The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS.
The human gut microbiome has profound influences on the host's health largely through its interference with various intestinal functions. As recent studies have suggested diversity in the human gut microbiome among human populations, it will be interesting to analyse how gut microbiome is correlated with geographical, cultural, and traditional differences. The Japanese people are known to have several characteristic features such as eating a variety of traditional foods and exhibiting a low BMI and long life span. In this study, we analysed gut microbiomes of the Japanese by comparing the metagenomic data obtained from 106 Japanese individuals with those from 11 other nations. We found that the composition of the Japanese gut microbiome showed more abundant in the phylum Actinobacteria, in particular in the genus Bifidobacterium, than other nations. Regarding the microbial functions, those of carbohydrate metabolism were overrepresented with a concurrent decrease in those for replication and repair, and cell motility. The remarkable low prevalence of genes for methanogenesis with a significant depletion of the archaeon Methanobrevibacter smithii and enrichment of acetogenesis genes in the Japanese gut microbiome compared with others suggested a difference in the hydrogen metabolism pathway in the gut between them. It thus seems that the gut microbiome of the Japanese is considerably different from those of other populations, which cannot be simply explained by diet alone. We postulate possible existence of hitherto unknown factors contributing to the population-level diversity in human gut microbiomes.
Probiotics are live microorganisms that potentially confer beneficial outcomes to host by modulating gut microbiota in the intestine. The aim of this study was to comprehensively investigate effects of probiotics on human intestinal microbiota using 454 pyrosequencing of bacterial 16S ribosomal RNA genes with an improved quantitative accuracy for evaluation of the bacterial composition. We obtained 158 faecal samples from 18 healthy adult Japanese who were subjected to intervention with 6 commercially available probiotics containing either Bifidobacterium or Lactobacillus strains. We then analysed and compared bacterial composition of the faecal samples collected before, during, and after probiotic intervention by Operational taxonomic units (OTUs) and UniFrac distances. The results showed no significant changes in the overall structure of gut microbiota in the samples with and without probiotic administration regardless of groups and types of the probiotics used. We noticed that 32 OTUs (2.7% of all analysed OTUs) assigned to the indigenous species showed a significant increase or decrease of ≥10-fold or a quantity difference in >150 reads on probiotic administration. Such OTUs were found to be individual specific and tend to be unevenly distributed in the subjects. These data, thus, suggest robustness of the gut microbiota composition in healthy adults on probiotic administration.
The BABA technique for endoscopic thyroid surgery is a feasible method of total thyroidectomy with a low rate of postoperative complications and, additionally, excellent cosmetic results. Therefore, in selected cases of thyroid cancer, the BABA endoscopic total thyroidectomy should be considered as a valid surgical option.
The present study was designed to assess the clinical characteristics and outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. Mean age of patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P < 0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04), higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/- 26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P < 0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC patients experienced disease recurrence with a median follow-up of 47.2 months (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence and overall survival in univariate and multivariate analysis (HR 3.89 in recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI: 1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive pathological features. Patients with MBC appeared to have inherently aggressive tumor biology with poorer clinical outcomes than those with general IDC or TN-IDC.
Younger patients (age < 35) showed worse prognosis than older patients (age, 35 to 50 years) only in the hormone receptor-unknown or hormone receptor-positive subgroups. Adjuvant tamoxifen therapy might provide less survival benefit when added to chemotherapy in very young breast cancer patients.
BackgroundScrub typhus is a mite-borne bacterial infection of humans caused by Orientia tsutsugamushi that causes a generalized vasculitis that may involve the tissues of any organ system. The aim of this study was to identify factors associated to severe complications from scrub typhus.MethodsWe conducted this prospective, case-control study on scrub typhus patients who presented to the Department of Internal Medicine at Chosun University Hospital between September, 2004 and December, 2006. Cases were 89 scrub typhus patients with severe complications and controls were 119 scrub typhus patients without severe complications.ResultsThere were significant differences in the absence of eschar, white blood cell (WBC) counts, hemoglobin, albumin, serum creatinine, fibrinogen, C-reactive protein (CRP), and active partial thromboplastin time (aPTT) between the two groups. Multivariate analysis demonstrated that only the following four factors were significantly associated with the severe complications of scrub typhus: (1) age ≥ 60 years (odd ratio [OR] = 3.13, P = 0.002, confidence interval [CI] = 1.53-6.41), (2) the absence of eschar (OR = 6.62, P = 0.03, CI = 1.22-35.8, (3) WBC counts > 10, 000/mm3 (OR = 3.6, P = 0.001, CI = 1.65-7.89), and (4) albumin ≤ 3.0 g/dL (OR = 5.01, P = 0.004, CI = 1.69-14.86).ConclusionsOur results suggest that clinicians should be aware of the potential for complications, when scrub typhus patients are older (≥ 60 years), presents without eschar, or laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level ≤ 3.0 g/dL. Close observation and intensive care for scrub typhus patients with the potential for complications may prevent serious complications with subsequent reduction in its mortality rate.
Background: The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients.
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