Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the 'antibiotics and secondary metabolite analysis shell-antiSMASH' (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, β-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically.

OBJECTIVE

To investigate the prevalence and correlates of recovery from Diagnostic and Statistical Manual version IV (DSM-IV) alcohol dependence by examining the past-year status of individuals who met the criteria for prior-to-past-year (PPY) dependence.

METHODS

Cross-sectional, retrospective survey of a nationally representative sample of US adults 18 years of age and over (first wave of a planned longitudinal survey).

METHODS

This analysis is based on data from the 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), in which data were collected in personal interviews conducted with one randomly selected adult in each sample household. A subset of the NESARC sample (total n = 43 093), consisting of 4422 US adults 18 years of age and over classified with PPY DSM-IV alcohol dependence, were evaluated with respect to their past-year recovery status: past-year dependence, partial remission, full remission, asymptomatic risk drinking, abstinent recovery (AR) and non-abstinent recovery (NR). Correlates of past-year status were examined in bivariate analyses and using multivariate logistic regression models.

RESULTS

Of people classified with PPY alcohol dependence, 25.0% were still classified as dependent in the past year; 27.3% were classified as being in partial remission; 11.8% were asymptomatic risk drinkers who demonstrated a pattern of drinking that put them at risk of relapse; 17.7% were low-risk drinkers; and 18.2% were abstainers. Only 25.5% of people with PPY dependence ever received treatment. Being married was associated positively with the odds of both AR and NR, and ethanol intake was negatively associated with both. Severity of dependence increased the odds of AR but decreased the odds of NR. The odds of AR (but not NR) increased with age and female gender but were decreased by the presence of a personality disorder. Treatment history modified the effects of college attendance/graduation, age at onset and interval since onset on the odds of recovery.

CONCLUSIONS

There is a substantial level of recovery from alcohol dependence. Information on factors associated with recovery may be useful in targeting appropriate treatment modalities.

We describe a novel cloning method termed SLiCE (Seamless Ligation Cloning Extract) that utilizes easy to generate bacterial cell extracts to assemble multiple DNA fragments into recombinant DNA molecules in a single in vitro recombination reaction. SLiCE overcomes the sequence limitations of traditional cloning methods, facilitates seamless cloning by recombining short end homologies (≥15 bp) with or without flanking heterologous sequences and provides an effective strategy for directional subcloning of DNA fragments from Bacteria Artificial Chromosomes (BACs) or other sources. SLiCE is highly cost effective as a number of standard laboratory bacterial strains can serve as sources for SLiCE extract. In addition, the cloning efficiencies and capabilities of these strains can be greatly improved by simple genetic modifications. As an example, we modified the DH10B Escherichia coli strain to express an optimized λ prophage Red recombination system. This strain, termed PPY, facilitates SLiCE with very high efficiencies and demonstrates the versatility of the method.

BACKGROUND

Despite the impact of medical regimen nonadherence on health outcomes after organ transplantation, there is mixed and conflicting evidence regarding the prevalence and predictors of posttransplant nonadherence. Clinicians require precise information on nonadherence rates in order to evaluate patients' risks for this problem.

METHODS

A total of 147 studies of kidney, heart, liver, pancreas/kidney-pancreas, or lung/heart-lung recipients published between 1981 and 2005 were included in a meta-analysis. Average nonadherence rates were calculated for 10 areas of the medical regimen. Correlations between nonadherence and patient psychosocial risk factors were examined.

RESULTS

Across all types of transplantation, average nonadherence rates ranged from 1 to 4 cases per 100 patients per year (PPY) for substance use (tobacco, alcohol, illicit drugs), to 19 to 25 cases per 100 PPY for nonadherence to immunosuppressants, diet, exercise, and other healthcare requirements. Rates varied significantly by transplant type in two areas: immunosuppressant nonadherence was highest in kidney recipients (36 cases per 100 PPY vs. 7 to 15 cases in other recipients). Failure to exercise was highest in heart recipients (34 cases per 100 PPY vs. 9 to 22 cases in other recipients). Demographics, social support, and perceived health showed little correlation with nonadherence. Pretransplant substance use predicted posttransplant use.

CONCLUSIONS

The estimated nonadherence rates, overall and by transplant type, allow clinicians to gauge patient risk and target resources accordingly. Nonadherence rates in some areas--including immunosuppressant use--appear unacceptably high. Weak correlations of most patient psychosocial factors with nonadherence suggest that attention should focus on other classes of variables (e.g., provider-related and systems-level factors), which may be more influential.

The aromatic amino acids phenylalanine, tyrosine, and tryptophan in plants are not only essential components of protein synthesis, but also serve as precursors for a wide range of secondary metabolites that are important for plant growth as well as for human nutrition and health. The aromatic amino acids are synthesized via the shikimate pathway followed by the branched aromatic amino acids biosynthesis pathway, with chorismate serving as a major intermediate branch point metabolite. Yet, the regulation and coordination of synthesis of these amino acids are still far from being understood. Recent studies on these pathways identified a number of alternative cross-regulated biosynthesis routes with unique evolutionary origins. Although the major route of Phe and Tyr biosynthesis in plants occurs via the intermediate metabolite arogenate, recent studies suggest that plants can also synthesize phenylalanine via the intermediate metabolite phenylpyruvate (PPY), similarly to many microorganisms. Recent studies also identified a number of transcription factors regulating the expression of genes encoding enzymes of the shikimate and aromatic amino acids pathways as well as of multiple secondary metabolites derived from them in Arabidopsis and in other plant species.

Neural probes are micromachined multichannel electrode arrays that facilitate the functional stimulation and recording of neurons in the peripheral and central nervous system. For long-term implantations, surface modification is necessary for maintaining the stable connection between electrodes and neurons. The conductive polymer polypyrrole (PPy) and synthetic peptide DCDPGYIGSR were co-deposited on the electrode surface by electrochemical polymerization. The stability of PPy/DCDPGYIGSR coatings was tested in soaking experiments. It was found that the peptide was entrapped in the PPy film and did not diffuse away within 7 weeks of soaking in DI water. Coated probes were implanted in guinea pig brain for periods of 1, 2 and 3 weeks. Recording tests were performed and the impedance was monitored. The explanted probes and tissue were examined by immunocytochemical studies. Significantly more neurofilament positive staining was found on the coated electrode which indicated that the coatings had established strong connections with the neuronal structure in vivo. Good recordings were obtained from the coated sites that had neurons attached. First week tissue sections had no significant gliosis. In week 2, a layer of non-neuronal tissue consisting of mostly meningeal fibroblasts and ECM protein including at least fibronectin was formed around the probe tracks of both coated and uncoated probes. Astrocytes started to form a loosely organized layer by the end of the third week.

Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40-50% longer neurites and 40-90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications.

Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be approximately 50 nm by ellipsometry. We are able to release 0.5 mug/cm(2) Dex in 1 CV cycle and a total of almost 16 mug/cm(2) Dex after 30 CV cycles. In vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

Five protein serine/threonine phosphatases (PP) have been identified by cloning cDNA from mammalian and Drosophila libraries. These novel enzymes, which have not yet been detected by the techniques of protein chemistry and enzymology, are termed PPV, PP2Bw, PPX, PPY and PPZ. The complete amino acid sequences of PPX, PPY and PPZ and an almost complete sequence of PPV are presented. In the catalytic domain PPV and PPX are more similar to PP2A (57-69% identity) than PP1 (45-49% identity), while PPY and PPZ are more similar to PP1 (66-68% identity) than PP2A (44% identity). The cDNA for PP2Bw encodes a novel Ca2+/calmodulin-dependent protein phosphatase only 62% identical to PP2B in the catalytic domain. Approaches for determining the cellular functions of these protein phosphatases are discussed.

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.

OBJECTIVE

The purpose of this study was to investigate the effects of transitional life events related to education, employment, and family formation on the likelihood of recovery from alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), distinguishing the short- and long-term effects of these events and potential effect modification by treatment history, gender, and severity of dependence.

METHODS

This analysis is based on data from the Wave 1 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of U.S. adults 18 years of age and older. The analytic sample consisted of 4,422 individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence. Time-dependent proportional hazards models were used to estimate the effects of completing school, starting full-time work, getting married, becoming separated/divorced/widowed, and becoming a parent on the outcomes of nonabstinent recovery (NR; e.g., low-risk asymptomatic drinking) and abstinent recovery (AR).

RESULTS

Entry into and exit from a first marriage each increased the likelihood of NR during the first 3 years after those events occurred (hazard rate ratio [HRR] = 1.37 and 1.76, respectively). However, individuals who were still dependent 3 or more years after those events occurred had a decreased likelihood of subsequent NR (HRR = 0.70 for both events), as did those who were still dependent 3 or more years after completing schooling (HRR = 0.54). The likelihood of AR was more than doubled in the 3 years after first becoming a parent (HRR = 2.22) but was decreased among individuals still dependent 3 or more years after starting full-time work. For the outcome of NR, all of the negative effects associated with still being dependent 3 or more years after the occurrence of key life events were more strongly negative among individuals with less severe cases of dependence.

CONCLUSIONS

Transitional life events demonstrate many effects on recovery, including both direct effects consistent with role socialization and associations more reflective of selectivity than causation. Taken as a whole, these events appear to contribute to (but by no means fully explain) the high rates of recovery from alcohol dependence that have been observed even in the absence of treatment.

Uniform polypyrrole (PPy) nanoparticles are fabricated from a facile one-step aqueous dispersion polymerization. Owing to their high photothermal conversion efficiency and photostability compared with the well-known Au nanorods, as well as their good colloidal stability and biocompatibility, the resulting PPy nanoparticles can used as a novel promising photothermal ablation coupling agent for targeted treatment of cancer.

BACKGROUND

Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices.

RESULTS

Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from $1,557 to $1,772 for the group without AIDS and from cost saving to $111 for patients with AIDS.

CONCLUSIONS

HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.

OBJECTIVE

To investigate the effect of help-seeking on the likelihood of recovery from Diagnostic and Statistical Manual version IV (DSM-IV) alcohol dependence, specifically examining the impact of model selection, factors that moderate the effect of help-seeking and distinctions between the effects of 12-Step participation and formal treatment.

METHODS

This analysis is based on data from the Wave 1 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of US adults 18 years of age and over. The analytical sample consisted of 4422 individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence.

METHODS

Logistic regression, proportional hazards and time-dependent proportional hazards models were used to estimate the effects of help-seeking on three outcomes: (1) any recovery from alcohol dependence, which required full remission of all symptoms of alcohol abuse and dependence and excluded asymptomatic drinkers whose alcohol consumption exceeded low-risk drinking guidelines; (2) non-abstinent recovery (NR), representing low-risk asymptomatic drinkers; and (3) abstinent recovery (AR), representing abstainers.

RESULTS

Only one-quarter of individuals with PPY-onset alcohol dependence had ever sought help for alcohol problems, including 3.1% who had participated in 12-Step programs only, 5.4% who had received formal treatment only and 17.0% with both 12-Step and formal treatment. Based on the most appropriate model, help-seeking increased the likelihood of any recovery [hazard rate ratio (HRR) = 2.38], NR (HRR = 1.50) and AR (HRR = 4.01). The impact of help-seeking on AR did not show any significant variation across the exposure period but was modified by severity among other factors. Individuals who participated in 12-Step programs in addition to formal treatment had almost twice the chance of recovery and more than more than twice the chance of AR compared with those who received formal treatment alone.

CONCLUSIONS

Help-seeking plays a significant role in the achievement of abstinent recovery from alcohol dependence, with 12-Step participation playing a major role. Appropriate model selection is critical to assessing the impact of help-seeking.

We report the application of visible-light photoredox catalysis for the formation of C-C bonds between tertiary N-arylamines and nitroalkanes via an oxidative aza-Henry reaction. In the presence of 1 mol % Ir(ppy)(2)(dtbbpy)PF(6), efficient coupling of nitroalkanes with in situ-generated iminium ions provides the desired products in up to 96% yield. Mechanistic studies suggest that reductive quenching of the Ir(3+) excited state by the tertiary amine leads to the ammonium radical cation, with subsequent catalyst turnover (Ir(2+) ->> Ir(3+)) likely effected by atmospheric oxygen.

Bacteria communicate via small diffusible molecules and thereby mediate group-coordinated behavior, a process referred to as quorum sensing. The prototypical quorum sensing system found in Gram-negative bacteria consists of a LuxI-type autoinducer synthase that produces N-acyl homoserine lactones (AHLs) as signals and a LuxR-type receptor that detects the AHLs to control expression of specific genes. However, many proteobacteria have proteins with homology to LuxR receptors yet lack any cognate LuxI-like AHL synthase. Here we show that in the insect pathogen Photorhabdus luminescens the orphan LuxR-type receptor PluR detects endogenously produced α-pyrones that serve as signaling molecules at low nanomolar concentrations. Additionally, the ketosynthase PpyS was identified as pyrone synthase. Reconstitution of the entire system containing PluR, the PluR-target operon we termed pcf and PpyS in Escherichia coli demonstrated that the cell-cell communication circuit is portable. Our research thus deorphanizes a signaling system and suggests that additional modes of bacterial communication may await discovery.

All medullary central chemoreceptor sites contain neurokinin-1 receptor immunoreactivity (NK1R-ir). We ask if NK1R-ir neurons and processes are involved in chemoreception. At one site, the retrotrapezoid nucleus/parapyramidal region (RTN/Ppy), we injected a substance P-saporin conjugate (SP-SAP; 0.1 pmol in 100 nl) to kill NK1R-ir neurons specifically, or SAP alone as a control. We made measurements for 15 days after the injections in two groups of rats. In group 1, with unilateral injections made in the awake state via a pre-implanted guide cannula, we compared responses within rats using initial baseline data. In group 2, with bilateral injections made under anaesthesia at surgery, we compared responses between SP-SAP- and SAP-treated rats. SP-SAP treatment reduced the volume of the RTN/Ppy region that contained NK1R-ir neuronal somata and processes by 44 % (group 1) and by 47 and 40 % on each side, respectively (group 2). Ventilation (.V(E)) and tidal volume (V(T)) were decreased during air breathing in sleep and wakefulness (group 2; P < 0.001; two-way ANOVA) and P(a,CO2) was increased (group 2; P < 0.05; Student's t test). When rats breathed an air mixture containing 7 % CO(2) during sleep and wakefulness, .V(E) and V(T) were lower (groups 1 and 2; P < 0.001; ANOVA) and the Delta.V(E) in air containing 7 % CO(2) compared to air was decreased by 28-30 % (group 1) and 17-22 % (group 2). SP-SAP-treated rats also slept less during air breathing. We conclude that neurons with NK1R-ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal.

In this study, the biocompatibility of the electrically conductive polymer polypyrrole (PPy) with nerve tissue was evaluated in vitro and in vivo. The extraction solution of PPy powder, which was synthesized chemically, was tested for acute toxicity, subacute toxicity, pyretogen, quantitative measure of cell viability, hemolysis, allergen, and micronuclei. The PPy membrane was synthesized electrochemically on the indium tin oxide conductive borosilicate glass. The dorsal root ganglia from 1-3-day-old Sprague-Dawley rats were cultured above PPy membrane and observed by light or scanning electron microscopy. The PPy-silicone tube (PPy membrane on the inner surface of the silicone tube) also synthesized electrochemically was used to bridge across 10-mm sciatic nerve gap in rats. Twenty-four weeks after the operation to rats, the regenerated tissues were observed by electrophysiological and histological techniques. PPy extraction solution showed no evidence of acute and subacute toxicity, pyretogen, hemolysis, allergen, and mutagenesis, and the Schwann cells from the PPy extraction solution group showed better survival rate and proliferation rate as compared with the saline solution control group. The migration of the Schwann cells and the neurite extension from dorsal root ganglia on the surface of PPy membrane-coated glass was better than those of bare glass. There was only lightly inflammation during 6 months of the postoperation, when the PPy-silicone tube bridged across the gap of the transected sciatic nerve. The regeneration of nerve tissue in the PPy-silicone tube was slightly better than that in the plain silicone tube by means of electrophysiological and histological examination. The results of this study indicate that PPy has a good biocompatibility with rat peripheral nerve tissue and that PPy might be a candidate material for bridging the peripheral nerve gap.

BACKGROUND

Adherence to the medical regimen after pediatric organ transplantation is important for maximizing good clinical outcomes. However, the literature provides inconsistent evidence regarding prevalence and risk factors for nonadherence posttransplant.

METHODS

A total of 61 studies (30 kidney, 18 liver, 8 heart, 2 lung/heart-lung, and 3 with mixed recipient samples) were included in a meta-analysis. Average rates of nonadherence to six areas of the regimen, and correlations of potential risk factors with nonadherence, were calculated.

RESULTS

Across all types of transplantation, nonadherence to clinic appointments and tests was most prevalent, at 12.9 cases per 100 patients per year (PPY). The immunosuppression nonadherence rate was six cases per 100 PPY. Nonadherence to substance use restrictions, diet, exercise, and other healthcare requirements ranged from 0.6 to 8 cases per 100 PPY. Only the rate of nonadherence to clinic appointments and tests varied by transplant type: heart recipients had the lowest rate (4.6 cases per 100 PPY vs. 12.7-18.8 cases per 100 PPY in other recipients). Older age of the child, family functioning (greater parental distress and lower family cohesion), and the child's psychological status (poorer behavioral functioning and greater distress) were among the psychosocial characteristics significantly correlated with poorer adherence. These correlations were small to modest in size (r=0.12-0.18).

CONCLUSIONS

These nonadherence rates provide benchmarks for clinicians to use to estimate patient risk. The identified psychosocial correlates of nonadherence are potential targets for intervention. Future studies should focus on improving the prediction of nonadherence risk and on testing interventions to reduce risk.

Neural prostheses transduce bioelectric signals to electronic signals at the interface between neural tissue and neural microelectrodes. A low impedance electrode-tissue interface is important for the quality of signal during recording as well as quantity of applied charge density during stimulation. However, neural microelectrode sites exhibit high impedance because of their small geometric surface area. Here we analyze nanostructured-conducting polymers that can be used to significantly decrease the impedance of microelectrode typically by about two orders of magnitude and increase the charge transfer capacity of microelectrodes by three orders of magnitude. In this study poly(pyrrole) (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes were electrochemically polymerized on the surface of neural microelectrode sites (1250 microm(2)). An equivalent circuit model comprising a coating capacitance in parallel with a pore resistance and interface impedance in series was developed and fitted to experimental results to characterize the physical and electrical properties of the interface. To confirm that the fitting parameters correlate with physical quantities of interface, theoretical equations were used to calculate the parameter values thereby validating the proposed model. Finally, an apparent diffusion coefficient was calculated for PPy film (29.2+/-1.1 x 10(-6) cm(2)/s), PPy nanotubes (PPy NTs) (72.4+/-3.3 x 10(-6) cm(2)/s), PEDOT film (7.4+/-2.1 x 10(-6) cm(2)/s), and PEDOT nanotubes (PEDOT NTs) (13.0+/-1.8 x 10(-6) cm(2)/s). The apparent diffusion coefficient of conducting polymer nanotubes was larger than the corresponding conducting polymer films.

For patients receiving liver or other organ transplants for diseases associated with substance use, risk for relapse posttransplantation is a prominent clinical concern. However, there is little consensus regarding either the prevalence or risk factors for relapse to alcohol or illicit drug use in these patients. Moreover, the evidence is inconsistent as to whether patients with pretransplantation substance use histories show poorer posttransplantation medical adherence. We conducted a meta-analysis of studies published between 1983 and 2005 to estimate relapse rates, rates of nonadherence to the medical regimen, and the association of potential risk factors with these rates. The analysis included 54 studies (50 liver, 3 kidney, and 1 heart). Average alcohol relapse rates (examined only in liver studies) were 5.6 cases per 100 patients per year (PPY) for relapse to any alcohol use and 2.5 cases per 100 PPY for relapse with heavy alcohol use. Illicit drug relapse averaged 3.7 cases per 100 PPY, with a significantly lower rate in liver vs. other recipients (1.9 vs. 6.1 cases). Average rates in other areas (tobacco use, immunosuppressant and clinic appointment nonadherence) were 2 to 10 cases per 100 PPY. Risk factors could be examined only for relapse to any alcohol use. Demographics and most pretransplantation characteristics showed little correlation with relapse. Poorer social support, family alcohol history, and pretransplantation abstinence of < or =6 months showed small but significant associations with relapse (r = 0.17-0.21). Future research should focus on improving the prediction of risk for substance use relapse, and on testing interventions to promote continued abstinence posttransplantation.

Multifunctional nanoplatforms that are safe and have multiple therapeutic functions together with imaging capabilities are highly demanded in the development of new cancer theranostic approaches. A number of near-infrared (NIR)-absorbing inorganic nanomaterials, although having shown great promise not only to photothermally ablate tumors but also to enhance the efficacy of other types of therapies, are not biodegradable and would be retained in the body for a long time. Herein, we develop a multifunctional nanocomposite by coating magnetic iron oxide nanoclusters with a near-infrared light-absorbing polymer polypyrrole (PPy), obtaining Fe3O4@PPy core-shell nanoparticles, which after functionalization with polyethylene glycol could be used for imaging-guided, remotely controlled cancer combination therapy. In this system, the Fe3O4 core, which could be gradually decomposed in physiological environments, is useful for magnetically controlled drug delivery as well as a magnetic resonance imaging contrast. The PPy shell, as an organic polymer, is able to load therapeutic molecules with aromatic structures and also exhibits a strong photothermal effect, which can be used to enhance the chemotherapeutic efficacy, showing an outstanding in vivo synergistic antitumor effect. Our work encourages further exploration of light-absorbing polymer-based nanocomposites for cancer combination therapy under remote physical controls.

BACKGROUND

The burden of malaria has decreased in parts of Africa following the scaling up of control interventions. However, similar data are limited from high transmission settings.

METHODS

A cohort of 100 children, aged six weeks to 10 months of age, were enrolled in an area of high malaria transmission intensity and followed through 48 months of age. Children were given a long-lasting insecticide-treated bed net (LLIN) at enrolment and received all care, including monthly blood smears and treatment with artemisinin-based combination therapy (ACT) for uncomplicated malaria, at a dedicated clinic. The incidence of malaria was estimated by passive surveillance and associations between malaria incidence and age, calendar time and season were measured using generalized estimating equations.

RESULTS

Reported compliance with LLINs was 98% based on monthly routine evaluations. A total of 1,633 episodes of malaria were observed, with a median incidence of 5.3 per person-year (PPY). There were only six cases of complicated malaria, all single convulsions. Malaria incidence peaked at 6.5 PPY at 23 months of age before declining to 3.5 PPY at 48 months. After adjusting for age and season, the risk of malaria increased by 52% from 2008 to 2011 (RR 1.52, 95% CI 1.10-2.09). Asymptomatic parasitaemia was uncommon (monthly prevalence <10%) and rarely observed prior to 24 months of age.

CONCLUSIONS

In Tororo, despite provision of LLINs and prompt treatment with ACT, the incidence of malaria is very high and appears to be rising. Additional malaria control interventions in high transmission settings are likely needed.

BACKGROUND

Current Controlled Trials Identifier NCT00527800.