Aceso: PICO-guided Evidence Summarization on Medical Literature.
Evidence-Based Medicine (EBM) aims to apply the best available evidence gained from scientific methods to clinical decision making. A generally accepted criterion to formulate evidence is to use the PICO framework, where PICO stands for Problem/Population, Intervention, Comparison, and Outcome. Automatic extraction of PICO-related sentences from medical literature is crucial to the success of many EBM applications. In this work, we present our Aceso system, which automatically generates PICO-based evidence summaries from medical literature. In Aceso 1, we adopt an active learning paradigm, which helps to minimize the cost of manual labeling and to optimize the quality of summarization with limited labeled data. An UMLS2Vec model is proposed to learn a vector representation of medical concepts in UMLS 2, and we fuse the embedding of medical knowledge with textual features in summarization. The evaluation shows that our approach is better on identifying PICO sentences against state-of-the-art studies and outperforms baseline methods on producing high-quality evidence summaries.


Phase II study of carboplatin in children with progressive low-grade gliomas.
To assess the rate of tumor response and activity of carboplatin in stabilizing the growth of progressive low-grade gliomas. Eligible patients received carboplatin 560 mg/m(2) intravenously every 4 weeks for 1 year after maximum tumor response or until disease progression or unacceptable toxicity. Between October 1993 and October 2000, 81 children (median age, 79 months; range, 6 to 204) were enrolled onto this study. Patients received a median of 11 cycles of carboplatin (range, one to 29). Median follow-up from the time of enrollment was 55 months (range, 10 to 93). The overall objective response (complete response [CR] + partial response [PR] + minor response [MR]) and disease stabilization (CR + PR + stable disease + MR) rates to carboplatin treatment were 28% (95% confidence interval [CI], 18% to 38%) and 85% (95% CI, 74% to 93%), respectively. Eleven and 14 patients suffered progressive disease on study and after stopping therapy, respectively. Toxicity was predominantly myelosuppression and included grade 3/4 neutropenia in 56 patients and grade 3/4 thrombocytopenia in 40 patients. The 3-year failure-free survival (FFS) and overall survival (OS) for all patients were 64% (95% CI, 54% to 76%) and 84% (95% CI, 76% to 93%), respectively. Patients with diencephalic tumors had inferior FFS and OS compared with those with tumor at other sites (38% v 74% for FFS, P =.011; 54% v 91% for OS, P =.004). Neurofibromatosis type 1 patients with progressive low-grade glioma had a significantly better OS (95% v 80%; P =.052). Carboplatin, in the schedule used in this study, produced disease stabilization or improvement in a majority of children with progressive low-grade glioma, with manageable toxicity. Improved treatment strategies are particularly required for patients with diencephalic tumors.


Stigma and discrimination limit access to mental health care.
This editorial provides an overview of how far access to mental health care is limited by perceptions of stigma and anticipated discrimination. Globally over 70% of young people and adults with mental illness receive no treatment from healthcare staff. The rates of non-treatment are far higher in low income countries. Evidence from some descriptive studies and epidemiological surveys suggest that potent factors increasing the likelihood of treatment avoidance, or long delays before presenting for care include: (i) lack of knowledge about the features and treatability of mental illnesses; (ii) ignorance about how to access assessment and treatment; (iii) prejudice against people who have mental illness, and (iv) expectations of discrimination against people who have a diagnosis of mental illness. The associations between low rates of help seeking, and stigma and discrimination are as yet poorly understood and require more careful characterisation and analysis, providing the platform for more effective action to ensure that a greater proportion of people with mental illness are effectively treated in future.


Different cytokine production and Toll-like receptor expression induced by heat-killed invasive and carrier strains of Neisseria meningitidis.
Neisseria meningitidis may cause severe invasive disease. The carriage state of the pathogen is common, and the reasons underlying why the infection becomes invasive are not fully understood. The aim of this study was to compare the differences between invasive and carrier strains in the activation of innate immunity. The monocyte expression of TLR2, TLR4, CD14, and HLA-DR, cytokine production, and the granulocyte oxidative burst were analyzed after in vitro stimulation by heat-killed invasive (n = 14) and carrier (n = 9) strains of N. meningitidis. The expression of the cell surface markers in monocytes, the oxidative burst, and cytokine concentrations were measured using flow cytometry. Carrier strains stimulated a higher production of inflammatory cytokines and oxidative burst in granulocytes than invasive strains (all p < 0.001), whereas invasive strains significantly up-regulated TLR2, TLR4 (p < 0.001), and CD14 (p < 0.01) expression on monocytes. Conversely, the monocyte expression of HLA-DR was higher after the stimulation by carrier strains (p < 0.05) in comparison to invasive strains. The LPS inhibitor polymyxin B abolished the differences between the strains. Our findings indicate different immunostimulatory potencies of invasive strains of N. meningitidis compared with carrier strains.


Biological invasions, climate change and genomics.
The rate of biological invasions is expected to increase as the effects of climate change on biological communities become widespread. Climate change enhances habitat disturbance which facilitates the establishment of invasive species, which in turn provides opportunities for hybridization and introgression. These effects influence local biodiversity that can be tracked through genetic and genomic approaches. Metabarcoding and metagenomic approaches provide a way of monitoring some types of communities under climate change for the appearance of invasives. Introgression and hybridization can be followed by the analysis of entire genomes so that rapidly changing areas of the genome are identified and instances of genetic pollution monitored. Genomic markers enable accurate tracking of invasive species' geographic origin well beyond what was previously possible. New genomic tools are promoting fresh insights into classic questions about invading organisms under climate change, such as the role of genetic variation, local adaptation and climate pre-adaptation in successful invasions. These tools are providing managers with often more effective means to identify potential threats, improve surveillance and assess impacts on communities. We provide a framework for the application of genomic techniques within a management context and also indicate some important limitations in what can be achieved.


Adolescents' self-perceptions of their strengths.
A sample of 960 adolescents drawn from the general population was asked to complete a 22-item scale relating to their self-perceived strengths. The mean score for the 492 boys was 14.9 and that for the 486 girls was 14.4; the difference was not statistically significant. There were, nevertheless, differences for some of the items. In particular, more boys saw themselves as good at sport, confident, popular, having lots of hobbies, and attractive, while more girls saw themselves as reliable, kind, independent, and affectionate. Regression analysis suggested that boys' strengths depended upon parent, peer and school attachment, part-time work, and the number of physical activities with which they were involved. Girls' strengths were best predicted by parent attachment and the number of physical activities with which they were involved.


End-diastolic segmentation of intravascular ultrasound images enables more reproducible volumetric analysis of atheroma burden.
Volumetric intravascular ultrasound (IVUS) analysis is currently performed at a fixed frame interval, neglecting the cyclic changes in vessel dimensions occurring during the cardiac cycle that can affect the reproducibility of the results. Analysis of end-diastolic (ED) IVUS frames has been proposed to overcome this limitation. However, at present, there is lack of data to support its superiority over conventional IVUS. The present study aims to compare the reproducibility of IVUS volumetric analysis performed at a fixed frame interval and at the ED frames, identified retrospectively using a novel deep-learning methodology. IVUS data acquired from 97 vessels were included in the present study; each vessel was segmented at 1 mm interval (conventional approach) and at ED frame twice by an expert analyst. Reproducibility was tested for the following metrics; normalized lumen, vessel and total atheroma volume (TAV), and percent atheroma volume (PAV). The mean length of the analyzed segments was 50.0 ± 24.1 mm. ED analysis was more reproducible than the conventional analysis for the normalized lumen (mean difference: 0.76 ± 4.03 mm3 vs. 1.72 ± 11.37 mm3 ; p for the variance of differences ratio < 0.001), vessel (0.30 ± 1.79 mm3 vs. -0.47 ± 10.26 mm3 ; p < 0.001), TAV (-0.46 ± 4.03 mm3 vs. -2.19 ± 14.39 mm3 ; p < 0.001) and PAV (-0.12 ± 0.59% vs. -0.34 ± 1.34%; p < 0.001). Results were similar when the analysis focused on the 10 mm most diseased segment. The superiority of the ED approach was due to a more reproducible detection of the segment of interest and to the fact that it was not susceptible to the longitudinal motion of the IVUS probe and the cyclic changes in vessel dimensions during the cardiac cycle. ED IVUS segmentation enables more reproducible volumetric analysis and quantification of TAV and PAV that are established end points in longitudinal studies assessing the efficacy of novel pharmacotherapies. Therefore, it should be preferred over conventional IVUS analysis as its higher reproducibility is expected to have an impact on the sample size calculation for the primary end point.


Highly biocidal poly(vinyl alcohol)-hydantoin/starch hybrid gels: A "Trojan Horse" for Bacillus subtilis.
Poly (vinyl alcohol) (PVA) cryogels can be functionalized with n-Halamines to confer biocidal features useful for their application as wound-dressing tools. Their efficacy can be boosted by stably embedding a polymeric bacterial food source (e.g., starch) in the gel matrix. The bioavailability of the food source lures bacteria inside the gel network via chemotactic mechanisms, promoting their contact with the biocidal functionalities and their consequent inactivation. The synthesis of a novel hydantoin-functionalized PVA (H-PVA-hyd) is proposed. The newly synthesized H-PVA-hyd polymer was introduced in the formulation of H-PVA-based cryogels. To promote the cryogelation of the systems we exploited phase-separation mechanisms employing either a PVA carrying residual acetate groups (L-PVA) or starch as phase-segregating components. The permanence of the biocidal functionality after swelling was investigated via proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FT-IR) microscopy. The activated H-PVA-hyd cryogels have been tested against bacteria with amylolytic activity (Bacillus subtilis) and the outcomes were analyzed by direct observation via confocal laser scanning microscopy (CLSM). The cryogels containing starch resulted in being the most effective (up to 90% bacterial killing), despite carrying a lower amount of hydantoin groups than their starch-free counterparts, suggesting that their improved efficacy relies on a "Trojan Horse" type of mechanism.


Probiotic Supplementation Decreases Chemotherapy-induced Gastrointestinal Side Effects in Patients With Acute Leukemia.
In children with acute leukemia, gut microbiota is modified secondary to chemotherapy administration, leading to gastrointestinal side effects. Probiotics are microorganisms that can restore gut microbiota and may help alleviate gastrointestinal symptoms. The aim of this pilot study was to assess the effects of probiotic supplementation on chemotherapy-induced gastrointestinal side effects in children with acute leukemia (AL). In this randomized pilot study, patients under 17 years of age diagnosed with AL who were on remission induction or remission reinduction chemotherapy were randomly assigned to receive probiotic supplementation (a concentration of 5×109 CFU per sachet was administered at a standard dose twice daily, by mouth) or no probiotic supplementation. The primary endpoint was the prevalence of gastrointestinal side effects. Vomiting, nausea, flatulence, dyspepsia, diarrhea, constipation, abdominal pain, and abdominal distention were assessed in both groups. Gastrointestinal side effects were less prevalent in the probiotic group, and 3 of the 8 gastrointestinal side effects (nausea, vomiting, and abdominal distension) significantly decreased in the probiotic group (P<0.05). We found for diarrhea a relative risk of 0.5 (95% confidence interval [CI], 0.2-1.2; P=0.04); for nausea an RR of 0.5 (95% CI, 0.4-0.8; P=0.04) and for vomiting an RR of 0.4 (95% CI, 0.2-0.9; P=0.04). Daily supplementation with Lactobacillus rhamnosus reduced chemotherapy-induced gastrointestinal side effects in children with AL.


Amyloid precursor-like protein 2 suppresses irradiation-induced apoptosis in Ewing sarcoma cells and is elevated in immune-evasive Ewing sarcoma cells.
Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G 1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.


Predictors of violence in young tourists: a comparative study of British, German and Spanish holidaymakers.
International youth holiday resorts feature many of the key risk factors for violence, including large numbers of bars and nightclubs and high levels of substance use. However, little information currently exists on the extent of violence amongst holidaymakers or factors that increase risks of involvement in fights on holiday. A cross-sectional comparative survey of 3003 British, German and Spanish holidaymakers aged 16-35 years, undertaken in the departure areas of Ibiza and Majorca (Spain) airports. Nightlife was the most common reason for destination choice in both locations. Overall, more than half of participants reported drinking to drunkenness at least 2 days per week during their holiday (59.3% Majorca, 58.0% Ibiza; significantly lower in Spanish participants in both locations). Levels of illicit drug use were highest in Ibiza and in British and Spanish holidaymakers. Levels of violence were highest in Majorca, where 6.4% of participants reported involvement in a fight, compared with 2.8% in Ibiza. However, after controlling for confounding factors, holiday destination was not a significant predictor of violence. Predictors of fighting were being male, young, British, frequent drunkenness and use of cannabis or cocaine during the holiday. Use of ecstasy on holiday was associated with not being involved in violence. High levels of substance use contribute to violence being a relatively common feature of young people's visits to international holiday resorts. To protect the health and well-being of holidaymakers and local populations in popular resorts, violence and substance use prevention must adapt to an increasingly globalized nightlife.


Parkinson's disease and the gastrointestinal microbiome.
Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.


Nanoparticle-based cerebral drug-delivery systems and antiangiogenic approach in gliomas treatment.
The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.


Rebound thymic hyperplasia detected by 18F-FDG PET/CT after radioactive iodine ablation therapy for thyroid cancer.
Rebound thymic hyperplasia (RTHP) is not an uncommon finding after radiation or chemotherapy in patients with various malignancies. However, there are limited case reports of this phenomenon after radioactive iodine ablation therapy (RIAT) in differentiated thyroid cancer (DTC). The goal of this study was to evaluate the incidence, patterns, and factors affecting RTHP after RIAT using (18)F-FDG PET/CT. The study design was a retrospective review of 2550 patients (568 men, 1982 women; age 13-79 years) who underwent FDG PET/CT imaging after total thyroidectomy and RIAT from June 2009 through June 2012. Patients were divided into four age-related subgroups. Overall incidence, age-related incidences, and sex distribution were evaluated in patients with thymic FDG uptake on PET/CT (RTHP+). The correlation between incidence of RTHP and age was assessed using the Cochran-Armitage trend test. The Wilcoxon rank-sum test and multiple regression were applied to investigate the effect of applied dose of radioactive iodine (RAI) and age on the incidence of RTHP. Correlations of standardized uptake value (SUV) and thymic volume with age and morphologic type were also evaluated. Overall incidence of RTHP after RIAT was 1.49%, and all of the RTHP+ patients except one were female. The Cochran-Armitage trend test revealed significantly decreased incidence from the second to fifth decade (8.84%, 1.74%, 0.98%, and 0.39% respectively; p<0.001). In each age-related subgroup, the RAI dose was significantly higher in the RTHP+ than RTHP- group (p<0.001), while there was no difference in RAI dose in RTHP+ patients among age-related subgroups (p=0.838). SUVmean and SUVmax of RTHP revealed no meaningful correlation with RAI dose or age. There were no differences among morphologic patterns of RTHP in age distribution and ablation dose. RTHP after RIAT showed a strong female predominance, despite the higher administration dose of RAI in male patients. Although the decreased incidence of RTHP after RIAT with age is similar to the pattern of RTHP induced by other causes, the fact that older patients, even sixth decade patients, can present with RTHP after RIAT is noteworthy in the management of DTC.


The Reduction of Carbonyl Compounds with Dicyclopentylzinc: A New Example of Asymmetric Amplifying Autocatalysis.
A previously unknown reduction of carbonyl compounds with dicyclopentylzinc is reported. Aldehydes react in mild conditions yielding corresponding primary alcohols and cyclopentene. Although cyclohexanone and acetophenone are inert to dicyclopentylzinc, a variety of heterocyclic ketones reacted readily, yielding reasonable to high yields of corresponding secondary alcohols. When the reaction was catalyzed with (-)-(1R,2S)-ephedrine, 3-acetylpyridine (10) resulted in a high yield of (S)-1-(pyridin-3-yl)ethanol (19) with >99% ee. 5-Acetyl-2-bromopyridine (11) also provided the corresponding optically active alcohol 20, albeit with a much lower optical yield. When 10% of 19 with 92% ee was used as an autocatalyst, 55% yield of the same compound was obtained, with 95% ee and 96% ee in two independent experiments. A three-stage reaction sequence starting from "no chirality" reaction yielded 19 with 6% ee. Thus, amplifying autocatalysis was detected in the reaction of ketone 10 with dicylopentylzinc.


Palladium alters cigarette smoke toxicological profile, but accumulates in the lungs of rats during inhalation exposure.
The use of a palladium (Pd) catalyst has been proposed to promote combustion of tobacco, thereby reducing concentrations of certain toxic components of smoke, including polyaromatic hydrocarbons (PAHs). In the present work, toxicological comparisons were made using experimental cigarettes containing no added Pd, against otherwise similar cigarettes containing three different amounts of Pd as potassium tetrachloropalladate added to the tobacco. A full analysis of smoke chemistry was made, along with a subchronic 90-day inhalation study with mainstream smoke (rats exposed to 150 mg/m(3) of total particulate matter, 6 h/day for 90 consecutive days) and in vitro evaluations of Salmonella mutagenicity, cytotoxicity, and in vivo clastogenicity (micronucleus). Addition of Pd to the tobacco resulted in 20-30% reductions in the concentrations of 6 PAHs and 2 aromatic amines, but it also resulted in transfer of Pd to smoke and in 10-50% increases in concentrations of several tobacco-specific nitrosamines. Mutagenicity was reduced by about 50% in 2 of 5 strains of Salmonella (with S9 only), while the cytotoxicity and micronucleus assays showed no changes. Histopathology responses were similar across the four smoke inhalation groups. Smoke Cd was reduced by 40-70% in the smoke, leading to lower lung concentrations; however, the presence of Pd in smoke led to accumulation of Pd in the lungs increasing in both a dose-and an exposure-related manner. While catalysts such as Pd addition may alter the typical chemical/toxicological profile of smoke, a concern arises regarding the "risk-benefit" of the addition of such chemically active materials as Pd to cigarette tobacco, leading to potential pulmonary accumulation with unknown consequences.


Sonography of the posterior fossa.
An anatomic correlation of sonographic images and anatomy in cadavers was undertaken to establish a foundation for sonographically assisted recognition of structures and their relation to pathology. Such information would be useful for orientation purposes during surgery, for biopsies, and for follow-up studies. A specially designed technique of placing metal markers with sonographically guided needles was used. Anatomic cuts and dissections were subsequently performed. Sonographic clinical material obtained during surgery and in postoperative controls was analyzed based on this experimental work and previous investigations in this area. Detailed anatomy of the posterior fossa can be demonstrated with sonography.


Molecular characterization and interstrain variability of pHPS1, a plasmid isolated from the Sydney strain (SS1) of Helicobacter pylori.
The 5846-bp circular plasmid pHPS1 of Helicobacter pylori Sydney strain, SS1, was cloned, sequenced, and structurally characterized. The SS1 strain is widely used in animal studies of H. pylori infection. The sequence of pHPS1 revealed three open reading frames (ORFs), all of which are transcribed. Two ORFs encode putative plasmid replication proteins, RepA and RepB, similar to replicases resident on theta plasmids. In contrast, the function of ORF2 remains cryptic due to the absence of sequence similarity with any known protein in sequence databases. In addition, species specificity of these three coding regions was shown using DNA dot blot hybridization in 57 diverse clinical H. pylori isolates and 32 Helicobacter and Campylobacter strains. RepA appears to be the predominant plasmid replication protein of H. pylori and the deduced amino acid sequence was highly conserved (76-96%) in 8 H. pylori isolates, including SS1. RepB was detected in 3 H. pylori isolates examined in this study, 2 of which possess only the repB gene. Analysis of the protein sequences of these two replicases, together with previously characterized H. pylori plasmid replication proteins, supports the formation of a distinct class of H. pylori plasmid proteins. Moreover, comprehensive analysis of the whole genome sequence of H. pylori strain 26695, pHPS1, and other H. pylori plasmid sequences that are available revealed interesting insights as to the occurrence of plasmid-mediated recombination within H. pylori. Common regions between plasmids and chromosome sequences of H. pylori were identified in this study which could only have arisen by genetic recombination, thus providing the first line of evidence, albeit indirectly, of the contribution of H. pylori plasmids in generating an extensive genetic heterogeneity characteristic of this important gastroduodenal pathogen.


Design of a Scaffold Parameter Selection System with Additive Manufacturing for a Biomedical Cell Culture.
Open-source 3D printers mean objects can be quickly and efficiently produced. However, design and fabrication parameters need to be optimized to set up the correct printing procedure; a procedure in which the characteristics of the printing materials selected for use can also influence the process. This work focuses on optimizing the printing process of the open-source 3D extruder machine RepRap, which is used to manufacture poly(ε-caprolactone) (PCL) scaffolds for cell culture applications. PCL is a biocompatible polymer that is free of toxic dye and has been used to fabricate scaffolds, i.e., solid structures suitable for 3D cancer cell cultures. Scaffold cell culture has been described as enhancing cancer stem cell (CSC) populations related to tumor chemoresistance and/or their recurrence after chemotherapy. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. Design and fabrication parameters were first determined with SolidWorks and Slic3r software and subsequently optimized following a novel sequential flowchart. In the flowchart described here, the parameters were gradually optimized step by step, by taking several measurable variables of the resulting scaffolds into consideration to guarantee high-quality printing. Three deposition angles (45°, 60° and 90°) were fabricated and tested. MCF-7 breast carcinoma cells and NIH/3T3 murine fibroblasts were used to assess scaffold adequacy for 3D cell cultures. The 60° scaffolds were found to be suitable for the purpose. Therefore, PCL scaffolds fabricated via the flowchart optimization with a RepRap 3D printer could be used for 3D cell cultures and may boost CSCs to study new therapeutic treatments for this malignant population. Moreover, the flowchart defined here could represent a standard procedure for non-engineers (i.e., mainly physicians) when manufacturing new culture systems is required.


MLRs in children are consistently present during wakefulness, stage 1, and REM sleep.
Auditory middle latency responses (MLRs) were recorded continuously from normal children, ages 4 to 9 years, during natural sleep. Concurrently obtained EEG recordings were used to determine stages of sleep. Wave Pa was consistently present during wakefulness, alpha, stage 1, and REM sleep. Wave Pa detectability was poor during stage 4 sleep. The probability of obtaining wave Pa during stage 4 increased systematically with age. During stages 2 and 3, Pa detectability was variable. The inconsistency of MLRs in children currently limits their clinical use. These data indicate that the occurrence of MLRs in children is not haphazard, and that the MLR in children can be reliably obtained during certain states of arousal. A straightforward clinical application of these findings is that efforts to obtain MLRs be concentrated during periods favorable for recording the response. We suggest practical strategies for detecting optimal sleep stages.


Detection of Oxacillin Resistance in Staphylococcus aureus Isolated from the Neonatal and Pediatric Units of a Brazilian Teaching Hospital.
To determine, by phenotypic and genotypic methods, oxacillin susceptibility in Staphylococcus aureus strains isolated from pediatric and neonatal intensive care unit patients seen at the University Hospital of the Botucatu School of Medicine. A total of 100 S. aureus strains isolated from the following materials were studied: 25 blood cultures, 21 secretions, 12 catheters, 3 cannulae and one chest drain from 62 patients in the neonatal unit, and 36 blood cultures, one pleural fluid sample and one peritoneal fluid sample from 38 patients in the pediatric unit. Resistance of the S. aureus isolates to oxacillin was evaluated by the disk diffusion method with oxacillin (1 μg) and cefoxitin (30 μg), agar screening test using Mueller-Hinton agar supplemented with 6 μg/ml oxacillin and 4% NaCl, and detection of the mecA gene by PCR. In addition, the isolates were tested for β-lactamase production using disks impregnated with Nitrocefin and hyperproduction of β-lactamase using amoxicillin (20 μg) and clavulanic acid (10 μg) disks. Among the 100 S. aureus strains included in the study, 18.0% were resistant to oxacillin, with 16.1% MRSA being detected in the neonatal unit and 21.0% in the pediatric unit. The oxacillin (1 μg) and cefoxitin (30 μg) disk diffusion methods presented 94.4% and 100% sensitivity, respectively, and 98.8% specificity. The screening test showed 100% sensitivity and 98.8% specificity. All isolates produced β-lactamase and one of these strains was considered to be a hyperproducer. The 30 μg cefoxitin disk diffusion method presented the best result when compared to the 1 μg oxacillin disk. The sensitivity of the agar screening test was similar to that of the cefoxitin disk diffusion method and higher than that of the oxacillin disk diffusion method. We observed variations in the percentage of oxacillin-resistant isolates during the study period, with a decline over the last years which might be related to improved nosocomial infection control and the rational use of antibiotics.


Serological Follow-Up Study Indicates High Seasonal Coronavirus Infection and Reinfection Rates in Early Childhood.
Seasonal human coronaviruses (HCoVs) cause respiratory infections, especially in children. Currently, the knowledge on early childhood seasonal coronavirus infections and the duration of antibody levels following the first infections is limited. Here we analyzed serological follow-up samples to estimate the rate of primary infection and reinfection(s) caused by seasonal coronaviruses in early childhood. Serum specimens were collected from 140 children at ages of 13, 24, and 36 months (1, 2, and 3 years), and IgG antibody levels against recombinant HCoV nucleoproteins (N) were measured by enzyme immunoassay (EIA). Altogether, 84% (118/140) of the children were seropositive for at least one seasonal coronavirus N by the age of 3 years. Cumulative seroprevalences for HCoVs 229E, HKU1, NL63, and OC43 increased by age, and they were 45%, 27%, 70%, and 44%, respectively, at the age of 3 years. Increased antibody levels between yearly samples indicated reinfections by 229E, NL63, and OC43 viruses in 20-48% of previously seropositive children by the age of 3 years. Antibody levels declined 54-73% or 31-77% during the year after seropositivity in children initially seropositive at 1 or 2 years of age, respectively, in case there was no reinfection. The correlation of 229E and NL63, and OC43 and HKU1 EIA results, suggested potential cross-reactivity between the N specific antibodies inside the coronavirus genera. The data shows that seasonal coronavirus infections and reinfections are common in early childhood and the antibody levels decline relatively rapidly. IMPORTANCE The rapid spread of COVID-19 requires better knowledge on the rate of coronavirus infections and coronavirus specific antibody responses in different population groups. In this work we analyzed changes in seasonal human coronavirus specific antibodies in young children participating in a prospective 3-year serological follow-up study. We show that based on seropositivity and changes in serum coronavirus antibody levels, coronavirus infections and reinfections are common in early childhood and the antibodies elicited by the infection decline relatively rapidly. These observations provide further information on the characteristics of humoral immune responses of coronavirus infections in children.


A carbon price floor in the reformed EU ETS: Design matters!
Despite the reform of the European Emissions Trading System (EU ETS), discussions about complementing it with a carbon price floor (CPF) are ongoing. This paper analyzes the effect of a European CPF in the reformed EU ETS using a Hotelling model of the EU ETS, amended by the market stability reserve (MSR), and the cancellation mechanism. Two CPF designs are compared: (1) a buyback program and (2) a top-up tax. The buyback program sets a minimum price for the allowances from the implementation year onwards. After the announcement, firms anticipate the CPF, which immediately increases the carbon price to the discounted CPF level. Therefore, firms emit less and bank more allowances, leading to more intake into the MSR, and more cancellation of allowances. The top-up tax imposes a tax on emissions, which enhances the market price of allowances to the CPF level from the implementation year onwards. Firms increase their short-run emissions in anticipation of the upcoming tax. Only after the implementation year firms start to lower their emissions. Thus, the effect on aggregate cancellation is ambiguous. Despite being equivalent in a static setting, the design choice for the CPF matters in a dynamic context, such as the EU ETS.


Recent advances in the field of renal potassium excretion: what can we learn from potassium channels?
Potassium channels in the apical and basolateral membranes of tubule cells serve several important functions. They contribute to the generation of the cell-negative potential, mediate volume reductions following cell swelling and play a key role in secretion of potassium in both the thick ascending limb of Henle's loop and principal tubule cells of the initial and cortical collecting tubules. Secretion of potassium occurs via a well-defined class of potassium channels distinguished by their low single channel conductance, mild inward rectification, high sensitivity to inhibition by low pH, millimolar concentrations of ATP, arachidonic acid and PKC, and stimulation by vasopressin and pretreatment with a high potassium diet. Genes encoding several isoforms of this channel have been cloned and the proteins located to the apical membranes of cells lining the thick ascending limb of Henle's loop and the collecting tubules, and progress made concerning their structure-function relationship.


Facilitative glucose transporter expression in human cancer tissue.
Glucose utilisation by cancer cells is greatly enhanced when compared with that by normal tissue. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate. Facilitative hexose uptake is achieved by five transmembrane transporters, termed glut1-5, which are protein products of their respective GLUT genes. Glut types differ in their kinetics, which are tailored to the requirements of the cell type they serve, although more than one glut may be expressed by a particular cell type. Herein are reviewed the results from approximately 30 studies which examined glut expression in human cancer tissue. These studies measured GLUT messenger RNA (mRNA) either using the reverse-transcriptase polymerase chain reaction or by Northern blot analysis, or detected glut proteins using the appropriate antibodies. Tumour tissue is frequently associated with the abnormal and/or over-expression of gluts, especially glut1. Some tumour cells express specific GLUT mRNA but not the respective protein. Some studies have reported associations between glut expression and proliferative indices, whilst others suggest that glut may be of prognostic significance, especially in lung cancer.


Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.
Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo. Furthermore, borneol markedly increased the number of autophagosomes in the glioma cells, which coincided with increased expression of beclin-1 and LC3. And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E. In addition, silencing mTORC1 and eIF4E upregulated Beclin-1 and LC3 and decreased the expression of HIF-1α, thereby inhibiting tumor cell proliferation. Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.


Spinal infusion of N-methyl-D-aspartate antagonist MK801 induces hypersensitivity to the spinal alpha-2 agonist ST91 in the rat.
MK801 (MK), an N-methyl-D-aspartate (NMDA) receptor antagonist, attenuates tolerance to spinal opioids. Whether this applies to other G-protein-coupled receptor systems is unknown. This study examines the effects of continuous spinal MK on tolerance to the antinociceptive effect of continuous spinal infusion of the alpha-2 agonist ST91 (ST). Intrathecal (i.t.) infusion pumps were implanted in rats which delivered for 7 days: saline (1 microl/h); ST (40 nmol/microl/h); MK (10 nmol/microl/h) + ST (40 nmol/microl/h); or MK (10 nmol/microl/h). Antinociception was measured daily on the hot plate. On day 8, groups received i.t. boluses of ST to generate dose-response curves. A separate ST-infused group received MK (10 nmol i.t.) on day 7. Each group received ST (40 nmol i.t.) 7 days after discontinuation of infusion. Co-infusion of MK with ST resulted in attenuation of the right shift in dose response seen in ST-infused rats and a small preservation of effect on daily testing. However, MK-infused rats showed a significant left shift in ST dose response. Acutely administered, MK did not restore ST sensitivity. One week after cessation of infusion, ST and ST + MK groups showed shorter duration of effect after i.t. ST bolus than controls. In conclusion, chronic spinal MK partially attenuates loss of sensitivity to chronic spinal ST. This supports the hypothesis that opioid- and adrenoceptor-induced tolerances are similarly modulated by the NMDA receptor. However, the increased sensitivity induced by MK alone suggests that NMDA receptor antagonism may not prevent the development of tolerance itself but may alter the expression of tolerance by inducing sensitivity via other alterations in cellular function.


Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk assessment.
The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.


[Effect of phosphorylation of myosin light chains on the interaction of myosin minifilaments with F-actin].
The effect of phosphorylation of light chains-2 (LC2) of rabbit skeletal muscle myosin on the interaction of myosin minifilaments with F-actin as well as on the actin-stimulated Mg2+-ATPase of minifilaments was studied. It was shown that in the absence of KCl the degree of F-actin-induced stimulation of myosin minifilament Mg2+-ATPase with phosphorylated LC2 exceeds 2-4-fold that with unphosphorylated LC2. Phosphorylation of LC2 considerably increases the rate of actin-stimulated Mg2+-ATPase reaction of myosin minifilaments but exerts only a very weak influence on the affinity of minifilaments for F-actin. After addition of KCl the differences in the actin-stimulated Mg2+-ATPase activity disappear in a great degree; in the presence of 50 mM KCl they do not exceed 50%. It was assumed that the observed specific influence of LC2 phosphorylation on the kinetic parameters of actin-stimulated Mg2+-ATPase reaction of myosin minifilaments is due to unique properties of the minifilaments (e.g., their ability to ordered self-assembly as a result of interaction between the heads of myosin molecules) which reflect their structural peculiarities.


legless insertional mutation: morphological, molecular, and genetic characterization.
Limb morphogenesis is an excellent model system to study pattern formation during vertebrate development. The legless (lgl) insertional mutation can serve as a tool to analyze specific events in limb development at the embryologic, genetic, and molecular levels. Hemizygous mice of this transgenic line are phenotypically normal, but homozygous mutants are inviable and exhibit limb, brain, and craniofacial malformations, as well as situs inversus. By morphological analysis of mutant hindlimb buds we show absence of a normal apical ectodermal ridge, a structure required for limb bud outgrowth, and an unusually high degree of mesenchymal and ectodermal cell death. Mutant embryos are extremely sensitive to retinoic acid, a known teratogen with a proposed role in limb development. The hindlimb malformations in legless mutants are less severe when bred into the BALB/c background, suggesting the involvement of other strain-specific genes. Molecular analysis of the disrupted region indicates two tightly linked insertion sites. Sequences flanking the transgene insertions have been cloned and mapped to chromosome 12, near the iv (situs inversus viscerum) locus. Consistent with this, complementation tests confirm allelism of lgl and iv and suggest that the transgene insertion may have disrupted more than one gene. Phylogenetically conserved sequences flanking the transgene insertions were identified and used to isolate candidate lgl and iv cDNAs.


Drivers of individual niche variation in coexisting species.
Although neglected by classic niche theory, individual variation is now recognized as a prevalent phenomenon in nature with evolutionary and ecological relevance. Recent theory suggests that differences in individual variation across competitors can affect species coexistence and community patterns. However, the degree of individual variation is flexible across wild populations and we still know little about the ecological drivers of this variation across populations of single species and, especially, across coexisting species. Here, we aimed to (a) elucidate the major drivers of individual niche variation in natural communities and (b) to determine how consistent this variation is across coexisting species and communities. We analysed natural patterns of individual-level niche variation in four species of coexisting generalist frogs across a wide range of tropical communities. Specifically, we used gut contents and stable isotopes (δ13 C and δ15 N) from frog species and their prey to quantify individual niche specialization. Then, we combined data on local community structure, availability of prey, phylogenetic relationships and predator-prey size models to test how this variation is related to four ecological factors which are predicted to be key drivers of individual specialization: intraspecific competition, interspecific competition, ecological opportunity (i.e., diversity of resources) and predation. We found that the degree of individual trophic specialization varied by up to ninefold across populations within the same species. This sizable variation in trophic specialization across populations was at least partially explained by gradients of density of competitors (both conspecifics and heterospecifics) and intraguild predation. However, the specific relationships between individual specialization and these ecological gradients were strongly species-specific. As consequences, the identity of the species with more individual variation changed among sites and there was typically no spatial correlation in the degree of individual specialization across coexisting species. Our results show that individual niche specialization within and across species can be strongly context-dependent and that hierarchies of individual variation among coexisting species are not necessarily consistent across communities. Recent theory suggests that this pattern could lead to concurrent changes in competitive interactions across sites and thereby could play a key role in species coexistence at the landscape level. Our results suggest that individual variation across and within coexisting species has the potential to affect not only species coexistence at local communities, but also regional diversity patterns.


Molecular Signature of 18F-FDG PET Biomarkers in Newly Diagnosed Multiple Myeloma Patients: A Genome-Wide Transcriptome Analysis from the CASSIOPET Study.
The International Myeloma Working Group recently fully incorporated 18F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these 18F-FDG PET biomarkers could be fully endorsed as risk classifiers by the hematologist community, further characterization of underlying molecular aspects was necessary. Methods: Reported prognostic biomarkers (18F-FDG avidity, SUVmax, number of focal lesions, presence of paramedullary disease [PMD] or extramedullary disease) were extracted from 18F-FDG PET imaging at baseline in a group of 139 patients from CASSIOPET, a companion study of the CASSIOPEIA cohort (ClinicalTrials.gov identifier NCT02541383). Transcriptomic analyses using RNA sequencing were realized on sorted bone marrow plasma cells from the same patients. An association with a high-risk gene expression signature (IFM15), molecular classification, progression-free survival, a stringent clinical response, and minimal residual disease negativity were explored. Results:18F-FDG PET results were positive in 79.4% of patients; 14% and 11% of them had PMD and extramedullary disease, respectively. Negative 18F-FDG PET results were associated with lower levels of expression of hexokinase 2 (HK2) (fold change, 2.1; adjusted P = 0.04) and showed enrichment for a subgroup of patients with a low level of bone disease. Positive 18F-FDG PET results displayed 2 distinct signatures: either high levels of expression of proliferation genes or high levels of expression of GLUT5 and lymphocyte antigens. PMD and IFM15 were independently associated with a lower level of progression-free survival, and the presence of both biomarkers defined a group of "double-positive" patients at very high risk of progression. PMD and IFM15 were related neither to minimal residual disease assessment nor to a stringent clinical response. Conclusion: Our study confirmed and extended the association between imaging biomarkers and transcriptomic programs in MM. The combined prognostic value of PMD and a high-risk IFM15 signature may help define MM patients with a very high risk of progression.


Capillibacterium thermochitinicola gen. nov., sp. nov., a novel anaerobic thermophilic chitinolytic bacterium from compost.
A novel Gram-negative, spore forming, obligately anaerobic, thermophilic, chitin-degrading bacterium, designated UUS1-1T, was isolated from compost on Ishigaki Island, Japan by enrichment culturing using chitin powder as the carbon source. The strain has unique, long, hair-like rod morphological features and exhibits strong degradation activity toward crystalline chitin under thermophilic conditions. Growth of the novel strain was observed at 45-65 °C (optimum, 55 °C) and pH 6.5-7.5 (optimum, pH 7.0). In addition to chitin, the strain utilized several other carbon sources, including N-acetylglucosamine, glucose, galactose, mannose, maltose, cellobiose, fructose and sucrose. The end products of chitin degradation were acetate, lactate, H2 and CO2. Phylogenetic tree analysis based on 16S rRNA gene sequences revealed a clear affiliation of the proposed bacterium to the phylum Firmicutes; the most closely related species were Hydrogenispora ethanolica LX-BT and Desulfotomaculum thermobenzoicum DSM6193T with similarities of 90.4 and 87.8 %, respectively. The G+C content of the genomic DNA was 52.1 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between the genomes of UUS1-1T and H. ethanolica LX-BT were 65.5 and 21.0 %, respectively. The cellular fatty acid composition of the strain was C16 : 0, anteiso-C15 : 0, C14 : 0, C12 : 0 3-OH and dimethyl acetal-C13 : 0. Based on phenotypic, chemotaxonomic and genotypic analysis, strain UUS1-1T represents a novel genus and species, for which the name Capillibacterium thermochitinicola gen. nov., sp. nov. is proposed. The type strain is UUS1-1T (=JCM 33882T=DSM 111537T).


Left atrial appendage occlusion using the LAmbre device in atrial fibrillation patients with a history of ischemic stroke: 1-Year outcomes from a multicenter study in China.
Patients with non-valvular atrial fibrillation (NVAF) and previous stroke have a significantly higher risk of stroke recurrence. This study aimed to examine the safety and efficacy of the LAmbre left atrial appendage occlusion device in NVAF patients with a history of stroke. We examined 103 consecutive NVAF patients in 11 Chinese medical centers who had a history of stroke or transient ischemic attacks (TIA) and underwent placement of the LAmbre device. Follow-up was conducted 1, 3, 6, and 12 months after the procedure. The primary endpoints were the incidence of new ischemic or hemorrhagic stroke, TIA, systemic embolism, or cardiac death. Secondary endpoints were serious perioperative or device-related complications and cerebral, gastrointestinal, or other bleeding events requiring transfusion of at least 2 units of packed red blood cells. Mean patient age was 67.63 ± 7.14 years; mean CHA2DS2-VASc score was 4.72 ± 1.18 and mean HAS-BLED score was 1.90 ± 1.00. LAmbre device placement was successful in 101 patients (98.05%). Mean follow-up was 12.2 months. Five patients (4.95%) developed a new pericardial effusion after the procedure; none required treatment. Eighty-six patients (85.15%) exhibited no peri-device leak (PDL). However, 13 (12.8%) had a small (0-3 mm) PDL and two (2.3%) had a moderate PDL (3-5 mm). One recurrent stroke occurred during follow-up (1.1%). No other complications occurred. This multicenter study shows the safety and efficacy of LAmbre left atrial appendage occlusion for NVAF patients with a history of stroke or TIA.


Occult Hepatitis C Virus Infection among Hemodialysis Patients: An Iranian Experience.
Patients with chronic kidney failure and those undergoing chronic hemodialysis (CHD) treatment are at high risk of infection with hepatitis C virus (HCV). The incidence of occult HCV infection (OCI) in CHD remains controversial and the real burden of HCV in this population may be affected by the rate of OCI. This study evaluates the molecular assessment of OCI in CHD in an Iranian population. All subjects on CHD in the South Khorasan province of Iran were invited for participation in the study. Whole blood samples were taken and serological, clinical, and demographic information was recorded. HCV-RNAs were checked in serum and peripheral blood mononuclear cells (PBMCs) using an in-house semi-nested PCR assay. Viral load was determined using a real-time PCR-based quantification kit. Sequencing was performed to determine genotypes. Overall, 120 cases participated in the study; 57.5% were male and the rest were female. In serum samples, no positive case was found for HCV-RNA. In PBMC samples, 2/120 (1.6%) were positive for HCV-RNA (95% CI, 0.002 to 0.059); the mean age of OCI positive cases was 37.5 ± 19.2 years which was significantly lower than OCI negative cases (P = 0.026). Only one case had detectable viral load which was 49 IU/mL. The only HCV genotype identified was 1a. This study showed that there is a risk of OCI among CHD patients; the very low and undetectable viral loads of OCI warrant further follow-up molecular testing for earlier diagnosis and treatment in the era of DAA.


Evaluation of biomechanical status of dysplastic human hips.
The evaluation of the biomechanical status of human hip joint was performed. Required parameters were assessed from standard antero-posterior rentgenographs and the value of contact stress on the weight bearing area is calculated. We analysed 45 dysplastic human hips and compared measured values to 81 healthy hips. The peak contact stress on the weight bearing area is considerably and statistically significantly higher in dysplastic hips compared to healthy hips. The Wiberg centre-edge angle is statistically significantly smaller in group of dysplastic hips compared to healthy hips.


Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth.
The Epstein-Barr virus (EBV)-associated cancer nasopharyngeal carcinoma (NPC) is rare in Europe and North America but is a real public health problem in some regions of the world, such as southern Asia, North Africa, and for Inuit populations. Due to the anatomy and location of the nasopharynx, surgery is rarely used to treat primary NPC cancers. Treatment by radiotherapy, combined or not with chemotherapy, are efficient for primary tumors but often do not protect against fatal relapses or metastases. Search for new therapeutic molecules through high content screening lead to the identification of Ivermectin (IVM) as a promising drug. IVM is a US Food and Drug Administration-approved macrocyclic lactone widely used as anthelmintic and insecticidal agent that has also shown protective effects against cancers. We show here that IVM has cytotoxic activity in vitro against NPC cells, in which it reduces MAPKs pathway activation through the inhibition PAK-1 activity. Moreover, all macrocyclic lactones tested and a PAK1 inhibitor are cytotoxic in vitro for EBV-positive and EBV-negative NPC tumor cells. We have also shown that IVM intraperitoneal repeated injections, at US Food and Drug Administration-approved doses, have no significant toxicity and decrease NPC subcutaneous tumors development in nude mice. Macrocyclic lactones appear as promising molecules against NPC targeting PAK-1 with no detectable adverse effect.


Au Exchange or Au Deposition: Dual Reaction Pathways in Au-CsPbBr3 Heterostructure Nanoparticles.
We have designed a facile synthetic strategy for the selective deposition of Au metal on all-inorganic CsPbBr3 perovskite nanocrystals that includes the addition of PbBr2 salt along with AuBr3 salt. PbBr2 is necessary because the addition of Au3+ to solutions of CsPbBr3 nanocrystals otherwise results in the exchange of Au3+ ions from solution with Pb2+ cations within the nanocrystal lattice to produce Cs2AuIAuIIIBr6 nanocrystals with a tetragonal crystal structure and a band gap of about 1.6 eV, in addition to Au metal deposition. Including excess Pb2+ ions in solution prevents the exchange reaction. Au metal deposits on the surface of the nanocrystals to produce the Au-CsPbBr3 heterostructure nanoparticles with an Au particle diameter determined by the Au3+ ion concentration. Fluorescence quenching caused by Au deposition monotonically increases with deposition size, but the fluorescence quantum yield (QY) is significantly greater than if any cation exchange has occurred. An optimized synthesis can produce Au-CsPbBr3 nanoparticles with 70% QY and no evidence of cation exchange.


[The effect of the thrombocytes on the formation of the hemostatic potential in the venous and arterial beds in stable stenocardia].
The coagulative activity was studied of the arterial and venous blood thrombocyte and thrombocyte-free plasma in 16 patients with stable angina. Changes in the general index of thrombophilia permitted the identification of activation of the hemostatic potential in the venous and arterial beds. The results secured suggested the important part that platelets have in formation of the hemostatic potential in both the venous and arterial beds in stable stenocardia. Discussed in the article is the role of the lungs in stabilization of the hemostatic potential in the arterial bed.


Prospective study of bacterial overgrowth syndrome in eight dogs.
Eight dogs with cutaneous lesions, clinical signs and cytological findings compatible with bacterial overgrowth syndrome were compared with four healthy dogs. The affected dogs were treated for 28 days with 30 mg/kg/day cephalexin. The results showed that the syndrome was a superficial cutaneous disorder characterised by marked pruritus, greasy seborrhoea, offensive odour, erythema, lichenification, hyperpigmentation, excoriations and alopecia involving principally the ventral aspect of the body, but no papules, pustules, epidermal collarettes or crusts; it was caused by overgrowths of Staphylococcus intermedius all over the body surface. Histopathological findings included a superficial, perivascular, hyperplastic and spongiotic dermatitis with a mixed inflammatory infiltrate, but no lesions suggestive of a true pyoderma. In the affected dogs, anti-staphylococcal immunoglobulin G levels were high, but anti-staphylococcal immunoglobulin E levels were low, suggesting that staphylococcal hypersensitivity is not the underlying pathogenic process. The antibiotic treatment improved the condition of all the dogs, but five of the eight had an underlying allergic skin disease.


Self-Assembly of Colloidal Nanocrystals: From Intricate Structures to Functional Materials.
Chemical methods developed over the past two decades enable preparation of colloidal nanocrystals with uniform size and shape. These Brownian objects readily order into superlattices. Recently, the range of accessible inorganic cores and tunable surface chemistries dramatically increased, expanding the set of nanocrystal arrangements experimentally attainable. In this review, we discuss efforts to create next-generation materials via bottom-up organization of nanocrystals with preprogrammed functionality and self-assembly instructions. This process is often driven by both interparticle interactions and the influence of the assembly environment. The introduction provides the reader with a practical overview of nanocrystal synthesis, self-assembly, and superlattice characterization. We then summarize the theory of nanocrystal interactions and examine fundamental principles governing nanocrystal self-assembly from hard and soft particle perspectives borrowed from the comparatively established fields of micrometer colloids and block copolymer assembly. We outline the extensive catalog of superlattices prepared to date using hydrocarbon-capped nanocrystals with spherical, polyhedral, rod, plate, and branched inorganic core shapes, as well as those obtained by mixing combinations thereof. We also provide an overview of structural defects in nanocrystal superlattices. We then explore the unique possibilities offered by leveraging nontraditional surface chemistries and assembly environments to control superlattice structure and produce nonbulk assemblies. We end with a discussion of the unique optical, magnetic, electronic, and catalytic properties of ordered nanocrystal superlattices, and the coming advances required to make use of this new class of solids.


A purified human platelet pellet lysate rich in neurotrophic factors and antioxidants repairs and protects corneal endothelial cells from oxidative stress.
Human platelet lysate (HPL) is a complex mixture of potent bioactive molecules instrumental in tissue repair and regeneration. Due to their remarkable safety, cost-effective production, and availability at global level from collected platelet concentrates, HPLs can become a powerful biotherapy for various therapeutic applications, if standardized and carefully validated through pre-clinical and clinical studies. In this work, the possibility to use a tailor-made HPL as a corneal transplant alternative to treat the gradual decrease in the number of corneal endothelial cells (CECs) associated with aging, was evaluated. The HPL preparation was thoroughly characterized using various proteomics tools that revealed a remarkable richness in multiple growth factors and antioxidants. Treatment of B4G12 and BCE C/D-1b CECs with the HPL increased their viability, enhanced the wound closure rate, and maintained cell growth and typical hexagonal morphology. Besides, this HPL significantly protected against tert-butyl hydroperoxide (TBHP)-induced oxidative stress as evidenced by increasing CEC viability, decreased cell death and reactive oxygen species formation, and enhanced antioxidant capacity. Proteomics analysis of treated CECs confirmed that HPL treatment triggered the corneal healing pathway and enhanced oxidative stress. These data strongly support further pre-clinical evaluation of this tailor-made HPL as a novel CEC regeneration biotherapy. HPL treatment may eventually represent a pragmatic and cost-effective alternative to corneal transplant to treat damages of the corneal endothelium which is a major cause of blindness worldwide.


Effects of xylanase and citric acid on the performance, nutrient retention, and characteristics of gastrointestinal tract of broilers fed low-phosphorus wheat-based diets.
An experiment was conducted to study the effects of xylanase and citric acid on the performance, nutrient retention, jejunal viscosity, and size and pH of the gastrointestinal tract of broilers fed a low-P wheat-based diet. The experiment was conducted as a 2 × 3 factorial arrangement with 2 levels of xylanase (0 and 200 mg/kg) and 3 levels of citric acid (0, 20, and 40 g/kg). Each of the 6 dietary treatments was fed to 4 replicate pens (17 birds/pen) from 0 to 24 d of age. Chromium oxide (3 g/kg) was added to the diets as an indigestible marker to determine the apparent nutrient retention. No interaction effect was observed between xylanase and citric acid in any measured response. Xylanase did not affect feed intake but significantly increased BW gain by 3.6% (P < 0.05) from 1 to 24 d of age and improved G:F by 3.9% (P < 0.01). The inclusion of 40 g/kg of citric acid decreased (P < 0.01) BW gain and feed intake by 8.6 and 12.5%, respectively. The inclusion of 20 and 40 g/kg of citric acid improved G:F by 2.3 and 4.5% (P < 0.05), respectively. Xylanase significantly decreased the viscosity of digesta and improved the retention of DM, CP, and energy, but did not have a significant effect on the retention of fat and P. Inclusion of 20 and 40 g/kg of citric acid in the diets increased P retention by 15.8 and 16.3% (P < 0.01), respectively. Citric acid significantly decreased the pH of crop contents (P < 0.05). In conclusion, citric acid, at the 40 g/kg inclusion level, reduced feed intake and BW gain but improved G:F and P retention. Xylanase decreased digesta viscosity, increased nutrient retention, and consequently improved the performance of broilers fed the low-P wheat-based diet. Thus, adding 20 g/kg of citric acid, especially in the starter period, and 200 mg/kg of xylanase to low-P wheat-based diets can be helpful.


Chemonucleolysis in the management of lumbar disc disease. A minimum six-year follow-up evaluation.
Of 208 chemonucleolysis procedures performed between April 1973 and June 1978, 189 (91%) were available for follow-up evaluation by comprehensive questionnaire after six to 11.2 years. Pain relief, activity level, and personal satisfaction are considered in patients otherwise eligible for discectomy. The procedures were done under general anesthesia with 18-gauge single needle technique using biplane image intensification and routine discography prior to Discase injection. Seventy-nine percent of patients were satisfied with their results, 85% males and 65% females. Sixty-two percent of workman's compensation patients and 57% of patients previously treated by laminectomy had a satisfactory result. Ninety-five percent of patients had disc space narrowing postoperatively. Complications were few and of no lasting concern. Of the failures, 12.7% had laminectomies within 18 months of injection while 9.5% had a satisfactory result for at least two years. Disc reexpansion was demonstrated after postinjection narrowing in 14% of 58 cases roentgenographically evaluated, including patients of the 2nd, 3rd, and 4th decade of life. Recurrence rate in the total series was 9.5%. Chemonucleolysis is the least traumatic invasive procedure capable of removing the nucleus pulposus and is most effective when used in the treatment of lumbar disc herniation with objective signs of nerve root compression. In this series, approximately 80% of patients were spared open surgery.


Socio-Economic and Environmental Factors Related to Spatial Differences in Human Non-Tuberculous Mycobacterial Diseases in the Czech Republic.
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that can induce pulmonary and non-pulmonary diseases in susceptible persons. It is reported that the prevalence of NTM diseases is increasing in developed countries, but this differs by regions and countries. NTM species distribution and the rate of diseases caused by NTM vary widely in the historical territories of Moravia and Silesia (Czech Republic). This epidemiologic study of NTM diseases covers the period 2012-2018, reviews isolates obtained from patients with clinical disease and investigates correlations with related socio-economic and environmental factors. Individual NTM patients were included only once during the studied period and results were presented as incidence rate per year. The most frequently isolated NTM meeting the microbiological and clinical criteria in the study were the Mycobacterium avium-intracellulare complex, followed by Mycobacteriumkansasii and Mycobacteriumxenopi. A previously described endemic incidence of M.kansasii in the Karviná district and M.xenopi in the Ostrava district was also observed in this study. The incidence of NTM patients in the whole studied territory was 1.10/100,000 inhabitants (1.33/100,000 in men and 0.88/100,000 in women). The annual incidence of lymphadenitis in children (≤5 years of age) was 2.35/100,000 of the population of children during the 7 year period but increased in the year 2018 to 5.95/100,000. The rate of human tuberculosis in the studied area was 1.97/100,000 inhabitants. The incidence of NTM pulmonary diseases correlated with a lower socio-economic status (r = 0.63) and a higher concentration of benzo[a]pyrene pollution in the air (r = 0.64).


Maternal Phthalates Exposure and Blood Pressure during and after Pregnancy in the PROGRESS Study.
Phthalate exposure is ubiquitous and may affect biological pathways related to regulators of blood pressure. Given the profound changes in vasculature during pregnancy, pregnant women may be particularly susceptible to the potential effects of phthalates on blood pressure. We examined associations of phthalate exposure during pregnancy with maternal blood pressure trajectories from mid-pregnancy through 72 months postpartum. Women with singleton pregnancies delivering a live birth in Mexico City were enrolled during the second trimester (n=892). Spot urine samples from the second and third trimesters were analyzed for 15 phthalate metabolites. Blood pressure and covariate data were collected over nine visits through 72 months postpartum. We used linear, logistic, and linear mixed models; latent class growth models (LCGMs); and Bayesian kernel machine regression to estimate the relationship of urinary phthalate biomarkers with maternal blood pressure. As a joint mixture, phthalate biomarker concentrations during pregnancy were associated with higher blood pressure rise during mid-to-late gestation. With respect to individual biomarkers, second trimester concentrations of monobenzyl phthalate (MBzP) and di(2-ethylhexyl) phthalate biomarkers (ΣDEHP) were associated with higher third trimester blood pressure. Two trajectory classes were identified by LCGM, characterized by increasing blood pressure through 72 months postpartum ("increase-increase") or decreased blood pressure through 18 months postpartum with a gradual increase thereafter ("decrease-increase"). Increasing exposure to phthalate mixtures during pregnancy was associated with higher odds of being in the increase-increase class. Similar associations were observed for mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and dibutyl phthalate (ΣDBP) biomarkers. When specific time periods were examined, we observed specific temporal relationships were observed for ΣDEHP, MECPTP, MBzP, and ΣDBP. In our cohort of pregnant women from Mexico City, exposure to phthalates and phthalate biomarkers was associated with higher blood pressure during late pregnancy, as well as with long-term changes in blood pressure trajectories. https://doi.org/10.1289/EHP8562.


Glycemic Control, Basal/Bolus Distribution, BMI and Meal Management in Children and Adolescents with Type 1 Diabetes and Advanced Hybrid Closed Loop.
Evidence about the impact of advanced hybrid closed loop (AHCL) on body mass index (BMI) and eating habits in children with type 1 diabetes (T1D) is lacking. This real-world study aimed at evaluating glycemic control, BMI, meals and basal/bolus distribution in young subjects with T1D treated by AHCL. Glycemic metrics, HbA1c, basal/bolus distribution, meals/day, BMI, total daily dose (TDD), and carbohydrates/kg (CHO/kg) have been evaluated in 83 subjects, aged 13 ± 4.5 years, in manual mode, 3 and 6 months after auto-mode. Time in range (TIR) increased after 3 months, exceeding the target of 70% and was maintained at 6 months. While coefficient of variation (CV) did not change, the glucose management indicator (GMI) decreased in auto-mode (6.7 ± 0.3 vs. 7.1 ± 0.5%; p < 0.001), as well as HbA1c. Basal proportion decreased in favor of boluses (38.3 ± 7.3 vs. 43.6 ± 10.9%; p < 0.001). Meals increased at 3 and 6 months (4.4 ± 1.2 vs. 5.0 ± 1.5, p 0.002 and 5.1 ± 1.7, p < 0.001), as well as TDD/kg, without changes in BMI and CHO consumed. No differences in meal composition have arisen from food diaries. In conclusion, AHCL ensured the achievement and maintenance of target TIR in young T1D subjects. The number of meals, TDD, and insulin bolus proportion increased over time, but BMI remained stable.


[Prepregnancy overweight is associated with excessive weight gain during pregnancy].
To evaluate the adequacy of gestational weight gain and to determine its association with maternal socioeconomic, demographic and nutritional factors and health care, to estimate the prevalence of low birth weight, macrosomia, preterm birth and cesarean delivery and to identify the association of these outcomes with the adequacy of weight gain. A cross-sectional study was performed in 2009/2010 to obtain socioeconomic, demographic, nutritional, dietary and physical activity data of pregnant women assisted by primary health care in a municipality of the state of São Paulo. Subsequently, data were collected from the medical records to evaluate gestational weight gain. Type of delivery, birth weight and gestational age at delivery were obtained from the Livebirths Information System. Gestational weight gain was evaluated according to the recommendations of the Institute of Medicine (2009). Associations were investigated by comparing the frequencies and by logistic regression, with excessive weight gain (yes, no) and insufficient gain (yes, no) being the dependent variables. A total of 212 pregnant women were studied: 50.5% had excessive gain and 19.8% insufficient weight gain. Only prepregnancy nutritional status was associated with adequacy of weight gain: compared with normal weight, prepregnancy overweight women had a four-fold higher chance to gain excessive weight (OR 4.66, 95%CI 2.19-9.4). Nearly a third of babies were born by caesarian section, 5.7% were premature, 7.1% were underweight and 4.7% were macrosomic. There was no association between adequacy of gestational weight gain and these outcomes. The proportion of inadequate gestational weight gain was high. Overweight pregnant women have a four-fold higher chance to gain excessive weight, and priority should be given to actions promoting adequate prenatal weight gain.


Alexithymia and Alcohol Dependence: The Roles of Negative Mood and Alcohol Craving.
Background: Alexithymia is a personality trait associated with emotion regulation difficulties. Up to 67% of alcohol-dependent patients in treatment have alexithymia. Objectives: The objective of this study was to investigate the direct and indirect effects of alexithymia, negative mood (stress, anxiety, and depression) and alcohol craving on alcohol dependence severity. Methods: Three hundred and fifty-five outpatients (mean age = 38.70, SD = 11.00, 244 males, range 18-71 years) undergoing Cognitive-Behavioral Therapy for alcohol dependence completed the Toronto Alexithymia Scale (TAS-20), Depression Anxiety Stress Scales (DASS-21), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Use Disorders Identification Test (AUDIT) prior to the first treatment session. Results: Alexithymia had an indirect effect on alcohol dependence severity, via both negative mood and alcohol craving (b = 0.03, seb = 0.008, 95% CI: 0.02-0.05). An indirect effect of negative mood on alcohol dependence via alcohol craving was also observed (b = 0.12, seb = 0.03, 95% CI: 0.07-0.16). Conclusions/importance: Alexithymia worked through negative mood and alcohol craving leading to increased alcohol dependence severity, indicating that craving had an indirect effect on the relationship between alexithymia and alcohol dependence severity. Targeting alcohol craving and negative mood for alcohol-dependent patients with alexithymia seems warranted.


Reliability of systolic blood pressure measured by parents in young children at home using a hand held doppler device and aneroid sphygmomanometer.
We report data regarding systolic BP monitoring in children aged <5 years performed over a 2-week period by parents at home using a hand-held doppler device and aneroid sphygmomanometer for SBP measurements (HDBPM). Our objectives were to compare health professional measured office systolic BP by doppler device (Office-SBPDoppler) with parent measured home systolic BP using the same doppler device (Home-SBPDoppler). We also report data evaluating reliability and optimal number of days of measurement required. We taught parents to measure systolic BP and assessed their technique using a hand-held doppler device and aneroid sphygmomanometer. We requested parents to perform three consecutive BP measurements twice daily (ideally morning and evening around similar times) when the child was awake, settled and cooperative. Over a 3-year period, data from 48 of 62 children who underwent HDBPM measurements were evaluated with median (IQR) age of 1.9 (0.9, 3.6) years, 27 (56%) boys and 14 (29%) on antihypertensive medication. Office-SBPDoppler was 2.9 ± 8.9 mmHg [95% confidence interval (CI), -14.4 to 20.4, P = 0.026] higher than Home-SBPDoppler. Mean Home-SBPDoppler between Week-1 and Week-2 monitoring was similar -0.45 ± 3.5 mmHg (95% CI, -7.35 to 6.45, P = 0.41). Morning HDBPM measurements were lower than evening with a mean difference of -2.77 ± 3.92 mmHg, P < 0.001). Over Week-1, mean Home-SBPDoppler was closer to mean Office-SBPDoppler with increasing cumulative days of monitoring and with smaller standard deviations suggesting that readings become more reliable from day 4 onwards. HDBPM is a reliable method for measuring systolic BP in young children with BP levels measured by parents comparable to those performed by health professional in clinic. HDBPM technique described here and performed by parents over a 7-day period with a minimum of 4-days, offers a reliable and reproducible technique to measure blood pressure at home.


Comparative analysis of virulence determinants and mass spectral profiles of Finnish and Lithuanian endodontic Enterococcus faecalis isolates.
Putative virulence factors of Enterococcus faecalis have been proposed by several workers and, by analogy, these have been linked to strains of endodontic origin. However, their distribution within the cell population is unknown. In the present study, isolates were taken from the dental root canals of two defined human populations, Lithuanian and Finnish, and examined for a range of virulence properties. In addition, surface-associated molecules and intracellular proteins were compared using matrix-assisted laser desorption-ionization/mass spectrometry (MALDI-TOF-MS) and ProteinChip capture/MS (SELDI-TOF-MS), respectively. Twenty-three Lithuanian and 35 Finnish dental root canal isolates were included. The esp, gelE, ace and efaA genes were detected by polymerase chain reaction, and cytolysin and gelatinase phenotypes were determined by hydrolysis of horse blood agar and gelatine agar, respectively. Protein extracts and surface-associated molecules of whole cells were analysed by SELDI-TOF-MS and MALDI-TOF-MS, respectively. Presence of esp (n = 15), cytolysin (n = 9), ace (n = 55) and efaA (n = 58) was not statistically different in the two samples, whereas gelE and gelatinase production was detected more frequently in the Finnish material (chi-squared, P < 0.01). Analysis of protein profiles by SELDI-TOF-MS showed clustering of cytolysin-producing strains, whereas MALDI-TOF-MS generated profiles that clustered according to the samples' origin and, furthermore, to atypical quinupristin-dalfopristin susceptibility. A high prevalence of virulence factors was demonstrated in both population types. SELDI-TOF-MS and MALDI-TOF-MS proved useful in distinguishing between different E. faecalis phenotypes and they may be useful technologies for elucidating the eco-distribution of E. faecalis in humans.


Two cases of neuro-Behcet's disease mimicking cerebral tumor.
Two cases of neuro-Behcet's disease with isolated, solitary fronto-temporal and mesencephalic lesions respectively are reported. The cases were misdiagnosed as cerebral tumor. The postoperative outcome of the first patient was not satisfactory as he developed hemispheric edema. The second patient, with mesencephalic lesion, was treated only with corticosteroids, and the patient improved significantly. The lesion in this case resolved completely at six-month follow-up. We conclude that distinguishing the isolated solitary cerebral lesion of the Behcet's disease from a tumor may prevent surgical intervention.


Differential Expression of Genes Related to Innate Immune Responses in Ex Vivo Spinal Cord and Cerebellar Slice Cultures Infected with West Nile Virus.
West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV in specific cell types and different regions of the brain modify immune protection is not fully understood. Here, we used a mouse ex vivo spinal cord slice culture (SCSC) and cerebellar slice culture (CSC) models to determine the innate immune responses specific to the CNS during WNV infection. Slices were prepared from the spinal cord and cerebellar tissue of 7⁻9-day-old mouse pups. Four-day-old SCSC or CSC were infected with 1 × 10³ or 1 × 10⁵ PFU of WNV, respectively. After 12 h exposure to WNV and 3 days post-infection in normal growth media, the pooled slice cultures were processed for total RNA extraction and for gene expression patterns using mouse Affymetrix arrays. The expression patterns of a number of genes were significantly altered between the mock- and WNV-treated groups, both in the CSCs and SCSCs. However, distinct differences were observed when CSC data were compared with SCSC. CSCs showed robust induction of interferons (IFNs), IFN-stimulated genes (ISGs), and regulatory factors. Some of the antiviral genes related to IFN were upregulated more than 25-fold in CSCs as compared to mock or SCSC. Though SCSCs had twice the number of dysregulated genes, as compared CSCs, they exhibited a much subdued IFN response. In addition, SCSCs showed astrogliosis and upregulation of astrocytic marker genes. In sum, our results suggest that early anti-inflammatory response to WNV infection in CSCs may be due to large population of distinct astrocytic cell types, and lack of those specialized astrocytes in SCSC may make spinal cord cells more susceptible to WNV damage. Further, the understanding of early intrinsic immune response events in WNV-infected ex vivo culture models could help develop potential therapies against WNV.


Performance Evaluation of IMU and DVL Integration in Marine Navigation.
Global navigation satellite system (GNSS) spoofing poses a significant threat to maritime logistics. Many maritime electronic devices rely on GNSS time, positioning, and speed for safe vessel operation. In this study, inertial measurement unit (IMU) and Doppler velocity log (DVL) devices, which are important in the event of GNSS spoofing or outage, are considered in conventional navigation. A velocity integration method using IMU and DVL in terms of dead-reckoning is investigated in this study. GNSS has been widely used for ship navigation, but IMU, DVL, or combined IMU and DVL navigation have received little attention. Military-grade sensors are very expensive and generally cannot be utilized in smaller vessels. Therefore, this study focuses on the use of consumer-grade sensors. First, the performance of a micro electromechanical system (MEMS)-based yaw rate angle with DVL was evaluated using 60 min of raw data for a 50 m-long ship located in Tokyo Bay. Second, the performance of an IMU-MEMS using three gyroscopes and three accelerometers with DVL was evaluated using the same dataset. A gyrocompass, which is equipped on the ship, is used as a heading reference. The results proved that both methods could achieve less than 1 km horizontal error in 60 min.


Antifungal activity of the lemongrass oil and citral against Candida spp.
Superficial mycoses of the skin are among the most common dermatological infections, and causative organisms include dermatophytic, yeasts, and non-dermatophytic filamentous fungi. The treatment is limited, for many reasons, and new drugs are necessary. Numerous essential oils have been tested for both in vitro and in vivo antifungal activity and some pose much potential as antifungal agents. By using disk diffusion assay, we evaluated the antifungal activity of lemongrass oil and citral against yeasts of Candida species (Candida albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis). This study showed that lemongrass oil and citral have a potent in vitro activity against Candida spp.


Methanogens and Iron-Reducing Bacteria: the Overlooked Members of Mercury-Methylating Microbial Communities in Boreal Lakes.
Methylmercury is a potent human neurotoxin which biomagnifies in aquatic food webs. Although anaerobic microorganisms containing the hgcA gene potentially mediate the formation of methylmercury in natural environments, the diversity of these mercury-methylating microbial communities remains largely unexplored. Previous studies have implicated sulfate-reducing bacteria as the main mercury methylators in aquatic ecosystems. In the present study, we characterized the diversity of mercury-methylating microbial communities of boreal lake sediments using high-throughput sequencing of 16S rRNA and hgcA genes. Our results show that in the lake sediments, Methanomicrobiales and Geobacteraceae also represent abundant members of the mercury-methylating communities. In fact, incubation experiments with a mercury isotopic tracer and molybdate revealed that only between 38% and 45% of mercury methylation was attributed to sulfate reduction. These results suggest that methanogens and iron-reducing bacteria may contribute to more than half of the mercury methylation in boreal lakes.IMPORTANCE Despite the global awareness that mercury, and methylmercury in particular, is a neurotoxin to which millions of people continue to be exposed, there are sizable gaps in the understanding of the processes and organisms involved in methylmercury formation in aquatic ecosystems. In the present study, we shed light on the diversity of the microorganisms responsible for methylmercury formation in boreal lake sediments. All the microorganisms identified are associated with the processing of organic matter in aquatic systems. Moreover, our results show that the well-known mercury-methylating sulfate-reducing bacteria constituted only a minor portion of the potential mercury methylators. In contrast, methanogens and iron-reducing bacteria were important contributors to methylmercury formation, highlighting their role in mercury cycling in the environment.


Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism.
Hepatic insulin resistance is a critical component in the development of type 2 diabetes mellitus. In many cases, insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate (IRS) proteins, IRS-1 and IRS-2. To investigate the specific functions of IRS-1 and IRS-2 in regulating liver function in vivo, we developed an adenovirus-mediated RNA interference technique in which short hairpin RNAs (shRNAs) are used to knock down IRS-1, IRS-2, or both, by 70-80% in livers of WT mice. The knockdown of IRS-1 resulted in an upregulation of the gluconeogenic enzymes glucose-6 phosphatase and phosphoenolpyruvate carboxykinase, as well as a marked increase in hepatic nuclear factor-4 alpha. Decreased IRS-1 was also associated with a decrease in glucokinase expression and a trend toward increased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes SREBP-1c and fatty acid synthase, as well as increased hepatic lipid accumulation. The concomitant injection of IRS-1 and IRS-2 adenoviral shRNAs resulted in systemic insulin resistance, glucose intolerance, and hepatic steatosis. The alterations in the dual-knockdown mice were associated with defective Akt activation and Foxo1 phosphorylation. Taken together, our results demonstrate that hepatic IRS-1 and IRS-2 have complementary roles in the control of hepatic metabolism, with IRS-1 more closely linked to glucose homeostasis and IRS-2 more closely linked to lipid metabolism.


Linking pollen limitation and seed dispersal effectiveness.
Seed production and dispersal are crucial ecological processes impacting plant demography, species distributions and community assembly. Plant-animal interactions commonly mediate both seed production and seed dispersal, but current research often examines pollination and seed dispersal separately, which hinders our understanding of how pollination services affect downstream dispersal services. To fill this gap, we propose a conceptual framework exploring how pollen limitation can impact the effectiveness of seed dispersal for endozoochorous and myrmecochorous plant species. We summarize the quantitative and qualitative effects of pollen limitation on plant reproduction and use Optimal Foraging Theory to predict its impact on the foraging behaviour of seed dispersers. In doing so, we offer a new framework that poses numerous hypotheses and empirical tests to investigate links between pollen limitation and seed dispersal effectiveness and, consequently, post-dispersal ecological processes occurring at different levels of biological organization. Finally, considering the importance of pollination and seed dispersal outcomes to plant eco-evolutionary dynamics, we discussed the implications of our framework for future studies exploring the demographic and evolutionary impacts of pollen limitation for animal-dispersed plants.


Structural alterations and inhibition of lysozyme activity upon binding interaction with rotenone: Insights from spectroscopic investigations and molecular dynamics simulation.
The pervasive employment of pesticides such as rotenone on a global scale represents a substantial hazard to human health through direct exposure. Therefore, exploring the interactions between such compounds and body macromolecules such as proteins is crucial in comprehending the underlying mechanisms of their detrimental effects. The present study aims to delve into the molecular interaction between rotenone and lysozyme by employing spectroscopic techniques along with Molecular dynamics (MD) simulation in mimicked physiological conditions. The binding interaction resulted in a fluorescence quenching characterized by both dynamic and static mechanisms, with static quenching playing a prominent role in governing this phenomenon. The analysis of thermodynamic parameters indicated that hydrophobic interactions primarily governed the spontaneous bonding process. FT-IR and circular dichroism findings revealed structural alternations of lysozyme upon complexation with rotenone. Also, complexation with rotenone declined the biological activity of lysozyme, thus rotenone could be considered an enzyme inhibitor. Further, the binding interaction substantially decreased the thermal stability of lysozyme. Molecular docking studies showed the binding location and the key residues interacting with rotenone. The findings of the spectroscopic investigations were confirmed and accurately supported by MD simulation studies.


Variations in Zebra Chip Disease Expression and Tuber Biochemistry in Response to Vector Density.
Zebra chip (ZC) disease, caused by 'Candidatus Liberibacter solanacearum', which is transmitted by the potato psyllid, has negatively affected potato production in the United States for over a decade. The present study was conducted to evaluate the affect of the number of bacteriliferous psyllids on 'Ca. L. solanacearum' titer, levels of amino acids, carbohydrates, phenolics, and, subsequently, symptom severity in potato tubers. 'Red La Soda' and 'Russet Norkotah' potato were planted in the field and later inoculated with 'Ca. L. solanacearum' using 5, 10, and 30 bacteriliferous potato psyllids. In both cultivars, the increase in the number of psyllids resulted in elevated 'Ca. L. solanacearum' titer and symptom severity. In the cases of amino acids and reducing sugars, responses to vector density appeared to be cultivar specific. Overall, phenolic compounds showed a consistent increase following infection, a response that, in most cases, was positively correlated with the number of infective psyllids. Results quantified the impact of the number of infective psyllids on 'Ca. L. solanacearum' titer and biochemical content of infected tubers previously shown to be correlated with the degree of symptom expression. Managing vector numbers is currently the only effective approach for minimizing losses to ZC in grower's fields. However, our findings on physiological responses to vector density suggest that, in combination with chemical control, development of more tolerant or resistant potato genotypes, with emphasis on interrupting pathways that are associated with increased phenolic activity levels, may lead to more sustainable management of ZC in the future.


[Cytokines as agents for the early pathogenetic therapy of radiation injuries. Their efficacy and mechanism of action].
It has been shown in experiments with three species of laboratory animals that an early administration (during the first hours following irradiation) of human recombinant interleukins 1 alpha and 1 beta separately (to mice, rats) or in combination with antibiotic therapy (dogs) substantially increases survivability, favours a more rapid regeneration of the cellular content of the bone marrow and peripheral blood, intensifies the processes of endogenous colony formation and DNA synthesis in the bone marrow and liver and lowers the expressivity of radiation-induced endotoxemia. The significance of using cytokines in the system of remedial measures in radiation pathology is discussed.


The effect of mindfulness meditation on dental anxiety during implant surgery: a randomized controlled clinical trial.
Dental implant surgery is almost always associated with patient anxiety. Anxiety during dental surgical procedures triggers an increase in sympathetic activity. Mindfulness meditation (MM) is often associated with high levels of relaxation in the form of increased parasympathetic tone and decreased sympathetic activity. However, the effect of MM on dental anxiety is not clear. The current study aimed to show the effects of a MM as a sedative technique during dental implant surgery by examining the State-Trait Anxiety Inventory (STAI-S), bispectral index (BIS), cortisol levels (CL), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and saturation (SpO2) parameters. HR, SBP, DBP, SpO2, BIS score and CLs were compared at the baseline, immediately before-, during-, and immediately after surgery between the test and control groups. We found that the MM resulted in significant decrease in BIS together with positive effects on hemodynamic parameters (decrease of HR, SBP, DBP and increase of SpO2), psychological findings (improvement on STAI-S scores) and biochemical outcomes (decreased CL). In conclusion, the results demonstrate that MM appeared to be a reliable strategy for managing stress during dental implant operation with benefits in psychological, physiological and biochemical outcomes.