farmacologia , Metano/metabolismo , Lactatos/metabolismo , Extratos Vegetais/farmacologia , Rúmen/metabolismo , Ração Animal/análiseRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic was reported to have increased depression among university students which was associated with impairments in their campus lives. This study examined changes in depressive states among Japanese university students during the COVID-19 pandemic. METHODS: A secondary data analysis from a factorial randomized controlled trial involving smartphone-based cognitive-behavioral therapy was performed. Six cohorts (N = 1626) underwent an 8-week intervention during the spring or autumn of 2019-2021, with a 9-month follow-up. We evaluated participants' depressive states weekly using the Patient Health Questionnaire-9 (PHQ-9) during the intervention, with monthly evaluations thereafter. The follow-up periods included Japan's four states of emergency (SOEs) to control COVID-19. Hypothesizing that SOEs caused a sudden worsening of depressive states, Study 1 compared the cohorts' PHQ-9 scores, and Study 2 employed time series analysis with a mixed-effects model to estimate identified changes in PHQ-9 scores. RESULTS: Although no changes in depressive states were observed in relation to the SOEs, Study 1 identified sudden increases in PHQ-9 scores at the 28-week evaluation point, which corresponded to the beginning of the new academic year for the three autumn cohorts. In contrast, the three spring cohorts did not exhibit similar changes. Study 2 showed that, for all three autumn cohorts (n = 522), the 0.60-point change was significant (95% CI 0.42-0.78; p < .001) at 28 weeks; that is, when their timeline was interrupted. CONCLUSIONS: While the results do not indicate any notable impact of the SOEs, they highlight the influence of the new academic year on university students' mental health during COVID-19. Trial registration UMIN, CTR-000031307. Registered on February 14, 2018.
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The objective of this study was to compare cashew nutshell extract (CNSE) to monensin and evaluate changes in in vitro mixed ruminal microorganism fermentation, nutrient digestibility, and microbial nitrogen outflow. Treatments were randomly assigned to 8 fermenters in a replicated 4 × 4 Latin square design with 4 experimental periods of 10 d (7 d for diet adaptation and 3 d for sample collection). Basal diets contained 43.5:56.5 forage: concentrate ratio and each fermenter was fed 106 g of DM/d divided equally between 2 feeding times. Treatments were control (CON, basal diet without additives), 2.5 µM monensin (MON), 0.1 mg CNSE granule/g DM (CNSE100), and 0.2 mg CNSE granule/g DM (CNSE200). On d 8 to10, samples were collected for pH, lactate, NH3-N, volatile fatty acids (VFA), mixed protozoa counts, organic matter (OM), and neutral detergent fiber (NDF) digestibility. Data were analyzed with the GLIMMIX procedure of SAS. Orthogonal contrasts were used to test the effects of (1) ADD (CON vs. MON, CNSE100, and CNSE200); (2) MCN (MON vs. CNSE100 and CNSE200); and (3) DOSE (CNSE100 vs. CNSE200). We observed that butyrate concentration in all treatments was lower compared with CON and the concentration for MON was lower compared with CNSE treatments. Protozoal population in all treatments was lower compared with CON. No effects were observed for pH, lactate, NH3-N, total VFA, OM, or N utilization. Within the 24-h pool, protozoal generation time, tended to be lower, while NDF digestibility tended to be greater in response to all additives. Furthermore, the microbial N flow, and the efficiency of N use tended to be lower for the monensin treatment compared with CNSE treatments. Overall, our results showed that both monensin and CNSE decreased butyrate synthesis and protozoal populations, while not affecting OM digestibility and tended to increase NDF digestibility; however, such effects are greater with monensin than CNSE nutshell.
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Anacardium , Monensin , Animais , Monensin/farmacologia , Monensin/metabolismo , Fermentação , Rúmen/metabolismo , Digestão , Dieta , Ácidos Graxos Voláteis/metabolismo , Butiratos/metabolismo , Lactatos/metabolismo , Ração Animal/análiseRESUMO
BACKGROUND: Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC. PATIENTS AND METHODS: This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30. RESULTS: Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P = 0.036). CONCLUSIONS: Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Receptores ErbB , RamucirumabRESUMO
Cashew nut shell extract (CNSE) is a byproduct of the cashew nut industry, containing bioactive compounds that alter rumen fermentation patterns. Therefore, study objectives were to evaluate the effects of CNSE (59% anacardic acid and 18% cardol) on production, rumen fermentation variables, metabolism, and inflammation in transition dairy cows. A total of 51 multiparous Holstein cows were used in a randomized design and assigned to treatment based on their previous 305-d mature equivalent milk and parity. Cows were assigned to 1 of 2 treatments 21 d before expected calving: (1) CON (control diet; n = 17) or (2) CNSE-5.0 (control diet and 5.0 g/d CNSE granule [containing 50% CNSE]; n = 34). Following parturition, 17 cows (preselected at initial treatment assignment) from the CNSE-5.0 treatment were reallocated into a third treatment group: CNSE-2.5 (control diet and 2.5 g/d CNSE granule; n = 17), resulting in 3 total treatments postpartum: (1) CON, (2) CNSE-2.5, and (3) CNSE-5.0. Prepartum rumen pH was unaltered by treatment; however, postpartum rumen pH was increased (0.31 units) in CNSE cows relative to CON. Prepartum rumen ammonia N concentration tended to be decreased (34%) in CNSE-5.0 cows compared with CON, and there tended to be a quadratic effect on postpartum ammonia N, as it was decreased in CNSE-2.5 compared with CON and CNSE-5.0. Prepartum dry matter intake (DMI) was unaffected by treatment; however, postpartum DMI was increased (8%) in CNSE cows relative to CON. No treatment differences were observed in pre- or postpartum digestibility measurements. Milk and protein yields from cows fed CNSE tended to be increased (6% and 7%, respectively) relative to CON. No treatment differences were detected for energy-corrected milk, feed efficiency, body weight, body condition score, energy balance, milk composition, milk urea nitrogen, or somatic cell count. Prepartum fecal pH decreased (0.12 units) in CNSE-5.0 cows relative to CON cows but was similar between treatments postpartum. Supplementing CNSE did not affect prepartum glucose, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), or insulin. However, prepartum circulating blood urea nitrogen tended to be decreased and glucagon was decreased in CNSE-5.0 cows compared with CON (9 and 20%, respectively). Additionally, CNSE supplementation decreased glucose and insulin concentrations postpartum relative to CON cows (6% and 20%, respectively). Quadratic effects were detected for postpartum circulating NEFA and BHB such that their levels were increased in CNSE-2.5 cows relative to CON and CNSE-5.0. Pre- and postpartum circulating serum amyloid A, lipopolysaccharide-binding protein, and haptoglobin were unaffected by treatment. Overall, CNSE influenced some key rumen fermentation variables, altered postabsorptive metabolism, and increased production parameters in transition dairy cows.
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Anacardium , Insulinas , Gravidez , Feminino , Bovinos , Animais , Lactação , Anacardium/metabolismo , Ácidos Graxos não Esterificados , Fermentação , Rúmen/metabolismo , Amônia/metabolismo , Nozes , Dieta/veterinária , Período Pós-Parto , Leite/química , Glucose/metabolismo , Suplementos NutricionaisRESUMO
The quantum vortex liquid (QVL) is an intriguing state of type-II superconductors in which intense quantum fluctuations of the superconducting (SC) order parameter destroy the Abrikosov lattice even at very low temperatures. Such a state has only rarely been observed, however, and remains poorly understood. One of the key questions is the precise origin of such intense quantum fluctuations and the role of nearby non-SC phases or quantum critical points in amplifying these effects. Here we report a high-field magnetotransport study of FeSe1-xSx and FeSe1-xTex which show a broad QVL regime both within and beyond their respective electron nematic phases. A clear correlation is found between the extent of the QVL and the strength of the superconductivity. This comparative study enables us to identify the essential elements that promote the QVL regime in unconventional superconductors and to demonstrate that the QVL regime itself is most extended wherever superconductivity is weakest.
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Over the years, there has been considerable variation in the bull conception rate (BCR) of Japanese Black cattle; moreover, several Japanese Black bulls with a low BCR of ≤10% have been identified. However, the alleles responsible for the low BCR are not determined yet. Therefore, in this study, we aimed to identify single-nucleotide polymorphisms (SNPs) for predicting low BCR. To this end, the genome of Japanese Black bulls was comprehensively examined by a genome-wide association study with whole-exome sequencing (WES), and the effect of the identified marker regions on BCR was determined. The WES analysis of six sub-fertile bulls with a BCR of ≤10% and 73 normal bulls with a BCR of ≥40% identified a homozygous genotype for low BCR in Bos taurus autosome 5 in the region between 116.2 and 117.9 Mb. The g.116408653G > A SNP in this region had the most significant effect on the BCR (P-value = 1.0 × 10-23), and the GG (55.4 ± 11.2%) and AG (54.4 ± 9.4%) genotypes in the SNP had a higher phenotype than the AA (9.5 ± 6.1%) genotype for the BCR. The mixed model analysis revealed that g.116408653G > A was related to approximately 43% of the total genetic variance. In conclusion, the AA genotype of g.116408653G > A is a useful index for identifying sub-fertile Japanese Black bulls. Some positive and negative effects of SNP on the BCR were presumed to identify the causative mutations, which can help evaluate bull fertility.
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Fertilização , Estudo de Associação Genômica Ampla , Bovinos/genética , Animais , Masculino , Estudo de Associação Genômica Ampla/veterinária , Alelos , Fertilização/genética , Genótipo , Fertilidade/genética , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Infecções Estafilocócicas , Cálculos Urinários , Infecções Urinárias , Urolitíase , Humanos , Staphylococcus saprophyticus , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
Electron quasiparticles play a crucial role in simplifying the description of many-body physics in solids with surprising success. Conventional Landau's Fermi-liquid and quasiparticle theories for high-temperature superconducting cuprates have, however, received skepticism from various angles. A path-breaking framework of electron fractionalization has been established to replace the Fermi-liquid theory for systems that show the fractional quantum Hall effect and the Mott insulating phenomena; whether it captures the essential physics of the pseudogap and superconducting phases of cuprates is still an open issue. Here, we show that excitonic excitation of optimally doped Bi2Sr2CaCu2O8+δ with energy far above the superconducting-gap energy scale, about 1 eV or even higher, is unusually enhanced by the onset of superconductivity. Our finding proves the involvement of such high-energy excitons in superconductivity. Therefore, the observed enhancement in the spectral weight of excitons imposes a crucial constraint on theories for the pseudogap and superconducting mechanisms. A simple two-component fermion model which embodies electron fractionalization in the pseudogap state provides a possible mechanism of this enhancement, pointing toward a novel route for understanding the electronic structure of superconducting cuprates.
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A 63-year-old woman had sustained a subcutaneous rupture of the flexor digitorum profundus tendon of the little finger due to osteoarthritis of the pisotriquetral joint. She underwent excision of the pisiform bone and reconstruction of the flexor digitorum profundus tendon of the little finger using an autogenous palmaris longus tendon graft. After surgery, a continuous ulnar nerve block was performed at the forearm under ultrasound and nerve stimulator guidance. During rehabilitation, she could not actively extend her little finger independently due to the block; however, she could actively extend it when the dorsum of the metacarpophalangeal joint was pressed by the occupational therapist, resulting in successful early active mobilisation. A continuous ulnar nerve block at the forearm may help to facilitate early active mobilisation after reconstructive surgery for little finger flexor tendon rupture. However, it may restrict the active extension of the little finger because the block does not spare the innervation of the intrinsic muscles responsible for little finger extension.
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There is considerable concern regarding antibiotic resistance in the water environment due to antibiotic residues from anthropogenic origins. The low antibiotic concentration in the water environment may promote the selection of antibiotic resistance. However, it is unclear how environmental factors affect resistance selection. We investigated the proliferation of quinolone-susceptible faecal bacteria (E. coli) exposed to low norfloxacin concentration (ng/L) at variable temperatures, exposure times, and carbon concentrations, simulating the conditions of the water environment. The induction of antibiotic resistance in thirteen E. coli isolates was more likely to occur at 37 °C. However, resistance also occurred at temperatures as low as 25 °C, provided a longer exposure time of 5 days. These results suggest that antibiotic resistance is more likely to be induced in regions where temperatures may reach 25-37 °C, such as tropical regions.
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Escherichia coli , Lagos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos , Lagos/microbiologia , Testes de Sensibilidade Microbiana , ÁguaRESUMO
BACKGROUND: Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC. MATERIALS AND METHODS: A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, and fluorouracil 2400 mg/m2) plus bevacizumab biweekly were enrolled. The primary endpoint was the objective response rate (ORR). Plasma samples were collected at pre-treatment, 8 weeks after treatment, and progression in participants included in the biomarker study. The levels of circulating tumour DNA (ctDNA) and specific KRAS and NRAS variants were evaluated using real-time PCR assays. RESULTS: There were 62 patients (median age: 62.5 years, 92% performance status 0, 27% right side) who were assessable for efficacy and 51 for biomarker analysis. ORR was 75.8% (95% confidence interval 65.1% to 86.5%). The median progression-free survival was 12.1 months, and the median overall survival (OS) was 30.2 months. In 78% of patients, RAS mutations disappeared in the ctDNA at 8 weeks after treatment; these patients tended to have better outcomes than those with RAS mutations. Interestingly, RAS mutations remained undetectable during progression in 62% of patients. Survival analysis indicated that the median OS from progression was significantly longer in patients with RAS mutation clearance than in those with RAS mutation in the ctDNA at disease progression (15.1 versus 7.3 months, hazard ratio: 0.21, P = 0.0046). CONCLUSIONS: Our biomarker study demonstrated no RAS mutations in ctDNA at disease progression in 62% of patients with RAS-mutant mCRC. Both OS and post-progression survival were better in patients with clearance of RAS mutations in ctDNA after triplet-based chemotherapy.
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DNA Tumoral Circulante , Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , DNA Tumoral Circulante/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Fluoruracila , Genes ras , Humanos , Leucovorina , Pessoa de Meia-Idade , Compostos Organoplatínicos , Estudos ProspectivosRESUMO
In high-frequency pulsed magnets, such as kickers in particle accelerators, it is essential to reduce eddy currents that could be induced in the magnet core during excitation not to distort and attenuate the magnetic field pulse. A novel iron lamination scheme with additional interlaminar insulation is proposed for the magnet core of such pulsed magnets. A laminated steel sheet core is formed by alternately stacking thin steel and insulation sheets. For application to matched kicker magnets for accelerators, test magnets with the new and conventional iron lamination were designed, assembled, and extensively evaluated. The pulsed magnetic field waveforms of two test magnets with the new lamination successfully matched to below 0.1% over the entire pulse duration, which was significantly better than those with the conventional lamination. Among the applications of the developed high-frequency pulsed magnets, beam injection kickers for the coming next generation light sources and future colliders, where suppression of the transient stored-beam oscillation during beam injection is crucial, are considered to be promising.
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Semen production traits are important aspects of bull fertility, because semen quantity leads to direct profits for artificial insemination centres, and semen quality is associated with the probability of achieving a pregnancy. Most genome-wide association studies (GWASs) for semen production traits have assumed that each quantitative trait locus (QTL) has an additive effect. However, GWASs that account for non-additive effects are also important in fitness traits, such as bull fertility. Here, we performed a GWAS using models that accounted for additive and non-additive effects to evaluate the importance of non-additive effects on five semen production traits in beef and dairy bulls. A total of 65 463 records for 615 Japanese Black bulls (JB) and 50 734 records for 873 Holstein bulls (HOL), which were previously genotyped using the Illumina BovineSNP50 BeadChip, were used to estimate genetic parameters and perform GWAS. The heritability estimates were low (ranged from 0.11 to 0.23), and the repeatability estimates were low to moderate (ranged from 0.28 to 0.45) in both breeds. The estimated repeatability was approximately twice as high as the estimated heritability for all traits. In this study, only one significant region with an additive effect was detected in each breed, but multiple significant regions with non-additive effects were detected for each breed. In particular, the region at approximately 64 Mbp on Bos taurus autosome 17 had the highest significant non-additive effect on four semen production traits in HOL. The rs41843851 single nucleotide polymorphism (SNP) in the region had a much lower P-value for the non-additive effect (P-value = 1.1 × 10-31) than for the additive effect (P-value = 1.1 × 10-8) in sperm motility. The AA and AB genotypes on the SNP had a higher phenotype than the BB genotype in HOL, and there was no bull with the BB genotype in JB. Our results showed that non-additive QTLs affect semen production traits, and a novel QTL accounting for non-additive effects could be detected by GWAS. This study provides new insights into non-additive QTLs that affect fitness traits, such as semen production traits in beef and dairy bulls.