Older, Less Regulated Medical Marijuana Programs Have Much Greater Enrollment Rates Than Newer ‘Medicalized’ Programs

Twenty-three states and the District of Columbia have passed laws implementing medical marijuana programs. The nineteen programs that were in operation as of October 2014 collectively had over one million participants. All states (including D.C.) with medical marijuana laws require physicians directly or indirectly to authorize the use of marijuana at their discretion, yet little is known about how medical marijuana programs vary regarding adherence to basic principles of medical practice and associated rates of enrollment. To explore this, we analyzed marijuana programs according to seven components of traditional medical care and pharmaceutical regulation. We then examined enrollment rates, while controlling for potentially confounding state characteristics. We found that fourteen of the twenty-four programs were nonmedical and collectively enrolled 99.4 percent of participants nationwide, with enrollment rates twenty times greater than programs deemed to be “medicalized.” Policy makers implementing or amending medical marijuana programs should consider the powerful relationship between less regulation and greater enrollment. Researchers should consider variations across programs when assessing programs’ population-level effects

The GraRS regulatory system controls Staphylococcus aureus susceptibility to antimicrobial host defenses

<p>Abstract</p> <p>Background</p> <p>Modification of teichoic acids with D-alanine by the products of the <it>dlt </it>operon protects Gram-positive bacteria against major antimicrobial host defense molecules such as defensins, cathelicidins, myeloperoxidase or phospholipase. The <it>gra</it>RS regulatory genes have recently been implicated in the control of D-alanylation in <it>Staphylococcus aureus</it>.</p> <p>Results</p> <p>To determine the impact of the GraRS regulatory system on resistance to antimicrobial host defense mechanisms and virulence of <it>S. aureus</it>, we compared inactivation of <it>S. aureus </it>SA113 wild type and its isogenic <it>gra</it>RS deletion mutant by the human cathelicidin LL-37 or human neutrophil granulocytes <it>in vitro</it>, and the ability to cause infection <it>in vivo</it>. We show here that <it>gra</it>RS deletion considerably alters bacterial surface charge, increases susceptibility to killing by human neutrophils or the defense peptide LL-37, and attenuates virulence of <it>S. aureus </it>in a mouse infection model.</p> <p>Conclusion</p> <p>Our results indicate that <it>S. aureus </it>can regulate its surface properties in order to overcome innate host defenses.</p

Quantification of the Lewis Basicities and Nucleophilicities of 1,3,5-Tris(dialkylamino)benzenes

AbstractEquilibrium constants for the formation of Wheland complexes from 1,3,5‐tris(dialkylamino)benzenes and benzhydrylium ions (Ar2CH+) have been determined photometrically in dichloromethane solution at 20 °C. The Lewis basicity of the ring carbons increases in the series trimorpholinobenzene<tripiperidinobenzene<tripyrrolidinobenzene. Wheland complexes, which are formed with equilibrium constants 102<K/M−1<106 in the reactions of triaminobenzenes with carbenium ions, show temperature‐dependent dynamic 1H NMR spectra, due to rapid reverse reactions and recombination at different positions of the triaminobenzenes. Since the rates of the formation of the Wheland complexes are too high to be measured directly, they were calculated as the product of photometrically determined equilibrium constants and the rate constants for the reverse reactions, which were derived from the dynamic 1H NMR spectra. The experimentally determined equilibrium and rate constants were in good agreement with the results of DFT calculations using the SMD solvent model. The calculations show that in all cases the Wheland complexes are thermodynamically more stable than the ammonium ions formed by attack of the benzhydrylium ions at the amino group of the title compounds, which explains the exclusive formation of Wheland complexes in thermodynamically controlled reactions. With nucleophilicity parameters in the range 10<N<15 the triaminobenzenes have comparable nucleophilic reactivities as enamines, silyl ketene acetals as well as stabilized phosphonium and sulfonium ylides

Associations between diagnostic pathways and care experience in colorectal cancer: evidence from patient-reported data.

OBJECTIVE: To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care. DESIGN: Patient survey linked to information on diagnostic route.English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment. MAIN OUTCOME MEASURES: Odds Ratios and adjusted proportions of negative evaluation of key aspects of care for colorectal cancer, including the experience of shared decision-making about treatment, specialist nursing and care coordination, by diagnostic route (ie, screening detection, emergency presentation, urgent and elective general practitioner referral). RESULTS: For 14 of 18 questions, there was evidence (p≤0.02) for variation in patient experience by diagnostic route, with 6-31 percentage point differences between routes in adjusted proportions of negative experience. Emergency presenters were more likely to report a negative experience for most questions, including those about adequacy of information about their diagnosis and sufficient explanation before operations. Screen-detected patients were least likely to report negative experiences except for support from primary care. Patients diagnosed through elective primary care referrals were most likely to report worse experience for questions for which overall variation by route was generally small. CONCLUSIONS: Screening-detected patients tend to report the best and emergency presenters the worst experience of subsequent care. Improvement efforts can target care integration for screening-detected patients and provision of information about the diagnosis and treatment of emergency presenters

Genomic insight into Campylobacter jejuni isolated from commercial turkey flocks in Germany using whole-genome sequencing analysis

Campylobacter (C.) jejuni is a zoonotic bacterium of public health significance. The present investigation was designed to assess the epidemiology and genetic heterogeneity of C. jejuni recovered from commercial turkey farms in Germany using whole-genome sequencing. The Illumina MiSeq® technology was used to sequence 66 C. jejuni isolates obtained between 2010 and 2011 from commercial meat turkey flocks located in ten German federal states. Phenotypic antimicrobial resistance was determined. Phylogeny, resistome, plasmidome and virulome profiles were analyzed using whole-genome sequencing data. Genetic resistance markers were identified with bioinformatics tools (AMRFinder, ResFinder, NCBI and ABRicate) and compared with the phenotypic antimicrobial resistance. The isolates were assigned to 28 different sequence types and 11 clonal complexes. The average pairwise single nucleotide-polymorphisms distance of 14,585 SNPs (range: 0–26,540 SNPs) revealed a high genetic distinction between the isolates. Thirteen virulence-associated genes were identified in C. jejuni isolates. Most of the isolates harbored the genes flaA (83.3%) and flaB (78.8%). The wlaN gene associated with the Guillain–Barré syndrome was detected in nine (13.6%) isolates. The genes for resistance to ampicillin (blaOXA), tetracycline [tet(O)], neomycin [aph(3')-IIIa], streptomycin (aadE) and streptothricin (sat4) were detected in isolated C. jejuni using WGS. A gene cluster comprising the genes sat4, aph(3′)-IIIa and aadE was present in six isolates. The single point mutation T86I in the housekeeping gene gyrA conferring resistance to quinolones was retrieved in 93.6% of phenotypically fluoroquinolone-resistant isolates. Five phenotypically erythromycin-susceptible isolates carried the mutation A103V in the gene for the ribosomal protein L22 inferring macrolide resistance. An assortment of 13 β-lactam resistance genes (blaOXA variants) was detected in 58 C. jejuni isolates. Out of 66 sequenced isolates, 28 (42.4%) carried plasmid-borne contigs. Six isolates harbored a pTet-like plasmid-borne contig which carries the tet(O) gene. This study emphasized the potential of whole-genome sequencing to ameliorate the routine surveillance of C. jejuni. Whole-genome sequencing can predict antimicrobial resistance with a high degree of accuracy. However, resistance gene databases need curation and updates to revoke inaccuracy when using WGS-based analysis pipelines for AMR detection

Efeitos de variações metodológicas sobre a identificação do lactato mínimo

The aim of this study was to analyze the influence of increment pattern as well as the stage duration on lactate minimum (LM) determination. Volunteers were eight physical active males [22.4 + 1.9 years; 177 ± 4.2 cm; 73.6 ± 5.4 kg; 23,4 ± 1,3 kg.(m2)-1] that performed, on different days, two incremental tests on cycle ergometer after lactic acidosis induction through 30 seconds Wingate test. Test 1- initial load of 1.75 kp and increments of 0.25 kp at each stage of 3 min until volitional exhaustion to determine the intensity corresponding to LM (LM1); Test 2- the intensities were 0.5 kp below, 0.5 kp above and the intensity at LM1 (at), the test 2 was composed by two parts (2a - stages of 3 min and 2b - stages of 6 min). The lactate concentration ([lac]), heart rate (HR) and exercise intensities corresponding to LM observed during parts 2a (LM2a) and 2b (LM2b) were compared to LM1. Differences were observed between the [lac] corresponding to LM1 and LM2a (4.9 ± 2.4 vs 6.2 ± 1.9 mM), as well as between the HR corresponding to LM2b (167 ± 14 bpm) and the HR corresponding to LM1 (159 ± 17 bpm) and LM2a (158 ± 12 bpm) (p < 0.05). However, no differences were observed for the intensities corresponding to LM1, LM2a and LM2b (2.6 ± 0.3 vs 2.6 ± 0.5 vs 2.6 ± 0.3 kp, respectively). We concluded that the methodological variations applied on present study did not interfere on the exercise intensity corresponding to LM.O objetivo do presente estudo foi analisar a influência de diferentes intensidades e durações de estágios incrementais sobre a determinação do lactato mínimo (LM). Fizeram parte deste estudo oito homens fisicamente ativos [22,4 ± 1,9 anos; 177,0 ± 4,2 cm; 73,6 ± 5,4 kg; 23,4 ± 1,3 kg&#9679;(m²)-1] que realizaram, em dias diferentes, dois testes incrementais em cicloergômetro após hiperlactacidemia induzida por um teste de Wingate de 30 segundos. Teste 1- carga inicial de 1,75 kp e incrementos de 0,25 kp a cada estágio de três minutos até exaustão voluntária para determinar a intensidade correspondente ao LM (LM1). Teste 2- alternando-se as cargas entre 0,5 kp abaixo, 0,5 kp acima e na intensidade do LM1, o teste 2 foi composto por duas partes seqüenciais (2a - estágios de três minutos e 2b - estágios de seis minutos). As concentrações de lactato sangüíneo ([lac]), freqüência cardíaca (FC) e intensidades (int) correspondentes ao LM dos testes 2a (LM2a) e 2b (LM2b) foram comparadas com o LM1. Foram observadas diferenças entre as [lac] correspondentes ao LM1 e LM2a (4,9 ± 2,4 vs 6,2 ± 1,9 mM) bem como entre a FC correspondente ao LM2b (167 ± 14 bpm) e os valores de FC correspondentes ao LM1 (159 ± 17 bpm) e LM2a (158 ± 12 bpm) (p < 0,05). Contudo, não foram observadas diferenças entre as int correspondentes ao LM1, LM2a e LM2b (2,6 ± 0,3 vs 2,6 ± 0,5 vs 2,6 ± 0,3 kp, respectivamente). Concluímos que as variações metodológicas empregadas não resultaram em alterações na intensidade de exercício correspondente ao LM

Molecular Basis of Resistance to Muramidase and Cationic Antimicrobial Peptide Activity of Lysozyme in Staphylococci

It has been shown recently that modification of peptidoglycan by O-acetylation renders pathogenic staphylococci resistant to the muramidase activity of lysozyme. Here, we show that a Staphylococcus aureus double mutant defective in O-acetyltransferase A (OatA), and the glycopeptide resistance-associated two-component system, GraRS, is much more sensitive to lysozyme than S. aureus with the oatA mutation alone. The graRS single mutant was resistant to the muramidase activity of lysozyme, but was sensitive to cationic antimicrobial peptides (CAMPs) such as the human lysozyme-derived peptide 107R-A-W-V-A-W-R-N-R115 (LP9), polymyxin B, or gallidermin. A comparative transcriptome analysis of wild type and the graRS mutant revealed that GraRS controls 248 genes. It up-regulates global regulators (rot, sarS, or mgrA), various colonization factors, and exotoxin-encoding genes, as well as the ica and dlt operons. A pronounced decrease in the expression of the latter two operons explains why the graRS mutant is also biofilm-negative. The decrease of the dlt transcript in the graRS mutant correlates with a 46.7% decrease in the content of esterified d-alanyl groups in teichoic acids. The oatA/dltA double mutant showed the highest sensitivity to lysozyme; this mutant completely lacks teichoic acid–bound d-alanine esters, which are responsible for the increased susceptibility to CAMPs and peptidoglycan O-acetylation. Our results demonstrate that resistance to lysozyme can be dissected into genes mediating resistance to its muramidase activity (oatA) and genes mediating resistance to CAMPs (graRS and dlt). The two lysozyme activities act synergistically, as the oatA/dltA or oatA/graRS double mutants are much more susceptible to lysozyme than each of the single mutants

Racial differences in cumulative disadvantage among women and its relation to health: Development and preliminary validation of the CSI-WE

Background: Cumulative disadvantage (CD) is a measure of accumulated social, economic, and person-related stressors due to unequal access to resources and opportunities, which increases a person's biological risk for disease. The purpose of this research was to develop an instrument tailored to women's experiences that had intervention and translational potential. In addition, we explored whether CD contributed to racial health disparities among black and white women. Methods: In-depth life course interviews were used to assess stressful experiences of 15 black and 15 white women. Using information from the interviews, we developed the Cumulative Stress Inventory of Women's Experiences (CSI-WE) as a quantitative instrument to measure stressful life experiences from childhood to adulthood. The CSI-WE was then administered to the original 30 women for validation and feedback. Results: Qualitative and quantitative assessments were highly correlated, which suggested that the CSI-WE reliably captured the experiences of the interviewed women. Black participants reported significantly higher numbers of childhood and adult stressors, more acute adulthood and lifetime stressors, and worse adult physical self-rated health. Conclusions: This study supports the preliminary validity of an instrument that once fully validated may be used in future studies to elucidate the experiences of CD among black and white women and examines how these experiences relate to perceived and objective health status

Timely sleep facilitates declarative memory consolidation in infants

Human infants devote the majority of their time to sleeping. However, very little is known about the role of sleep in early memory processing. Here we test 6- and 12-mo-old infants’ declarative memory for novel actions after a 4-h [Experiment (Exp.) 1] and 24-h delay (Exp. 2). Infants in a nap condition took an extended nap (≥30 min) within 4 h after learning, whereas infants in a no-nap condition did not. A comparison with age-matched control groups revealed that after both delays, only infants who had napped after learning remembered the target actions at the test. Additionally, after the 24-h delay, memory performance of infants in the nap condition was significantly higher than that of infants in the no-nap condition. This is the first experimental evidence to our knowledge for an enhancing role of sleep in the consolidation of declarative memories in the first year of life