Characteristics of Vibrio vulnificus isolates from clinical and environmental sources.

Researchers have developed multiple methods to characterize clinical and environmental strains of Vibrio vulnificus. The aim of our study was to use four assays to detect virulence factors in strains from infected patients and those from surface waters/sediments/oysters of South Carolina and the Gulf of Mexico. Vibrio vulnificus strains from clinical (n = 81) and environmental (n = 171) sources were tested using three real-time PCR methods designed to detect polymorphisms in the 16S rRNA, vcg and pilF genes and a phenotypic method, the ability to ferment D-mannitol. Although none of the tests correctly categorized all isolates, the differentiation between clinical and environmental isolates was similar for the pilF, vcgC/E and 16S rRNA assays, with sensitivities of 74.1-79.2% and specificities of 77.4-82.7%. The pilF and vcgC/E assays are comparable in efficacy to the widely used 16S rRNA method, while the D-mannitol fermentation test is less discriminatory (sensitivity = 77.8%, specificity = 61.4%). Overall percent agreement for the D-mannitol fermentation method was also lower (66.7%) than overall percent agreement for the 3 molecular assays (78.0%-80.2%). This study demonstrated, using a large, diverse group of Vibrio vulnificus isolates, that three assays could be used to distinguish most clinical vs environmental isolates; however, additional assays are needed to increase accuracy.

The key components of a successful model of midwifery-led continuity of carer, without continuity at birth: findings from a qualitative implementation evaluation.

BACKGROUND: Recent UK maternity policy changes recommend that a named midwife supports women throughout their pregnancy, birth and postnatal care. Whilst many studies report high levels of satisfaction amongst women receiving, and midwives providing, this level of continuity of carer, there are concerns some midwives may experience burnout and stress. In this study, we present a qualitative evaluation of the implementation of a midwife-led continuity of carer model that excluded continuity of carer at the birth. METHODS: Underpinned by the Conceptual Model for Implementation Fidelity, our evaluation explored the implementation, fidelity, reach and satisfaction of the continuity of carer model. Semi-structured interviews were undertaken with midwives (n = 7) and women (n = 15) from continuity of carer team. To enable comparisons between care approaches, midwives (n = 7) and women (n = 10) from standard approach teams were also interviewed. Interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: For continuity of carer team midwives, manageable caseloads, extended appointment times, increased team stability, and flexible working patterns facilitated both care provided and midwives' job satisfaction. Both continuity of carer and standard approach midwives reported challenges in providing postnatal continuity given the unpredictable timing of labour and birth. Time constraints, inadequate staffing and lack of administrative support were reported as additional barriers to implementing continuity of carer within standard approach teams. Women reported continuity was integral to building trust with midwives, encouraged them to disclose mental health issues and increased their confidence in making birth choices. CONCLUSIONS: Our evaluation highlighted the successful implementation of a continuity of carer model for ante and postnatal care. Despite exclusion of the birth element in the model, both women and midwives expressed high levels of satisfaction in comparison to women and midwives within the standard approach. Implementation successes were largely due to structural and resource factors, particularly the combination of additional time and smaller caseloads of women. However, these resources are not widely available within the resources of maternity unit budgets. Future research should further explore whether a continuity of carer model focusing on antenatal and postnatal care delivery is a feasible and sustainable model of care for all women.

Use of progression criteria to support monitoring and commissioning decision making of public health services: lessons from Better Start Bradford.

BACKGROUND: Commissioning and monitoring of community-based interventions is a challenge due to the complex nature of the environment and the lack of any explicit cut-offs to guide decision making. At what point, for example, is participant enrolment to interventions, course completion or satisfaction deemed to be acceptable or sufficient for continued funding? We aimed to identify and quantify key progression criteria for fourteen early years interventions by (1) agreeing the top three criteria for monitoring of successful implementation and progress; and (2) agreeing boundaries to categorise interventions as 'meeting anticipated target' (green); 'falling short of targets' (amber) and 'targets not being met' (red). METHODS: We ran three workshops in partnership with the UK's Big Lottery Fund commissioned programme 'Better Start Bradford' (implementing more than 20 interventions to improve the health, wellbeing and development of children aged 0-3) to support decision making by agreeing progression criteria for the interventions being delivered. Workshops included 72 participants, representing a range of professional groups including intervention delivery teams, commissioners, intervention-monitoring teams, academics and community representatives. After discussion and activities, final decisions were submitted using electronic voting devices. All participants were invited to reconsider their responses via a post-workshop questionnaire. RESULTS: Three key progression criteria were assigned to each of the 14 interventions. Overall, criteria that participants most commonly voted for were recruitment, implementation and reach, but these differed according to each intervention. Cut-off values used to indicate when an intervention moved to 'red' varied by criteria; the lowest being for recruitment, where participants agreed that meeting less than 65% of the targeted recruitment would be deemed as 'red' (falling short of target). CONCLUSIONS: Our methodology for monitoring the progression of interventions has resulted in a clear pathway which will support commissioners and intervention teams in local decision making within the Better Start Bradford programme and beyond. This work can support others wishing to implement a formal system for monitoring the progression of public health interventions.

Ultrathin Y2O3:Eu3+nanodiscs: spectroscopic investigations and evidence for reduced concentration quenching.

Here, we report the synthesis and spectral properties of ultrathin nanodiscs (NDs) of Y2O3:Eu3+. It was found that the NDs of Y2O3:Eu3+ with a thickness of about 1 nm can be fabricated in a reproducible, facile and self-assembling process, which does not depend on the Eu3+ concentration. The thickness and morphology of these NDs were determined with small angle x-ray scattering and transmission electron microscopy. We found that the crystal field in these nanoparticles deviates from both the cubic and monoclinic characteristics, albeit the shape of the 5D0 â†’ 7F J (J = 0, 1, 2) transitions shows some similarity with the transitions in the monoclinic material. The Raman spectra of the non-annealed NDs manifest various vibration modes of the oleic acid molecules, which are used to stabilise the NDs. The annealed NDs show two very weak Raman lines, which may be assigned to vibrational modes of Y2O3 NDs. The concentration quenching of the Eu3+ luminescence of the NDs before annealing is largely suppressed and might be explained in terms of a reduction of the phonon density of states.

Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response.

In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention.

Toward dynamic control over TiO2 nanocrystal monolayer-by-monolayer film formation by electrophoretic deposition in nonpolar solvents.

The controlled electrophoretic deposition of monolayers and ultrathin films of 4.0 nm TiO(2) nanocrystals from stable, nonpolar solvent-based suspensions is reported. Stable suspensions were prepared in hexane, and the electrophoretic mobility of the nanocrystals was enhanced by a combination of a liquid-liquid extraction followed by mechanical surfactant removal by high-speed centrifugation. The controlled evolution of the density of TiO(2) nanocrystal monolayers was studied by transmission electron microscopy and optical transmittance spectroscopy. Ultrathin films were assembled while maintaining monolayer-by-monolayer growth and uniform density of the film. A time-dependent, equivalent circuit model has been proposed to characterize the electrophoretic current that was recorded during our experiments. Further, we demonstrate that the proposed model, coupled with the mobility, provides a means to estimate the deposition rate and, hence, the time necessary to fabricate a submonolayer, a monolayer, and multilayers of nanocrystals.

Transit Use and Health Care Costs: A Cross-sectional Analysis.

INTRODUCTION: Greater transit use is associated with higher levels of physical activity, which is associated with lower health risks and better health outcomes. However, there is scant evidence about whether health care costs differ based on level of transit ridership. METHODS: A sample (n=947) of members of Kaiser Permanente in the Portland, Oregon area were surveyed in 2015 about their typical use of various modes of travel including transit. Electronic medical record-derived health care costs were obtained among these members for the prior three years. Analysis examined proportional costs between High transit users (3+ days/week), Low transit users (1-2 days/week), and Non-users adjusting for age and sex, and then individually (base models) and together for demographic and health status variables. RESULTS: In separate base models across individual covariates, High transit users had lower total health care costs (59-69% of Non-user's costs) and medication costs (31-37% of Non-users' costs) than Non-users. Low transit users also had lower total health care (69%-76% of Non-users' costs) and medication costs (43-57% transit of Non-user's costs) than Non-users. High transit users' outpatient costs were also lower (77-82% of Non-users). In fully-adjusted models, total health care and medication costs were lower among High transit users' (67% and 39%) and Low transit users' (75% and 48%) compared to Non-users, but outpatient costs did not differ by transit use. CONCLUSIONS: Findings have implications for the potential cost benefit of encouraging and supporting more transit use, although controlled longitudinal and experimental evidence is needed to confirm findings and understand mechanisms.

Understanding the growth of Eu(2)O(3) nanocrystal films made via electrophoretic deposition.

Eu(2)O(3) nanocrystals, surface-functionalized with oleic acid, were assembled into transparent thin films via electrophoretic deposition (EPD). Suspended in a non-polar solvent (hexane), the nanocrystals were cast into stable films on both the cathode and the anode. We characterized the nanocrystal films using optical microscopy, energy dispersive spectroscopy and photoluminescence spectroscopy. Scanning electron microscopy and atomic force microscopy provided information regarding the morphology, topology and surface coverage of the films. These homogeneous, densely packed films were composed predominantly of agglomerates (approximately 15 nm) of the Eu(2)O(3) nanocrystals rather than of individual nanocrystals. Nonetheless, the films possessed low root mean square (RMS) roughness (approximately 1.4 nm). High transparency of the film in the visible region was facilitated by the dense packing and the small diameter of the agglomerates, which reduced transmission losses due to scattering. The effect of EPD process parameters (applied voltage and nanocrystal concentration) on the growth uniformity and the thickness of the films was examined via surface contact profilometry. We discovered a correlation among the said EPD process parameters, the overall quality and thickness of these transparent films, which provided insight into the mechanisms of the nanocrystal deposition process.

Detection and remediation of human-origin pollution at two public beaches in Virginia using multiple source tracking methods.

Two public beaches (Anderson and Hilton) in Newport News, Virginia, were frequently closed to swimming in 2004 due to high Enterococcus spp. counts that exceeded the regulatory standard. The microbial source tracking (MST) methods of antibiotic resistance analysis (ARA) and fluorometry (to detect optical brighteners) were used in the summer of 2004 to determine the origins of fecal pollution at the two beaches. Both MST methods detected substantial human-origin pollution at the two beaches, in locations producing consistently high levels of Enterococcus spp. Investigations by municipal officials led to the fluorometric detection and subsequent repair of sewage infrastructure problems at both beaches. The success of the mitigation efforts was confirmed during the summer of 2005 using ARA and fluorometry, with the results cross-validated by pulsed-field gel electrophoresis (PFGE).

Assessment of the 16S-23S rDNA intergenic spacer region in Enterococcus spp. for microbial source tracking.

A new library-based microbial source tracking (MST) approach intended for initial application in the coastal waters of Virginia was evaluated. Host-origin isolates of Enterococcus spp. were collected from beaches and the surrounding tidewater region of Virginia and used to construct a library based on the pattern of DNA band lengths produced by the amplification of the 16S-23S rDNA intergenic spacer (IGS) region, and subsequent digestion with MboI. Initial results from small host-origin libraries (64 and 200 total isolates) with discriminant analysis (DA) and logistic regression (LR) yielded high average rates of correct classification (ARCC) for a four-source classification split (birds, dogs, sewage, and wildlife), with ARCCs ranging from 83 to 100%. However, the poor results obtained when classification was attempted on a non-library validation set (VS, ARCCs of 47 and 48%, respectively, using DA and LR) demonstrated that a library of 200 isolates was insufficient to adequately represent the diversity of the enterococci in the sampled region. An increase in the library size to 1029 total isolates was accompanied by a reduction in the ARCC of the library to 42.7% with DA and 45.7% with LR, plus similarly poor results obtained from the VS. The low correct classification rates generated by the larger known-source library were unsuitable for field application. Many reported MST methods have been based on results obtained using small host-origin libraries without external validation. Our results indicate that such an approach can be very misleading, and that larger libraries and external validation is essential for the confirmation of preliminary results.

Temporal and Environmental Factors Driving Vibrio Vulnificus and V. Parahaemolyticus Populations and Their Associations With Harmful Algal Blooms in South Carolina Detention Ponds and Receiving Tidal Creeks.

Incidences of harmful algal blooms (HABs) and Vibrio infections have increased over recent decades. Numerous studies have tried to identify environmental factors driving HABs and pathogenic Vibrio populations separately. Few have considered the two simultaneously, though emerging evidence suggests that algal blooms enhance Vibrio growth and survival. This study examined various physical, nutrient, and temporal factors associated with incidences of HABs, V. vulnificus, and V. parahaemolyticus in South Carolina coastal stormwater detention ponds, managed systems where HABs often proliferate, and their receiving tidal creek waters. Five blooms occurred during the study (2008-2009): two during relatively warmer months (an August 2008 cyanobacteria bloom and a November 2008 dinoflagellate bloom) followed by increases in both Vibrio species and V. parahaemolyticus, respectively, and three during cooler months (December 2008 through February 2009) caused by dinoflagellates and euglenophytes that were not associated with marked changes in Vibrio abundances. Vibrio concentrations were positively and significantly associated with temperature and dissolved organic matter, dinoflagellate blooms, negatively and significantly associated with suspended solids, but not significantly correlated with chlorophyll or nitrogen. While more research involving longer time series is needed to increase robustness, findings herein suggest that certain HAB species may augment Vibrio occurrences during warmer months.

The influence of phosphorylation on the activity and structure of the neuronal IQ motif protein, PEP-19.

PEP-19 is a 7.6 kDa neuronally expressed polypeptide that contains a single calmodulin-binding IQ motif. The calmodulin-binding activity of several neuronal IQ motif proteins is regulated by phosphorylation of a conserved serine. We propose that the serine residue within the IQ motif of PEP-19 is phosphorylated, and that phosphorylation modifies the activity of PEP-19. Camstatin, a functionally active 25-residue fragment of PEP-19's IQ motif, binds calmodulin and inhibits neuronal nitric oxide synthase. A truncated camstatin-in which the IQ motif serine is the only phosphorylatable residue-was screened against 42 different kinases. Truncated camstatin is selectively phosphorylated by four isoforms of protein kinase C. Furthermore, treatment of full-length PEP-19 with PKCgamma catalyzes phosphorylation of the same serine residue. Fluorescent anisotropy shows that phosphorylation of camstatin inhibits its binding to calmodulin. NMR solution structures indicate that both camstatin and phospho-camstatin exist in similar dynamic turn-like conformations. This suggests that camstatin's greater affinity for calmodulin is due not to a change in the conformation of the phospho-peptide, but rather, to a disruption of hydrophobic interactions between phospho-camstatin and calmodulin caused by the presence of the hydrophilic phosphate group. The H(alpha) chemical shifts and the circular dichroism spectra of the camstatins are consistent with those of "nascent helices". We submit that PEP-19 is a PKC substrate, and that the phosphorylation state of PEP-19 may play a role in the modulation of calmodulin-dependent signaling.

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.

Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.

A new mixed disulfide species in human cataractous and aged lenses.

The process of ageing in the normal human eye lens is unique among tissues due to the absence of turnover in the structural proteins. These proteins accumulate a variety of modifications throughout their lifetime. Significantly, the cysteine residues are subject to disulfide formation with the low molecular weight thiol compounds present in the lens. It has been shown that accumulation of glutathione and cysteine mixed disulfides in the proteins of normal human lens is a function of age. In this report a third mixed disulfide species gamma-glutamylcysteine (gamma-Glu-Cys), has been identified by comparison with standards which were produced through two distinct methods. This new mixed disulfide is only prominent in old lenses (> 60 years) and cataractous lenses. In these situations its level may approach those of cysteine mixed disulfide. The appearance of gamma-Glu-Cys may be coincident with biochemical abnormalities preceding cataract formation. This protein modification may be a result of changes in the GSH biosynthetic pathway within the lens.

Helix geometry and hydration in an A-DNA tetramer: IC-C-G-G.

The DNA oligomer of sequence IC-C-G-G has been synthesized, and its X-ray crystal structure solved at a resolution of 2.0 A, using anomalous scattering from iodines in phase analysis: 48 cycles of Jack-Levitt restrained least-squares refinement resulted in a residual error of 19.9% over all data, or 16.5% for two-sigma data. Two double-helical tetramers stack in the crystal to form a continuous octamer, except for the two missing phosphate connections across the center. The octamer has a mean helix rotation of 33.7 degrees (10.7 base-pairs per turn), rise of 2.87 A, mean inclination angle of base-pairs of 14 degrees, and mean base-pair propeller twist of +16.3 degrees. Local variations in both helix rotation and base plane roll angles, including those across the center of the octamer, are as predicted from base sequence by sum functions sigma 1 and sigma 2. The three known DNA octamers: IC-C-G-G/IC-C-G-G, G-G-T-A-T-A-C-C and G-G-C-C-G-G-C-C, make up a graded series in this order, with monotonically changing structural parameters. An exhaustive comparison of torsion angle correlations among the known A helices confirms some structural expectations and reveals some new features. 86 water molecules have been located per double-helical IC-C-G-G tetramer (the asymmetric unit), of which 451/2 per tetramer lie within a first hydrogen-bonded shell of hydration. No ordered water structure is observed comparable to the minor groove spine of hydration in B-DNA.

Efficacy of estradiol vaginal cream in postmenopausal women.

In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group.

Digoxin bioavailability: formulations and rates of infusions.

The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr. The mean peak serum concentration of digoxin after the 1-hr intravenous infusion was 5 ng/ml, after the 3-hr infusion, 3.5 ng/ml, and after the oral solution, 2.0 ng/ml. There was an equivalent bioavailability of the oral solution and reference tablets of digoxin. The digoxin in capsules tended to be better absorbed than the reference tablets. There was 21% more digoxin excreted over 6 days after the 3 hr iv infusion than after the 1 hr iv infusion. This indicates that the calculated bioavailability of an orally administered dose of digoxin may vary with the rapidity of injection of the intravenous standard. It is estimated that an oral tablet of digoxin of 0.5 mg has about the same bioavailability as 0.35 of digoxin given by slow intravenous infusion (or 0.4 mg if calculated against a rapid intravenous injection).

Changes in content and composition of brain phospholipids in malnourished children.

The content and composition of phospholipids were studied in the brain of children who died from severe malnutrition within the first 2 years of life, and compared with those obtained from well-nourished children who died of accidents, or of illnesses not known to affect the central nervous system. Each brain was separated into the constituent major parts--the forebrain, brain stem, and the cerebellum. With the exception of a few marasmic children under 1 year of age whose forebrain and cerebellum had higher phospholipid concentration than normal, the concentration of the lipids on dry weight basis in all brain regions of the malnourished children was the same, regardless of age, as that in the children who were normal nutritionally. However, the phospholipid:DNA ratio in the forebrain and the cerebellum of most of the malnourished children under 1 year of age was higher than normal. The brain stem of only a few malnourished children aged around 1 year also had higher phospholipid:DNA ratio than normal. Among the different phospholipids, sphingomyelin was found to be selectively decreased in each brain part of the malnourished children aged 1 year or more.