Phytochemical prospection and evaluation of antimicrobial, antioxidant and antibiofilm activities of extracts and essential oil from leaves of Myrsine umbellata Mart. (Primulaceae).

The species Myrsine umbellata is a native plant of Brazil, whose barks are traditionally used in herbal medicine to treat liver disorders and combat leprosy. Therefore, the aim of the study was to identify the phytochemical prospection of ethanolic (EE) and acetonic (EA) extracts by colorimetric tests and by gas chromatography coupled to mass spectrometry (GC-MS) of the essential oil (EO) of M. umbellata leaves; evaluate the antimicrobial activity in front of standard ATCC strains by the broth microdilution technique; the antioxidant potential by DPPH reduction method and antibiofilm action by crystal violet assay and cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based on optical density. Phytochemical prospection of EE and EA detected the presence of free steroids, alkaloids, flavonoids (flavones, flavononoids, flavonols and xanthons) and tannins in both extracts (EE and EA) and saponins only in EE. In EO, the majority compounds identified were elixene, caryophyllene (E), spatulenol, d-Cadinene and aromadendrene. EA showed antimicrobial activity with MIC and MBC/MFC values ranging from 3.12 to 100 mg.mL-1, highlighting its efficiency on the Gram-positive strain S. epidermidis. EE showed antimicrobial potential in the range of 3.12 to 200 mg.mL-1, and the Gram-negative E. coli strain was the most susceptible. However, OE showed bacteriostatic potential against S. Typhimurium, S. Abaetetuba, P. aeruginosa, and S. epidermidis strains. The ability to sequester free radicals was evident in EA extract with antioxidant activity of 89.55% and in EE with 63.05%. The antibiofilm potential was observed in EE extract which eradicated the mature biofilm biomass of all tested bacteria with high activity (50% to 84.28%) and EO also showed antibiofilm effect on mature biofilm of UEL enteroaggregative E. coli, S. aureus and S. Enteritidis strains with biomass reduction percentage of 63.74%, 68.04% and 86.19%, respectively. These results indicate the potential of M. umbellata extracts and as a source of plant bioactivity for the development of new alternative strategies for the control of planktonic or biofilm-resistant microorganisms.

Observational Study of the Association between Hyponatremia and Rhabdomyolysis in Patients Presenting to Hospital.

Hyponatremia may be a risk factor for rhabdomyolysis, but the association is not well defined and may be confounded by other variables. The aims of this study were to determine the prevalence and strength of the association between hyponatremia and rhabdomyolysis and to profile patients with hyponatremia. In a cross-sectional study of 870 adults admitted to hospital with rhabdomyolysis and a median peak creatine kinase of 4064 U/L (interquartile range, 1921−12,002 U/L), glucose-corrected serum sodium levels at presentation showed a U-shape relationship to log peak creatine kinase. The prevalence of mild (130−134 mmol/L), moderate (125−129 mmol/L), and severe (<125 mmol/L) hyponatremia was 9.4%, 2.5%, and 2.1%, respectively. We excluded patients with hypernatremia and used multivariable linear regression for analysis (n = 809). Using normal Na+ (135−145 mmol/L) as the reference category, we estimated that a drop in Na+ moving from one Na+ category to the next was associated with a 25% higher creatine kinase after adjusting for age, alcohol, illicit drugs, diabetes, and psychotic disorders. Multifactorial causes of rhabdomyolysis were more common than single causes. The prevalence of psychotic and alcohol use disorders was higher in the study population compared to the general population, corresponding with greater exposure to psychotropic medications and illicit drugs associated with hyponatremia and rhabdomyolysis. In conclusion, we found an association between hyponatremia and the severity of rhabdomyolysis, even after allowing for confounders.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

Assessment of liver cirrhosis for patients with Child's A classification before hepatectomy using dynamic contrast-enhanced MRI.

AIM: To determine the feasibility of semi-quantitative haemodynamic parameters derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to assess liver fibrosis. MATERIALS AND METHODS: Seventy-five patients with Child's A classification (males/females=24/51; average age, 58 years; range, 30-80 years) received DCE-MRI 3 days prior to hepatectomy. Semi-quantitative haemodynamic parameters, including the wash-in slope, wash-out slope, and time-to-peak, were calculated from DCE-MRI data. Liver fibrosis of the resected non-tumour liver was graded pathologically from F0 (no fibrosis) to F6 (cirrhosis) in the regions corresponding to those assessed by DCE-MRI. RESULTS: The wash-out slope showed higher interobserver and intra-observer reliabilities than the wash-in slope and time-to-peak. There was a significant positive correlation between the wash-out slope and pathological grade of fibrosis (Spearman's correlation coefficient: r=0.5331, p<0.0001). The area under the receiver operating characteristic curve was 0.8066 when using the wash-out slope to differentiate cirrhosis (grade F6) from non-cirrhosis (grades F0-5). Using the cut-off point that maximised specificity, the sensitivity was 62.07%, specificity was 91.30%, positive predictive value was 81.81%, negative predictive value was 79.25%, and accuracy was 80%. CONCLUSIONS: The wash-out slope derived from DCE-MRI might be potentially useful in assessing liver cirrhosis in patients with Child's A classification before hepatectomy.

VE/VCO2 Slope and Functional Capacity in Patients Post-Heart Transplantation.

BACKGROUND: The ventilatory efficiency represented cardiovascular, pulmonary, and musculoskeletal performance into an integrate index has been used as long-term and short-term prognostic variables in congestive heart failure. The heart failure patients post heart transplantation, whether the ventilatory efficiency was also normalized is still unknown. METHODS: This was a cross-sectional study. We measured ventilation to carbon dioxide production slope and oxygen consumption in peak exercise (peak VO2) by cardiopulmonary exercise test, which represented ventilatory efficiency and functional capacity respectively. Strength of hand grip, the 30-second chair stand test, and 6-minute walking test were also evaluated. Patients with ventilation to carbon dioxide production slope <30 were defined as the normal group; others were defined as the abnormal group. Independent t tests and paired t tests were used when appropriate. The level of statistical significance was set at .05. RESULTS: There were 51 clinically stable post-heart transplantation patients (age 53 ± 12.4 years; 86.3% were male) at 65.14 ± 41.17 months after transplantation. The ventilation to carbon dioxide production slope was 29.2 ± 5.6, which significantly improved compared to that recorded 1 month after heart transplantation (32.6 ± 6.4). There were 20 patients in the abnormal group, characterized by lower 6-minute walking test distance (normal vs abnormal, 422.5 ± 97.8 vs 532.6 ± 87.6 m) and peak VO2 (normal vs abnormal, 14.9 ± 5.3 vs 18.8 ± 5.1 mL/kg/min). The abnormal ventilation to carbon dioxide production slope was significantly correlated with 6-minute walking test distances in multivariate analyses. CONCLUSION: Our findings indicate that the ventilation to carbon dioxide production slope is partially abnormal among patients post-heart transplantation. A ventilation to carbon dioxide production slope above the normal range is characterized by a lower peak VO2 during cardiopulmonary exercise test and lower 6-minute walking test distance. The ventilation to carbon dioxide production slope is also significantly negatively correlated with peak VO2, peak work rate, and 6-minute walking test distance. The prognostic utility of the ventilation to carbon dioxide production slope for patients post-heart transplantation requires further investigation.

Oxygen Consumption at Anaerobic Threshold Predicts Cardiac Events After Heart Transplantation.

OBJECTIVES: The ventilatory efficiency and functional capacity measured by the cardiopulmonary exercise test (CPET) have been used as important prognostic variables in congestive heart failure. This study sought to identify whether these predictors before heart transplantation (HTX) play a key role in predicting adverse events in patients with heart failure after HTX. METHODS: This was a retrospective cohort study design. HTX recipients were included for analysis. Ventilation to carbon dioxide production slope (VE/VCO2 slope) and oxygen consumption (VO2) during exercise were collected by CPET, which represented ventilator efficiency and functional capacity respectively. Cardiac-related events 2 years after HTX were recorded by chart review. We divided patients into 2 groups based on VE/VCO2 slope = 34, peak VO2 = 14 mL/kg/min and VO2 at aerobic threshold (AT) = 11 mL/kg/min. Kaplan-Meier survival curves was used to represent the events rate between groups and Log rank test was used to test significance. RESULTS: A total of 87 patients after HTX were included. Mean (SD) age was 48 (11) years and 73 were male; 28 subjects suffered from events, and 76 cardiac events were recorded. The mean (SD) data of peak VO2, VO2 at AT, and VE/VCO2 slope analyzed from CPET were 17.8 (5.6) mL/kg/min, 15.4 (4.4) mL/kg/min, and 33.1 (8.2) mL/kg/min, respectively. Lower VO2 at AT contributed to increase events rate (P < .05). CONCLUSION: Aerobic capacity may better predict 2-year cardiac events in patients after HTX. Strategies to improve aerobic capacity should be focused on in the cohort.

An abbreviated Faecal Incontinence Quality of Life Scale for Chinese-speaking population with colorectal cancer after surgery: cultural adaptation and item reduction.

No instrument is available to assess the impact of faecal incontinence (FI) of quality of life for Chinese-speaking population. The purpose of the study was to adapt the Faecal Incontinence Quality of Life Scale (FIQL) for patients with colorectal cancer, assess the factor structure and reduce the items for brevity. A sample of 120 participants were enrolled. Internal consistency, test-retest reliability, and convergent and contrasted-groups validity were assessed. Construct validity was analysed using an exploratory and confirmatory factor analyses (CFA). The internal consistency (Cronbach's α of the total scale and four subscales = 0.98 and 0.97, 0.96, 0.92, 0.82 respectively), test-retest reliability (intraclass correlation coefficients ≥.98 for all scales with p < .001) and significant correlations of all scales with selected subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey and the Wexner scale suggested satisfactory reliability and validity. The severe FI group (with a Wexner score ≥9) scored significantly lower on the scale than the less severe FI group (with a Wexner score <9) did (p < .001). The CFA supported a two-factor structure and demonstrated an excellent model fit of the 15-item abbreviated version of the FIQL-Chinese. The FIQL-Chinese has satisfactory validity and reliability and the abbreviated version may be more practical and applicable.

Trajectories of Nutritional Status and Cognitive Impairment among Older Taiwanese with Hip Fracture.

OBJECTIVE: This paper describes the trajectories of nutritional status and cognitive impairment and their correlation among older Taiwanese over 1 year after hip-fracture surgery. DESIGN: Secondary analysis of data from a clinical trial evaluating the effects of three types of post-discharge care for 292 older hip-fracture patients (age >60 years). MEASUREMENTS: Nutritional status was assessed by the Mini Nutritional Assessment before and 1, 3, 6, 12 months after hospital discharge. Cognitive function was measured by the Mini-Mental State Examination before surgery, at hospital discharge, 6 and 12 months after discharge. Trajectories of nutritional status and cognitive impairment were depicted by latent class growth modeling, whereas linkages between nutritional-status and cognitive-impairment trajectories were assessed by multinomial logistic regression. RESULTS: Nutritional status in general improved significantly, particularly during the first 3 months after discharge. We identified three trajectories of nutritional status: malnourished (15.4%), at risk for malnutrition (38.9%), and well-nourished (45.7%). In contrast, cognitive changes followed four largely linear but distinct trajectories: moderately impaired (12.2%), mildly impaired (27.8%), borderline impaired (21.8%), and cognitively intact (38.2%). Trajectories of nutritional status were significantly associated with cognitive-function trajectories. For instance, relative to malnourished patients, well-nourished patients were 95% less likely (OR=0.05, CI =0.01-0.24) to be moderately cognitively impaired. CONCLUSION: A good nutritional-status trajectory after hip fracture was associated with better cognitive function. To treat and care for elderly hip-fractured patients, specific interventions need to target those who are malnourished or at risk of malnutrition to decrease their risk for cognitive impairment.

A report on emergent uranyl binding phenomena by an amidoxime phosphonic acid co-polymer.

The development of technology to harvest the uranium dissolved in seawater would enable access to vast quantities of this critical metal for nuclear power generation. Amidoxime polymers are the most promising platforms for achieving this separation, yet the design of advanced adsorbents is hindered by uncertainty regarding the uranium binding mode. In this work we use XAFS to investigate the uranium coordination environment in an amidoxime-phosphonic acid copolymer adsorbent. In contrast to the binding mode predicted computationally and from small molecule studies, a cooperative chelating model is favoured, attributable to emergent behavior resulting from inclusion of amidoxime in the polymer. Samples exposed to seawater also display a feature consistent with a µ(2)-oxo-bridged transition metal, suggesting the formation of an in situ specific binding site. These findings challenge long held assumptions and provide new opportunities for the design of advanced adsorbent materials.

Oxygen Uptake Efficiency Slope Predicts Major Cardiac Events in Patients With End-Stage Heart Failure.

INTRODUCTION: Oxygen uptake efficiency slope (OUES) has been shown as a predictor of stable heart failure (HF) survival. However, there is a lack of evidence for end-stage HF. OBJECTIVES: We aimed to investigate the prognostic value of OUES in end-stage HF patients. METHODS: The study design was a retrospective cohort. End-staged HF patients who had cardiopulmonary exercise testing (CPET) for evaluation between 2004 and 2009 were included. The primary outcomes were cardiac death and heart transplantation. The independent survival predictors were determined using Cox regression hazard model adjusted for demographics, New York Heart Association (NYHA) classification, medication, and left ventricular ejection fraction (LVEF). The Kaplan-Meier survival curves and log-rank test were used. Probability values less than .05 were considered significant. RESULTS: Mean age of the 128 patients was 50 ± 12 years and 93 were male. Mean LVEF was 23% ± 9%. Forty-three subjects suffered cardiac events (5 cardiac deaths and 38 urgent heart transplantations) during the 2-year follow-up period. Cox regression indicated that OUES and diuretics were significant predictors of 2-year survival, although peak oxygen uptake and ventilatory equivalent of carbon dioxide were not. Patients with high OUES (≥1.6) had a higher survival rate (P < .001; odds ratio [OR], 13.10; 95% confidence interval [CI], 3.30-58.63). The Kaplan-Meier curves show survival was significantly higher in those with OUES ≥1.6. CONCLUSIONS: OUES might be an aid in prognosis of patients with end-stage HF and useful in the assessment of patients unable to perform maximal exercise testing.

Mapping the Orientation of White Matter Fiber Bundles: A Comparative Study of Diffusion Tensor Imaging, Diffusional Kurtosis Imaging, and Diffusion Spectrum Imaging.

BACKGROUND AND PURPOSE: White matter fiber tractography relies on fiber bundle orientation estimates from diffusion MR imaging. However, clinically feasible techniques such as DTI and diffusional kurtosis imaging use assumptions, which may introduce error into in vivo orientation estimates. In this study, fiber bundle orientations from DTI and diffusional kurtosis imaging are compared with diffusion spectrum imaging as a criterion standard to assess the performance of each technique. MATERIALS AND METHODS: For each subject, full DTI, diffusional kurtosis imaging, and diffusion spectrum imaging datasets were acquired during 2 independent sessions, and fiber bundle orientations were estimated by using the specific theoretic assumptions of each technique. Angular variability and angular error measures were assessed by comparing the orientation estimates. Tractography generated with each of the 3 reconstructions was also examined and contrasted. RESULTS: Orientation estimates from all 3 techniques had comparable angular reproducibility, but diffusional kurtosis imaging decreased angular error throughout the white matter compared with DTI. Diffusion spectrum imaging and diffusional kurtosis imaging enabled the detection of crossing-fiber bundles, which had pronounced effects on tractography relative to DTI. Diffusion spectrum imaging had the highest sensitivity for detecting crossing fibers; however, the diffusion spectrum imaging and diffusional kurtosis imaging tracts were qualitatively similar. CONCLUSIONS: Fiber bundle orientation estimates from diffusional kurtosis imaging have less systematic error than those from DTI, which can noticeably affect tractography. Moreover, tractography obtained with diffusional kurtosis imaging is qualitatively comparable with that of diffusion spectrum imaging. Because diffusional kurtosis imaging has a shorter typical scan time than diffusion spectrum imaging, diffusional kurtosis imaging is potentially more suitable for a variety of clinical and research applications.

Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma.

The transcription factor interferon regulatory factor 5 (IRF5) is upregulated in Hodgkin lymphoma (HL) and is a key regulator of the aberrant transcriptome characteristic of this disease. Here we show that IRF5 upregulation in HL is driven by transcriptional activation of a normally dormant endogenous retroviral LOR1a long terminal repeat (LTR) upstream of IRF5. Specifically, through screening of RNA-sequencing libraries, we detected LTR-IRF5 chimeric transcripts in multiple HL cell lines but not in normal B-cell controls. In HL, the LTR was in an open and hypomethylated epigenetic state, and we further show the LTR is the site of transcriptional initiation. Among HL cell lines, usage of the LTR promoter strongly correlates with overall levels of IRF5 mRNA and protein, indicating that LTR transcriptional awakening is a major contributor to IRF5 upregulation in HL. Taken together, oncogenic IRF5 overexpression in HL is the result of a specific LTR transcriptional activation. We propose that such LTR derepression is a distinct mechanism of oncogene activation ('onco-exaptation'), and that such a mechanism warrants further investigation in molecular and cancer research.

Prognostic value of oxygen consumption and ventilatory equivalent slope in female candidates referred for heart transplantation--experience of a single Asian center.

BACKGROUND: Ventilatory equivalent (ventilation/CO2 production, VE/VCO2) slope has been suggested to be a much more accurate predicator than peak oxygen consumption (VO2) during exercise for prognosis in patients with heart failure. However, patients tested were predominately male. METHODS: To investigate whether peak VO2 and VE/VCO2 slope predict the prognosis of female patients with heart failure, we retrospectively collected data of 39 female candidates referred for heart transplantation (HTx) from 2004 to 2011. Both peak VO2 and VE/VCO2 slope were obtained from the results of an exercise pulmonary function test. The outcome was death or mechanical devices implantation or HTx. Logistic regression was used for data analysis. RESULTS: Mean age and heart failure survival score were 55.8 ± 13.7 years and 7.3 ± 0.7, respectively. Each increment of VE/VCO2 slope decreased 2-year event-free rate (odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.79 to 0.98) in the female group. The predictions of VE/VCO2 slope for 1-year event-free survival did not reach statistical significance (OR = 0.92, 95% CI = 0.84 to 1.00). On the other hand, peak VO2 was not a strong predictor for 1- and 2-year event-free survival (OR = 1.22 and 1.16, 95% CI = 0.96 to 1.55 and 0.94 to 1.44, respectively). CONCLUSIONS: Impairment in exercise ventilation holds a clinical and long-term prognostic impact in female patients with heart failure. The role of peak VO2 during exercise in prognostic prediction among the cohort should be further investigated.

Effect of extraperitoneal bupivacaine analgesia in laparoscopic inguinal hernia repair: a meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic total extraperitoneal (TEP) inguinal hernioplasty is significantly less painful than open repair, but it is not completely painless. Local anesthetics are thought to decrease postoperative pain when placed at the surgical site. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of extraperitoneal bupivacaine treatment during laparoscopic inguinal hernia repair for the reduction of postoperative pain. METHODS: We conducted a systematic review and meta-analysis of RCTs that investigated the outcomes of extraperitoneal bupivacaine analgesia versus control in laparoscopic TEP hernia repair. Pain was assessed using a visual analog scale at 4-6 h and at 24 h following the surgery. The secondary outcomes included complications and analgesia consumption. RESULTS: We reviewed eight trials that included a total of 373 patients. We found no difference between the groups in postoperative pain reduction following laparoscopic TEP inguinal hernia repair. The intensity of pain was not significantly different between the bupivacaine treatment group and the control group. The pooled mean differences in pain scores were -0.26 (95% CI -0.72 to 0.21) at 4-6 h and -0.47 (95% CI -1.24 to 0.29) at 24 h. No bupivacaine-related complications were reported. CONCLUSION: Extraperitoneal bupivacaine treatment during laparoscopic TEP inguinal hernioplasty is not more efficacious for the reduction of postoperative pain than placebo.

A human study model for nitric oxide research in sinonasal disease.

Sinus nitric oxide (NO) measurements present a novel and promising approach to help overcome difficulties and confounding variables associated with nasal NO measurements such as the nasal cycle, ostial patency, and individual contribution to total NO production of each sinus. Conflicting results reported on nasal NO measurements in various sinonasal diseases are presumed to originate from the variable diffusion of sinus NO into the nose where it is measured. This study presents a novel technique and research method for direct measurement of sinus NO. The authors' original technique of individual, non-destructive catheterization of the sinuses through their natural ostia is developed and refined to allow accurate measurements of NO produced in the sinuses. Our study indicates that reproducible catheterization of the sinuses through their natural ostia can be performed in the clinical research setting under local and topical anesthesia. The model can be used to test the effects of various conditions on nasal and sinus NO production in a variety of disease models and the variables affecting sinonasal gas exchange can be differentially studied. Volunteer healthy adult human subjects without nasal allergies are used. An endoscopic nasal exam with topical anesthesia followed by in vitro allergy testing is performed to determine eligibility. Sinus computerized tomography (CT) scans are used to delineate anatomic features and to calculate paranasal sinus volumes. Continuous flow sinus air sampling and NO measurement with a chemiluminescence analyzer is obtained through polyethylene tube catheters (PEC) placed endoscopically into an aerated major paranasal sinus. Catheters are introduced through natural ostia under local and topical anesthesia. Nasal and differential sinus NO measurements are performed.