A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.

The global threat of multidrug-resistant Gram-negative bacterial pathogens necessitates the development of new and effective antibiotics. FtsZ is an essential and highly conserved cytoskeletal protein that is an appealing antibacterial target for new antimicrobial therapeutics. However, the effectiveness of FtsZ inhibitors against Gram-negative species has been limited due in part to poor intracellular accumulation. To address this limitation, we have designed a FtsZ inhibitor (RUP4) that incorporates a chlorocatechol siderophore functionality that can chelate ferric iron (Fe3+) and utilizes endogenous siderophore uptake pathways to facilitate entry into Gram-negative pathogens. We show that RUP4 is active against both Klebsiella pneumoniae and Acinetobacter baumannii, with this activity being dependent on direct Fe3+ chelation and enhanced under Fe3+-limiting conditions. Genetic deletion studies in K. pneumoniae reveal that RUP4 gains entry through the FepA and CirA outer membrane transporters and the FhuBC inner membrane transporter. We also show that RUP4 exhibits bactericidal synergy against K. pneumoniae when combined with select antibiotics, with the strongest synergy observed with PBP2-targeting ß-lactams or MreB inhibitors. In the aggregate, our studies indicate that incorporation of Fe3+-chelating moieties into FtsZ inhibitors is an appealing design strategy for enhancing activity against Gram-negative pathogens of global clinical significance.

Structure-based design and optimization of a new class of small molecule inhibitors targeting the P-stalk binding pocket of ricin.

Ricin, a category-B agent for bioterrorism, and Shiga toxins (Stxs), which cause food poisoning bind to the ribosomal P-stalk to depurinate the sarcin/ricin loop. No effective therapy exists for ricin or Stx intoxication. Ribosome binding sites of the toxins have not been targeted by small molecules. We previously identified CC10501, which inhibits toxin activity by binding the P-stalk pocket of ricin toxin A subunit (RTA) remote from the catalytic site. Here, we developed a fluorescence polarization assay and identified a new class of compounds, which bind P-stalk pocket of RTA with higher affinity and inhibit catalytic activity with submicromolar potency. A lead compound, RU-NT-206, bound P-stalk pocket of RTA with similar affinity as a five-fold larger P-stalk peptide and protected cells against ricin and Stx2 holotoxins for the first time. These results validate the P-stalk binding site of RTA as a critical target for allosteric inhibition of the active site.

The Anticancer Drug Bleomycin Shows Potent Antifungal Activity by Altering Phospholipid Biosynthesis.

Invasive fungal infections are difficult to treat with limited drug options, mainly because fungi are eukaryotes and share many cellular mechanisms with the human host. Most current antifungal drugs are either fungistatic or highly toxic. Therefore, there is a critical need to identify important fungal specific drug targets for novel antifungal development. Numerous studies have shown the fungal phosphatidylserine (PS) biosynthetic pathway to be a potential target. It is synthesized from CDP-diacylglycerol and serine, and the fungal PS synthesis route is different from that in mammalian cells, in which preexisting phospholipids are utilized to produce PS in a base-exchange reaction. In this study, we utilized a Saccharomyces cerevisiae heterologous expression system to screen for inhibitors of Cryptococcus PS synthase Cho1, a fungi-specific enzyme essential for cell viability. We identified an anticancer compound, bleomycin, as a positive candidate that showed a phospholipid-dependent antifungal effect. Its inhibition on fungal growth can be restored by ethanolamine supplementation. Further exploration of the mechanism of action showed that bleomycin treatment damaged the mitochondrial membrane in yeast cells, leading to increased generation of reactive oxygen species (ROS), whereas supplementation with ethanolamine helped to rescue bleomycin-induced damage. Our results indicate that bleomycin does not specifically inhibit the PS synthase enzyme; however, it may affect phospholipid biosynthesis through disruption of mitochondrial function, namely, the synthesis of phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which helps cells maintain membrane composition and functionality. IMPORTANCE Invasive fungal pathogens cause significant morbidity and mortality, with over 1.5 million deaths annually. Because fungi are eukaryotes that share much of their cellular machinery with the host, our armamentarium of antifungal drugs is highly limited, with only three classes of antifungal drugs available. Drug toxicity and emerging resistance have limited their use. Hence, targeting fungi-specific enzymes that are important for fungal survival, growth, or virulence poses a strategy for novel antifungal development. In this study, we developed a heterologous expression system to screen for chemical compounds with activity against Cryptococcus phosphatidylserine synthase, Cho1, a fungi-specific enzyme that is essential for viability in C. neoformans. We confirmed the feasibility of this screen method and identified a previously unexplored role of the anticancer compound bleomycin in disrupting mitochondrial function and inhibiting phospholipid synthesis.

Does the adenosine deaminase (ADA) gene confer risk of sleepwalking?

Sleepwalking is a common non-rapid eye movement (NREM) parasomnia and a significant cause of sleep-related injuries. While evidence suggest that the occurrence of this condition is partly determined by genetic factors, its pattern of inheritance remains unclear, and few molecular studies have been conducted. One promising candidate is the adenosine deaminase (ADA) gene. Adenosine and the ADA enzyme play an important role in the homeostatic regulation of NREM sleep. In a single sleepwalking family, genome-wide analysis identified a locus on chromosome 20, where ADA lies. In this study, we examined if variants in the ADA gene were associated with sleepwalking. In total, 251 sleepwalking patients were clinically assessed, and DNA samples were compared to those from 94 unaffected controls. Next-generation sequencing of the whole ADA gene was performed. Bio-informatic analysis enabled the identification of variants and assessed variants enrichment in our cohort compared to controls. We detected 25 different coding and non-coding variants, of which 22 were found among sleepwalkers. None were enriched in the sleepwalking population. However, many missense variants were predicted as likely pathogenic by at least two in silico prediction algorithms. This study involves the largest sleepwalking cohort in which the role of a susceptibility gene was investigated. Our results did not reveal an association between ADA gene and sleepwalking, thus ruling out the possibility of ADA as a major genetic factor for this condition. Future work is needed to identify susceptibility genes.

Effects of dietary xylooligosaccharide prebiotic supplementation on growth, antioxidant and intestinal immune-related genes expression in common carp Cyprinus carpio fed a high-fat diet.

This study investigated the effects of xylooligosaccharide (XOS) supplementation on growth, intestinal enzyme, antioxidant and immune-related genes in common carp Cyprinus carpio fed a high-fat diet (HFD). One hundred and ninety two fish with an initial weight of 19.61 ± 0.96 g were allocated into 24 tanks (eight fish per tank in four replicate) and were fed the control diet, HFD, HFD with 0.5%, 1%, 2% and 3% XOS supplementation. From the result, fish offered HFD with 1% XOS supplementation significantly obtained a higher body mass index and feed efficiency ratio, whereas condition factor was higher in fish fed HFD supplemented with 2% XOS but no difference was attributed to other supplemented group compared to control group. Also, fish fed HFD supplemented with 1%-2% XOS significantly improved protease, lipase, creatine kinase and sodium/potassium ATPase activities compared to other groups. Fish offered HFD were significantly lower in superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), myeloperoxidase, acid phosphatase, lysozyme activities and immunoglobulin content, but the opposite result was found for aspartate transaminase, alanine transaminase activities, malondialdehyde, protein carbonyl and cortisol content as compared with the control. However, this effect was reversed with HFD supplemented with XOS. Also, interleukin 1ß, interleukin 8, tumour necrosis factors, interferons, caspase-3 and caspase-9 in the intestine were all up-regulated in the HFD group, while the reverse pattern was found in SOD, GPX, lysozyme-C, complement 3 and mucin 5b (muc5b), than the control group. These effects were all enhanced by feeding the XOS diet, especially those fed 1%-3% supplementation. In conclusion, XOS inclusion can improve the growth, digestive enzymes, antioxidants and immune response of common carp fed HFD.

Benzothiazolyl and Benzoxazolyl Hydrazones Function as Zinc Metallochaperones to Reactivate Mutant p53.

We identified a set of thiosemicarbazone (TSC) metal ion chelators that reactivate specific zinc-deficient p53 mutants using a mechanism called zinc metallochaperones (ZMCs) that restore zinc binding by shuttling zinc into cells. We defined biophysical and cellular assays necessary for structure-activity relationship studies using this mechanism. We investigated an alternative class of zinc scaffolds that differ from TSCs by substitution of the thiocarbamoyl moiety with benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones. Members of this series bound zinc with similar affinity and functioned to reactivate mutant p53 comparable to the TSCs. Acute toxicity and efficacy assays in rodents demonstrated C1 to be significantly less toxic than the TSCs while demonstrating equivalent growth inhibition. We identified C85 as a ZMC with diminished copper binding that functions as a chemotherapy and radiation sensitizer. We conclude that the benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones can function as ZMCs to reactivate mutant p53 in vitro and in vivo.

Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder.

OBJECTIVE: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD). METHODS: We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex. RESULTS: We found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD. CONCLUSION: Our results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.

Pesticides and the evolution of the genetic structure of Anopheles coluzzii populations in some localities in Benin (West Africa).

BACKGROUND: Changes in the natural habitats of insect groups are determined the genetic polymorphisms between individuals. The objective of this study was to establish the genetic structure of the Anopheles coluzzii populations in four localities of Benin. METHODS: Insecticide surveys and larval sampling were conducted on 4 study localities, including Cotonou, Ketou, Zagnanado, and Sô-Ava. Molecular characterizations were performed on the Anopheles mosquitoes collected with the allelic and genotypic frequencies of kdr gene determined. The multiple comparison Chi square test for proportions was performed with R version 3.3.3. Next, the observed heterozygosity, expected heterozygosity, and indices of fixation, and genetic differentiation were estimated. Finally, the Hardy-Weinberg equilibrium (EHW) was determined to assess whether panmixia exists in the different populations of mosquitoes of the agroecological zones under study. RESULTS: Carbamates, pyrethroids, organophosphorus and organochlorines use have been reported in all localities except Sô-Ava. Anopheles coluzzii was strongly represented across all study localities. The L1014F allele was observed in the localities of Kétou, Cotonou and Zagnanado. Likewise, insecticide selection pressure of homozygous resistant individuals (L1014F/L1014F) was significantly higher in Kétou, Cotonou and Zagnanado (p value < 0.05). Surprisingly in Sô-Ava, a relatively high frequency of the L1014F allele despite the reported absence of pesticide use was observed. All mosquito populations were found to be deficient in heterozygosity across the study sites (FIS< 0). No genetic differentiation (FST< 0) was observed in the localities of Zagnanado and Kétou. CONCLUSION: The survey on the use of insecticides showed that insecticide selection pressures differ across the investigated localities. It would be desirable to rotate or apply formulations of combined products with different modes of action. Doing so would enable a better management of resistant homozygous individuals, and mitigate the resistance effect of commonly used insecticides.

Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017.

Zoonotic transmission of parapoxvirus from animals to humans has been reported; clinical manifestations are skin lesions on the fingers and hands after contact with infected animals. We report a human infection clinically suspected as being ecthyma contagiosum. The patient, a 65-year-old woman, had 3 nodules on her hands. She reported contact with a sheep during the Aïd-el-Fitr festival in France during 2017. We isolated the parapoxvirus orf virus from these nodules by using a nonconventional cell and sequenced the orf genome. We identified a novel orf virus genome and compared it with genomes of other orf viruses. More research is needed on the genus Parapoxvirus to understand worldwide distribution of and infection by orf virus, especially transmission between goats and sheep.

Protochlamydia phocaeensis sp. nov., a new Chlamydiales species with host dependent replication cycle.

Chlamydiae are pathogenic and symbiotic bacteria, which form an important part of amoeba-associated microorganisms. In this paper, we report the isolation, developmental cycle and genome analysis of Protochlamydia phocaeensis sp. nov., an obligate intracellular parasite with a large host spectrum, able to infect Acanthamoeba castellanii, Acanthamoeba polyphaga, and Vermamoeba vermiformis. The genome size is 3,424,182 bp with a GC content of 42%. This bacterium displayed a particular developmental cycle depending on the infected host. The P. phocaeensis showed typical inclusion vacuoles in A. castellanii, while these were absent in V. vermiformis. Since "Chlamydiae-amoebae" interactions are supposed to depend on the chlamydial species, our findings speculate that variations in the developmental cycle of certain Chlamydiae are also host dependent.

The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder.

The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

High-Throughput Isolation of Giant Viruses in Liquid Medium Using Automated Flow Cytometry and Fluorescence Staining.

The isolation of giant viruses using amoeba co-culture is tedious and fastidious. Recently, the procedure was successfully associated with a method that detects amoebal lysis on agar plates. However, the procedure remains time-consuming and is limited to protozoa growing on agar. We present here advances for the isolation of giant viruses. A high-throughput automated method based on flow cytometry and fluorescent staining was used to detect the presence of giant viruses in liquid medium. Development was carried out with the Acanthamoeba polyphaga strain widely used in past and current co-culture experiments. The proof of concept was validated with virus suspensions: artificially contaminated samples but also environmental samples from which viruses were previously isolated. After validating the technique, and fortuitously isolating a new Mimivirus, we automated the technique on 96-well plates and tested it on clinical and environmental samples using other protozoa. This allowed us to detect more than 10 strains of previously known species of giant viruses and seven new strains of a new virus lineage. This automated high-throughput method demonstrated significant time saving, and higher sensitivity than older techniques. It thus creates the means to isolate giant viruses at high speed.

Case-Control and Family-Based Association Study of Specific PTPRD Variants in Restless Legs Syndrome.

BACKGROUND: The exact genetic causes within each of the known restless legs syndrome (RLS) loci are still unknown. Recently, it was suggested that an intronic protein tyrosine phosphatase, receptor type δ (PTPRD) single-nucleotide polymorphism (SNP) (reference SNP no. rs2381970) is associated with its expression, which may lead to RLS and other related phenotypes. Another study identified 3 nonsynonymous PTPRD variants in familial RLS cases: p.Q447E (a residue change from glutamine to glutamic acid at position 447), p.T781A (a residue change from threonine to alanine at position 781), and p.R995C (a residue change from arginine to cysteine at position 995). METHODS: Two cohorts of sporadic RLS, a French-Canadian cohort and a cohort from the United States, with a total of 577 patients and 455 controls, and an additional familial RLS cohort with a total of 635 individuals (140 families) were genotyped for these 4 variants (rs2381970, p.Q447E, p.T781A, and p.R995C) by using specific TaqMan probes, and the effects of each variant as well as haplotypes were analyzed. RESULTS: None of the 4 PTPRD-specific variants or haplotypes that were tested were associated with RLS in the case-control cohorts or in the familial cohort. The frequencies of the rs2381970 variant in the French-Canadian and US cohorts were 0.07 and 0.04, respectively, and their frequencies in the respective control populations were 0.06 and 0.04, respectively (P > 0.4 for both). Similar results were obtained for the 3 nonsynonymous variants. CONCLUSIONS: Although the PTPRD gene is well established as an RLS-associated locus, the rs2381970 SNP and the 3 nonsynonymous PTPRD variants are not likely to cause or affect the risk for developing RLS in the study population. More studies in other populations are needed to determine their potential role in RLS.

Isolation of new Brazilian giant viruses from environmental samples using a panel of protozoa.

The Megavirales are a newly described order capable of infecting different types of eukaryotic hosts. For the most part, the natural host is unknown. Several methods have been used to detect these viruses, with large discrepancies between molecular methods and co-cultures. To isolate giant viruses, we propose the use of different species of amoeba as a cellular support. The aim of this work was to isolate new Brazilian giant viruses by comparing the protozoa Acanthamoeba castellanii, A. polyphaga, A. griffini, and Vermamoeba vermiformis (VV) as a platform for cellular isolation using environmental samples. One hundred samples were collected from 3 different areas in September 2014 in the Pampulha lagoon of Belo Horizonte city, Minas Gerais, Brazil. PCR was used to identify the isolated viruses, along with hemacolor staining, labelling fluorescence and electron microscopy. A total of 69 viruses were isolated. The highest ratio of isolation was found in A. polyphaga (46.38%) and the lowest in VV (0%). Mimiviruses were the most frequently isolated. One Marseillevirus and one Pandoravirus were also isolated. With Brazilian environmental samples, we demonstrated the high rate of lineage A mimiviruses. This work demonstrates how these viruses survive and circulate in nature as well the differences between protozoa as a platform for cellular isolation.

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study.

OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. RESULTS: Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p < 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6). INTERPRETATION: Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences.

Comorbidity and medication in REM sleep behavior disorder: a multicenter case-control study.

OBJECTIVE: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. METHODS: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis. RESULTS: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3-2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4-3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8-7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1-3.3; depression: OR 1.6, 95% CI 1.0-2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1-3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3-3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8-15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0-118.8; nonsmoking: OR 2.4, 95% CI 0.4-13.2) and consequent pulmonary disease. CONCLUSIONS: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.

Discovery of 2-(phenoxypyridine)-3-phenylureas as small molecule P2Y1 antagonists.

Two distinct G protein-coupled purinergic receptors, P2Y1 and P2Y12, mediate ADP-driven platelet activation. The clinical effectiveness of P2Y12 blockade is well established. Recent preclinical data suggest that P2Y1 and P2Y12 inhibition provide equivalent antithrombotic efficacy, while targeting P2Y1 has the potential for reduced bleeding liability. In this account, the discovery of a 2-(phenoxypyridine)-3-phenylurea chemotype that inhibited ADP-mediated platelet aggregation in human blood samples is described. Optimization of this series led to the identification of compound 16, 1-(2-(2-tert-butylphenoxy)pyridin-3-yl)-3-4-(trifluoromethoxy)phenylurea, which demonstrated a 68 ± 7% thrombus weight reduction in an established rat arterial thrombosis model (10 mg/kg plus 10 mg/kg/h) while only prolonging cuticle and mesenteric bleeding times by 3.3- and 3.1-fold, respectively, in provoked rat bleeding time models. These results suggest that a P2Y1 antagonist could potentially provide a safe and efficacious antithrombotic profile.

A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study.

BACKGROUND: Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinson's disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response. METHODS: Four hundred and eighty-four sleep-clinic-based participants (242 idiopathic RBD patients and 242 controls) completed the screen during a multicenter case-control study. All participants underwent a polysomnogram to define gold-standard diagnosis according to standard criteria. RESULTS: We found a sensitivity of 93.8% and a specificity of 87.2%. Sensitivity and specificity were similar in healthy volunteers, compared to controls or patients with other sleep diagnoses. CONCLUSIONS: A single-question screen for RBD may reliably detect disease, with psychometric properties favorably comparable to those reported for longer questionnaires.

Antimicrobial activity of polyphenol-rich fractions from Sida alba L. (Malvaceae) against co-trimoxazol-resistant bacteria strains.

BACKGROUND: The increased resistance of microorganisms to the currently used antimicrobials has lead to the evaluation of other agents that might have antimicrobial activity. Medicinal plants are sources of phytochemicals which are able to initiate different biological activities including antimicrobials MATERIALS AND METHODS: In vitro antibacterial (MIC, MBC and time-kill studies) of polyphenol-rich fractions from Sida alba L. (Malvaceae) was assessed using ten bacteria strains (Gram-negative and Gram-positive). RESULTS: All test bacteria were susceptible to the polyphenol-rich fractions. Time-kill results showed that after 5 h exposition there was no viable microorganism in the initial inoculum and the effect of polyphenol-rich fractions was faster on Enterococcus faecalis (Gram-positive bacterium) comparatively to the other bacteria strains. CONCLUSION: The data analysis indicates that the tested of polyphenol-rich fractions has significant effects when compared with the standard antibiotic. These results therefore justify the traditional use of sida alba L., alone or in combination with other herbs to treat bacterial infections.