The new flora of northeastern USA: quantifying introduced plant species occupancy in forest ecosystems.
Introduced plant species have significant negative impacts in many ecosystems and are found in many forests around the world. Some factors linked to the distribution of introduced species include fragmentation and disturbance, native species richness, and climatic and physical conditions of the landscape. However, there are few data sources that enable the assessment of introduced species occupancy in native plant communities over broad regions. Vegetation data from 1,302 forest inventory plots across 24 states in northeastern and mid-western USA were used to examine and compare the distribution of introduced species in relation to forest fragmentation across ecological provinces and forest types, and to examine correlations between native and introduced species richness. There were 305 introduced species recorded, and 66 % of all forested plots had at least one introduced species. Forest edge plots had higher constancy and occupancy of introduced species than intact forest plots, but the differences varied significantly among ecological provinces and, to a lesser degree, forest types. Weak but significant positive correlations between native and introduced species richness were observed most often in intact forests. Rosa multiflora was the most common introduced species recorded across the region, but Hieracium aurantiacum and Epipactus helleborine were dominant in some ecological provinces. Identifying regions and forest types with high and low constancies and occupation by introduced species can help target forest stands where management actions will be the most effective. Identifying seemingly benign introduced species that are more prevalent than realized will help focus attention on newly emerging invasives.


Estimating Health-State Utility for Economic Models in Clinical Studies: An ISPOR Good Research Practices Task Force Report.
Cost-utility models are increasingly used in many countries to establish whether the cost of a new intervention can be justified in terms of health benefits. Health-state utility (HSU) estimates (the preference for a given state of health on a cardinal scale where 0 represents dead and 1 represents full health) are typically among the most important and uncertain data inputs in cost-utility models. Clinical trials represent an important opportunity for the collection of health-utility data. However, trials designed primarily to evaluate efficacy and safety often present challenges to the optimal collection of HSU estimates for economic models. Careful planning is needed to determine which of the HSU estimates may be measured in planned trials; to establish the optimal methodology; and to plan any additional studies needed. This report aimed to provide a framework for researchers to plan the collection of health-utility data in clinical studies to provide high-quality HSU estimates for economic modeling. Recommendations are made for early planning of health-utility data collection within a research and development program; design of health-utility data collection during protocol development for a planned clinical trial; design of prospective and cross-sectional observational studies and alternative study types; and statistical analyses and reporting.


A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.
The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels--1×10(10) viral particles, 2.5×10(10) viral particles, and 5×10(10) viral particles--with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.).


General practitioners' knowledge and concern about electromagnetic fields.
Our aim is to explore general practitioners' (GPs') knowledge about EMF, and to assess whether different knowledge structures are related to the GPs' concern about EMF. Random samples were drawn from lists of GPs in Germany in 2008. Knowledge about EMF was assessed by seven items. A latent class analysis was conducted to identify latent structures in GPs' knowledge. Further, the GPs' concern about EMF health risk was measured using a score comprising six items. The association between GPs' concern about EMF and their knowledge was analysed using multiple linear regression. In total 435 (response rate 23.3%) GPs participated in the study. Four groups were identified by the latent class analysis: 43.1% of the GPs gave mainly correct answers; 23.7% of the GPs answered low frequency EMF questions correctly; 19.2% answered only the questions relating EMF with health risks, and 14.0% answered mostly "don't know". There was no association between GPs' latent knowledge classes or between the number of correct answers given by the GPs and their EMF concern, whereas the number of incorrect answers was associated with EMF concern. Greater EMF concern in subjects with more incorrect answers suggests paying particular attention to misconceptions regarding EMF in risk communication.


The use of complementary and alternative medicine by patients with diabetes mellitus in Bahrain: a cross-sectional study.
CAM use is widespread, especially among patients with diabetes. The Gulf States have a high prevalence of diabetes, alongside a long tradition of CAM use. The aim of this study is to establish the prevalence of CAM use among patients with diabetes mellitus in Bahrain and to examine the characteristics of the CAM users. A questionnaire was developed and administered to a convenience sample of patients with diabetes (n = 402) above the age of 20 attending two hospital diabetes clinics. Data were analysed using descriptive statistics and non-parametric tests of association. 63% of responders utilized CAM within the previous 12 months. CAM users were more likely to be female, to have had diabetes for longer and to have complications of their diabetes. 64% of CAM users stated that they had used CAM for managing their diabetic condition, with 46% of these having used it solely for their diabetes. Respondents using CAM to manage their diabetes were more likely to be male, to be using CAM on a daily basis and to have informed their physician of their CAM use. There is a high rate of CAM use in patients with diabetes attending two hospital diabetes clinics in Bahrain. There is also a high rate of non-disclosure of CAM use to physicians. There is a continuing need for health professionals to be more aware and better trained in order to inform their decision making and communication related to CAM use.


The rise of medical training in Portuguese speaking African countries.
Medical training has shown to be strategic for strengthening health systems, especially in those countries identified to have critical shortage of human resources for health. In the past few years, several studies have been conducted to characterize and identify major challenges faced by medical schools worldwide, and particularly in Africa. Nevertheless, none has previously addressed medical training issues in Portuguese Speaking African Countries (PSAC). The aim of this study was to establish baseline knowledge of the PSAC's medical schools in terms of creation and ownership, programmes offered, applicants and registered students, barriers to increased intake of students, teaching workforce and available resources. A quantitative, observational, multicentric, cross-sectional study of all medical schools active in 2012 in the PSAC. An adapted version of the questionnaires developed by Chen et al. (2012) was sent to all medical schools electronically. Data were analyzed using descriptive statistics. A total of nine medical schools answered the questionnaire (three from Angola, two from Guinea Bissau and four from Mozambique). Since 2006 an effort has been made to increase the number of medical trainees. Besides the medical degree offered by all schools, some offered other undergraduate and postgraduate training programmes. The number of applicants to medical schools largely outnumbers the available vacancies in all countries but insufficient infrastructures and lack of teaching personnel are important constraints to increase vacancies. The teaching personnel are mainly trained abroad, employed part-time by the medical school and do not have a PhD qualification. Governments in the PSAC have significantly invested in training to address medical shortages. However, medical schools are still struggling to give an adequate and effective response. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country and develop local faculty capacity.


miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulation.
Thymidylate synthase (TYMS) is a target of the most widely used chemotherapeutic agents against gastrointestinal malignancies, the fluoropyrimidine-based therapy. TYMS expression levels have been identified as predictive biomarkers for 5-fluoruracil (FU) response in colorectal cancer, but their clinical utility remains controversial. The complexity of fluoropyrimidine response must require more mechanisms that currently have not been completely elucidated. In this context, microRNAs (miRNA) may play a role in modulating chemosensitivity. By carrying out an in silico analysis coupled to experimental validation, we detected that miR-192 and miR-215 target TYMS expression in colorectal cancer cell lines. However, downregulation of TYMS by these miRNAs does not sensitize colorectal cancer cell lines to FU treatment. The overexpression of miR-192/215 significantly reduces cell proliferation by targeting cell cycle progression. This effect was partially associated with p53 status, because reduction of cell proliferation and cell cycle arrest was associated with p21 and p27 induction. The decrease of S-phase cells by these miRNAs mitigates the effects of S phase-specific drugs and suggests that other mechanisms different from TYMS overexpression are essential to direct FU resistance. Finally, ectopic expression of miR-192/215 might have stronger impact to predict FU response than TYMS inhibition. Prospective studies to elucidate the role of these miRNAs as predictive biomarkers to FU are necessary.


Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions.
This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against Staphylococcus aureus grown in the presence of Pseudomonas aeruginosa. Since the P. aeruginosa exoproduct 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) is known to cause a respiratory deficiency in S. aureus and respiratory-deficient S. aureus are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 μg/ml) against S. aureus in coculture with P. aeruginosa. Kill kinetics were also assessed using P. aeruginosa mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of S. aureus by 3.4 log10 CFU/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when S. aureus was in coculture with the lasR rhlR, pqsA, pqsL, or lasA mutant of P. aeruginosa. The bactericidal effect of TO against S. aureus in coculture with the pqsL mutant was restored by supplemental HQNO. In an S. aureus monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the pqsL mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant S. aureus (MRSA) in coculture with P. aeruginosa, and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against S. aureus when cocultured with P. aeruginosa. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and P. aeruginosa.


Simple route to enhanced photocatalytic activity of p25 titanium dioxide nanoparticles by silica addition.
Silica doped TiO2(P25) nanoparticles are tested for its photocatalytic activity in the degradation of bacteriophage MS2. During our studies it was found that treatment of TiO2(P25) in the glass flasks sealed with silicone grease resulted in a significant improvement in the catalytic activity of the titania. Further improvement can be made by the purposeful reaction of TiO2(P25) with 2.5 wt % silica. This non in situ method of incorporating silica to TiO2(P25) nanoparticles is tested for their role in killing of viruses, and it is found that the rate constant is three times higher to kill viruses with the addition of silica. BET measurements show no significant change/increase in the surface area of silica doped TiO2(P25)-SiO2, compared to the undoped TiO2(P25). Further studies show that the addition of silica increases the adsorption of viruses onto the catalyst. There is a significant difference in the activity of the TiO2(P25)-SiO2 samples in the presence of methanol, supporting the notion that hydroxide radical (HO·) is responsible for the antiviral action. The TiO2(P25)-SiO2 either produces more HO· than non silica-doped material, or the enhanced adsorption of MS2 to the catalyst results in greater exposure to the HO·, or both mechanisms may work in concert. XPS studies suggest the formation of silica species on the surface of the TiO2(P25), while UV-visible spectroscopy suggests that the presence of the silica results in a small increase in the measured band gap. We suggest that the enhanced catalytic activity is a result of increased adsorption and/or band bending which can occur at the interface within TiO2(P25)-SiO2. One result of this would be a reduction of the electron-hole recombination, the formation of a greater concentration of OH·, and hence an improved catalytic performance.


Identification of a segment of the Escherichia coli Tsx protein that functions as a bacteriophage receptor area.
The Escherichia coli outer membrane protein Tsx functions as a nucleoside-specific channel and serves as the receptor for colicin K and a number of T-even-type bacteriophages, including phage T6. To identify those segments of the Tsx protein that are important for its phage receptor function, we devised a selection and screening procedure which allowed us to isolate phage-resistant strains synthesizing normal amounts of Tsx. Three different Tsx-specific phages (T6, Ox1, and H3) were employed for the selection of phage-resistant derivatives of a strain expressing a tsx(+)-lacZ+ operon fusion, and 28 tsx mutants with impaired phage receptor function were characterized. Regardless of the Tsx-specific phage used for the initial mutant selection, cross-resistance against a set of six different Tsx phages invariably occurred. With one exception, these mutant Tsx proteins could still serve as a colicin K receptor. DNA sequence analysis of 10 mutant tsx genes revealed the presence of four distinct tsx alleles: two point mutations, an 18-bp deletion, and a 27-bp tandem duplication. In three isolates, Asn-249 was replaced by a Lys residue (tsx-504), and in four others, residue Asn-254 was replaced by Lys (tsx-505). The deletion (tsx-506; one isolate) removed six amino acids (residue 239 to residue 244) from the 272-residue Tsx polypeptide chain, and the DNA duplication (tsx-507; two isolates) resulted in the addition of nine extra amino acids (residue 229 to residue 237) to the Tsx protein. In contrast to the wild-type Tsx protein and the other mutant Tsx proteins the Tsx-507 protein was cleaved by trypsin when intact cells were treated with this protease. The Tsx proteins encoded by the four tsx alleles still functioned in deoxyadenosine uptake in vivo, demonstrating that their nucleoside-specific channel activity was not affected by the alterations that caused the loss of their phage receptor function. HTe changes in the Tsx polypeptide that confer resistance against the Tsx-specific phages are clustered in a small region near the carboxy terminus of Tsx. Our results are discussed in terms of a model for the topological organization of the carboxy-terminal end of the Tsx protein within the outer membrane.


Load-specific physical activity scores are related to tibia bone architecture.
Assessment of physical activity in clinical bone studies is essential. Two bone-specific physical activity scoring methods, the Bone Loading History Questionnaire (BLHQ) and Bone-Specific Physical Activity Questionnaire (BPAQ), have shown correlations with bone density and geometry, but not architecture. The purpose of this study was to determine relationships between physical activity scoring methods and bone architecture in non-Hispanic white adolescent females (N = 24; 18-19 years of age). Bone loading scores (BLHQ [hip and spine] and past BPAQ) and energy expenditure (7-day physical activity recall) were determined from respective questionnaires. Estimates of trabecular and cortical bone architecture at the nondominant radius and tibia were assessed via magnetic resonance imaging. Total body and regional areal bone mineral density (aBMD), as well as total body fat mass and fat-free soft tissue (FFST) mass were assessed via dual energy X-ray absorptiometry. Pearson's correlations and partial correlations adjusting for height, total body fat mass, and FFST were performed. Hip BLHQ scores were correlated with midtibia cortical volume (r = .43; p = .03). Adjusted hip and spine BLHQ scores were correlated with all midtibia cortical measures (r = .50-0.58; p < .05) and distal radius apparent trabecular number (r = .46-0.53; p < .05). BPAQ scores were correlated with all midtibia cortical (r = .41-0.51; p < .05) and most aBMD (r = .47-0.53; p < .05) measures. Energy expenditure was inversely associated with femoral neck aBMD only after statistical adjustment (r = .49, p < .05). These data show that greater load-specific physical activity scores, but not energy expenditure, are indicative of greater midtibia cortical bone quality, thus supporting the utility of these instruments in musculoskeletal research.


Inhibition of parvalbumin-expressing interneurons results in complex behavioral changes.
Reduced expression of the Gad1 gene-encoded 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of schizophrenia. GAD67 downregulation occurs in multiple interneuronal sub-populations, including the parvalbumin-positive (PVALB+) cells. To investigate the role of the PV-positive GABAergic interneurons in behavioral and molecular processes, we knocked down the Gad1 transcript using a microRNA engineered to target specifically Gad1 mRNA under the control of Pvalb bacterial artificial chromosome. Verification of construct expression was performed by immunohistochemistry. Follow-up electrophysiological studies revealed a significant reduction in γ-aminobutyric acid (GABA) release probability without alterations in postsynaptic membrane properties or changes in glutamatergic release probability in the prefrontal cortex pyramidal neurons. Behavioral characterization of our transgenic (Tg) mice uncovered that the Pvalb/Gad1 Tg mice have pronounced sensorimotor gating deficits, increased novelty-seeking and reduced fear extinction. Furthermore, NMDA (N-methyl-d-aspartate) receptor antagonism by ketamine had an opposing dose-dependent effect, suggesting that the differential dosage of ketamine might have divergent effects on behavioral processes. All behavioral studies were validated using a second cohort of animals. Our results suggest that reduction of GABAergic transmission from PVALB+ interneurons primarily impacts behavioral domains related to fear and novelty seeking and that these alterations might be related to the behavioral phenotype observed in schizophrenia.


Molecular tagging thermometry for transient temperature mapping within a water droplet.
We present the progress made in developing a molecular tagging thermometry (MTT) technique for achieving spatially and temporally resolved temperature measurements within a small water droplet over a solid surface. For MTT measurement, a pulsed laser is used to tag phosphorescent 1-BrNp.Mbeta-CD.ROH molecules premixed with water. Long-lived laser-induced phosphorescence is imaged at two successive times after the same laser excitation pulse. The temperature measurement is achieved by taking advantage of the temperature dependence of the phosphorescence lifetime, which is estimated from the intensity ratio of the acquired phosphorescence image pair. The measured transient temperature distributions can be used to quantify the unsteady heat transfer process inside convectively cooled water droplets over smooth or rough surfaces.


Theoretical aspects of dynamic nuclear polarization in the solid state - the solid effect.
Dynamic nuclear polarization has gained high popularity in recent years, due to advances in the experimental aspects of this methodology for increasing the NMR and MRI signals of relevant chemical and biological compounds. The DNP mechanism relies on the microwave (MW) irradiation induced polarization transfer from unpaired electrons to the nuclei in a sample. In this publication we present nuclear polarization enhancements of model systems in the solid state at high magnetic fields. These results were obtained by numerical calculations based on the spin density operator formalism. Here we restrict ourselves to samples with low electron concentrations, where the dipolar electron-electron interactions can be ignored. Thus the DNP enhancement of the polarizations of the nuclei close to the electrons is described by the Solid Effect mechanism. Our numerical results demonstrate the dependence of the polarization enhancement on the MW irradiation power and frequency, the hyperfine and nuclear dipole-dipole spin interactions, and the relaxation parameters of the system. The largest spin system considered in this study contains one electron and eight nuclei. In particular, we discuss the influence of the nuclear concentration and relaxation on the polarization of the core nuclei, which are coupled to an electron, and are responsible for the transfer of polarization to the bulk nuclei in the sample via spin diffusion.


Catching-up but telomere loss: half-opening the black box of growth and ageing trade-off in wild king penguin chicks.
One of the reasons for animals not to grow as fast as they potentially could is that fast growth has been shown to be associated with reduced lifespan. However, we are still lacking a clear description of the reality of growth-dependent modulation of ageing mechanisms in wild animals. Using the particular growth trajectory of small king penguin chicks naturally exhibiting higher-than-normal growth rate to compensate for the winter break, we tested whether oxidative stress and telomere shortening are related to growth trajectories. Plasma antioxidant defences, oxidative damage levels and telomere length were measured at the beginning and at the end of the post-winter growth period in three groups of chicks (small chicks, which either passed away or survived the growth period, and large chicks). Small chicks that died early during the growth period had the highest level of oxidative damage and the shortest telomere lengths prior to death. Here, we show that small chicks that grew faster did it at the detriment of body maintenance mechanisms as shown by (i) higher oxidative damage and (ii) accelerated telomere loss. Our study provides the first evidence for a mechanistic link between growth and ageing rates under natural conditions.


Too Tired to Tell the Truth: Self-Control Resource Depletion and Dishonesty.
The opportunity to profit from dishonesty evokes a motivational conflict between the temptation to cheat for selfish gain and the desire to act in a socially appropriate manner. Honesty may depend on self-control given that self-control is the capacity that enables people to override antisocial selfish responses in favor of socially desirable responses. Two experiments tested the hypothesis that dishonesty would increase when people's self-control resources were depleted by an initial act of self-control. Depleted participants misrepresented their performance for monetary gain to a greater extent than did non-depleted participants (Experiment 1). Perhaps more troubling, depleted participants were more likely than non-depleted participants to expose themselves to the temptation to cheat, thereby aggravating the effects of depletion on cheating (Experiment 2). Results indicate that dishonesty increases when people's capacity to exert self-control is impaired, and that people may be particularly vulnerable to this effect because they do not predict it.


Atoxigenic Aspergillus flavus Isolates Endemic to Almond, Fig, and Pistachio Orchards in California with Potential to Reduce Aflatoxin Contamination in these Crops.
In California, aflatoxin contamination of almond, fig, and pistachio has become a serious problem in recent years due to long periods of drought and probably other climatic changes. The atoxigenic biocontrol product Aspergillus flavus AF36 has been registered for use to limit aflatoxin contamination of pistachio since 2012 and for use in almond and fig since 2017. New biocontrol technologies employ multiple atoxigenic genotypes because those provide greater benefits than using a single genotype. Almond, fig, and pistachio industries would benefit from a multi-strain biocontrol technology for use in these three crops. Several A. flavus vegetative compatibility groups (VCGs) associated with almond, fig, and pistachio composed exclusively of atoxigenic isolates, including the VCG to which AF36 belongs to, YV36, were previously characterized in California. Here, we report additional VCGs associated with either two or all three crops. Representative isolates of 12 atoxigenic VCGs significantly (P < 0.001) reduced (>80%) aflatoxin accumulation in almond and pistachio when challenged with highly toxigenic isolates of A. flavus and A. parasiticus under laboratory conditions. Isolates of the evaluated VCGs, including AF36, constitute valuable endemic, well-adapted, and efficient germplasm to design a multi-crop, multi-strain biocontrol strategy for use in tree crops in California. Availability of such a strategy would favor long-term atoxigenic A. flavus communities across the affected areas of California, and this would result in securing domestic and export markets for the nut crop and fig farmer industries and, most importantly, health benefits to consumers.


Protective effects of L-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide.
Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin. The changes in renal haemodynamics were suggested to play a role in cisplatin-induced nephrotoxicity. The aim of the present study was to investigate the effect of modulation of nitric oxide on the severity of cisplatin-induced nephrotoxicity using an experimental rat model. A nitric oxide precursor, L-arginine and an inhibitor of nitric oxide synthase, L-NAME were used. After six days of cisplatin injection, acute nephrotoxicity was demonstrated by a marked increase in serum creatinine and blood urea nitrogen. Histological examination of the kidneys confirmed the occurrence of renal damage. Moreover, cisplatin induced an increase in the level of lipid peroxides and oxidized glutathione and a depletion of reduced glutathione. The activities of the antioxidant enzymes glutathione peroxidase and superoxide dismutase were also lowered. Besides, there was a reduction in the kidney total nitrate/nitrite levels. L-arginine significantly attenuated the oxidative stress and nephrotoxic effect of cisplatin. On the other hand, L-NAME was found to aggravate cisplatin nephrotoxicity. In conclusion, the decrease in the kidney nitric oxide level contributes, at least in part, in the mechanism underlying the nephrotoxicity of cisplatin. Furthermore, L-arginine shows nephroprotective effects and might be useful in improving the therapeutic index of cisplatin.


Serological reactivity and bacterial genotypes in Chlamydia trachomatis urogenital infections in Guadeloupe, French West Indies.
To determine the prevalence and genotypes of Chlamydia trachomatis urogenital infection in Guadeloupe, French West Indies, and to compare C trachomatis direct detection to serological testing. From March to November 2000, 971 consecutive patients (888 women and 83 men) who had been referred to the clinical laboratory of the Institut Pasteur de la Guadeloupe for routine testing for genital infection were recruited. Samples were subjected to a nucleic acid amplification assay (AMP CT, Gen-Probe, San Diego, California, USA). Genotypes were determined by omp1 PCR-restriction fragment length polymorphism analysis. Serological testing was carried out with the commercially available peptide-based ELISA assay (SERO-CT IgG/IgA, Savyon/BMD, Marne-La-Vallée, France). Positive AMP CT test results were obtained for 102 (10.5%) of the 971 samples. The prevalence of infection was 16.9% in men and 9.8% in women. The most common genotypes were E (34.3%), F (23.9%), Da (13.4%), I (9%) and Ia (7.5%). No relationship was found between genogroups and age, sex or clinical symptoms. With AMP CT used as a reference, the sensitivity, specificity, positive and negative predictive values of SERO-CT were 81.1%, 56%, 34.5% and 91.2%, respectively, for IgG and 55.4%, 76.8%, 59.4% and 85.8%, respectively, for IgA. IgG seroprevalence rates were very low (1/5, 20%) in patients infected with genotype Ia strains. The prevalence found in Guadeloupe did not differ significantly from that found in mainland France. The genotypes Da, F, I and Ia were more prevalent in Guadeloupe; however, the SERO-CT assay was unable to detect serum antibodies in 80% of the patients infected with genotype Ia strains.


Porcine-derived soft block bone substitutes for the treatment of severe class II furcation-involved mandibular molars: a prospective controlled follow-up study.
No evidence exists regarding the advantages of periodontal regeneration treatment for furcation defects using soft block bone substitutes. Therefore, this randomized controlled trial aimed to assess the clinical and radiographic outcomes of regenerative therapy using porcine-derived soft block bone substitutes (DPBM-C, test group) compared with porcine-derived particulate bone substitutes (DPBM, control group) for the treatment of severe class II furcation defects in the mandibular molar regions. Thirty-five enrolled patients (test group, n=17; control group, n=18) were available for a 12-month follow-up assessment. Clinical (probing pocket depth [PPD] and clinical attachment level [CAL]) and radiographic (vertical furcation defect; VFD) parameters were evaluated at baseline and 6 and 12 months after regenerative treatment. Early postoperative discomfort (severity and duration of pain and swelling) and wound healing outcomes (dehiscence, suppuration, abscess formation, and swelling) were also assessed 2 weeks after surgery. For both treatment modalities, significant improvements in PPD, CAL, and VFD were found in the test group (PPD reduction of 4.1±3.0 mm, CAL gain of 4.4±2.9 mm, and VFD reduction of 4.1±2.5 mm) and control group (PPD reduction of 2.7±2.0 mm, CAL gain of 2.0±2.8 mm, and VFD reduction of 2.4±2.5 mm) 12 months after the regenerative treatment of furcation defects (P<0.05). However, no statistically significant differences were found in any of the measured clinical and radiographic parameters, and no significant differences were observed in any early postoperative discomfort and wound healing outcomes between the 2 groups. Similar to DPBM, DPBM-C showed favorable clinical and radiographic outcomes for periodontal regeneration of severe class II furcation defects in a 12-month follow-up period. Clinical Research Information Service Identifier: KCT0007305.


Perceptions of drug users regarding hepatitis C screening and care: a qualitative study.
Illicit drug users have a high prevalence of HCV and represent the majority of newly infected persons in the U.S. Despite the availability of effective HCV treatment, few drug users have been evaluated or treated for HCV. Racial and ethnic minorities have a higher incidence and prevalence of HCV and higher HCV-related mortality. Factors contributing to poor engagement in care are incompletely understood. Fourteen mixed-gender focus groups of either African American or Latino/a drug users (N = 95) discussed barriers to HCV testing and treatment. Themes were identified through content analysis of focus group discussions. Many drug users were tested for HCV in settings where they were receiving care. Outside of these settings, most were unaware of voluntary test sites. After testing HCV positive, drug users reported not receiving clear messages regarding the meaning of a positive HCV test, the impact of HCV infection, or appropriate next steps including HCV clinical evaluations. Many drug users perceived treatment as unimportant because they lacked symptoms, healthcare providers minimized the severity of the diagnosis, or providers did not recommend treatment. Mistrust of the motivations of healthcare providers was cited as a barrier to pursuing treatment. Social networks or social interactions were a source of HCV-related information and were influential in shaping drug users perceptions of treatment and its utility. Drug users perceived a paucity of settings for self-initiated HCV testing and poor provider-patient communication at test sites and during medical encounters. Notably, drug users reported having an unclear understanding about the meaning of a positive HCV test, the health implications of HCV infection, the importance of clinical evaluations and monitoring, and of treatment options for HCV. Efforts to improve the delivery of clinical messages about HCV infection for drug users at test settings and clinical encounters are needed.


Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver.
A novel organic anion transporting polypeptide (Oatp)4(1) was isolated from rat liver that is 35 amino acids longer than the reported rat liver specific organic anion transporter (rlst)-1 and exhibits a 64% amino acid sequence identity with the human OATP-C (LST-1/OATP2; gene symbol SLC21A6). When expressed in Xenopus laevis oocytes, Oatp4 (Slc21a10) mediated polyspecific uptake of a variety of organic anions including taurocholate (K(m) approximately 27 microM), bromosulfophthalein (K(m) approximately 1.1 microM) and steroid conjugates. Based on nuclease protection analysis Oatp4 appears to be the predominant transcript in rat liver indicating that rlst-1 plays a minor role in overall hepatic organic anion uptake.


Two isomorphous Co(ii) coordination polymers based on new α,α-disubstituted derivatives of zoledronic acid: synthesis, structures and properties.
Two novel α,α-disubstituted derivatives of zoledronic acid, namely 1-hydroxy-2-(1H-imidazol-1-yl)-2-methylpropylidene-1,1-diphosphonic acid (H4L1) and 1-hydroxy-2-[1-(1H-imidazol-1-yl)cyclopropyl]ethylidene-1,1-diphosphonic acid (H4L2) were synthesized and structurally characterized by single-crystal X-ray diffraction. The reaction of cobalt acetate with H4L1 and H4L2 carried out under hydrothermal conditions afforded two isomorphous Co3(HL1)2(H2O)6·6H2O (1a) and Co3(HL2)2(H2O)6·6H2O (2a) complexes. Both compounds are characterized by means of X-ray crystallography, IR and NIR-Vis-UV spectroscopic methods. Furthermore, their magnetic properties and thermal stabilities are reported. The crystals of 1a and 2a feature infinite 1D polymeric chains built from alternately arranged dinuclear [Co2(HL1/HL2)(H2O)2]2 units and {Co1O6} octahedra running along the [1[combining macron]10] crystallographic direction. In both compounds, crystallographically distinct Co1 and Co2 atoms are six-coordinated. As is reflected in T values (T - index of tetragonality), the coordination environment of Co1 generates a slightly elongated octahedron (T = 0.94), whereas a slightly compressed octahedron (T = 1.06 for 1a and 1.05 for 2a) is formed around Co2. An assumption that the d-d type absorption is mainly attributed to the inversion related Co2 centers, whose population is two times higher than that of Co1, afforded a good correlation between calculated transition energies and experimental NIR-Vis-UV spectra. The magnetic susceptibility measurements analyzed in terms of a spin-3/2 Heisenberg trimer chain revealed that Co1Co2 interactions within the trimer are antiferromagnetic whereas Co2Co2 intertrimer interactions are ferromagnetic.


Success and virulence in Toxoplasma as the result of sexual recombination between two distinct ancestries.
Toxoplasma gondii is a common human pathogen causing serious, even fatal, disease in the developing fetus and in immunocompromised patients. Despite its ability to reproduce sexually and its broad geographic and host range, Toxoplasma has a clonal population structure comprised principally of three lines. We have analyzed 15 polymorphic loci in the archetypal type I, II, and III strains and found that polymorphism was limited to, at most, two rather than three allelic classes and no polymorphism was detected between alleles in strains of a given type. Multilocus analysis of 10 nonarchetypal isolates likewise clustered the vast majority of alleles into the same two distinct ancestries. These data strongly suggest that the currently predominant genotypes exist as a pandemic outbreak from a genetic mixing of two discrete ancestral lines. To determine if such mixing could lead to the extreme virulence observed for some strains, we examined the F(1) progeny of a cross between a type II and III strain, both of which are relatively avirulent in mice. Among the progeny were recombinants that were at least 3 logs more virulent than either parent. Thus, sexual recombination, by combining polymorphisms in two distinct and competing clonal lines, can be a powerful force driving the natural evolution of virulence in this highly successful pathogen.


Stimulus-driven attentional capture by a static discontinuity between perceptual groups.
After C. L. Folk, R. W. Remington, and J. C. Johnston (1992) proposed their contingent-orienting hypothesis, there has been an ongoing debate over whether purely stimulus-driven attentional capture can occur for visual events that are salient by virtue of a distinctive static property (as opposed to a dynamic property such as abrupt onset). The present study identified 3 methodological criteria for establishing that attentional capture is stimulus driven and not contingent on top-down attentional control settings. In 5 experiments, attentional capture occurred for a static discontinuity at the boundary between one group of homogeneous items (red Xs) abutted next to a group of homogeneous items that were featurally different (green Xs) within a single row. Experiment 1 intentionally violated one of the criteria for demonstrating stimulus-driven capture so as to establish that contingent attentional capture can occur for this novel type of static cue. In the remaining 4 experiments, even with all 3 criteria for stimulus-driven capture partially or completely satisfied, the static discontinuity captured attention. These attentional capture effects are the first to be obtained when all 3 criteria for establishing that they are purely stimulus driven have been satisfied.


Colorectal cancer screenings: a single center experience.
evaluating the impact of screening programmes on colorectal cancer (CRC) in Italy. we studied 1292 patients with colorectal cancer. Data were collected from January 2004 through December 2015 in Parma University Hospital. We compared clinophatological features to evaluate the real impact of screening programmes on detecting early stage colorectal cancers in target population. screening programmes with fecal occult blood test (FOBT) and colonoscopy covered only patients from 50 to 69. In our study we reported that the 52,3% of patients with CRC were over 70 and out of screen time, while only 47,7% were under 70. Early detection seems to be related to early stage of CRC and to an improved overall survival. The importance of early detection in colorectal cancers represents the most important outcome for OS. The risk of colorectal cancer is increased in elderly. Actual screening programmes cover less than 50% of population with colorectal cancer. Screening should be considered for patients over 70, due to the high number of new diagnosis in symptomatic disease and worst prognosis, in accordance with advanced cancer stage and comorbidities in elderly.


First Report of Leaf Spot Caused by Corynespora cassiicola on Rose of Sharon in Korea.
Rose of Sharon, Hibiscus syriacus L., is a flowering shrub in the family Malvaceae planted as the national flower of South Korea. In September 2012, previously unknown leaf spots with premature defoliation were observed on dozens of Rose of Sharon plants growing in the shaded area in a park of Dongducheon, Korea. The same symptoms were found on Rose of Sharon in several localities of Korea in 2012. The symptoms usually started as small, dark brown to grayish leaf spots, eventually causing leaf yellowing with significant premature defoliation. The diseased leaves retained for a while green color at the margin of the spots. Representative samples (n = 5) were deposited in the Korea University Herbarium (KUS). Conidiophores of the fungus observed microscopically on the leaf spots were erect, brown to dark brown, single or in clusters, amphigenous but mostly hypophyllous, and measured 80 to 400 × 5 to 10 μm. Conidia were borne singly or in short chains, ranging from cylindrical to broadest at the base and tapering apically, straight to slightly curved, pale olivaceous brown, 2 to 16 pseudoseptate, 50 to 260 × 9 to 20 μm, each with a conspicuous thickened hilum. On potato dextrose agar, single-spore cultures of two isolates were identified as Corynespora cassiicola (Berk. & M.A. Curtis) C.T. Wei on the basis of morphological and cultural characteristics (1,2). Two monoconidial isolates were preserved at the Korean Agricultural Culture Collection (KACC46956 and KACC46957). Genomic DNA was extracted using the DNeasy Plant Mini DNA Extraction Kit (Qiagen Inc., Valencia, CA). The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 and sequenced. The resulting sequences of 520 bp were deposited in GenBank (Accession Nos. KC193256, KC193257). A BLAST search in GenBank revealed that the sequences showed 100% identity with those of numerous C. cassiicola isolates from diverse substrates. To conduct a pathogenicity test, a conidial suspension (ca. 2 × 104 conidia/ml) was prepared in sterile water by harvesting conidia from 2-week-old cultures of KACC46956, and the suspension was sprayed onto the leaves of three healthy 2-year-old plants. Inoculated plants were kept in humid chambers for the first 48 h and thereafter placed in the glasshouse. After 10 days, typical leaf spot symptoms developed on the leaves of all three inoculated plants. C. cassiicola was reisolated from the lesions, confirming Koch's postulates. Control plants treated with sterile water remained symptomless. C. cassiicola is cosmopolitan with a very wide host range (1,2). Though Corynespora hibisci Goto was recorded to be associated with brown spot disease of H. syriacus in Japan (4), there is no previous record of C. cassiicola on H. syriacus (3). To our knowledge, this is the first report of Corynespora leaf spot on Rose of Sharon in Korea. According to our field observations in Korea, this disease was found in August and September, following a prolonged period of moist weather. Severe infection resulted in leaf yellowing and premature defoliation, reducing tree vigor and detracting the beauty of green leaves. References: (1) L. J. Dixon et al. Phytopathology 99:1015, 2009. (2) M. B. Ellis. Dematiaceous Hyphomycetes. Commonw. Mycol. Inst., Kew, UK, 1971. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved November 22, 2012. (4) K. Goto. Ann. Phytopathol. Soc. Japan 12:14, 1942.


Role of gut microbiota in regulating gastrointestinal dysfunction and motor symptoms in a mouse model of Parkinson's disease.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by motor and non-motor gastrointestinal (GI) deficits. GI symptoms' including compromised intestinal barrier function often accompanies altered gut microbiota composition and motor deficits in PD. Therefore, in this study, we set to investigate the role of gut microbiota and epithelial barrier dysfunction on motor symptom generation using a rotenone-induced mouse model of PD. We found that while six weeks of 10 mg/kg of chronic rotenone administration by oral gavage resulted in loss of tyrosine hydroxylase (TH) neurons in both germ-free (GF) and conventionally raised (CR) mice, the decrease in motor strength and coordination was observed only in CR mice. Chronic rotenone treatment did not disrupt intestinal permeability in GF mice but resulted in a significant change in gut microbiota composition and an increase in intestinal permeability in CR mice. These results highlight the potential role of gut microbiota in regulating barrier dysfunction and motor deficits in PD.


Fabrication of twisted nematic structure and vector grating cells by one-step exposure on photocrosslinkable polymer liquid crystals.
We present a simple yet efficient method to automatically fabricate the twisted nematic structure by one-step exposure on an empty glass cell coated with photocrosslinkable polymer liquid crystal (PCLC) films. The resultant photoalignment directions of two substrates can be orthogonal to each other by controlling the difference between the exposure energy for upper and lower PCLC films and the twisted nematic (TN) structure can be automatically fabricated. The vector grating liquid crystalline cell with TN structure was also fabricated by means of a developed method, and the diffraction properties were well explained by the theoretical calculation on the basis of Jones calculus.


In vitro and in vivo degradation of microfiber bioresorbable coronary scaffold.
The degradation of Mirage Bioresorbable Microfiber Scaffold was evaluated in vitro and in vivo. The degradation in polymer molecular weight (MW), strut morphology, and integrity was accessed using gel permeation chromatography (GPC), X-ray micro-computed tomography (micro-CT) evaluation. To simulate the physiological degradation in vitro, scaffolds were deployed in silicone mock vessels connected to a peristaltic pumping system, which pumps 37°C phosphate-buffered saline (PBS, pH 7.4) at a constant rate. At various time points (30D, 60D, 90D, 180D, 270D, and 360D), the MW of microfibers decreased to 57.3, 49.8, 36.9, 13.9, 6.4, and 5.1% against the baseline. The in vivo degradation study was performed by implanting scaffolds in internal thoracic arteries (ITAs) of mini-swine. At the scheduled sacrifice time points (30D, 90D, 180D, 270D, 360D, and 540D), the implanted ITAs were excised for GPC analysis; the MW of the implanted scaffolds dropped to 58.5, 34.7, 24.8, 16.1, 12.9, and 7.1, respectively. Mass loss of scaffolds reached 72.4% at 540D of implantation. Two stages of hydrolysis were observed in in vitro and in vivo degradation kinetics, and the statistical analysis suggested a positive correlation between in vivo and in vitro degradation. After 6 months of incubation in animals, significant strut degradation was seen in the micro-CT evaluation in all sections as strut fragments and separations. The micro-CT results further confirmed that every sample at 720D had X-ray transmission similar to surrounding tissue, thereby indicating full degradation within 2 years. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1842-1850, 2018.


Hypoxic vasoconstriction increases with postnatal age in lungs from newborn rabbits.
Previous studies on the pressor response of the newborn pulmonary circulation to hypoxia have used intact animals and have reported conflicting results. Some have found an increase in responsiveness with increasing age; others have found a decrease. To circumvent many problems inherent in studies of pulmonary vascular reactivity in intact animals, we have developed methods for studying isolated, blood-perfused lungs from newborn rabbits. These methods have been used to study the influence of postnatal age on hypoxic pulmonary vasoconstriction. Two sets of experiments were performed. In the first, a stimulus response curve for hypoxic pulmonary vasoconstriction was constructed, using lungs from 19 rabbit pups that were 3-8 days old. At a constant blood flow, pulmonary artery pressure increased progressively as alveolar oxygen tension decreased so that the maximum increase from baseline (29.4 +/- 4.7%) occurred at PIO2 = 0. The pressor response to hypoxia was highly reproducible, and the entire system remained stable for over 2-3 hours. In the second set of experiments, we compared the pulmonary vascular response to hypoxia obtained using lungs from an additional 21 pups that were 3-8 days old with that obtained using lungs from 23 pups that were 10-14 days old. In response to the same hypoxic stimulus, pulmonary artery pressure increased more in lungs from older rabbit pups (56 +/- 4%) than in lungs from younger rabbit pups (34 +/- 7%) (p less than 0.001). We conclude that isolated perfused lungs from newborn rabbits exhibit a reproducible pressor response to alveolar hypoxia and that this response increases as a function of postnatal age.


Effects of macro- versus nanoporous silicon substrates on human aortic endothelial cell behavior.
Human aortic endothelial cells play a key role in the pathogenesis of atherosclerosis, which is a common, progressive, and multifactorial disease that is the clinical endpoint of an inflammatory process and endothelial dysfunction. Study and development of new therapies against cardiovascular disease must be tested in vitro cell models, prior to be evaluated in vivo. To this aim, new cell culture platforms are developed that allow cells to grow and respond to their environment in a realistic manner. In this work, the cell adhesion and morphology of endothelial cells are investigated on functionalized porous silicon substrates with two different pore size configurations: macroporous and nanoporous silicon. Herein, we modified the surfaces of porous silicon substrates by aminopropyl triethoxysilane, and we studied how different pore geometries induced different cellular response in the cell morphology and adhesion. The cell growth over the surface of porous silicon becomes an attractive field, especially for medical applications. Surface properties of the biomaterial are associated with cell adhesion and as well as, with proliferation, migration and differentiation.


Perceived Risk of Human Papillomavirus Infection and Cervical Cancer among Adolescent Women in Taiwan.
High-risk types of human papillomavirus (HPV) are a critical etiologic factor behind cervical cancer. Adolescents are a vulnerable group for HPV infection. However, the literature on adolescent women for HPV infection and cervical cancer is limited. This study was to investigate HPV-related knowledge and perceived risk of HPV infection and cervical cancer among Taiwanese adolescent women in order to assess intervention strategies for prevention of cervical cancer and maintenance of reproductive health. A descriptive cross-sectional study design was implemented. There were 610 adolescent women from three colleges in Southern Taiwan who participated in this study. Data were collected using an anonymous self-administered questionnaire survey. The results showed that the percentage of appropriate answers to HPV-related knowledge questions was only 36.8%, and smoking as the leading cause of cervical cancer received the lowest mean score for appropriate answers among the HPV-related knowledge items. The perceived risk of HPV infection and cervical cancer were moderate, with relatively lower susceptibility to infection with HPV than to cervical cancer (p < .001). Only 11.5% of the participants reported that they had received information about HPV vaccination from healthcare professionals. Participants lacked a comprehensive understanding of cervical cancer prevention and were not aware of their susceptibility to HPV infection. Adolescent women rarely obtained HPV-related information from healthcare professionals. Appropriate education strategies should be developed and conducted by healthcare professionals to reduce the risk of cervical cancer threat from adolescence.


Three-dimensional focal curves generated by one-dimensional gradient-index tapers.
Three-dimensional focal curves generated by one-dimensional gradient-index taper have been obtained when the taper is illuminated by an off-axis plane wave. The intensity distribution along the focal curve was evaluated by taking into account the particular form of the exit pupil produced by this gradient-index medium.


Pseudomonas putida strain PCL1444, selected for efficient root colonization and naphthalene degradation, effectively utilizes root exudate components.
Previously, we have described the selection of a plant-bacterium pair that is efficient in rhizoremediating naphthalene pollution in microcosm studies. After repeated selection for efficient root tip colonization upon inoculation of seeds of grass cv. Barmultra and for stable and efficient growth on naphthalene, Pseudomonas putida PCL1444 was selected as the most efficient colonizer of Barmultra roots. Here, we report the analysis of Barmultra root exudate composition and our subsequent tests of the growth rate of the bacterium and of the expression of the naphthalene degradation genes on individual exudate components. High performance liquid chromatography analysis of the organic acid and sugar root-exudate components revealed that glucose and fructose are the most abundant sugars, whereas succinic acid and citric acid are the most abundant organic acids. Tn5luxAB mutants of PCL1444 impaired in naphthalene degradation appeared to be impaired in genes homologous to genes of the upper naphthalene degradation pathway present in various Pseudomonas strains and to genes of the lower pathway genes for naphthalene degradation in P. stutzeri. Highest expression for both pathways involved in naphthalene degradation during growth in minimal medium with the carbon source to be tested was observed at the start of the logarithmic phase. Naphthalene did not induce the upper pathway, but a different pattern of expression was observed in the lower pathway reporter, probably due to the conversion of naphthalene to salicylic acid. Salicylic acid, which is described as an intermediate of the naphthalene degradation pathway in many Pseudomonas strains, did induce both pathways, resulting in an up to sixfold higher expression level at the start of the logarithmic phase. When expression levels during growth on the different carbon sources present in root exudate were compared, highest expression was observed on the two major root exudate components, glucose and succinic acid. These results show an excellent correlation between successful naphthalene rhizoremediation by the Barmultra-P. putida PCL1444 pair and both efficient utilization of the major exudate components for growth and high transcription of the naphthalene catabolic genes on the major exudate components. Therefore, we hypothesize that efficient root colonizing and naphthalene degradation is the result of the applied colonization enrichment procedure.


Maternal Prepregnancy Weight and Children's Behavioral and Emotional Outcomes.
This study investigated associations between maternal prepregnancy BMI and child behaviors at ages 9-11 years and examine interaction by race and gender. The National Longitudinal Survey of Youth and the Children and Young Adults surveys are U.S.-based, ongoing longitudinal studies, initiated in 1979 and 1986, respectively. Mothers (n=2,952) reported pregnancy and child (n=5,660) developmental information at multiple time points. Child total, internalizing, and externalizing problems at ages 9-11 years were assessed using the Behavior Problems Index (BPI), collected biennially until 2012. Associations between prepregnancy BMI and child BPI outcomes were examined, as well as two- and three-way interactions by race and gender. Analyses were conducted in 2017. Boys whose mothers had higher prepregnancy weights exhibited higher total BPI and externalizing scores at ages 9-11 years versus those with normal-weight mothers. Boys with severely obese mothers had higher total BPI (mean difference=7.99, 95% CI=3.53, 12.46) and externalizing (mean difference=5.77, 95% CI=1.50, 10.04) scores. Prepregnancy underweight was associated with boys' higher total BPI (mean difference=2.34, 95% CI=0.02, 4.66) and externalizing (mean difference=3.30, 95% CI=0.69, 5.91); these associations were not significant in sensitivity analyses. No associations emerged for girls or internalizing problems. Two-way interactions by race and three-way interactions by race and gender were not significant. Maternal prepregnancy weight was associated with BPI level among boys. Boys with severely obese mothers exhibited markedly higher behavioral problems at ages 9-11 years versus those with normal-weight mothers, regardless of race. Maintaining healthy prepregnancy weight may be important for preventing boys' deleterious behavior outcomes in middle childhood.


Key components of supporting and assessing decision making ability.
People's ability to make decisions may be impaired for a wide range of reasons, including by mental health problems and learning disabilities. Individual autonomy, the ability to make decisions about our own lives, is a fundamental tenet of democratic societies. This has been reinforced by laws governing substitute and supported decision making and most significantly by the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). Article 12 of the UNCRPD requires everyone to have equal recognition before the law and, to achieve this, the necessary support and safeguards must be available. There has been considerable debate about the important theoretical and philosophical issues involved and growing research about the practice complexities of supporting and assessing decision making ability or mental capacity. This article aims to present some of the key components of the support and assessment process to inform further service development and training in this area. The key components were identified as part of a qualitative, participatory research project which explored the decision making experiences of people with mental health problems and/or learning disabilities. The conventional approach to the assessment of capacity is to consider four main components, whether the person is able to: understand, retain, use and weigh, and communicate the information needed to make the decision at that time. The findings from this research study suggest that people generally don't usually talk about their experiences of decision making in terms of these four components and approaches to supporting people to make decisions don't necessarily break the support down to explicitly address the assessment process. However, considering support for all aspects of the functional test may be helpful to ensure it is as comprehensive as possible. The challenges involved in providing effective support and assessing decision making ability are discussed and the article concludes with some of the implications for training, service development and practice.


Parental perceptions regarding mandatory mouthguard use in competitive youth soccer.
To understand factors that influence parental perceptions regarding mandatory mouthguard use in competitive youth soccer. A web based survey of parents whose 8-14 year old children participated in outdoor competitive youth soccer during the fall of 2002. Questions focused on: previous injury, education provided, dentist/physician recommendations, and parental perceptions of mouthguard use. The outcome variable was parental agreement with the statement "mouthguards should be mandatory for competitive youth soccer". Logistic regression and chi(2) were performed using STATA 8.0. Altogether 120 parents participated. The children had a mean (SD) age of 11.8 (1.5) years and 48% were female; 14% wore mouthguards and 11% suffered orofacial injuries. Nineteen percent of parents reported receiving educational material from the youth soccer organization. Although 92% of parents believed that mouthguards were effective in reducing orofacial injuries, only one half agreed that mouthguards should be mandatory. Thirty percent of respondents reported that their dentist/physician recommended mouthguards for competitive youth soccer. Logistic regression showed that dentist/physician recommendation and parental female gender were independently associated with parental agreement for mandatory mouthguard use (odds ratio 2.9, 95% confidence interval (CI) 1.2 to 7.3; odds ratio 3.0, 95% CI 1.1 to 6.5). Few athletes wear mouthguards during competitive youth soccer. Health care professionals in this study did not capitalize on the apparent influence they have on parental beliefs regarding mouthguard use. Efforts are needed by both health professionals and soccer organizations to educate parents about orofacial injuries and mouthguard use in competitive youth soccer.


VEGF receptor signaling in vertebrate development.
The secreted glycoprotein vascular endothelial growth factor A (VEGF or VEGFA) affects many different cell types and modifies a wide spectrum of cellular behaviors in tissue culture models, including proliferation, migration, differentiation and survival. The versatility of VEGF signaling is reflected in the complex composition of its cell surface receptors and their ability to activate a variety of different downstream signaling molecules. A major challenge for VEGF research is to determine which of the specific signaling pathways identified in vitro control development and homeostasis of tissues containing VEGF-responsive cell types in vivo.


Does gradually returning to work improve time to sustainable work after a work-acquired musculoskeletal disorder in British Columbia, Canada? A matched cohort effectiveness study.
This study investigates if gradual return to work (GRTW) is associated with full sustainable return to work (RTW) for seriously injured workers with a musculoskeletal disorder (MSD), in British Columbia, Canada. This is an effectiveness study using a retrospective cohort study design. Accepted workers' compensation lost-time claims were extracted for workers with an MSD who were on full work disability for at least 30 days, between 2010 and 2015 (n=37 356). Coarsened exact matching yielded a final matched cohort of 12 494 workers who experienced GRTW at any point 30 days post-injury and 12 494 workers without any GRTW. The association between GRTW and sustainable RTW through to end of 12 months was estimated with multivariable quantile regression. Workers who were provided with GRTW experienced more time-loss days until sustainable RTW between the 2nd and 5th months after the first time-loss day (<50th quantile of time loss), but less time-loss days until sustainable RTW between the 6th and 12th months of work disability (70th quantile of time loss), with the largest effect for women, workers with soft-tissue injuries and workers in the manufacturing or trades sector (all in the 60th and 70th percentile, after 6-7 months of time loss). For seriously injured workers with at least 30 days of disability due to a work-acquired MSD, the effect of GRTW becomes apparent at longer disability durations (more than 6 months), with larger beneficial effects for women, workers with soft-tissue injuries and for trade and manufacturing sectors.


On the factors affecting product distribution in laccase-catalyzed oxidation of a lignin model compound vanillyl alcohol: experimental and computational evaluation.
Laccases (EC 126.96.36.199) are multicopper oxidases, which can oxidize phenolic substrates by the concomitant reduction of oxygen to water. The phenolic substructures of lignin are also oxidized by laccases, resulting mainly in various polymerized products. Several model compound studies indicate that variations in the reaction media, such as the pH and the enzyme dosage used, have an impact on the observed product distribution of laccase promoted oxidation, but no detailed study has been reported to explain these results. In the present study, a monomeric lignin model compound, vanillyl alcohol, was oxidized in laccase-catalyzed reactions by varying the pH, enzyme dosage and temperature. The energies of all the observed products and potential intermediates were calculated by applying density functional theory (DFT) and the polarizable continuum solvation model (PCM). The observed predominant product at pH 4.5 to 7.5 was clearly the 5-5' dimer, although the thermodynamic product according to the calculated free energies was vanillin, the difference being 5.6 kcal mol(-1). The hydrogen bonding is shown to give an additional stabilizing effect on the transition state leading to the 5-5' dimer, but also a kinetic barrier reduces the formation of vanillin. Based on the calculated pKa-values of the proposed intermediates we suggest that the rearomatization reactions of the quinones formed in the radical reactions under mildly acidic and neutral conditions would preferentially occur through deprotonation rather than through protonation.


Chorioamnionitis in Rats Precipitates Extended Postnatal Inflammatory Lymphocyte Hyperreactivity.
Preterm birth is an important cause of perinatal brain injury (PBI). Neurological injury in extremely preterm infants often begins in utero with chorioamnionitis (CHORIO) or inflammation/infection of the placenta and concomitant placental insufficiency. Studies in humans have shown dysregulated inflammatory signaling throughout the placental-fetal brain axis and altered peripheral immune responses in children born preterm with cerebral palsy (CP). We hypothesized that peripheral immune responses would be altered in our well-established rat model of CP. Specifically, we proposed that isolated peripheral blood mononuclear cells (PBMCs) would be hyperresponsive to a second hit of inflammation throughout an extended postnatal time course. Pregnant Sprague-Dawley dams underwent a laparotomy on embryonic day 18 (E18) with occlusion of the uterine arteries (for 60 min) followed by intra-amniotic injection of lipopolysaccharide (LPS, 4 μg/sac) to induce injury in utero. Shams underwent laparotomy only, with equivalent duration of anesthesia. Laparotomies were then closed, and the rat pups were born at E22. PBMCs were isolated from pups on postnatal day 7 (P7) and P21, and subsequently stimulated in vitro with LPS for 3 or 24 h. A secreted inflammatory profile analysis of conditioned media was performed using multiplex electrochemiluminescent immunoassays, and the composition of inflammatory cells was assayed with flow cytometry (FC). Results indicate that CHORIO PBMCs challenged with LPS are hyperreactive and secrete significantly more tumor necrosis factor α (TNFα) and C-X-C chemokine ligand 1 at P7. FC confirmed increased intracellular TNFα in CHORIO pups at P7 following LPS stimulation, in addition to increased numbers of CD11b/c immunopositive myeloid cells. Notably, TNFα secretion was sustained until P21, with increased interleukin 6, concomitant with increased expression of integrin β1, suggesting both sustained peripheral immune hyperreactivity and a heightened activation state. Taken together, these data indicate that in utero injury primes the immune system and augments enhanced inflammatory signaling. The insidious effects of primed peripheral immune cells may compound PBI secondary to CHORIO and/or placental insufficiency, and thereby render the brain susceptible to future chronic neurological disease. Further understanding of inflammatory mechanisms in PBI may yield clinically important biomarkers and facilitate individualized repair strategies and treatments.


Influenza virus proteins as factors involved in interspecies transmission.
Influenza A viruses cause recurrent epidemics and global pandemics. One of the unique features of influenza virus is the ability to overcome interspecies barrier. Reassortment of viral genes and the accumulation of mutations contribute to the emergence of new influenza virus variants. The replication of influenza A virus in a specific host depends on many factors e.g. activity of viral proteins, host response system and environmental conditions. In this review the role of viral proteins as a condition for crossing the species barriers is discussed.


Preoperative balance control compensation in patients with a vestibular schwannoma: does tumor size matter?
The influence of tumor size on postural control of patients with vestibular schwannoma (VS) remains to be determined. This study aimed to compare the postural performances of VS patients, according to the size of the tumor, with healthy subjects. The six conditions (C1-C6) of the sensory organization test (SOT) were carried out in 87 patients, split into four groups according to the Koos classification (stage I-IV), and in 72 aged-matched controls to evaluate postural control. The vestibular reflectivity and compensation were estimated with videonystagmography. Among patients, lower C5 and C6 scores were found in stage I and IV patients than in stage II and III patients, whereas vestibular compensation did not impact the tumor size influence on the postural control. The scores were significantly (p<0.001) lower for all the groups of patients than the controls in the vestibular-related SOT conditions (C5-C6). Patients with an unilateral VS displayed altered postural performances compared to the control subjects and tumor size had a bell-like pattern effect on balance control. The tumor size could be seen as a determining factor in the implementation of adaptive mechanisms that lead to the postural compensation and might be dissociated from vestibular compensation.


Effectiveness of Global Postural Re-education for Treatment of Spinal Disorders: A Meta-analysis.
The aim of this study was to investigate the effects of global postural re-education (GPR) on the treatment of spinal disorders by performing a systematic review and a meta-analysis. MEDLINE, Scopus, and PEDro databases were searched without language or publication date restrictions. Data on pain and function were used to evaluate the effectiveness of GPR. Randomized controlled trials and controlled clinical trials analyzing the effectiveness of GPR on spinal disorders were selected. The standardized mean difference (SMD) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis was performed using the Comprehensive Meta-analysis 3.3 software. Seven randomized controlled trials and 4 controlled clinical trials were included in the meta-analysis. The results showed a medium improvement on pain (SMD = -0.63; 95% CI, -0.43 to -0.83) and function (SMD = -0.48; 95% CI, -0.25 to -0.72) after GPR treatment. The positive effect, which was greater in patients with ankylosing spondylitis followed by low back pain and neck pain, was more significant during the intermediate follow-up than immediately after treatment. This meta-analysis provides reliable evidence that GPR may be an effective method for treating spinal disorders by decreasing pain and improving function.


Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1.
Inflammasomes are cytosolic multiprotein complexes assembled by intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and they initiate innate immune responses to invading pathogens and danger signals by activating caspase-1 (ref. 1). Caspase-1 activation leads to the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, as well as lytic inflammatory cell death known as pyroptosis. Recently, a new non-canonical inflammasome was described that activates caspase-11, a pro-inflammatory caspase required for lipopolysaccharide-induced lethality. This study also highlighted that previously generated caspase-1 knockout mice lack a functional allele of Casp11 (also known as Casp4), making them functionally Casp1 Casp11 double knockouts. Previous studies have shown that these mice are more susceptible to infections with microbial pathogens, including the bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium), but the individual contributions of caspase-1 and caspase-11 to this phenotype are not known. Here we show that non-canonical caspase-11 activation contributes to macrophage death during S. typhimurium infection. Toll-like receptor 4 (TLR4)-dependent and TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent interferon-β production is crucial for caspase-11 activation in macrophages, but is only partially required for pro-caspase-11 expression, consistent with the existence of an interferon-inducible activator of caspase-11. Furthermore, Casp1(-/-) mice were significantly more susceptible to infection with S. typhimurium than mice lacking both pro-inflammatory caspases (Casp1(-/-) Casp11(-/-)). This phenotype was accompanied by higher bacterial counts, the formation of extracellular bacterial microcolonies in the infected tissue and a defect in neutrophil-mediated clearance. These results indicate that caspase-11-dependent cell death is detrimental to the host in the absence of caspase-1-mediated innate immunity, resulting in extracellular replication of a facultative intracellular bacterial pathogen.


Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy.
The circadian clock gene Period2 (PER2) has been suggested to be a tumor suppressor. However, detailed mechanistic evidence has not been provided to support this hypothesis. We found that loss of PER2 enhanced invasion and activated expression of epithelial-mesenchymal transition (EMT) genes including TWIST1, SLUG, and SNAIL. This finding was corroborated by clinical observation that PER2 down-regulation was associated with poor prognosis in breast cancer patients. We further demonstrated that PER2 served as a transcriptional corepressor, which recruited polycomb proteins EZH2 and SUZ12 as well as HDAC2 to octamer transcription factor 1 (OCT1) (POU2F1) binding sites of the TWIST1 and SLUG promoters to repress expression of these EMT genes. Hypoxia, a condition commonly observed in tumors, caused PER2 degradation and disrupted the PER2 repressor complex, leading to activation of EMT gene expression. This result was further supported by clinical data showing a significant negative correlation between hypoxia and PER2. Thus, our findings clearly demonstrate the tumor suppression function of PER2 and elucidate a pathway by which hypoxia promotes EMT via degradation of PER2.


treespace: Statistical exploration of landscapes of phylogenetic trees.
The increasing availability of large genomic data sets as well as the advent of Bayesian phylogenetics facilitates the investigation of phylogenetic incongruence, which can result in the impossibility of representing phylogenetic relationships using a single tree. While sometimes considered as a nuisance, phylogenetic incongruence can also reflect meaningful biological processes as well as relevant statistical uncertainty, both of which can yield valuable insights in evolutionary studies. We introduce a new tool for investigating phylogenetic incongruence through the exploration of phylogenetic tree landscapes. Our approach, implemented in the R package treespace, combines tree metrics and multivariate analysis to provide low-dimensional representations of the topological variability in a set of trees, which can be used for identifying clusters of similar trees and group-specific consensus phylogenies. treespace also provides a user-friendly web interface for interactive data analysis and is integrated alongside existing standards for phylogenetics. It fills a gap in the current phylogenetics toolbox in R and will facilitate the investigation of phylogenetic results.


Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights.
Sequencing of tumors is now routine and guides personalized cancer therapy. Mutant allele fractions (MAFs, or the 'mutation dose') of a driver gene may reveal the genomic structure of tumors and influence response to targeted therapies. We performed a comprehensive analysis of MAFs of driver alterations in unpaired primary and metastatic colorectal cancer (CRC) at our institution from 2010 to 2015 and studied their potential clinical relevance. Of 763 CRC samples, 622 had detailed annotation on overall survival in the metastatic setting (OSmet) and 89 received targeted agents matched to KRAS (MEK inhibitors), BRAF (BRAF inhibitors), or PIK3CA mutations (PI3K pathway inhibitors). MAFs of each variant were normalized for tumor purity in the sample (adjMAFs). We found lower adjMAFs for BRAFV600E and PIK3CA than for KRAS, NRAS, and BRAF non-V600 variants. TP53 and BRAFV600E adjMAFs were higher in metastases as compared to primary tumors, and high KRAS adjMAFs were found in CRC metastases of patients with KRAS wild-type primary tumors previously exposed to EGFR antibodies. Patients with RAS- or BRAFV600E -mutated tumors, irrespective of adjMAFs, had worse OSmet. There was no significant association between adjMAFs and time to progression on targeted therapies matched to KRAS, BRAF, or PIK3CA mutations, potentially related to the limited antitumor activity of the employed drugs (overall response rate of 4.5%). In conclusion, the lower BRAFV600E and PIK3CA adjMAFs in subsets of primary CRC tumors indicate subclonality of these driver genes. Differences in adjMAFs between metastases and primary tumors suggest that approved therapies may result in selection of BRAFV600E - and KRAS-resistant clones and an increase in genomic heterogeneity with acquired TP53 alterations. Despite significant differences in prognosis according to mutations in driver oncogenes, adjMAFs levels did not impact on survival and did not help predict benefit with matched targeted agents in the metastatic setting.


Terrestrial emigration behaviour of two invasive crayfish species.
To disperse between isolated waterbodies, freshwater organisms must often cross terrestrial barriers and many freshwater animals that are incapable of flight must rely on transport via flooding events, other animals or anthropogenic activity. Decapods such as crayfish, on the other hand, can disperse to nearby waterbodies by walking on land, a behaviour that has facilitated the spread of invasive species. Overland movement could play a key role in the management of non-native crayfish, though to what extent terrestrial emigration occurs in different species is poorly understood. Here, we directly compared the terrestrial emigration tendency of two non-native crayfish species in Great Britain; red swamp (Procambarus clarkii) and signal (Pacifastacus leniusculus) crayfish. We found that both species emigrated from the water and that there was no significant difference in terms of their terrestrial emigration tendency, suggesting that there is a risk both of these species will migrate overland and disperse to new habitats. This study shows that terrestrial emigration is an important behavioural trait to consider when preventing the escape of crayfish from aquaculture and further spread of invasive species.


Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.
Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants.


Escape from the matrix: multiple mechanisms for fibroblast activation in pulmonary fibrosis.
Lung fibrosis is a recognized feature of many chronic lung diseases and is central to the pathogenesis of idiopathic pulmonary fibrosis, a disease that carries a prognosis worse than many cancers. Current research into this condition is defining the key pathways of activation either in resident fibroblasts, matrix-producing cells derived from circulating fibrocytes, or epithelial cells that appear to transdifferentiate to fibroblast-like cells. The downstream signaling pathways are also being delineated as well as the gene interactions leading to altered cell phenotype. These studies have led to an appreciation that multiple pathways, including inflammatory and coagulation cascades, are involved in the pathogenesis of idiopathic pulmonary fibrosis. As these facts come to light, we are exploring promising new approaches to treat fibroses and halt the inexorable progression that is a feature of these disorders. This article reviews these findings and our current concepts of the key molecular events leading to tissue damage and excessive matrix deposition in lung fibrosis. It also highlights the need for new studies to delineate alternative pathogenetic mechanisms and integrate these pathways so we have a framework to better understand their importance in individual patients.


Altered Lipidome Composition Is Related to Markers of Monocyte and Immune Activation in Antiretroviral Therapy Treated Human Immunodeficiency Virus (HIV) Infection and in Uninfected Persons.
Background: HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD) risk. Alterations in the composition of saturated (SaFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are related to inflammation and CVD progression in HIV-uninfected (HIV-) populations. The relationships among the lipidome and markers of monocyte and immune activation in HIV-infected (HIV+) individuals are not well understood. Methods: Concentrations of serum lipids and their fatty acid composition were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated HIV+ individuals and 20 HIV- individuals. Results: HIV+ individuals had increased levels of free fatty acids (FFAs) with enrichment of SaFAs, including palmitic acid (16:0) and stearic acid (18:0), and these levels were directly associated with markers of monocyte (CD40, HLA-DR, TLR4, CD36) and serum inflammation (LBP, CRP). PUFA levels were reduced significantly in HIV+ individuals, and many individual PUFA species levels were inversely related to markers of monocyte activation, such as tissue factor, TLR4, CD69, and SR-A. Also in HIV+ individuals, the composition of lysophosphatidylcholine (LPC) was enriched for SaFAs; LPC species containing SaFAs were directly associated with IL-6 levels and monocyte activation. We similarly observed direct relationships between levels of SaFAs and inflammation in HIV uninfected individuals. Further, SaFA exposure altered monocyte subset phenotypes and inflammatory cytokine production in vitro. Conclusions: The lipidome is altered in ART-treated HIV infection, and may contribute to inflammation and CVD progression. Detailed lipidomic analyses may better assess CVD risk in both HIV+ and HIV- individuals than does traditional lipid profiling.


Characterization of the mesenteronal infection with Western equine encephalomyelitis virus in an incompetent strain of Culex tarsalis.
Interactions of western equine encephalomyelitis (WEE) virus are compared with mesenterons of 2 genetically selected susceptible (WS) and refractory (WR) lines of Culex tarsalis. Both WS and WR females had similar susceptibility when parenterally inoculated with virus, thus it was initially thought that resistance in WR Cx. tarsalis was associated with a mesenteronal infection barrier. Present data on viral growth in mesenterons dissected from females fed on virus-soaked pledgets suggest that virus infected and multiplied in some WR mesenterons, but to significantly lower titers than in WS mesenterons. The proportion of WR females with infected mesenterons varied depending on the time after feeding, incubation temperature, and whether mesenterons were incubated with WEE viral antibody before viral assay. The percentage of WR mesenterons infected did not increase significantly when diethylaminoethyl dextran was added to the infectious bloodmeal, the pH of the infectious bloodmeal was altered, or virus was introduced by intrathoracic inoculation into the hemocoel. It was concluded that the low titers of virus detected in both WR mesenterons and whole mosquitoes were influenced by the genetic ability of WR Cx. tarsalis to modulate WEE viral titers to low or undetectable levels after peroral or parenteral infection. These findings make it difficult to determine what proportion of the WR mesenterons are resistant to infection with WEE virus. WS and WR Cx. tarsalis were equally susceptible to peroral infection with the flavivirus St. Louis encephalitis and the bunyavirus Turlock.


Fighting microbial infections: A lesson from amphibian skin-derived esculentin-1 peptides.
Due to the growing emergence of resistance to commercially available antibiotics/antimycotics in virtually all clinical microbial pathogens, the discovery of alternative anti-infective agents, is greatly needed. Gene-encoded antimicrobial peptides (AMPs) hold promise as novel therapeutics. In particular, amphibian skin is one of the richest storehouses of AMPs, especially that of the genus Rana, with esculentins-1 being among the longest (46 amino acids) AMPs found in nature to date. Here, we report on the recently discovered in vitro and in vivo activities and mechanism of action of two derivatives of the N-terminal part of esculentin-1a and -1b peptides, primarily against two relevant opportunistic microorganisms causing a large number of life-threatening infections worldwide; i.e. the Gram-negative bacterium Pseudomonas aeruginosa and the yeast Candida albicans. Because of distinct advantages compared to several mammalian AMPs, the two selected frog skin AMP-derivatives represent attractive candidates for the development of new antimicrobial compounds with expanded properties, for both human and veterinary medicine.


Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment.
To our knowledge, no studies have addressed whether maternal anemia of inflammation (AI) affects newborn iron status, and few have addressed risk factors for specific etiologies of maternal anemia. The study aims were to evaluate 1) the contribution of AI and iron deficiency anemia (IDA) to newborn iron endowment, 2) hepcidin as a biomarker to distinguish AI from IDA among pregnant women, and 3) risk factors for specific etiologies of maternal anemia. We measured hematologic biomarkers in maternal blood at 12 and 32 wk of gestation and in cord blood from a randomized trial of praziquantel in 358 pregnant women with Schistosoma japonicum in The Philippines. IDA was defined as anemia with serum ferritin <30 ng/mL and non-IDA (NIDA), largely due to AI, as anemia with ferritin ≥30 ng/mL. We identified cutoffs for biomarkers to distinguish IDA from NIDA by using area under the curve (AUC) analyses and examined the impact of different causes of anemia on newborn iron status (primary outcome) by using multivariate regression modeling. Of the 358 mothers, 38% (n = 136) had IDA and 9% (n = 32) had NIDA at 32 wk of gestation. At 32 wk of gestation, serum hepcidin performed better than soluble transferrin receptor (sTfR) in identifying women with NIDA compared with the rest of the cohort (AUCs: 0.75 and 0.70, respectively) and in identifying women with NIDA among women with anemia (0.73 and 0.72, respectively). The cutoff that optimally distinguished women with NIDA from women with IDA in our cohort was 6.1 µg/L. Maternal IDA, but not NIDA, was associated with significantly lower newborn ferritin (114.4 ng/mL compared with 148.4 µg/L; P = 0.042). Hepcidin performed better than sTfR in identifying pregnant women with NIDA, but its cost may limit its use. Maternal IDA, but not NIDA, is associated with decreased newborn iron stores, emphasizing the need to identify this cause and provide iron therapy. This trial was registered at www.clinicaltrials.gov as NCT00486863.


Percutaneous renal artery revascularization after prolonged ischemia secondary to blunt trauma: pooled cohort analysis.
We aimed to identify factors related to technical and clinical success of percutaneous revascularization for blunt renal arterial trauma. All cases of percutaneous revascularization for blunt renal arterial trauma were searched in the available literature. We included a case of iatrogenic renal artery occlusion at our institution treated by percutaneous stenting 20 hours after injury. A pooled cohort analysis of percutaneous revascularization for blunt renal artery injury was then performed to analyze factors related to technical and clinical success. Clinical failure was defined as development of new hypertension, serum creatinine rise, or significant asymmetry in split renal function. A total of 53 cases have been reported, and 54 cases were analyzed including our case. Median follow-up was 6 months. Technical success was 88.9% and clinical success was 75%. Of 12 treatment failures (25%), 66.7% occurred during the first postprocedure month. Time from injury to revascularization was not a predictor of clinical success (OR=1.00, P = 0.681). Renal artery occlusion was significantly associated with clinical failure (OR=7.50, P = 0.017) and postintervention antiplatelet therapy was significantly associated with treatment success (OR=0.16, P = 0.043). At 37-month follow-up, the stented renal artery in our case remained patent and the patient was normotensive with preserved glomerular filtration rate. Percutaneous revascularization for blunt renal arterial injury resulted in relatively high technical and clinical success. Time-to-revascularization was independent of successful outcomes. Clinical success was significantly associated with a patent renal artery at the time of intervention and with postprocedure antiplatelet therapy.


Safety evaluation and lipid-lowering effects of food-grade biopolymer complexes (ε-polylysine-pectin) in mice fed a high-fat diet.
ε-Polylysine (ε-PL) is a potent cationic antimicrobial, but its application as a food additive is currently limited because it tends to precipitate with anionic species in food matrices. Previous research has shown that the formation of an electrostatic complex between cationic ε-PL and anionic pectin (P) improved the physical stability of ε-PL while maintaining its antimicrobial activity. However, the impact of complexation on the effects of ε-PL on health is currently unknown. A subchronic toxicity study was therefore carried out to determine the safety of ingested ε-PL-P complexes using high-fat diet-fed male and female mice. After a 13-week dietary treatment with P, ε-PL, or ε-PL-P complexes, no significant toxicological effects were observed on the survival, mean body weight, food consumption, and organ weights of the animals, suggesting that the complexes were safe for oral consumption. Interestingly, the ε-PL-P complexes were found to have several beneficial health effects: suppression of high-fat diet-induced elevation of serum aspartate aminotransferase and alanine aminotransferase activities, reduction in serum total triglyceride and cholesterol levels, and an increase in fecal excretion of triglycerides. These effects were much stronger in female mice than in male mice. Moreover, the lipid-lowering effects were observed only for the ε-PL-P complexes but not for ε-PL or P alone at the same doses. Overall, our results demonstrate the oral safety of ε-PL-P complexes and their gender-specific lipid-lowering effects in high-fat diet-fed mice, which provide an important basis for the utilization of ε-PL-P complexes in food systems as functional ingredients.


X gene and precore region mutations in the hepatitis B virus genome in persons positive for antibody to hepatitis B e antigen: comparison between asymptomatic "healthy" carriers and patients with severe chronic active hepatitis.
Hepatitis B virus (HBV) carriers with antibody to hepatitis e antigen comprise asymptomatic carriers (ASCs), who have low replication levels of HBV, and patients with chronic active hepatitis (CAH), who have high levels of viral replication. To investigate whether defects in the X protein might be responsible for this difference in the level of viral replication, nucleotide sequences of X and precore gene regions in serum HBV were analyzed in 19 ASCs and 9 CAH patients. All patients had a point mutation creating a stop codon in the precore region. Seventeen ASCs (87.3%) had identical mutations consisting of 4 noncontiguous 1-bp deletions or an 8-bp deletion, both of which truncate the normal X protein, whereas no CAH patient had an X gene mutation (P < .001). Thus, deletion of the X protein might be responsible for the low levels of viral replication in ASCs.


Treatment of Cognitive Deficits in Genetic Disorders: A Systematic Review of Clinical Trials of Diet and Drug Treatments.
Knowing the underlying etiology of intellectual disability in genetic disorders holds great promise for developing targeted treatments. Although successful preclinical studies and many positive clinical studies have been reported, it is unclear how many purported therapies have become established treatments. The quality of the clinical trials may be an important determinant for achieving clinical impact. To evaluate clinical impact, strengths, and weaknesses of clinical trials of diet or drug treatments to improve cognitive function in patients with a genetic disorder. MEDLINE, EMBASE, PsycINFO, and Cochrane databases were searched from inception date to January 26, 2014, for clinical trials with cognitive outcomes in patients with genetic disorders. Outcome measures of randomized clinical trials (RCTs) were compared between trial registries and reports, and trials were evaluated for the quality of design using the Jadad score and Consolidated Standards of Reporting Trials (CONSORT) criteria. We identified 169 trial reports of 80 treatments for 32 genetic disorders. Seventy-five trials (44.4%) reported potential efficacy, of which only 2 therapies are now established treatments, namely, dietary restriction for phenylketonuria and miglustat for Niemann-Pick disease type C. The median sample size for RCTs was 25 (range, 2-537). Only 30 of 107 RCTs (28.0%) had acceptable Jadad scores exceeding 3. Reporting of key CONSORT items was poor. Reported outcome measures matched preregistered outcome measures in trial registries in only 5 of 107 RCTs (4.7%). The number of trials in the field of cognitive genetic disorders is rapidly growing, but clinical impact has been limited because few drugs have become established treatments and the benefit of most drugs remains unclear. Most trials have small sample sizes and low quality of design. Predefinition of outcome measures, improved trial reporting and design, and international collaboration to increase recruitment are needed to unequivocally determine efficacy of drugs identified in preclinical research.