Effects of Lactobacillus plantarum CJLP55 on Clinical Improvement,Skin Condition and Urine Bacterial Extracellular Vesicles in Patients with Acne Vulgaris: A Randomized,Double-Blind,Placebo-Controlled Study

Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.     

Pretreatment Clinical Mediastinal Nodal Bulk and Extent do not Influence Survival in N2-Positive Stage IIIA Non-small Cell Lung Cancer Patients Treated with Trimodality Therapy

Background

Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status.

Methods

We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011.

Results

After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS).

Conclusion

ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.     

Diagnostic value of the radioisotope erection penogram for vasculogenic impotence

Radioisotope erection penography of 113 consecutive impotent patients (41 with psychogenic and 72 with vasculogenic impotence) and 15 normal potent men were obtained. Twenty minutes after intracavernous injection of 99mtechnetium-pertechnetate 40 mg. papaverine hydrochloride were administered into the corpus cavernosum to induce erection. A gamma camera with a pinhole collimator was used to monitor the radioactivity. Various penogram indexes were calculated from the time activity curve and their usefulness was evaluated. Index A1 was useful to differentiate vasculogenic and psychogenic importance. Indexes V1 and V2 were useful to differentiate arteriogenic and venogenic impotence. The radioisotope erection penogram is a simple, less invasive and valuable screening test in the identification of vasculogenic impotence, and is effective in differentiating arteriogenic and venogenic impotence.     

Characteristics of bioimpedance-determined fluid shifts according to intradialytic blood pressure difference

This study was designed to identify the fluid spaces that are most changed during ultrafiltration (UF) according to intradialytic blood pressure (BP) difference. BP data were collected five times (before hemodialysis [HD] and 1–4 h of HD). Intradialytic BP difference was calculated as the highest minus lowest of these BP measurements. Intradialytic systolic BP (SBP) difference over 20 mm Hg and diastolic BP (DBP) difference over 10 mm Hg were defined as wide intradialytic SBP difference (SYS-W) and DBP difference (DIA-W), respectively. We measured the various fluid spaces before HD and 1–4 h of HD, and 30 min after HD using a portable, whole-body bioimpedance spectroscopy (BIS). In this study, 85 prevalent patients aged over 18 years with a fixed dry weight (65.38 ± 12.45 years, 54.18% men, 52.50% patients with diabetes), undergoing HD had participated. 1) Mean relative reduction of extracellular water (ECW) was significantly higher in SYS-W than in narrow intradialytic SBP difference (SYS-N) patients from 1 h to 30 min after HD. 2) Mean relative reduction of intracellular water (ICW) was significantly lower in DIA-W than in narrow intradialytic DBP difference (DIA-N) patients from 1 h to 30 min after HD. 3) ECW of patients with SYS-W was significantly lower than that of patients with SYS-N. Patients with SYS-W have the characteristics of fluid shifts in which reduction of ECW was steeper than patients with SYS-N whereas fluid shifts of ICW were lower in patients with DIA-W than patients with DIA-N.     

Quantitative apparent diffusion coefficients and T2 relaxation times in characterizing contrast enhancing brain tumors and regions of peritumoral edema

PURPOSE: To investigate the potential value and relationship of in vivo quantification of apparent diffusion coefficients (ADCs) and T2 relaxation times for characterizing brain tumor cellularity and tumor-related edema. MATERIALS AND METHODS: A total of 26 patients with newly diagnosed gliomas, meningiomas, or metastases underwent diffusion-weighted and six-echo multisection T2-preparation imaging. Regions of interest (ROIs) were drawn on conventional MR images to include tumor (as defined by contrast agent enhancement) and immediate and peripheral edema. Areas of necrosis were excluded. Median values of ADCs and T2 in the ROIs were calculated. RESULTS: ADCs for gliomas were similar to those for meningiomas or metastases in all regions. Tumor T2 values for gliomas (159.5+/-30.6 msec) were significantly higher than those for meningiomas or metastases (125.0+/-31.1 msec; P=0.005). Immediate-edema T2 values for meningiomas or metastases (226.0+/-44.1 msec) were significantly higher than those for gliomas (203.5+/-32.8 msec; P=0.033). Peripheral-edema T2 values for gliomas (219.5+/-41.9 msec) were similar to those for meningiomas or metastases (202.5+/-26.5 msec; P=0.377). Both immediate- and peritumoral-edema ADCs and T2 values were significantly higher than those in tumor for both tumor types. ADCs and T2 values from all regions correlated significantly for gliomas (r=0.95; P<0.0001) and for meningiomas or metastases (r=0.81; P<0.0001). CONCLUSION: The higher immediate-edema T2 values for nonglial tumors than for gliomas suggest tumor-related edema (vasogenic vs. infiltrated) can be further characterized by using T2 values. There were significant correlations between ADC and T2 values.     

Synthesis of 2′,3′-dideoxyisoguanosine from guanosine

2,3'-Dideoxyisoguanosine was synthesized from guanosine via intermediate 6-[(4-methylphenyl)thio]-2-oxo-9-(2',3',5'-tri-O-acetyl-beta-D-ribofuran osyl)-2,3-dihydropurine (4). The 2-oxo, 6-amino and 5'-hydroxy triprotected isoguanosine derivative was utilized to reduce high polarity and promote poor solubility of intermediates. The protecting groups for oxo and 6-amino were easily removed in reduction of olefin in ribose without additional reaction steps. 2',3'-Vicinal diol in ribose sugar moiety was transformed to olefin with Bu3SnH by radical reaction via bisxanthate. Removing 5'-O-TBDMS protecting group gave final product, 2',3'-dideoxyisoguanosine (12) in a 10% overall yield.     

Castration-resistant prostate cancer: new science and therapeutic prospects

There is a growing number of new therapies targeting different pathways that will revolutionize patient management strategies in castration-resistant prostate cancer (CRPC) patients. Today there are more clinical trial options for CRPC treatment than ever before, and there are many promising agents in late-stage clinical testing. The hypothesis that CRPC frequently remains driven by a ligand-activated androgen receptor (AR) and that CRPC tissues exhibit substantial residual androgen levels despite gonadotropin-releasing hormone therapy, has led to the evaluation of new oral compounds such as abiraterone and MDV 3100. Their results, coupled with promising recent findings in immunotherapy (eg sipuleucel-T) and with agents targeting angiogenesis (while awaiting the final results of the CALGB trial 90401) will most probably impact the management of patients with CRPC in the near future. Other new promising agents need further development. With our increased understanding of the biology of this disease, further trial design should incorporate improved patient selection so that patient populations are those who may be most likely to benefit from treatment.     

Polymorphisms of miR‐146a,miR‐149, miR‐196a2, and miR‐499 are associated with osteoporotic vertebral compression fractures in Korean postmenopausal women

Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case–control association study to determine the association between miR‐146a, miR‐149, miR‐196a2, and miR‐499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non‐OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X‐ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre‐miRNA sequences including miR‐146aC>G (rs2910164), miR‐149T>C (rs2292832), miR‐196a2T>C (rs11614913), and miR‐499A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction‐restriction fragment length polymorphism analysis. The TT genotype of miR‐149aT>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22–0.85, p = 0.014), whereas the miR‐146aCG/ miR‐196a2TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057–25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR‐146a, ‐149, ‐196a2, and ‐449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR‐146aG/‐149T/‐196a2C/‐449G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919–638.6, p = 0.001). Our findings suggest that the TT genotype of miR‐149aT>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR‐146aCG/ miR‐196a2TC combined genotype and the miR‐146aG/‐149T/‐196a2C/‐449G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244–253, 2018.     

Influences of passivating elements on the corrosion and biocompatibility of super stainless steels

Biometals need high corrosion resistance since metallic implants in the body should be biocompatible and metal ion release should be minimized. In this work, we designed three kinds of super stainless steel and adjusted the alloying elements to obtain different microstructures. Super stainless steels contain larger amounts of Cr, Mo, W, and N than commercial alloys. These elements play a very important role in localized corrosion and, thus, their effects can be represented by the "pitting resistance equivalent number (PREN)." This work focused on the behavior which can arise when the bare surface of an implant in the body is exposed during walking, heavy exercise, and so on. Among the experimental alloys examined herein, Alloy Al and 316L stainless steels were mildly cytotoxic, whereas the other super austenitic, duplex, and ferritic stainless steels were noncytotoxic. This behavior is primarily related to the passive current and pitting resistance of the alloys. When the PREN value was increased, the passivation behavior in simulated body solution was totally different from that in acidic chloride solution and, thus, the Cr(2)O(3)/Cr(OH)(3) and [Metal oxide]/[Metal + Metal oxide] ratios of the passive film in the simulated body solution were larger than those in acidic chloride solution. Also, the critical current density in simulated body solution increased and, thus, active dissolution may induce metal ion release into the body when the PREN value and Ni content are increased. This behavior was closely related to the presence of EDTA in the simulated body solution.     

Comparison of treatment adherence between selective serotonin reuptake inhibitors and moclobemide in patients with social anxiety disorder

Objective

With respect to the pharmacotherapy of social anxiety disorder (SAD), it has been suggested that treatment duration is an important factor that can significantly predict responses. The present study aimed to compare the treatment adherence of SAD patients who were taking either SSRIs or reversible inhibitors of MAO-A (moclobemide) by measuring treatment duration and all-cause discontinuation rates of pharmacotherapy in a natural clinical setting.

Methods

We retrospectively analysed the data of 172 patients diagnosed with SAD. Depending on their medication, we divided the patients into two groups, SSRI (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation every 2 weeks after starting treatment was calculated by life table survival methods. A multi-variable Cox proportional hazard regression was used to analyze the potential influence of explanatory variables.

Results

Treatment duration was significantly longer in the SSRI group [46.41±56.96, median=12.0 (weeks)] than in the moclobemide group [25.53±34.74, median=12.0 (weeks), Z=2.352, p=0.019]. Overall, all-cause discontinuation rates were significantly lower with SSRIs (81%) than moclobemide (96%, χ²=4.532, p=0.033).

Conclusion

The SSRI group had a longer treatment duration and lower all-cause discontinuation rate than moclobemide. Further, only the type of medication had a significant effect on all-cause discontinuation rates and therefore, we could predict better treatment adherence with the SSRIs in the treatment of SAD.