Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenol, 2,4-bis(1,1-dimethylethyl) of marine bacterial origin inhibits quorum sensing mediated biofilm formation in the uropathogen Serratia marcescens

Intercellular communication in bacteria (quorum sensing, QS) is an important phenomenon in disease dissemination and pathogenesis, which controls biofilm formation also. This study reports the anti-QS and anti-biofilm efficacy of seaweed Gracilaria gracilis associated Vibrio alginolyticus G16 against Serratia marcescens. Purification and mass spectrometric analysis revealed the active principle as phenol, 2,4-bis(1,1-dimethylethyl) [PD]. PD affected the QS regulated virulence factor production in S. marcescens and resulted in a significant (p < 0.05) reduction in biofilm (85%), protease (41.9%), haemolysin (69.9%), lipase (84.3%), prodigiosin (84.5%) and extracellular polysaccharide (84.62%) secretion without hampering growth, as evidenced by XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. qPCR analysis confirmed the down-regulation of the fimA, fimC, flhD and bsmA genes involved in biofilm formation. Apart from biofilm inhibition and disruption, PD increased the susceptibility of S. marcescens to gentamicin when administered synergistically, which opens another avenue for combinatorial therapy where PD can be used to enhance the efficacy of conventional antibiotics.
Colour Doppler Imaging of the Uteroplacental Circulation in the Mid‐Trimester: Features of the Uterine Artery Flow‐Velocity Waveform that Predict Abnormal Pregnancy Outcome

EDITORIAL COMMENT: We accepted this paper for publication because it presents data on the use of colour Doppler imaging in a screening test in healthy nulliparas to assess whether abnormal pregnancy outcome can be identified. Unexpectedly there were 4 perinatal deaths in this series and table 4 indicates that in the only case in which the perinatal death was potentially avoidable the 24‐week uterine Doppler studies were normal. There is mounting evidence that Doppler imaging of uteroplacental circulation is useful in the management of identified high‐risk pregnancies but the value of the method as a screening test remains unproven. If larger studies confirm the reliability of this investigation to detect patients who are destined to develop preeclampsia then a possible application of this is identification of women who warrant prophylactic aspirin therapy since recent results show that aspirin therapy is not indicated routinely in nulliparas
Mini-review: Marine natural products and their synthetic analogs as antifouling compounds: 2009–2014

This review covers 214 marine natural compounds and 23 of their synthetic analogs, which were discovered and/or synthesized from mid-2009 to August 2014. The antifouling (AF) compounds reported have medium to high bioactivity (with a threshold of EC50 < 15.0 mg ml−1). Among these compounds, 82 natural compounds were identified as new structures. All the compounds are marine-derived, demonstrating that marine organisms are prolific and promising sources of natural products that may be developed as environmentally friendly antifoulants. However, this mini-review excludes more than 200 compounds that were also reported as AF compounds but with rather weak bioactivity during the same period. Also excluded are terrestrial-derived AF compounds reported during the last five years. A brief discussion on current challenges in AF compound research is also provided to reflect the authors’ own views in terms of future research directions.
Should Thiopurine Methyltransferase Genotypes and Phenotypes be Measured Before Thiopurine Therapy in Patients With Inflammatory Bowel Disease?

Background and Aims: Not all of the adverse effects to thiopurine therapy can be explained by thiopurine methyltransferase (TPMT) polymorphisms. This study was intended to evaluate the value of TPMT genotype and phenotype measurement during the first year of thiopurine therapy. Methods: Consecutive patients with inflammatory bowel disease (IBD) who were receiving azathioprine or 6-mercaptopurine were followed up for 12 months. TPMT genotypes and phenotypes were examined in patients with IBD before thiopurine therapy and in unrelated healthy volunteers by polymerase chain reaction and high-performance liquid chromatography. Results: A total of 199 patients and 300 healthy volunteers were included at 2 centers. Forty-seven of the 199 patients (23.62%) exhibited adverse effects during the entire course of thiopurine therapy. Two (1%) patients carrying TPMT*3C developed leucopenia at week 4 of azathioprine treatment. The TPMT*3C had a specificity of 100% (163/163) but a sensitivity of 5.56% (2/36) for predicting leucopenia. The calculated optimal cutoff activity for high TPMT activity and decreased TPMT activity was 4.75 U/mL red blood cells. The risk of leucopenia increased in the decreased TPMT group (odds ratio: 20.25; 95% confidence interval: 2.19–187.17; P = 0.004) and increased more during the initial 3 months of thiopurine therapy (odds ratio: 34.80; 95% confidence interval: 3.71–326.77; P = 0.001). Leucopenia occurred more frequently in the patients cotreated with 5-aminosalicylates than in those not cotreated (32.81% versus 11.11%, respectively, P < 0.001). Conclusions: The results of this study suggest that the value of TPMT genotyping before thiopurine therapy is limited in Chinese patients with IBD, considering the low sensitivity of predicting leucopenia, and that phenotyping is a more cost-effective tool that can be successfully used in patients. The coadministration of 5-aminosalicylates results in a high frequency of leucopenia in patients receiving azathioprine or 6-mercaptopurine.
Systemic lupus erythematosus: disease manifestations in patients from Central Punjab (Pakistan)

Systemic lupus erythematosus has variable systemic manifestations and severity across ethnic groups and geographical locations. Disease behavior recognition in the multiethnic and environmentally varied Indo-Pak subcontinent is hampered by a relative lack of organized census and health services. There are reports of severe systemic disease in the immigrant Western Pakistani population. We studied disease manifestations in 65 consecutively presenting patients with systemic lupus erythematosus at two tertiary care centers. Renal (65% of patients), pulmonary (61%) and cardiovascular (55%) involvement was much higher than data from most countries. Although variability in renal involvement has been best studied across different ethnic populations, we believe that the frequency of not only renal, but also other systemic involvement is higher and more severe in patients from Punjab (Pakistan).
Low Plasma Concentrations of Albumin Influence the Affinity Column–Mediated Immunoassay Method for the Measurement of Tacrolimus in Blood During the Early Period After Liver Transplantation

Background:Monitoring of tacrolimus (TAC) concentrations in transplanted patients is necessary to ensure effective immunosuppression and to avoid adverse side effects. The fully automated analysis of TAC by the affinity column–mediated immunoassay (ACMIA), which does not require a precipitation step, may represent an efficient alternative to liquid chromatography–tandem mass spectrometry (LC–MS/MS), including in the clinically urgent situation. The aim of this work was to compare the analytical performances of ACMIA with those of LC–MS/MS and to evaluate the influence of hematological parameters, time posttransplant, and type of transplant on the results obtained from routine blood samples. Methods:Performance characteristics of ACMIA were evaluated using quality control materials and samples spiked with TAC from the International Proficiency Testing Scheme. One hundred and fifty-eight whole-blood samples from patients who received a liver (n = 55) or kidney (n = 14) transplant were assayed by ACMIA and LC–MS/MS, and hematologic, biochemical, and demographic data were collected. Univariate and multivariate statistical analyses were also performed to assess associations between the interassay differences with clinical and laboratory parameters. Results:For artificially spiked samples, the average difference between results obtained by ACMIA and LC–MS/MS was 0.24 ± 0.51 ng/mL (2.91 ± 7.03%). Crosschecking of calibrators and controls by both methods was in accordance with the nominal concentrations of TAC. The lower limit of quantification of ACMIA was found to be 3.0 ng/mL. The results with the 2 methods using routine samples from the transplant recipients correlated well (Spearman's r = 0.90). However, the ACMIA method demonstrated a positive mean bias of 1.78 ng/mL in comparison with LC–MS/MS. Multivariate analysis showed that liver transplant and albumin plasma concentrations significantly and independently affected ACMIA results (P = 0.033 and P = 0.001, respectively). Samples from liver transplant recipients early postsurgery were associated with a larger method bias than those from renal transplant recipients. Conclusions:Results obtained by ACMIA must be interpreted cautiously, particularly at lower TAC concentrations. Patients with low plasma concentrations of albumin are likely to display higher concentrations of TAC compared with LC–MS/MS in the early postsurgery period.
Avaliação comparativa entre valvoplastia percutânea e comissurotomia a céu aberto na estenose mitral

PURPOSE: To compare immediate and late (12 months) follow up of clinical and Doppler echocardiographic results between percutaneous mitral balloon valvuloplasty and open commissurotomy in a prospective and randomized trial. METHODS: Eighty eight symptomatic patients with severe mitral stenosis and favorable anatomy were randomized in a prospective trial comparing the two procedures. All patients were submitted to clinical and Doppler echocardiographic evaluation before the procedures and immediate and twelve months thereafter. RESULTS: Mean mitral gradient (mmHg) decreased from 12.2±5.8 to 5.80±2.7 (p<0.001) in commissurotomy group (CG) and from 11.7±6.1 to 5.0±2.4 (p<0.001) in the balloon valvuloplasty group (VG). Mitral valve area (cm2) increased from 0.98±0.21 to 2.52±0.46 in CG and from 1.05±0.25 to 2.18±0.40 in VG (p<0.001). In both groups there was a slight decrease in mitral valve area at 12 month follow-up. There was no death in either group. One patient in the VG had moderate mitral regurgitation and underwent surgery. At the 12 month follow-up, all patients in CG and 97.7% of patients in VG were in New York Heart Association functional class I or II. CONCLUSION: Both procedures were safe and showed similar immediate improvement in mitral gradient and functional class. Mitral valve area had a greater increase immediately after commissurotomy, however there was a significantly greater reduction in the CG after 12 months of follow-up, when compared to balloon valvuloplasty. In both groups, mitral gradient remained reduced and most patients did not change functional class during the follow-up.
A Randomized, Phase I, 3-way Crossover Study to Examine the Effects of Food on the Pharmacokinetics of Single Doses of 400 mg Posaconazole Oral Suspension in Healthy Male Taiwanese Subjects

Purpose: The pharmacokinetic parameters of a single 400-mg oral dose of posaconazole suspension, administered under fasting and fed conditions, were compared in healthy male Taiwanese volunteers. Methods: After an overnight fast, 16 subjects received a single oral dose of posaconazole suspension (400 mg) under fasting conditions or immediately after a normal-fat (700–800 calories, 30% fat) or high-fat breakfast meal (800–1000 calories, 50% fat). The treatments were administered as per the 3 × 6 Williams square design, with a 1-week washout phase between treatments. Blood samples were drawn at predetermined time points (0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours). All plasma concentrations of posaconazole were measured by high-performance liquid chromatography. The observed maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0–t and AUC0–∞), time to reach Cmax (tmax), and plasma half-life (t1/2) were assessed. Results: Fourteen subjects completed the study; 2 subjects withdrew because of adverse events. Thirteen subjects were included in the pharmacokinetic analysis. Sixteen subjects were included in the safety analysis. The mean posaconazole Cmax, AUC0–t, and AUC0–∞ values were significantly lower under fasting conditions than after a normal- or a high-fat meal. The mean Cmax values under fasting, normal-fat, and high-fat conditions were 279.00 ± 123.32 ng/mL, 662.46 ± 251.02 ng/mL, and 608.38 ± 183.22 ng/mL, respectively (P < 0.0001); the mean AUC0–t values under each condition were 6828.56 ± 3349.12 ng·mL−1·h−1, 20,629.84 ± 8346.45 ng·mL−1·h−1, and 20,741.09 ± 7681.02 ng·mL−1·h−1, respectively (P < 0.0001); and the mean AUC0–∞ values under each condition were 7304.72 ± 3444.54 ng·mL−1·h−1, 21,326.65 ± 8495.01 ng·mL−1·h−1, and 21,626.08 ± 8193.31 ng·mL−1·h−1, respectively (P < 0.0001). The mean tmax value was significantly shorter at 3.15 hours under fasting conditions than at 4.88 hours after normal- or high-fat meals (P = 0.0176). The mean t1/2 values were 22.0, 20.8, and 22.0 hours, respectively. Conclusions: The posaconazole AUC increased by approximately 3-fold, Cmax by 2.2-fold, and tmax by 1.5-fold when healthy Taiwanese subjects were administered the drug with food compared with under fasting conditions. These parameters were similar when the drug was administered with either a normal- or high-fat meal.
A solid phase extraction based non-disruptive sampling technique to investigate the surface chemistry of macroalgae

The surface chemistry of aquatic organisms determines their biotic interactions. Metabolites in the spatially limited laminar boundary layer mediate processes, such as antifouling, allelopathy and chemical defense against herbivores. However, very few methods are available for the investigation of such surface metabolites. An approach is described in which surfaces are extracted by means of C18 solid phase material. By powdering wet algal surfaces with this material, organic compounds are adsorbed and can be easily recovered for subsequent liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) investigations. The method is robust, picks up metabolites of a broad polarity range and is easy to handle. It is more universal compared to established solvent dipping protocols and it does not cause damage to the test organisms. A protocol is introduced for the macroalgae Fucus vesiculosus, Caulerpa taxifolia and Gracilaria vermiculophylla, but it can be easily transferred to other aquatic organisms.
A COMPARISON OF ELDERLY COLLEGE STUDENTS IN TWO GEOGRAPHICALLY DIFFERENT AREAS

Numerous public and private institutions of higher learning have provided educational opportunities for the elderly. Typically the institutions either reduce or even waive tuition, and/or develop special curricula to serve the elderly student. Numerous descriptions of various programs and the surveys of the attitudes and problems of older students can be found in the literature. One shortcoming of the many reports is due to limited sampling. Institutions vary considerably as do the populations involved. This study compares elderly students enrolled in state colleges in the University System of Georgia with those enrolled in four private and public colleges in the state of Idaho. In both states, the overwhelming majority of elderly students were enthusiastic about their experiences on campus, desired no special privileges, and would recommend that other elderly enroll in college courses.
Compatibility interactions at the cellular level provide the basis for host specificity in the parasitic plant Orobanche.

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Determination by LC–MS/MS of Colistins A and B in Plasma and Ultrafiltrate From Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

Background: Colistin is a 50-year-old antibiotic, the use of which was ceased in the 70s and recently resumed as a “salvage therapy” against multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii. The narrow therapeutic range of colistin makes the choice of its correct dosage crucial, and monitoring of blood concentration is occasionally necessary for critically ill patients, including intensive care patients subjected to continuous renal replacement therapy. Methods: Two LC–MS/MS methods were developed and fully validated for the quantitative determination of colistins A and B in plasma and dialysis ultrafiltrate (UF) samples, ultimately arising from 4 patients undergoing continuous venovenous hemodiafiltration (CVVHDF). Results: The developed methods proved to be both specific and selective. They showed good fit and linearity over the entire range of interest. Trueness and accuracy proved satisfactory. Both methods have excellent intraassay precision (percent coefficient of variations were lower than 10%) and limit of detection values in the range 20–100 ng/mL, about 1–2 orders of magnitude below the concentrations commonly detected in real samples. The mean sieving coefficient (SC) values, measured after 10 minutes of CVVHDF, were 0.42 for colistin A and 0.48 for colistin B. SC values proved to be quite stable for 24 hours, but then declined to 0.24 for colistin A and 0.32 for colistin B, respectively, after 48 hours. At the median blood flow and effluent flow rate of 120 and 28 mL/min, clearance values for colistin B were higher than 15 mL/min. During the entire duration of CVVHDF sessions, the SC and clearance values for colistin A were significantly lower than colistin B. Conclusions: Two simple methods for the simultaneous determination of colistins A and B have been developed and validated. Their application in the clinical setting demonstrates that CVVHDF treatment lasting 48 hours produces a relatively constant and efficient removal of the drug.
Evidence for the involvement of Globosa-like gene duplications and expression divergence in the evolution of floral morphology in the Zingiberales.

SUMMARY *The MADS box transcription factor family has long been identified as an important contributor to the control of floral development. It is often hypothesized that the evolution of floral development across angiosperms and within specific lineages may occur as a result of duplication, functional diversification, and changes in regulation of MADS box genes. Here we examine the role of Globosa (GLO)-like genes, members of the B-class MADS box gene lineage, in the evolution of floral development within the monocot order Zingiberales. *We assessed changes in perianth and stamen whorl morphology in a phylogenetic framework. We identified GLO homologs (ZinGLO1-4) from 50 Zingiberales species and investigated the evolution of this gene lineage. Expression of two GLO homologs was assessed in Costus spicatus and Musa basjoo. *Based on the phylogenetic data and expression results, we propose several family-specific losses and gains of GLO homologs that appear to be associated with key morphological changes. The GLO-like gene lineage has diversified concomitant with the evolution of the dimorphic perianth and the staminodial labellum. *Duplications and expression divergence within the GLO-like gene lineage may have played a role in floral diversification in the Zingiberales.
Antibacterial activity of a novel antimicrobial peptide [W7]KR12-KAEK derived from KR-12 against Streptococcus mutans planktonic cells and biofilms

Abstract The aims of this study were to describe the synthesis of a novel synthetic peptide based on the primary structure of the KR-12 peptide and to evaluate its antimicrobial and anti-biofilm activities against Streptococcus mutans. The antimicrobial effect of KR-12 and [W7]KR12-KAEK was assessed by determining the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. The evaluation of anti-biofilm activity was assessed through total biomass quantification, colony forming unit counting and scanning electron microscopy. [W7]KR12-KAEK showed MIC and MBC values ranging from 31.25 to 7.8 and 62.5 to 15.6 μg ml−1, respectively. Furthermore, [W7]KR12-KAEK significantly reduced biofilm biomass (50–100%). Regarding cell viability, [W7]KR12-KAEK showed reductions in the number of CFUs at concentrations ranging from 62.5 to 7.8 μg ml−1 and 500 to 62.5 μg ml−1 with respect to biofilm formation and preformed biofilms, respectively. SEM micrographs of S. mutans treated with [W7]KR12-KAEK suggested damage to the bacterial surface. [W7]KR12-KAEK is demonstrated to be an antimicrobial agent to control microbial biofilms.