Αρχειοθήκη ιστολογίου

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Τρίτη 10 Νοεμβρίου 2015

Sensors, Vol. 15, Pages 28271-28286: Real-Valued Covariance Vector Sparsity-Inducing DOA Estimation for Monostatic MIMO Radar

In this paper, a real-valued covariance vector sparsity-inducing method for direction of arrival (DOA) estimation is proposed in monostatic multiple-input multiple-output (MIMO) radar. Exploiting the special configuration of monostatic MIMO radar, low-dimensional real-valued received data can be obtained by using the reduced-dimensional transformation and unitary transformation technique. Then, based on the Khatri–Rao product, a real-valued sparse representation framework of the covariance vector is formulated to estimate DOA. Compared to the existing sparsity-inducing DOA estimation methods, the proposed method provides better angle estimation performance and lower computational complexity. Simulation results verify the effectiveness and advantage of the proposed method.

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Remote Sensing, Vol. 7, Pages 14988-15013: A Comparative Study of Sampling Analysis in the Scene Classification of Optical High-Spatial Resolution Remote Sensing Imagery

Scene classification, which consists of assigning images with semantic labels by exploiting the local spatial arrangements and structural patterns inside tiled regions, is a key problem in the automatic interpretation of optical high-spatial resolution remote sensing imagery. Many state-of-the-art methods, e.g., the bag-of-visual-words model and its variants, the topic models and unsupervised feature learning-based approaches, share similar procedures: patch sampling, feature learning and classification. Patch sampling is the first and a key procedure, and it has a considerable influence on the results. In the literature, many different sampling strategies have been used, e.g., random sampling and saliency-based sampling. However, the sampling strategy that is most suitable for the scene classification of optical high-spatial resolution remote sensing images remains unclear. In this paper, we comparatively study the effects of different sampling strategies under the scenario of scene classification of optical high-spatial resolution remote sensing images. We divide the existing sampling methods into two types: random sampling and saliency-based sampling. Here, we consider the commonly-used grid sampling to be a specific type of random sampling method, and the saliency-based sampling consists of keypoint-based sampling and salient region-based sampling. To compare their performances, we rely on a standard bag-of-visual-words model to learn the global features for testing because of its simplicity, robustness and efficiency. In addition, we conduct experiments using a Fisher kernel framework to validate our conclusions. The experimental results obtained on two commonly-used datasets using different feature learning methods show that random sampling can provide comparable and even better performance than all of the saliency-based strategies.

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A qualitative evidence synthesis on the management of male obesity

BMJ Open

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Adherence to competing strategies for colorectal cancer screening over 3 years

The American Journal of Gastroenterology

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Lateral approach liver hanging maneuver in laparoscopic anatomical liver resections

Surgical Endoscopy

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Meta-analysis of laparoscopic surgery for recurrent Crohn’s disease

Surgery Today

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Identification of novel anti-hepatitis C virus agents by a quantitative high throughput screen in a cell-based infection assay

Antiviral Research

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Angiogenesis and vascular endothelial growth factor-a expression associated with inflammation in pediatric Crohn's disease

Journal of Gastrointestinal Surgery

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Dexmedetomidine versus morphine infusion following laparoscopic bariatric surgery: effect on supplemental narcotic requirement during the first 24 h

Surgical Endoscopy

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Tripterygium wilfordii hook F as maintenance treatment for Crohn's disease

The American Journal of the Medical Sciences

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Variation in treatment priorities for chronic hepatitis c: a latent class analysis

The Patient - Patient-Centered Outcomes Research

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Randomized comparison of surveillance intervals in familial colorectal cancer

Journal of Clinical Oncology

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Positive regulation of β-catenin–PROX1 signaling axis by DBC1 in colon cancer progression

Oncogene

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Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

Annals of Oncology

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Prospective cohort study comparing transient EUS guided elastography to EUS-FNA for the diagnosis of solid pancreatic mass lesions

Pancreatology

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Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: A single-centre experience

Current Oncology

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Influence of the intervention of exercise on obese type II diabetes mellitus: A meta-analysis

Primary Care Diabetes

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Characteristics of colonoscopic findings in the very elderly

Geriatrics and Gerontology International

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Changes in insulin sensitivity and secretion after sleeve gastrectomy

British Journal of Surgery

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Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients

Cancer Epidemiology, Biomarkers & Prevention

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Current status of immunomodulatory therapy in chronic hepatitis B, fifty years after discovery of the virus: Search for the “magic bullet” to kill cccDNA

Antiviral Research

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Blunting of colon contractions in diabetics with gastroparesis quantified by wireless motility capsule methods

PLOS ONE

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Family physicians’ intention to support women in making informed decisions about breast cancer screening with mammography: a cross-sectional survey

Background: The net benefits of routine breast cancer screening with mammography have been questioned, and there is evidence to indicate that supporting women to make an informed decision about breast cancer screening with mammography is preferable. The aims of this study were to assess the intention of family physicians to provide women with this support and the determinants of this intention, and to identify factors that might influence family physicians adopting this behavior. Methods: Family physicians from the province of Quebec, Canada, attending a 45-min lecture on informed decision making and cancer screening were asked to complete a questionnaire after the lecture regarding their intention to adopt the behavior. The questions, based on the Theory of Planned Behavior, measured physicians' intention and its determinants (attitude, perceived behavioral control, and socio-professional norm) regarding supporting women to make informed decisions about breast cancer screening with mammography. Open-ended questions were also used to explore complementary factors influencing their intention. Results: Out of 800 questionnaires distributed, 301 (38 %) were returned and 288 were included in data analysis. The mean ± standard deviation and median score for intention were respectively 1.9 ± 1.2 and 2.0 on a 6-point Likert scale (−3 to +3). Perceived behavioral control was the variable most strongly associated with intention (high versus low score, odds ratio = 15.7, 95 % CI 6.7–36.6), followed by attitude (high versus low score, odds ratio = 7.5, 95 % CI 3.3–16.8), then social norm (high versus low score, odds ratio = 5.8, 95 % CI 2.6–12.9). The most-reported barrier to adopting the behavior was time constraints (41 %) while the most-reported facilitator was availability of relevant decision support tools (29 %). Conclusions: Respondents showed strong intention to support women in informed decision-making about breast cancer screening, the strongest predictor being perceived behavioral control. These results could contribute to training physicians to integrate this behavior into their practices and to designing relevant decision support tools.

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Sharp-Hook Acupuncture (Feng Gou Zhen) for Patients with Periarthritis of Shoulder: A Randomized Controlled Trial

The Feng Gou Zhen (sharp-hook acupuncture) as a traditional form of ancient acupuncture is said to be particularly effective for managing periarthritis of shoulder. We conducted this randomized controlled trial to evaluate the effectiveness of Feng Gou Zhen as an add-on compared to conventional analgesics for patients with PAS. 132 patients were randomly assigned in a 1 : 1 ratio to either a acupuncture group receiving sharp-hook acupuncture plus acupoint injection with conventional analgesics or a control group. Patients from both groups were evaluated at week 0 (baseline), week 1, and week 4. The primary outcome measure was the change from baseline shoulder pain, measured by Visual Analogue Scale at 7 days after treatment. Secondary outcome measures include the (i) function of shoulder joint and (ii) McGill pain questionnaire. The results showed that patients in acupuncture group had better pain relief and function recovery compared with control group () at 1 week after treatment. Moreover, there were statistical differences between two groups in VAS and shoulder joint function and McGill pain questionnaire at 4 weeks after treatment (). Therefore, the sharp-hook acupuncture helps to relieve the pain and restore the shoulder function for patients with periarthritis of shoulder.

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Cross-Sectional Study of Respiratory Symptoms, Spirometry, and Immunologic Sensitivity in Epoxy Resin Workers

Abstract

Objectives

An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers.

Methods

Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products.

Results

We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23-infinity], p = 0.030) or wheeze (OR 4.44, [1.00-22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86-589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers.

Conclusions

In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization. Clin Trans Sci 2015; Volume #: 1–7



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JFMK, Vol. 1, Pages 16-29: Clinical Kinesiology and Posturology Applied to a Group of Italian Students. A Morphological Observational Study.

The percentage of children who develop postural deviations during their teens is constantly growing. Many hours of study in a sitting position, poor physical activity, and inadequate information become crucial factors leading to a wrong posture. The aim of this study was to investigate the prevalence of untreated structural alterations, ascribed to incorrect posture (paramorphisms or dysmorphisms), in the adolescent growth phase of students at high school. The anthropometric and postural analyses of a sample of adolescents allowed the correct evaluation of their structural situation in order to establish the presence of conditions different from an ideal posture. The presence of scoliotic deviations was ascertained in 36% of students. Almost half of the students showed a non-physiological curve of the cervical and lumbar spine. A consistent part of examined students showed a non-physiological condition of shoulders (28%), scapulas (>50%), pelvis (≈50%), and hips (36.25%). A prominent malleolus was observed in 17.5% of students; 6.25% had an asymmetry between the ankles; and 18.75% had a foot deformity. If we consider that 65% of students showed a non-physiological musculoskeletal condition, we can consequently hypothesize that during the primary and middle school no one bothered to correct these children under the postural profile. The lack of postural education in the Italian school system should be addressed, in order to prevent postural defects that, if detected in time, can still be re-educated.

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Insects, Vol. 6, Pages 943-960: Mating Success, Longevity, and Fertility of Diabrotica virgifera virgifera LeConte (Chrysomelidae: Coleoptera) in Relation to Body Size and Cry3Bb1-Resistant and Cry3Bb1-Susceptible Genotypes

Insect resistance to population control methodologies is a widespread problem. The development of effective resistance management programs is often dependent on detailed knowledge regarding the biology of individual species and changes in that biology associated with resistance evolution. This study examined the reproductive behavior and biology of western corn rootworm beetles of known body size from lines resistant and susceptible to the Cry3Bb1 protein toxin expressed in transgenic Bacillus thuringiensis maize. In crosses between, and within, the resistant and susceptible genotypes, no differences occurred in mating frequency, copulation duration, courtship duration, or fertility; however, females mated with resistant males showed reduced longevity. Body size did not vary with genotype. Larger males and females were not more likely to mate than smaller males and females, but larger females laid more eggs. Moderately strong, positive correlation occurred between the body sizes of successfully mated males and females; however, weak correlation also existed for pairs that did not mate. Our study provided only limited evidence for fitness costs associated with the Cry3Bb1-resistant genotype that might reduce the persistence in populations of the resistant genotype but provided additional evidence for size-based, assortative mating, which could favor the persistence of resistant genotypes affecting body size.

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Genes, Vol. 6, Pages 1201-1214: Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments

IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.

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Graded Resistance Exercise And Type 2 Diabetes in Older adults (The GREAT2DO study): methods and baseline cohort characteristics of a randomized controlled trial

Background: Type 2 diabetes (T2D) is projected to affect 439 million people by 2030. Medical management focuses on controlling blood glucose levels pharmacologically in a disease that is closely related to lifestyle factors such as diet and inactivity. Physical activity guidelines include aerobic exercise at intensities or volumes potentially unreachable for older adults limited by many co-morbidities. We aim to show for the first time the efficacy of a novel exercise modality, power training (high-velocity, high-intensity progressive resistance training or PRT), in older adults with T2D as a means for improving glycemic control and targeting many associated metabolic and physiological outcomes.Eligibility criteria included community-dwelling men and women previously diagnosed with T2D who met the current definition of metabolic syndrome according to the International Diabetes Federation. Participants were randomized to a fully supervised power training intervention or sham exercise control group for 12 months. Intervention group participants performed whole body machine-based power training at 80%1RM, 3 days per week. The control group undertook the same volume of non-progressive, low-intensity training. Participants were assessed at baseline, 6 months and 12 months and followed for a further 5 years, during which time participants were advised to exercise at moderate-high intensity. Glycemic control (HbA1c) and insulin resistance as measured by the homeostatic model assessment 2 (HOMA2-IR) were the primary outcomes of the trial. Outcome assessors were blinded to group assignment and participants were blinded to the investigators' hypothesis regarding the most effective intervention. Results: We recruited 103 participants (48.5 % women, 71.6 ± 5.6 years). Participants had 5.1 ± 1.8 chronic diseases, had been diagnosed with T2D for 8 ± 6 years and had a body mass index (BMI) of 31.6 ± 4.0 kg/m 2 . Fasting glucose and insulin were 7.3 ± 2.4 mmol/L and 10.6 ± 6.3 mU/L, respectively. HbA1c was 54 ± 12 mmol/mol. Eighty-six participants completed the 12-month assessment and follow-up is ongoing. This cohort had a lower-than-expected dropout (n = 14, 14 %) over the 12-month intervention period. Conclusions: Power training may be a feasible adjunctive therapy for improving glycemic control for the growing epidemic of T2D in older adults.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12606000436572 (24 September 2006).

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Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial

Background: Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans.Methods/DesignPatients submitted to unilateral, primary, open groin hernia repair will be included in this randomized, placebo-controlled, double-blind, crossover study. The experimental days take place 6–8 weeks after surgery, time-points at which patients are expected to be almost pain- free. Prior to administration of naloxone or placebo, the primary outcome (a summated measure of pain: at rest, during transition from supine to standing position, and evoked by pressure algometry) and the secondary outcomes (secondary hyperalgesia/allodynia, pressure pain thresholds, assessed at the surgical site and at the mirror-site in the contralateral groin, and, opioid withdrawal symptoms) will be assessed. These assessments will be repeated at each step of the target-controlled infusion of placebo or naloxone at estimated median (95 % CI) plasma concentrations of 344 ng/ml (130;567), 1059 ng/ml (400;1752) and 3196 ng/ml (1205;5276).DiscussionWe aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies.Trial registration numberEUDRACT: 2015-000793-36 (Registration date: 16 February 2015)Clinicaltrials.gov: NCT01992146 (Registration date: 12 December 2014)

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Automated analysis of single cells using Laser Tweezers Raman Spectroscopy

CrossMark.jpg

Analyst, 2015, Accepted Manuscript
DOI: 10.1039/C5AN01851J, Paper
Stephen Casabella, Peter Gardner, Patricia Scully, N J Goddard
In recent years, significant progress has been made into the label-free detection and discrimination of individual cancer cells using Laser Tweezers Raman Spectroscopy (LTRS). However, the majority of examples reported...
The content of this RSS Feed (c) The Royal Society of Chemistry


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Information, Vol. 6, Pages 733-749: Digital Information and Value

Digital information changes the ways in which people and organisations interact. This paper examines the nature of this change in the context of the author's Model for Information (MfI). It investigates the relationship between outcomes and value, selection processes and some attributes of information and explores how this relationship changes in the move from analogue to digital information. Selection processes shape the evolution of information ecosystems in which conventions are established for the ways in which information is used. The conventions determine norms for information friction and information quality as well as the sources of information and channels used. Digital information reduces information friction, often dramatically, and changes information quality. The increasing use of analytics in business increasingly delivers predictive or prescriptive digital information. These changes are happening faster than information ecosystem conventions can change. The relationships established in the paper enable an analysis of, and guide changes to, these conventions enabling a more effective use of digital information.

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IJMS, Vol. 16, Pages 26880-26913: Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

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IJMS, Vol. 16, Pages 26871-26879: Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS). More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1), heat shock 70 kDa protein 9 (HSPA9) and pyruvate kinase M2 (PKM2), were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL) suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

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IJMS, Vol. 16, Pages 26850-26870: Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target CellWall Integrity

Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2D and bck1D (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2D and bck1D showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAD, mpkCD) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention.

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Inorganics, Vol. 3, Pages 500-510: Holmium(III) Supermesityl-Imide Complexes Bearing Methylaluminato/Gallato Ligands

Heterobimetallic µ2-imide complexes [Ho(µ2-Nmes*){Al(CH3)4}]2 (1, supermesityl = mes* = C6H2tBu3-2,4,6) and [Ho(µ2-Nmes*){Ga(CH3)4}]2 (2) have been synthesized from homoleptic complexes Ho[M(CH3)4]3 (M = Al, Ga) via deprotonation of H2Nmes* or with K[NH(mes*)] according to a salt metathesis-protonolysis tandem reaction. Single-crystal X-ray diffraction of isostructural complexes [Ho(µ2-Nmes*){M(CH3)4}]2 (M = Al, Ga) revealed asymmetric Ho2N2 metallacycles with very short Ho–N bond lengths and secondary Ho arene interactions.

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IJMS, Vol. 16, Pages 26880-26913: Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

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IJMS, Vol. 16, Pages 26871-26879: Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS). More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1), heat shock 70 kDa protein 9 (HSPA9) and pyruvate kinase M2 (PKM2), were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL) suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

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IJMS, Vol. 16, Pages 26850-26870: Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target CellWall Integrity

Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2D and bck1D (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2D and bck1D showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAD, mpkCD) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention.

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IJMS, Vol. 16, Pages 26832-26849: Single-Cell Isolation and Gene Analysis: Pitfalls and Possibilities

During the last two decades single-cell analysis (SCA) has revealed extensive phenotypic differences within homogenous cell populations. These phenotypic differences are reflected in the stochastic nature of gene regulation, which is often masked by qualitatively and quantitatively averaging in whole tissue analyses. The ability to isolate transcripts and investigate how genes are regulated at the single cell level requires highly sensitive and refined methods. This paper reviews different strategies currently used for SCA, including harvesting, reverse transcription, and amplification of the RNA, followed by methods for transcript quantification. The review provides the historical background to SCA, discusses limitations, and current and future possibilities in this exciting field of research.

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IJERPH, Vol. 12, Pages 14312-14326: Kinetics and Mechanisms of Phosphorus Adsorption in Soils from Diverse Ecological Zones in the Source Area of a Drinking-Water Reservoir

On-site soils are increasingly used in the treatment and restoration of ecosystems to harmonize with the local landscape and minimize costs. Eight natural soils from diverse ecological zones in the source area of a drinking-water reservoir in central China are used as adsorbents for the uptake of phosphorus from aqueous solutions. The X-ray fluorescence (XRF) spectrometric and BET (Brunauer-Emmett-Teller) tests and the Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) spectral analyses are carried out to investigate the soils' chemical properties and their potential changes with adsorbed phosphorous from aqueous solutions. The intra-particle diffusion, pseudo-first-order, and pseudo-second-order kinetic models describe the adsorption kinetic processes. Our results indicate that the adsorption processes of phosphorus in soils occurred in three stages and that the rate-controlling steps are not solely dependent on intra-particle diffusion. A quantitative comparison of two kinetics models based on their linear and non-linear representations, and using the chi-square (χ2) test and the coefficient of determination (r2), indicates that the adsorptive properties of the soils are best described by the non-linear pseudo-second-order kinetic model. The adsorption characteristics of aqueous phosphorous are determined along with the essential kinetic parameters.

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IJERPH, Vol. 12, Pages 14301-14311: Exposure to Air Ions in Indoor Environments: Experimental Study with Healthy Adults

Since the beginning of the 20th century there has been a scientific debate about the potential effects of air ions on biological tissues, wellbeing and health. Effects on the cardiovascular and respiratory system as well as on mental health have been described. In recent years, there has been a renewed interest in this topic. In an experimental indoor setting we conducted a double-blind cross-over trial to determine if higher levels of air ions, generated by a special wall paint, affect cognitive performance, wellbeing, lung function, and cardiovascular function. Twenty healthy non-smoking volunteers (10 female, 10 male) participated in the study. Levels of air ions, volatile organic compounds and indoor climate factors were determined by standardized measurement procedures. Air ions affected the autonomous nervous system (in terms of an increase of sympathetic activity accompanied by a small decrease of vagal efferent activity): In the test room with higher levels of air ions (2194/cm3 vs. 1038/cm3) a significantly higher low to high frequency ratio of the electrocardiography (ECG) beat-to-beat interval spectrogram was found. Furthermore, six of nine subtests of a cognitive performance test were solved better, three of them statistically significant (verbal factor, reasoning, and perceptual speed), in the room with higher ion concentration. There was no influence of air ions on lung function and on wellbeing. Our results indicate slightly activating and cognitive performance enhancing effects of a short-term exposure to higher indoor air ion concentrations.

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IJERPH, Vol. 12, Pages 14285-14300: Arsenic and Other Metals’ Presence in Biomarkers of Cambodians in Arsenic Contaminated Areas

Chemical analyses of metal (Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Mo, Ba, and Pb) concentrations in hair, nails, and urine of Cambodians in arsenic-contaminated areas who consumed groundwater daily showed elevated levels in these biomarkers for most metals of toxicological interest. The levels of metals in biomarkers corresponded to their levels in groundwater, especially for As, whose concentrations exceeded the WHO guidelines for drinking water. About 75.6% of hair samples from the population in this study contained As levels higher than the normal level in unexposed individuals (1 mg·kg−1). Most of the population (83.3%) showed As urinary levels exceeding the normal (<50 ng·mg−1). These results indicate the possibility of arsenicosis symptoms in residents of the areas studied. Among the three biomarkers tested, hair has shown to be a reliable indicator of metal exposures. The levels of As (r2 = 0.633), Ba (r2 = 0.646), Fe (r2 = 0.595), and Mo (r2 = 0.555) in hair were strongly positively associated with the levels of those metals in groundwater. In addition, significant weak correlations (p < 0.01) were found between levels of exposure to As and As concentrations in both nails (r2 = 0.544) and urine (r2 = 0.243).

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IJMS, Vol. 16, Pages 26832-26849: Single-Cell Isolation and Gene Analysis: Pitfalls and Possibilities

During the last two decades single-cell analysis (SCA) has revealed extensive phenotypic differences within homogenous cell populations. These phenotypic differences are reflected in the stochastic nature of gene regulation, which is often masked by qualitatively and quantitatively averaging in whole tissue analyses. The ability to isolate transcripts and investigate how genes are regulated at the single cell level requires highly sensitive and refined methods. This paper reviews different strategies currently used for SCA, including harvesting, reverse transcription, and amplification of the RNA, followed by methods for transcript quantification. The review provides the historical background to SCA, discusses limitations, and current and future possibilities in this exciting field of research.

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Drug Delivery Using Novel Biological and Synthetic Materials



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Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases: Rationale, Aims, and Design of a Nationwide Prospective Registry—The EXCITING-ILD Registry

Despite a number of prospective registries conducted in past years, the current epidemiology of interstitial lung diseases (ILD) is still not well defined, particularly regarding the prevalence and incidence, their management, healthcare utilisation needs, and healthcare-associated costs. To address these issues in Germany, a new prospective ILD registry, "Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases" (EXCITING-ILD), is being conducted by the German Centre for Lung Research in association with ambulatory, inpatient, scientific pulmonology organisations and patient support groups. This multicentre, noninterventional, prospective, and observational ILD registry aims to collect comprehensive and validated data from all healthcare institutions on the incidence, prevalence, characteristics, management, and outcomes regarding all ILD presentations in the real-world setting. Specifically, this registry will collect demographic data, disease-related data such as ILD subtype, treatments, diagnostic procedures (e.g., HRCT, surgical lung biopsy), risk factors (e.g., familial ILD), significant comorbidities, ILD managements, and disease outcomes as well as healthcare resource consumption. The EXCITING-ILD registry will include in-patient and out-patient ILD healthcare facilities in more than 100 sites. In summary, this registry will document comprehensive and current epidemiological data as well as important health economic data for ILDs in Germany.

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Changes of Plantar Pressure and Gait Parameters in Children with Mild Cerebral Palsy Who Used a Customized External Strap Orthosis: A Crossover Study

Toe-in gait and crouch gait can make children with mild cerebral palsy fall and suffer improper balance during walking or ambulation training. A customized external strap orthosis for correcting leg alignment was used to resolve this problem. The purpose of this study was to research the immediate effects while wearing the customized external strap orthosis. Pressure platform was used to assess the plantar pressure through static and dynamic assessments and to record the changes in path of pressure trajectory. Motion image analysis system was used to record the gait parameters, which included gait speed, stride length, and cadence. The influence of both wearing and removing the orthosis on the dominant leg of children with mild cerebral palsy was analyzed. Nine children with mild cerebral palsy, who all had a dominant right leg, were recruited. After wearing the orthosis, all gait parameters improved, and foot motion changed in the stance phase of the gait cycle. The path of pressure trajectory closing to the midline was also observed during dynamic assessment. Changes in plantar pressure and path of pressure trajectory were observed and the orthosis device could provide immediate assistance to correct the leg alignment and improve the gait performance in children with mild cerebral palsy.

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Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells

Introduction. Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation). Methods. A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation. Results. Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5′(3′)-deoxyribonucleotidase. Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc. Discussion. This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis.

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Selection of the Strain Lactobacillus acidophilus ATCC 43121 and Its Application to Brewers’ Spent Grain Conversion into Lactic Acid

Six Lactobacillus strains were analyzed to select a bacterium for conversion of brewers' spent grain (BSG) into lactic acid. Among the investigated strains, L. acidophilus ATCC 43121 showed the highest yield of lactic acid production (16.1 g/L after 48 hours) when grown in a synthetic medium. It was then analyzed for its ability to grow on the hydrolysates obtained from BSG after acid-alkaline (AAT) or aqueous ammonia soaking (AAS) pretreatment. The lactic acid production by L. acidophilus ATCC 43121 through fermentation of the hydrolysate from AAS treated BSG was 96% higher than that from the AAT treated one, although similar yields of lactic acid per consumed glucose were achieved due to a higher (46%) glucose consumption by L. acidophilus ATCC 43121 in the AAS BSG hydrolysate. It is worth noting that adding yeast extract to the BSG hydrolysates increased both the yield of lactic acid per substrate consumed and the volumetric productivity. The best results were obtained by fermentation of AAS BSG hydrolysate supplemented by yeast extract, in which the strain produced 22.16 g/L of lactic acid (yield of 0.61 g/g), 27% higher than the value (17.49 g/L) obtained in the absence of a nitrogen source.

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Cancers, Vol. 7, Pages 2262-2276: Differences in Redox Regulatory Systems in Human Lung and Liver Tumors Suggest Different Avenues for Therapy

A common characteristic of many cancer cells is that they suffer from oxidative stress. They, therefore, require effective redox regulatory systems to combat the higher levels of reactive oxygen species that accompany accelerated growth compared to the normal cells of origin. An elevated dependence on these systems in cancers suggests that targeting these systems may provide an avenue for retarding the malignancy process. Herein, we examined the redox regulatory systems in human liver and lung cancers by comparing human lung adenocarcinoma and liver carcinoma to their respective surrounding normal tissues. Significant differences were found in the two major redox systems, the thioredoxin and glutathione systems. Thioredoxin reductase 1 levels were elevated in both malignancies, but thioredoxin was highly upregulated in lung tumor and only slightly upregulated in liver tumor, while peroxiredoxin 1 was highly elevated in lung tumor, but downregulated in liver tumor. There were also major differences within the glutathione system between the malignancies and their normal tissues. The data suggest a greater dependence of liver on either the thioredoxin or glutathione system to drive the malignancy, while lung cancer appeared to depend primarily on the thioredoxin system.

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