Association between Temporal Muscle Thickness and Overall Survival in Non-Small Cell Lung Cancer Patients with Brain Metastasis.

Temporal muscle thickness (TMT) has recently been suggested as a novel biomarker of sarcopenia in head and neck malignancies. However, few studies have evaluated TMT as a prognostic marker in patients with brain metastasis. This study investigated the association of TMT with overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastasis. The records of all NSCLC patients with brain metastasis between 2009 and 2018 at St. Vincent's Hospital were reviewed retrospectively. A total of 221 patients met our eligibility criteria. In the group with TMT thicker than the median, OS was longer than the group with TMT thinner than the median (240 days versus 139 days, p = 0.014). In multivariate analysis, the thicker TMT group had longer survival (HR 0.73 CI 0.56−0.96, p = 0.024). Male (HR 1.58 CI 1.19−2.09, p = 0.002) and older age (≥65 years) (HR 2.05 CI 1.53−2.74, p < 0.001) also showed statistical significance. We also performed subgroup analysis in older patients (≥65 years). In this subgroup of 107 patients, the thicker TMT group also showed longer OS than the thinner TMT group (209 days versus 82 days, p = 0.009). Our findings suggest that TMT can be a useful biomarker for OS in NSCLC patients with brain metastasis.

Clinical feasibility of modified procarbazine and lomustine chemotherapy without vincristine as a salvage treatment for recurrent adult glioma.

Procarbazine, lomustine and vincristine (PCV) chemotherapy is considered a salvage option for adult glioma; however, its significant toxicities frequently lead to dose reduction or discontinuation in patients with recurrent glioma. The current study evaluated the safety and efficacy of modified procarbazine and lomustine (PC) chemotherapy that omits vincristine and reduces the lomustine dose compared with those of conventional PCV chemotherapy. Using electronic medical records, all patients with adult recurrent glioma who received PC or PCV chemotherapy between 2009 and 2020 at Seoul St. Mary's Hospital or St. Vincent's Hospital were examined retrospectively. A total of 59 patients met the eligibility criteria. Among them, 15 patients received modified PC chemotherapy (PC group) and 44 patients received PCV chemotherapy (PCV group). The PC group presented a significantly lower hematology toxicity (anemia, 6.7 vs. 45.5%, P=0.02; thrombocytopenia 20.0 vs. 70.4%, P<0.001). Additionally, the clinical impacts of PC chemotherapy, including delay of a cycle, dose reduction, discontinuation of drug(s) or total cessation of chemotherapy, were significantly less frequent compared with the PCV group (26.7 vs. 68.2%, P=0.012). The overall survival of the PC group was also significantly longer than that of PCV group (396 vs. 232 days, P=0.042), while there was no significant difference in progression-free survival between the two groups (284.5 vs. 131 days, P=0.077). The results suggested that modified PC chemotherapy may be an alternative chemotherapeutic regimen with tolerable toxicity and without loss of clinical efficacy in patients with recurrent adult glioma. Further prospective and larger studies are required to validate our findings.

Evaluation of Evidence-Based Guidelines for Fever Management in Critically Ill Adult Patients With Brain Injury.

PURPOSE: The aim of this study was to evaluate the effectiveness of evidence-based guidelines for fever management of critically ill adult patients with brain injury. METHODS: We used a pretest-posttest design with 48 patients 19 years or older admitted to an intensive care unit after surgery for brain injury. We applied evidence-based guidelines only to an experimental group of 24 patients and compared with 24 control patients who did not receive evidence-based guidelines. Experimental and control groups were matched 1:1 using the Acute Physiology and Chronic Health Evaluation II score. Data included the proportion of patients with reduced fever and time to normalized temperature. RESULTS: The proportion of patients whose temperature fell to normal after fever was 4.5 times higher in the experimental group than in the control group. The time it took the patients' highest fever to fall to normal during their intensive care unit stay was 4.84 times faster in the experimental group than in the control group (hazard ratio, 4.84; 95% confidence interval, 1.79-13.11; P = .002). CONCLUSION: Evidence-based guidelines for fever management in patients with a brain injury can be used in nursing practice with rapid response, improving healthcare efficiency and contributing to better outcomes for critically ill patients.

Identification and profiling of novel microRNAs in the Brassica rapa genome based on small RNA deep sequencing.

BACKGROUND: MicroRNAs (miRNAs) are one of the functional non-coding small RNAs involved in the epigenetic control of the plant genome. Although plants contain both evolutionary conserved miRNAs and species-specific miRNAs within their genomes, computational methods often only identify evolutionary conserved miRNAs. The recent sequencing of the Brassica rapa genome enables us to identify miRNAs and their putative target genes. In this study, we sought to provide a more comprehensive prediction of B. rapa miRNAs based on high throughput small RNA deep sequencing. RESULTS: We sequenced small RNAs from five types of tissue: seedlings, roots, petioles, leaves, and flowers. By analyzing 2.75 million unique reads that mapped to the B. rapa genome, we identified 216 novel and 196 conserved miRNAs that were predicted to target approximately 20% of the genome's protein coding genes. Quantitative analysis of miRNAs from the five types of tissue revealed that novel miRNAs were expressed in diverse tissues but their expression levels were lower than those of the conserved miRNAs. Comparative analysis of the miRNAs between the B. rapa and Arabidopsis thaliana genomes demonstrated that redundant copies of conserved miRNAs in the B. rapa genome may have been deleted after whole genome triplication. Novel miRNA members seemed to have spontaneously arisen from the B. rapa and A. thaliana genomes, suggesting the species-specific expansion of miRNAs. We have made this data publicly available in a miRNA database of B. rapa called BraMRs. The database allows the user to retrieve miRNA sequences, their expression profiles, and a description of their target genes from the five tissue types investigated here. CONCLUSIONS: This is the first report to identify novel miRNAs from Brassica crops using genome-wide high throughput techniques. The combination of computational methods and small RNA deep sequencing provides robust predictions of miRNAs in the genome. The finding of numerous novel miRNAs, many with few target genes and low expression levels, suggests the rapid evolution of miRNA genes. The development of a miRNA database, BraMRs, enables us to integrate miRNA identification, target prediction, and functional annotation of target genes. BraMRs will represent a valuable public resource with which to study the epigenetic control of B. rapa and other closely related Brassica species. The database is available at the following link: http://bramrs.rna.kr [1].

Auxin response factor gene family in Brassica rapa: genomic organization, divergence, expression, and evolution.

Completion of the sequencing of the Brassica rapa genome enabled us to undertake a genome-wide identification and functional study of the gene families related to the morphological diversity and agronomic traits of Brassica crops. In this study, we identified the auxin response factor (ARF) gene family, which is one of the key regulators of auxin-mediated plant growth and development in the B. rapa genome. A total of 31 ARF genes were identified in the genome. Phylogenetic and evolutionary analyses suggest that ARF genes fell into four major classes and were amplified in the B. rapa genome as a result of a recent whole genome triplication after speciation from Arabidopsis thaliana. Despite its recent hexaploid ancestry, B. rapa includes a relatively small number of ARF genes compared with the 23 members in A. thaliana, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative genomic and mRNA sequencing analyses demonstrated that 27 of the 31 BrARF genes were transcriptionally active, and their expression was affected by either auxin treatment or floral development stage, although 4 genes were inactive, suggesting that the generation and pseudogenization of ARF members are likely to be an ongoing process. This study will provide a fundamental basis for the modification and evolution of the gene family after a polyploidy event, as well as a functional study of ARF genes in a polyploidy crop species.

Sequence and structure of Brassica rapa chromosome A3.

BACKGROUND: The species Brassica rapa includes important vegetable and oil crops. It also serves as an excellent model system to study polyploidy-related genome evolution because of its paleohexaploid ancestry and its close evolutionary relationships with Arabidopsis thaliana and other Brassica species with larger genomes. Therefore, its genome sequence will be used to accelerate both basic research on genome evolution and applied research across the cultivated Brassica species. RESULTS: We have determined and analyzed the sequence of B. rapa chromosome A3. We obtained 31.9 Mb of sequences, organized into nine contigs, which incorporated 348 overlapping BAC clones. Annotation revealed 7,058 protein-coding genes, with an average gene density of 4.6 kb per gene. Analysis of chromosome collinearity with the A. thaliana genome identified conserved synteny blocks encompassing the whole of the B. rapa chromosome A3 and sections of four A. thaliana chromosomes. The frequency of tandem duplication of genes differed between the conserved genome segments in B. rapa and A. thaliana, indicating differential rates of occurrence/retention of such duplicate copies of genes. Analysis of 'ancestral karyotype' genome building blocks enabled the development of a hypothetical model for the derivation of the B. rapa chromosome A3. CONCLUSIONS: We report the near-complete chromosome sequence from a dicotyledonous crop species. This provides an example of the complexity of genome evolution following polyploidy. The high degree of contiguity afforded by the clone-by-clone approach provides a benchmark for the performance of whole genome shotgun approaches presently being applied in B. rapa and other species with complex genomes.

Does human relaxin accelerate orthodontic tooth movement in rats?

Human relaxin was administered to young rats through either minipumps (group P) or subcutaneous injections (group I). Control rats received pump implants containing placebo (group C). Day 0 was the day of orthodontic appliance placement and activation to pull bilateral upper first molars forward, and day 14 was the end time point. Cephalometric radiographs (three repeated exposures) were taken at 0, 3, 5, 7, 10, and 14 days. The total length of three maxillary molar segments and the space between the first and second molars were measured under a dissecting microscope postmortem. Both groups P and I showed rapid tooth movement at day 3. Movement slowed, but it still increased gradually in group P while decreasing in group I after that. Concurrent tooth lateral drifts to the buccal side were smaller in both groups P and I. The length and space were larger in both groups P and I. Thus, administration of human relaxin may accelerate the early stages of orthodontic tooth movement in rats.

Trabecular organization in mandibular osteodistraction in growing and maturing rats.

PURPOSE: Our goal was to investigate the trabecular organization of the distraction regenerate during various consolidation phases and as a result of various distraction rates. MATERIALS AND METHODS: One hundred ninety-two growing and maturing rats (96 each) received unilateral mandibular osteotomies and distraction device placement. They were randomly allocated into 4 distraction rate groups (0, 0.2, 0.4, and 0.6 mm/day for 5 days) after a 3-day latency. Eight rats from each rate group were sacrificed at early (10 days), mid (24 days) and late (38 days) consolidation time points. Harvested hemimandibles were embedded in micro-bed resin, sectioned sagittally at 10 mum thickness and stained using the Von Kossa method. The histologic images were captured and processed using Adobe Photoshop (Version 7.0; Adobe Systems Inc, San Jose, CA). Custom-made software (MacAzimuth; written by Prof. J.M. Rensberger, University of Washington) was further used to analyze the orientation (anisotropy and angle distribution) and mass (density and thickness) of trabecular structures in the regenerates. RESULTS: Trabecular orientation significantly differed at the mid-consolidation time point with less anisotropy ( P < or = .000 to .023) and narrower angular distribution ( P < or = .007 to .021). Trabecular mass increased significantly from early to mid-consolidation ( P < or = .000 to .002). Growing rats showed greater trabecular organization than maturing rats did at the same time points ( P < or = .000 to .009). The trabecular organization parameters were associated significantly with bone mineral density and microdensity ( P < or = .000 to .044). CONCLUSION: The peak change in orientation occurred around the mid-consolidation with a greater increase in trabecular mass. Growing rats showed a greater capacity for trabecular organization at earlier time points. However, distraction rate did not have an effect on trabecular organization. These results suggest that trabecular organization can be used as an important indicator to evaluate bone maturation and quality in the distraction regenerate.