Structure Annotation of All Mass Spectra in Untargeted Metabolomics.

Urine metabolites are used in many clinical and biomedical studies but usually only for a few classic compounds. Metabolomics detects vastly more metabolic signals that may be used to precisely define the health status of individuals. However, many compounds remain unidentified, hampering biochemical conclusions. Here, we annotate all metabolites detected by two untargeted metabolomic assays, hydrophilic interaction chromatography (HILIC)-Q Exactive HF mass spectrometry and charged surface hybrid (CSH)-Q Exactive HF mass spectrometry. Over 9,000 unique metabolite signals were detected, of which 42% triggered MS/MS fragmentations in data-dependent mode. On the highest Metabolomics Standards Initiative (MSI) confidence level 1, we identified 175 compounds using authentic standards with precursor mass, retention time, and MS/MS matching. An additional 578 compounds were annotated by precursor accurate mass and MS/MS matching alone, MSI level 2, including a novel library specifically geared at acylcarnitines (CarniBlast). The rest of the metabolome is usually left unannotated. To fill this gap, we used the in silico fragmentation tool CSI:FingerID and the new NIST hybrid search to annotate all further compounds (MSI level 3). Testing the top-ranked metabolites in CSI:Finger ID annotations yielded 40% accuracy when applied to the MSI level 1 identified compounds. We classified all MSI level 3 annotations by the NIST hybrid search using the ClassyFire ontology into 21 superclasses that were further distinguished into 184 chemical classes. ClassyFire annotations showed that the previously unannotated urine metabolome consists of 28% derivatives of organic acids, 16% heterocyclics, and 16% lipids as major classes.

Urinary metabolite profiling combined with computational analysis predicts interstitial cystitis-associated candidate biomarkers.

Interstitial cystitis/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms present challenges for disease diagnosis and therapy. The goals of this study were to identify noninvasive biomarker candidates for IC from urine specimens and to potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR < 0.05) compared to that in controls. On the basis of strong correlation scores, fifteen metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC group, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed significantly increased levels of tyramine and 2-oxoglutarate in IC patients compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.

The Effect on Bone Outcomes of Home-based Exercise Intervention for Prostate Cancer Survivors Receiving Androgen Deprivation Therapy: A Pilot Randomized Controlled Trial.

BACKGROUND: Cancer treatment-induced bone loss has important long-term effects in prostate cancer survivors (PCSs) receiving androgen deprivation therapy (ADT), but little is known about preventive interventions. OBJECTIVE: The aim of this study was to examine the feasibility and preliminary effectiveness of a 6-month home-based exercise intervention in PCSs. METHODS: In this pilot, randomized controlled trial, 51 men (mean age, 70.8 years) were randomized to a 6-month home-based exercise intervention for preventing osteoporosis group (n = 26) or an exercise placebo intervention of stretching exercise group (n = 25). Primary outcomes were bone mineral density and bone turnover markers. Secondary outcomes were physical performance (level of physical activity, muscle strength, and balance) and health-related quality of life. RESULTS: The patient retention rate for 6 months was 80.4%. The mean adherence rate was 84.7% for weight-bearing exercise and 64.8% for resistance exercise. No adverse events during the study period were reported. Although primary outcomes did not differ significantly between the 2 groups, the home-based exercise intervention for preventing osteoporosis group demonstrated significantly greater increased muscle strength than the stretching exercise group. CONCLUSIONS: A home-based exercise program is relatively feasible and safe and may improve muscle strength but not bone outcomes. IMPLICATIONS FOR PRACTICE: Given the importance of preventing cancer treatment-induced bone loss among PCSs receiving ADT, a home-based exercise intervention can be considered, but further trials with a larger sample are required to determine its effect for bone outcomes.

Predictors of health-related quality of life in Korean prostate cancer patients receiving androgen deprivation therapy.

PURPOSE: We aimed to examine the level of psychological distress, fatigue, and health-related quality of life (HRQOL) and identify HRQOL predictors in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: Using a cross-sectional design, we recruited 161 men with prostate cancer receiving ADT (mean age, 73 years) at two university-based hospitals in South Korea. Participants completed a self-reported questionnaire. Measures included the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale, and the Functional Assessment of Cancer Therapy-Prostate (FACT-P). RESULTS: The mean scores were 3.3 (SD = 2.8) for anxiety with a prevalence of 8.9%, 5.7 (SD = 3.8) for depression with a prevalence of 25.5%, and 30.3 (SD = 7.4) for fatigue with a prevalence of 15.6%. The five FACT-P subscale means were 23.9 (SD = 4.3) for physical well-being, 15.4 (SD = 6.4) for social well-being, 18.5 (SD = 4.3) for emotional well-being, 17.3 (SD = 5.6) for functional well-being, and 30.3 (SD = 7.4) for the prostate cancer-specific subscale. Multiple linear regression analysis revealed that depression, which was inversely associated with all FACT-P subscales, was the strongest predictor of worse HRQOL. Fatigue and comorbid conditions were also associated with the HRQOL of multiple domains. CONCLUSION: This study suggests that intervention aimed at improving HRQOL of men receiving ADT should include depression, fatigue, and comorbidity management.

Comparisons of the prognostic predictors of traumatic brain injury according to admission Glasgow Coma Scale scores-based on 1- and 6-month assessments.

PURPOSE: The purpose of this study was to identify the clinical variables that predict functional and cognitive recovery at 1- and 6-month in both severe and moderate/mild traumatic brain injury patients. METHODS: The subjects of this study were 82 traumatically brain-injured patients who were admitted to a Neurological Intensive Care Unit at a university hospital. Potential prognostic factors included were age, motor and pupillary response, systolic blood pressure, heart rate, and the presence of intracranial hematoma at admission. RESULTS: The significant predictors of functional disability in severe traumatic brain injury subjects were, age, systolic blood pressure, the presence of intracranial hematoma, motor response, and heart rate at admission. In moderate/mild traumatic brain injury patients, motor response, abnormal pupil reflex, and heart rate at admission were identified as significant predictors of functional disability. On the other hand, the significant predictors of cognitive ability for severe traumatic brain injury patients were motor response and the presence of intracranial hematoma at admission, whereas those for moderate/mild patients were motor response, pupil reflex, systolic blood pressure at admission, and age. CONCLUSIONS: The results of the present study indicate that the significant predictors of TBI differ according to TBI severity on admission, outcome type, and outcome measurement time. This can be meaningful to critical care nurses for a better understanding on the prediction of brain injury patients. On the other hand, the model used in the present study appeared to produce relatively low explicabilities for functional and cognitive recovery although a direct comparison of our results with those of others is difficult due to differences in outcome definition and validation Methods. This implies that other clinical variables should be added to the model used in the present study to increase its predicting power for determining functional and cognitive outcomes.

Bone health and its correlates in Korean prostate cancer patients receiving androgen deprivation therapy.

PURPOSE: This study aimed to examine bone health status, identify factors associated with bone mineral density (BMD), and determine potential risk factors for osteoporosis in Korean prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Using a cross-sectional descriptive design, we recruited 139 men with prostate cancer receiving ADT at two university-based hospitals in South Korea. Participants completed a self-reported questionnaire and underwent dual energy X-ray absorptiometry testing. BMD (gm/cm(2)), bone health status (normal BMD, osteopenia, and osteoporosis), and lifestyle variables (physical activity, smoking, and alcohol consumption) were measured. RESULTS: The prevalence in our sample was 49.6% for osteopenia and 17.3% for osteoporosis. In multivariate linear regression analyses, BMD was positively associated with body mass index, number of comorbidities, and level of physical activity and negatively associated with being unemployed or retired, having a lower monthly income, and being treated with gonadotropin-releasing hormone therapy alone. In logistic regression analyses, potential risk factors for osteoporosis were low monthly income (OR = 4.33, p = 0.011), receipt of radiation therapy (OR = 4.69, p = 0.018), and lack of regular physical activity (OR = 2.63, p = 0.035). CONCLUSIONS: Our results suggest that a proportion of prostate cancer survivors who are receiving ADT warrant monitoring to prevent osteoporosis, particularly men of lower economic status and those having lower levels of physical activity. Nurses can play an important role in screening these high risk groups.

Transvaginal cystocele repair by purse-string technique reinforced with three simple sutures: surgical technique and results.

PURPOSE: Different techniques for cystocele repair including the conventional anterior colporrhaphy and mesh technique are known. Our goal was to evaluate the anatomical success and safety of our method of transvaginal anterior vaginal wall repair by the purse-string technique reinforced with three simple additional sutures in the repair of cystocele over a 4-year follow-up period. METHODS: This was a retrospective review of 69 consecutive patients (grades 2 to 4) who underwent the above operations between 2001 and 2011, including their success rates as assessed by use of the Baden-Walker halfway classification system. RESULTS: Of the patients, 62 patients (98%) were completely cured of cystocele and 1 patient showed grade 2 cystocele recurrence that required no further treatment. Two patients with grade 4 cystocele were completely cured. There was no vaginal erosion related to the cystocele repair. CONCLUSIONS: Transvaginal anterior colporrhaphy by a purse-string technique reinforced with simple additive sutures appears to be a simple, safe, and easily performed approach in cystocele repair. There is no need for other material for reinforcement, even in high-grade cystocele, which is an advantage of our technique.

Effects of a sexual rehabilitation intervention program on stroke patients and their spouses.

The present study was conducted to examine whether a sexual rehabilitation intervention program, which was developed during the present study and designed for stroke patients and their spouses, was effective in terms of sexual knowledge and satisfaction and frequency of sexual activity at 1 month after intervention. The study subjects were conveniently selected from stroke patients admitted to the neurology department at a university hospital located in Incheon, South Korea. A total of 46 subjects (12 couples for the experimental group and 11 couples for the control group) were included. Sexual knowledge, sexual satisfaction, frequency of sexual activity, level of cognitive function, and performance with respect to daily living activities were measured. The results obtained demonstrated that the devised sexual rehabilitation intervention program significantly increased sexual satisfaction and frequency of sexual activity, but that it did not promote sexual knowledge. The present study has meaning because the intervention program could be used as a practical guideline for post-stroke sexual rehabilitation. In addition, the findings of this study provide evidence regarding the usefulness of sexual education and counseling on the sexual health of post-stroke patients and their spouses.