Effectiveness of a Worksite Intervention for Male Construction Workers on Dietary and Physical Activity Behaviors, Body Mass Index, and Health Outcomes: Results of a Randomized Controlled Trial.

Abstract:
PURPOSE
To evaluate the effectiveness of an individually tailored intervention for improvement in lifestyle behavior, health indicators, and prevention and reduction of overweight among construction workers.

DESIGN
Randomized controlled trial.

SETTING
Various blue-collar departments of a large construction company in the Netherlands.

PARTICIPANTS
Blue-collar workers randomized to an intervention (n = 162) or a control group (n = 152).

INTERVENTION
The intervention group received individual coaching sessions, tailored information, and materials to improve lifestyle behavior during a 6-month period, and the control group received usual care.

MEASURES
Body weight, body mass index (BMI), waist circumference, physical activity (PA) levels, dietary behavior, blood pressure, and blood cholesterol were assessed.

ANALYSIS
Effectiveness of the intervention on outcome measures at 6- and 12-month follow-up was assessed by using linear and logistic regression models adjusting for baseline levels.

RESULTS
After 6 months, a statistically significant intervention effect was found on body weight ( B = -1.06, P = .010), BMI ( B = -0.32, P = .010), and waist circumference ( B = -1.38, P = .032). At 6 months, the percentage of those meeting public health guidelines for PA increased significantly in the intervention group compared to the control group ( B = 2.06, P = .032), and for sugar-sweetened beverages, an intervention effect was found at 6 months as well ( B = -2.82, P = .003). At 12 months, for weight-related outcomes, these differences were slightly smaller and no longer statistically significant. The intervention was not effective on the total amount of moderate to vigorous PA and other dietary and health outcomes.

CONCLUSION
Intervention participants showed positive changes in vigorous PA and intake of sugar-sweetened beverages compared to controls, as well as effects on weight-related outcomes at 6 months. Long-term effects were still promising but not statistically significant.

Viester|Laura|L|
Verhagen|Evert A L M|EALM|
Bongers|Paulien M|PM|
van der Beek|Allard J|AJ|

construction workers
physical activity
dietary behavior
health promotion
weight control


ROS and GSH-responsive S-nitrosoglutathione functionalized polymeric nanoparticles to overcome multidrug resistance in cancer.

Abstract: Multidrug resistance of cancer cells is one of the major obstacle for chemotherapeutic efficiency. Nitric oxide (NO) has raised the potential to overcome multidrug resistance (MDR) with low side effects. Herein, we report a reactive oxygen species (ROS) and glutathione (GSH) responsive nanoparticle for the delivery of NO prodrug such as S-nitrosoglutathione (GSNO), which was chemically conjugated to an amphiphilic block copolymer. The GSNO functionalized nanoparticles show high NO loading capacity, good stability and sustained NO release with specific GSH activated NO-releasing kinetics. Such GSNO functionalized nanoparticles delivered doxorubicin (DOX) in a ROS triggered manner and increased the intracellular accumulation of DOX. However, in normal healthy cells, showing physiological concentrations of ROS, these nanoparticles presented good biocompatibility. The present work indicated that these multifunctional nanoparticles can serve as effective co-delivery platforms of NO and DOX to selectively kill chemo-resistant cancer cells through increasing chemo-sensitivity. STATEMENT OF SIGNIFICANCE: In this work, we constructed nitric oxide donor (S-nitrosoglutathione, GSNO) functionalized amphiphilic copolymer (PEG-PPS-GSNO) to deliver doxorubicin (DOX). The developed PEG-PPS-GSNO@DOX nanoparticles presented high NO capacity, ROS triggered DOX release and GSH triggered NO release. Thus NO reversed the chemo-resistance in HepG2/ADR cells increasing intrcellular accumulation of DOX. Furthermore, these PEG-PPS-GSNO@DOX nanoparticles exhibited biocompatibility to healthy cells and toxicity to cancer cells, due to elevated ROS.

Wu|Wen|W| Chen|Min|M| Luo|Tingrong|T| Fan|Ying|Y| Zhang|Jinqiang|J| Zhang|Yan|Y| Zhang|Qianyu|Q| Sapin-Minet|Anne|A| Gaucher|Caroline|C| Xia|Xuefeng|X|

D066244:Proton Magnetic Resonance Spectroscopy

S-nitrosoglutathione
Multidrug resistance of cancer
Nitric oxide
Glutathione-responsive
Reactive oxygen species-responsive


Alcohol sedation in adult Drosophila is regulated by Cysteine proteinase-1 in cortex glia.

Abstract: Although numerous studies have demonstrated that neuronal mechanisms regulate alcohol-related behaviors, very few have investigated the direct role of glia in behavioral responses to alcohol. The results described here begin to fill this gap in the alcohol behavior and gliobiology fields. Since Drosophila exhibit conserved behavioral responses to alcohol and their CNS glia are similar to mammalian CNS glia, we used Drosophila to begin exploring the role of glia in alcohol behavior. We found that knockdown of Cysteine proteinase-1 (Cp1) in glia increased Drosophila alcohol sedation and that this effect was specific to cortex glia and adulthood. These data implicate Cp1 and cortex glia in alcohol-related behaviors. Cortex glia are functionally homologous to mammalian astrocytes and Cp1 is orthologous to mammalian Cathepsin L. Our studies raise the possibility that cathepsins may influence behavioral responses to alcohol in mammals via roles in astrocytes.

Lee|Kristen M|KM|0000-0003-4527-6468
Mathies|Laura D|LD|
Grotewiel|Mike|M|


Evi1 Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of All-Trans Retinoic Acid on Flt3-ITD/Npm1c-Driven Acute Myeloid Leukemia Cells.

Abstract: All-trans retinoic acid (atRA) has a dramatic impact on the survival of patients with acute promyelocytic leukemia, but its therapeutic value in other types of acute myeloid leukemia (AML) has so far remained unclear. Given that AML is a stem cell-driven disease, recent studies have addressed the effects of atRA on leukemic stem cells (LSCs). atRA promoted stemness of MLL-AF9-driven AML in an Evi1-dependent manner but had the opposite effect in Flt3-ITD/Nup98-Hoxd13-driven AML. Overexpression of the stem cell-associated transcription factor EVI1 predicts a poor prognosis in AML, and is observed in different genetic subtypes, including cytogenetically normal AML. Here, we therefore investigated the effects of Evi1 in a mouse model for cytogenetically normal AML, which rests on the combined activity of Flt3-ITD and Npm1c mutations. Experimental expression of Evi1 on this background strongly promoted disease aggressiveness. atRA inhibited leukemia cell viability and stem cell-related properties, and these effects were counteracted by overexpression of Evi1. These data further underscore the complexity of the responsiveness of AML LSCs to atRA and point out the need for additional investigations which may lay a foundation for a precision medicine-based use of retinoids in AML.

EVI1
all-trans retinoic acid
FLT3-ITD
AML
MECOM
leukemia stem cells


The structural requirements of organophosphorus insecticides (OPI) for reducing chicken embryo NAD(+) content in OPI-induced teratogenesis in chickens.

Abstract: The objective of this study was to determine the structural requirements of organophosphorus insecticides (OPI) for reducing chicken embryo nicotinamide adenine dinucleotide (NAD(+)) content in OPI-induced teratogenesis and compare them with those needed for OPI inhibition of yolk sac membrane kynurenine formamidase (KFase), the proposed primary target for OPI teratogens in chicken embryos. The comparative molecular field analysis (COMFA) of three-dimensional quantitative structure-activity relationship (3D QSAR) revealed the electrostatic and steric fields as good predictors of OPI structural requirements to reduce NAD(+) content in chicken embryos. The dominant electrostatic interactions were localized at nitrogen-1, nitrogen-3, nitrogen of 2-amino substituent of the pyrimidinyl of pyrimidinyl phosphorothioates, and at the oxygen of crotonamide carbonyl in crotonamide phosphates. Bulkiness of the substituents at carbon-6 of the pyrimidinyls and/or N-substituents of crotonamides was the steric structural component that contributed to superiority of those OPI for reducing embryonic NAD(+) levels. Both electrostatic and steric requirements are similar to those defined in our previous study for OPI inhibition of chicken embryo yolk sac membrane KFase. The findings of this study provide another piece of evidence for the cause-and-effect relationship between yolk sac membrane KFase inhibition and reduced embryo NAD(+) content in NAD-associated OPI-induced teratogenesis in chickens.

Three-dimensional quantitative structure–activity relationship


Comparative urbanization of birds in China and Europe based on birds associated with trees.

Abstract: Urbanization effects on living organisms are spatially heterogeneous. Here we quantified the abundance of birds per tree in forested urban and rural habitats for 85,829 trees mainly in China and Europe. A population model was based on the assumption that: 1) birds have a normally distributed habitat preference; 2) an increase in population size linked to the habitat preference; 3) a population size dependent on the habitat preference; and 4) the removal of a certain fraction of individuals giving rise to extinction. We tested for large-scale differences in the impact of urbanization on the frequency distribution of the difference in abundance between urban and rural habitats in China and parts of Europe. The difference in the frequency distribution of urban population density of birds in trees minus rural population density of birds in trees in China and Europe was statistically significant, suggesting that the abundance of birds differed between trees in urban and rural habitats, but more so in China than in Europe. We hypothesize that more pronounced differences in China than in Europe may have arisen due to the Four Pests Campaign in 1958-1962 that resulted in death of hundreds of millions of birds (mainly tree sparrows Passer montanus, but also numerous other less common species that were starting to become urbanized around 1960). Species that were less common in 1960 could not sustain reductions in population size in urban areas and hence these species are still rare or absent in urban areas today 60 years later.

Møller|Anders Pape|AP|
Xia|Canwei|C|
ZHou|Bo|B|
Che|Xianli|X|
CHu|Xingzhi|X|
Feng|Changzhang|C|
Laursen|Karsten|K|
Morelli|Federico|F|
Li|Wangming|W|
Liu|Jianping|J|
Quan|Qing|Q|
Zhang|Min|M|
Zhang|Qiang|Q|
ZHan|Qiangwen|Q|
Ma|Laikun|L|
Wang|Haitao|H|
Zou|Fasheng|F|
Liang|Wei|W|

distribution
habitat preference
ANOSIM
community composition
frequency skewness
human-bird interactions
kurtosis
sociality


Interaction of DNA with likely-charged lipid monolayers: An experimental study.

Abstract: Anionic lipids are increasingly being used in lipoplexes for synthetic gene vectors as an alternative to cationic lipids. This is primarily due to their lower toxicity, which makes them biocompatible and adaptable to be tissue specific. However, anionic lipoplexes require the presence of multivalent cations to promote the electrostatic attraction between DNA and anionic lipid mono- and bilayers. In this work we provide for the first time experimental results of the adsorption of linear DNA onto anionic/zwitterionic lipid monolayers without any addition of cations. This is demonstrated experimentally by means of Langmuir monolayers of DOPE/DOPG (1:1) lipids spread on a water subphase that contains calf thymus DNA. The adsorption of DNA onto anionic/zwitterionic lipid monolayers is discussed in terms of the surface pressure-molecular area isotherms recorded in the absence and in the presence of different electrolytes. Measurements of the surface potential provide additional evidence of the different interaction of DNA anionic/zwitterionic lipid monolayers depending on the presence and nature of electrolyte. These experimental results are further analysed in terms of the overall dipole moment normal to the monolayers providing new insight into the behaviour of anionic lipoplexes and the role of zwitterionic lipids.

Luque-Caballero|German|G| Maldonado-Valderrama|Julia|J| Quesada-Pérez|Manuel|M| Martín-Molina|Alberto|A|

DNA
Lipids
Monolayer
Anionic
Lipoplexes
Zwitterionic
DOPE
DOPG
Surface potential
Dipole moment
Surface pressure


Enhanced Nanoassembly-Incorporated Antibacterial Composite Materials.

Abstract: The rapid advancement of peptide- and amino-acid-based nanotechnology offers new approaches for the development of biomedical materials. The utilization of fluorenylmethyloxycarbonyl (Fmoc)-decorated self-assembling building blocks for antibacterial and anti-inflammatory purposes represents promising advancements in this field. Here, we present the antibacterial capabilities of the nanoassemblies formed by Fmoc-pentafluoro-l-phenylalanine-OH, their substantial effect on bacterial morphology, as well as new methods developed for the functional incorporation of these nanoassemblies within resin-based composites. These amalgamated materials inhibit and hinder bacterial growth and viability and are not cytotoxic toward mammalian cell lines. Importantly, due to the low dosage required to confer antibacterial activity, the integration of the nanoassemblies does not affect their mechanical and optical properties. This approach expands on the growing number of accounts on the intrinsic antibacterial capabilities of self-assembling building blocks and serves as a basis for further design and development of enhanced composite materials for biomedical applications.

D000900:Anti-Bacterial Agents
D001672:Biocompatible Materials
D003188:Composite Resins
D003764:Dental Materials
D049329:Nanostructures
D036103:Nanotechnology

self-assembly
antibacterial materials
biomaterials
nanostructures
resin composite restoratives


Proteomics Approaches for Biomarker and Drug Target Discovery in ALS and FTD.

Abstract: Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are increasing in prevalence but lack targeted therapeutics. Although the pathological mechanisms behind these diseases remain unclear, both ALS and FTD are characterized pathologically by aberrant protein aggregation and inclusion formation within neurons, which correlates with neurodegeneration. Notably, aggregation of several key proteins, including TAR DNA binding protein of 43 kDa (TDP-43), superoxide dismutase 1 (SOD1), and tau, have been implicated in these diseases. Proteomics methods are being increasingly applied to better understand disease-related mechanisms and to identify biomarkers of disease, using model systems as well as human samples. Proteomics-based approaches offer unbiased, high-throughput, and quantitative results with numerous applications for investigating proteins of interest. Here, we review recent advances in the understanding of ALS and FTD pathophysiology obtained using proteomics approaches, and we assess technical and experimental limitations. We compare findings from various mass spectrometry (MS) approaches including quantitative proteomics methods such as stable isotope labeling by amino acids in cell culture (SILAC) and tandem mass tagging (TMT) to approaches such as label-free quantitation (LFQ) and sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) in studies of ALS and FTD. Similarly, we describe disease-related protein-protein interaction (PPI) studies using approaches including immunoprecipitation mass spectrometry (IP-MS) and proximity-dependent biotin identification (BioID) and discuss future application of new techniques including proximity-dependent ascorbic acid peroxidase labeling (APEX), and biotinylation by antibody recognition (BAR). Furthermore, we explore the use of MS to detect post-translational modifications (PTMs), such as ubiquitination and phosphorylation, of disease-relevant proteins in ALS and FTD. We also discuss upstream technologies that enable enrichment of proteins of interest, highlighting the contributions of new techniques to isolate disease-relevant protein inclusions including flow cytometric analysis of inclusions and trafficking (FloIT). These recently developed approaches, as well as related advances yet to be applied to studies of these neurodegenerative diseases, offer numerous opportunities for discovery of potential therapeutic targets and biomarkers for ALS and FTD.

Hedl|Thomas J|TJ|
San Gil|Rebecca|R|
Cheng|Flora|F|
Rayner|Stephanie L|SL|
Davidson|Jennilee M|JM|
De Luca|Alana|A|
Villalva|Maria D|MD|
Ecroyd|Heath|H|
Walker|Adam K|AK|
Lee|Albert|A|

proteomics
amyotrophic lateral sclerosis
frontotemporal dementia
protein aggregation
mass spectrometry


Effects of a comprehensive antimicrobial stewardship program in a surgical intensive care unit.

Abstract:
OBJECTIVES
We evaluated the effects of a comprehensive antimicrobial stewardship program (ASP) in a surgical intensive care unit (SICU).

METHODS
The ASP was implemented from March 2018 to February 2019 at an SICU in a teaching hospital. An infectious disease physician and a pharmacist visited the SICU 3 times per week for prospective audit and feedback. Outcomes were compared between the ASP period and the same months in the preceding year (pre-ASP period). The primary outcome measure was the use of anti-pseudomonal beta-lactams (APBL). Appropriate antimicrobial de-escalation and ICU mortality rates were also compared.

RESULTS
A total of 182 and 149 patients were included in the study for the pre-ASP and ASP periods, respectively. Although disease severity was higher in the ASP group (septic shock 39.0% in pre-ASP vs 65.1% in ASP group, P<0.001), the use of APBL as a definitive treatment was lower during ASP (68.7% vs 57.7%, OR 0.62, 95% CI 0.40-0.98). Appropriate antimicrobial de-escalation improved (63.2% vs 94.6%, P<0.001). ICU mortality was comparable (7.7% vs 7.4%) and significantly lower during the ASP, after adjustment (adjusted OR 0.41, 95% CI 0.18-0.92, P=0.032).

CONCLUSIONS
A comprehensive ASP decreased the use of APBL and was associated with improved patient outcomes.

Kim|Si-Ho|SH|
Yoon|Jin Gu|JG|
Park|Hyo Jung|HJ|
Won|Hojeong|H|
Ryoo|Sung Suk|SS|
Choi|Eunsil|E|
Park|Eun-Kyung|EK|
Huh|Kyungmin|K|
Park|Chi-Min|CM|

D000900:Anti-Bacterial Agents
D000890:Anti-Infective Agents
D000073602:Antimicrobial Stewardship
D003422:Critical Care
D006801:Humans
D007362:Intensive Care Units

Antimicrobial stewardship
Mortality
Critical care
Drug resistance
Microbial


Genetic profiling of protein burden and nuclear export overload.

Abstract: Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload.

genetic profiling
genetics
protein burden
nuclear export
S. cerevisiae
genomics
overexpression


Endoparasite Infections of the European Hedgehog (Erinaceus europaeus) in Central Italy.

Abstract: The European hedgehog is a synanthropic mammal, widely distributed in Europe. This species usually inhabits the edges of deciduous or mixed woods, but it is also very common in private gardens and public parks. Despite its popularity and frequency of contacts both with humans and with wild and domestic animals, few studies have examined the endoparasitic fauna of the hedgehog in Italy. In the present study, endoparasites of naturally deceased hedgehogs (n = 40) from central Italy (Latium and Tuscany regions) were investigated, along with concurrent gross and histopathological lesions. The most prevalent identified endoparasites were Crenosoma striatum (45%), Capillaria erinacei (42.5%) and Brachylaemus erinacei (22.5%), in accordance with previous reports from hedgehogs in southern Italy. In few subjects, Physaloptera clausa, Acanthocephalans and Cystoisospora rastegaeivae coccidia were also identified. The infection by the lungworm C. striatum was found to be significantly associated (p < 0.01) with bronchial hyperplasia and peribronchiolitis upon histopathological examination. Awareness of the most common parasitic infections in the hedgehog and of their effects on the health of these animals is extremely important, especially in wildlife rescue centers, where European hedgehog represents the most frequently hospitalized mammal species.

hedgehog
Crenosoma striatum
Capillaria erinacei
Brachylaemus erinacei
Physaloptera clausa
wildlife
Cystoisospora rastegaievae


Experimental Comparison of Radon Domain Approaches for Resident Space Object's Parameter Estimation.

Abstract: The fast and uncontrolled rise of the space objects population is threatening the safety of space assets. At the moment, space awareness solutions are among the most calling research topic. In fact, it is vital to persistently observe and characterize resident space objects. Instrumental highlights for their characterization are doubtlessly their size and rotational period. The Inverse Radon Transform (IRT) has been demonstrated to be an effective method for this task. The analysis presented in this paper has the aim to compare various approaches relying on IRT for the estimation of the object's rotation period. Specifically, the comparison is made on the basis of simulated and experimental data.

Ghio|Selenia|S|0000-0002-9894-0839 Martorella|Marco|M| Staglianò|Daniele|D| Petri|Dario|D| Lischi|Stefano|S| Massini|Riccardo|R|

comparison
Radon
RSO
SIRTA
SSA
SST
autocorrelation
micro-Doppler
period estimation
radar
rotating targets
space debris
time-frequency


Intracerebroventricular injection of lipopolysaccharide increases gene expression of connexin32 gap junction in rat hippocampus.

Abstract:
INTRODUCTION
Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx). Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS) diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 - among Connexins- is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS) on Cx32 gene and protein expressions in rat hippocampus is evaluated.

METHODS
LPS (2.5µg/rat) was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus.

RESULTS
Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P < 0.001). However, no significant change was observed in Cx32 protein level.

CONCLUSION
LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

Abbasian|Mohammad|M| Sayyah|Mohammad|M| Babapour|Vahab|V| Mahdian|Reza|R|


Global Myocardial Work Is Superior to Global Longitudinal Strain to Predict Significant Coronary Artery Disease in Patients With Normal Left Ventricular Function and Wall Motion.

Abstract:
BACKGROUND
Noninvasive detection of functionally significant coronary artery disease (CAD) by echocardiography remains challenging, with the need to perform stress imaging to detect ischemia. The aim of this study was to determine whether global myocardial work (MW), derived from noninvasive left ventricular (LV) pressure-strain loops at rest, can predict significant CAD in patients without regional wall motion abnormalities and preserved LV ejection fraction (EF).

METHODS
One hundred and fifteen patients referred for coronary angiography who had EF ≥ 55%, no resting regional wall motion abnormalities, and no chest pain were assessed using echocardiography. Global MW was derived from noninvasive LV pressure-strain loops constructed from speckle-tracking echocardiography indexed to brachial systolic blood pressure. Global constructive work represented the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation. Global wasted work represented energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation. Global MW efficiency was derived from the percentage ratio of constructive work to the sum of constructive work and wasted work.

RESULTS
Patients with significant CAD demonstrated a significantly reduced global MW (P < .001) compared with those without CAD. Global longitudinal strain was significantly reduced (P < .001) in patients with multivessel CAD but not those with single-vessel CAD (P = .47). Receiver operating characteristic curve analysis demonstrated that global MW was the most powerful predictor of significant CAD (area under the curve = 0.786) and was superior to global longitudinal strain (area under the curve = 0.693). The optimal cutoff global MW value to predict significant CAD was 1,810 mm Hg% (sensitivity, 92%; specificity, 51%).

CONCLUSIONS
Noninvasive global MW derived using LV pressure-strain loops at rest is a more sensitive index than global longitudinal strain to detect significant CAD in patients with no regional wall motion abnormalities and normal EF. This is a potential valuable clinical tool to assist in the early diagnosis of CAD.

Edwards|Natalie F A|NFA|
Scalia|Gregory M|GM|
Shiino|Kenji|K|
Sabapathy|Surendran|S|
Anderson|Bonita|B|
Chamberlain|Robert|R|
Khandheria|Bijoy K|BK|
Chan|Jonathan|J|

D000368:Aged
D017023:Coronary Angiography
D003324:Coronary Artery Disease
D003430:Cross-Sectional Studies
D025401:Echocardiography, Stress
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D011237:Predictive Value of Tests
D011446:Prospective Studies
D016277:Ventricular Function, Left

Myocardial work
Strain
Coronary artery disease
Speckle-tracking


The impact of progesterone supplementation on pregnancy rates after intrauterine insemination in patients developing a single follicle.

Abstract: The objective was to determine whether progesterone support affects pregnancy rates in patients who develop a single follicle. This was a non-randomized prospective controlled study performed on 591 intrauterine insemination (IUI) cycles that developed a single follicle; 337 women received 100 mg oral progesterone daily. The pregnancy rate was 24.3%, or 82 out of 337, in the group receiving progesterone support compared with 14.96%, or 254 out of 591, in the group with no progesterone support. IUI luteal phase supplementation with oral progesterone may improve clinical pregnancy rates when begun the day after insemination.

Güven|Davut|D| Batıoğlu|Ali|A| Sari|Seher|S| Bakay|Kadir|K|

progesterone
pregnancy
Intrauterine insemination
live-birth rates


Treating patients with renal cell carcinoma and bone metastases.

Abstract: Bone metastases (BMs) are common and cause morbidity in cancer patients. This review focuses on evidence in BMs from metastatic renal cell carcinoma (mRCC) management and discusses current evidence on the role of systemic treatments in BMs management, bone-targeting agents' benefits in skeletal-related events prevention and local therapeutic approaches to BM in mRCC. Areas covered: A comprehensive review of literature concerning incidence, prognosis, and therapeutic approaches of BMs was performed, focusing on the latest emerging evidence in management of BMs from mRCC. Expert commentary: One-third of mRCC patients present metastatic disease to the bone. BMs impact negatively the prognosis and decrease quality of life. Adequate management of BMs from RCC requires a multimodal evaluation to optimize care and quality of life. Both tyrosine-kinase inhibitors and immunotherapy may be effective in BMs treatment. BMs cause severe complications such as fracture, spinal cord compression, and pain requiring surgery or radiotherapy and several local approaches are available to achieve a local control of the disease. Defining prognosis of systemic disease and identifying the main goal of treatment is crucial for the selection of the best strategy.

D001859:Bone Neoplasms
D002292:Carcinoma, Renal Cell
D003131:Combined Modality Therapy
D006801:Humans
D007167:Immunotherapy
D007680:Kidney Neoplasms
D011379:Prognosis
D047428:Protein Kinase Inhibitors
D011788:Quality of Life

bone metastases
Mrcc
systemic treatments
bone target agents
local treatment


Temperature-Program Assisted Synthesis of Novel Z-Scheme CuBi₂O₄/β-Bi₂O₃ Composite with Enhanced Visible Light Photocatalytic Performance.

Abstract: Novel Z-Scheme CuBi₂O₄/β-Bi₂O₃ composite photocatalysts with different mass ratios and calcination temperatures were firstly synthesized by the hydrothermal method following a temperature-programmed process. The morphology, crystal structure, and light absorption properties of the as-prepared samples were systematically characterized, and the composites exhibited enhanced photocatalytic activity toward diclofenac sodium (DS) degradation compared with CuBi₂O₄ and β-Bi₂O₃ under visible light irradiation. The optimal photocatalytic efficiency of the composite, achieved at the mass ratio of CuBi₂O₄ and β-Bi₂O₃ of 1:2.25 and the calcination temperature of 600 °C is 92.17%. After the seventh recycling of the composite, the degradation of DS can still reach 82.95%. The enhanced photocatalytic activity of CuBi₂O₄/β-Bi₂O₃ is closely related to OH•, h⁺ and O₂•-, and the photocatalytic mechanism of CuBi₂O₄/β-Bi₂O₃ can be explained by the Z-Scheme theory.

Chen|Xiaojuan|X| Li|Ning|N| Zhu|Runliang|R| Li|Shuai|S| Yu|Chunmo|C| Xia|Wei|W| Xu|Song|S| Chen|Xin|X|

Z-Scheme
visible light
CuBi2O4/β-Bi2O3
organics
semiconductors
temperature programmed


Tobacco-related cancers in Europe: The scale of the epidemic in 2018.

Abstract:
BACKGROUND
Tobacco smoking is the major preventable cause of cancer. Despite the longstanding decline in smoking prevalence, lung cancer remains one of the most frequently diagnosed cancers in both sexes. We aimed to estimate the current cancer burden attributable to smoking in Europe.

METHODS
Smoking-related cancer incidence by country, cancer type, sex and age in Europe was estimated from GLOBOCAN 2018. We applied a modified version of the indirect method to estimate the population attributable fraction (PAF) for lung cancer and applied Levin's formula to estimate the PAF for other smoking-related cancer sites.

RESULTS
In Europe in 2018, 572,000 and 186,000 cancer cases were attributable to tobacco smoking in males and females respectively, accounting for 28% (males) and 10% (females) of all cancer cases. By region, the largest and the lowest PAF due to smoking in males occurred in Eastern Europe (35% of all cancer cases) and Northern Europe (21%), respectively. Among women, this pattern was reversed (16% in Northern Europe and 6% in Eastern Europe). Lung cancer accounted for more than half of the total cancer burden attributable to smoking (382,000). Other major contributors to the total PAF were lip, oral cavity and pharynx, bladder and laryngeal cancers in men (27% out of total PAF) and colorectal, pancreatic, oral cavity and pharyngeal cancers (21%) in women.

CONCLUSIONS
Tobacco smoking was responsible for one in five cancer cases in Europe in 2018. The introduction and robust implementation of tobacco control programmes are critical to reduce this cancer burden in the future.

Kulhánová|Ivana|I|
Forman|David|D|
Vignat|Jerome|J|
Espina|Carolina|C|
Brenner|Hermann|H|
Storm|Hans H|HH|
Bauld|Linda|L|
Soerjomataram|Isabelle|I|

Cancer
Europe
Smoking
Population attributable fraction


Vascular Cell Senescence Contributes to Blood-Brain Barrier Breakdown.

Abstract:
BACKGROUND AND PURPOSE
Age-related changes in the cerebrovasculature, including blood-brain barrier (BBB) disruption, are emerging as potential risks for diverse neurological conditions. Because the accumulation of senescent cells in tissues is increasingly recognized as a critical step leading to age-related organ dysfunction, we evaluated whether senescent vascular cells are associated with compromised BBB integrity.

METHODS
Effects of vascular cell senescence on tight junction and barrier integrity were studied using an in vitro BBB model, composed of endothelial cells, pericytes, and astrocytes. In addition, tight junction coverage in microvessels and BBB integrity in BubR1 hypomorphic (BubR1(H/H)) mice, which display senescence cell-dependent phenotypes, were examined.

RESULTS
When an in vitro BBB model was constructed with senescent endothelial cells and pericytes, tight junction structure and barrier integrity (evaluated by transendothelial electric resistance and tracer efflux assay using sodium fluorescein and Evans blue-albumin were significantly impaired. Endothelial cells and pericytes from BubR1(H/H) mice had increased senescent-associated β-galactosidase activity and p16(INK4a) expression, demonstrating an exacerbation of senescence. The coverage by tight junction proteins in the cortical microvessels were reduced in BubR1(H/H) mice, consistent with a compromised BBB integrity from permeability assays. Importantly, the coverage of microvessels by end-feet of aquaporin 4-immunoreactive astrocytes was not altered in the cortex of the BubR1(H/H) mice.

CONCLUSIONS
Our results indicate that accumulation of senescent vascular cells is associated with compromised BBB integrity, providing insights into the mechanism of BBB disruption related to biological aging.

Yamazaki|Yu|Y|
Baker|Darren J|DJ|
Tachibana|Masaya|M|
Liu|Chia-Chen|CC|
van Deursen|Jan M|JM|
Brott|Thomas G|TG|
Bu|Guojun|G|
Kanekiyo|Takahisa|T|

D019941:Cyclin-Dependent Kinase Inhibitor p16

tight junctions
endothelial cells
pericytes
permeability
aging
brain


Evaluation of a Stepped Care Approach to Manage Depression and Diabetes Distress in Patients with Type 1 Diabetes and Type 2 Diabetes: Results of a Randomized Controlled Trial (ECCE HOMO Study).

Abstract:
INTRODUCTION
Depression is a common and serious complication of diabetes. Treatment approaches addressing the specific demands of affected patients are scarce.

OBJECTIVE
The aim of this work was to test whether a stepped care approach for patients with diabetes and depression and/or diabetes distress yields greater depression reduction than treatment-as-usual.

METHODS
Two-hundred and sixty patients with diabetes and elevated depressive symptoms (CES-D ≥16) and/or elevated diabetes distress (PAID ≥40) were randomized to stepped care for depression or diabetes treatment-as-usual. The primary outcome was the rate of meaningful depression reduction at the 12-month follow-up according to the HAMD (score <9 or reduction by ≥50%). Secondary outcomes were changes in depression scores (HAMD/CES-D), diabetes distress (PAID), diabetes acceptance (AADQ), well-being (WHO-5), quality of life (EQ-5D/SF-36), self-care behavior (SDSCA/DSMQ), HbA1c, and biomarkers of inflammation.

RESULTS
One-hundred and thirty-one individuals were assigned to stepped care and 129 to treatment-as-usual. Overall, 15.4% were lost to follow-up. Meaningful depression reduction was observed in 80.2 versus 51.2% in stepped care versus treatment-as-usual (p < 0.001, intention-to-treat analysis). Of the secondary measures, the HAMD (∆ -3.2, p < 0.001), WHO-5 (∆ 1.5, p = 0.007), and AADQ (∆ -1.0, p = 0.008) displayed significant treatment effects, while effects on CES-D (∆ -2.3, p = 0.065), PAID (∆ -3.5, p = 0.109), and SDSCA (∆ 0.20, p = 0.081) were not significantly different. Both groups showed comparable changes in EQ-5D/SF-36, DSMQ, HbA1c, and biomarkers of inflammation (all p ≥ 0.19).

CONCLUSIONS
The stepped care approach improved depression, well-being, and acceptance. The results support that increasing treatment intensity on demand is effective and can help provide more optimal treatment. The inclusion of diabetes-specific interventions may be beneficial for patients with diabetes and elevated depression.

Schmitt|Andreas|A| Kulzer|Bernhard|B| Reimer|André|A| Herder|Christian|C| Roden|Michael|M| Haak|Thomas|T| Hermanns|Norbert|N|

Stepped care approach
Depressive symptoms
Cognitive-behavioral therapy
Emotional distress
Mood disorder


Synthesis and Bioactivities of New Membrane-Active Agents with Aromatic Linker: High Selectivity and Broad-Spectrum Antibacterial Activity.

Abstract: The worldwide emergence of microbial resistance to antibiotics constitutes an important and growing public health threat, and novel antibiotics are urgently needed. In this report, a series of symmetrical membrane-active agents linked by an aromatic nucleus were designed and synthesized. Some showed high antibacterial activity against clinical drug-resistant bacterial isolates including methicillin-resistant Staphylococcus aureus (MRSA), carbapenemase-producing Enterobacter aerogenes, and delhi metallo-β-lactamase-1-producing Enterobacteriaceae (NDM-1), as well as drug-sensitive bacteria including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Stenotrophomonas maltophilia. Lead compound 2n, with good selectivity for S. aureus (minimum inhibitory concentration [MIC] 0.25 μg/mL) versus mammalian erythrocytes (hemolytic concentration [HC50] 1211 μg/mL), had notable properties, including stability in complex mammalian fluids, rapid killing of pathogens, ability to eradicate established biofilms, and little induction of bacterial drug-resistance. In a mouse MRSA infection model, compound 2n exhibited a similar level of efficacy to vancomycin in killing bacteria and suppressing inflammation, demonstrating its therapeutic potential.

Chu|Wenchao|W| Yang|Yi|Y| Cai|Jianfeng|J|0000-0003-3106-3306 Kong|Hongtao|H| Bai|Mengmeng|M| Fu|Xiangjing|X| Qin|Shangshang|S| Zhang|En|E|0000-0002-4818-756X

membrane-active agents
selectivity
broad-spectrum antibacterial activity
antibiotics
low toxicity
structure−activity relationships


Nanoencapsulated methyl salicylate as a biorational alternative of synthetic antifungal and aflatoxin B1 suppressive agents.

Abstract: In view of the suspected negative impact of synthetic fungicides to the human health, nutritional quality, and non-targeted organisms, the use of plant-based antifungal agents has gained considerable interest to the agri-food industries. The aim of this study was to explore the antifungal and aflatoxin B1 (AFB1) inhibitory activity of chitosan (low molecular weight) encapsulated methyl salicylate. The nanoencapsulation of methyl salicylate (Ne-MS) has been characterized by SEM, FTIR, and XRD analysis. The encapsulation efficiency and loading capacity of Ne-MS ranged between 32-34% and 5-7% respectively. The minimum inhibitory concentration of Ne-MS (1.00 μL/mL) against the growth and aflatoxin B1 production by Aspergillus flavus was found to be lower than the free MS (1.50 μL/mL). Mode of action studies demonstrated that the Ne-MS cause a significant decrease in the ergosterol content, leakage of vital ions (Ca2+, Mg2+, and K+), utilization of different carbon source by the A. flavus. Further, the docking result showed ver1 and omt A gene of AFB1 biosynthesis are the possible molecular site of action of methyl salicylate. The in situ study revealed that Ne-MS had no significant negative impact on the organoleptic properties of the food system (maize) which strengthen its potential as a biorational alternative of synthetic fungicides.

Kujur|Anupam|A|
Yadav|Amrita|A|
Kumar|Akshay|A|
Singh|Prem Pratap|PP|
Prakash|Bhanu|B|

Nanoencapsulation
Methyl salicylate
Antifungal
Aflatoxin B1
Mode of action


Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine Pathogen Vibrio parahaemolyticus.

Abstract: We investigated global patterns of variation in 157 whole-genome sequences of Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans, have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a 27-fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by cyclic dimeric GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further "top down" analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations.

Cui|Yujun|Y| Yang|Xianwei|X| Didelot|Xavier|X| Guo|Chenyi|C| Li|Dongfang|D| Yan|Yanfeng|Y| Zhang|Yiquan|Y| Yuan|Yanting|Y| Yang|Huanming|H| Wang|Jian|J| Wang|Jun|J| Song|Yajun|Y| Zhou|Dongsheng|D| Falush|Daniel|D| Yang|Ruifu|R|

whole-genome sequencing
coalescent theory
molecular epidemiology
population genetics
population structure


Strategies to improve the medical device life cycle in Mexico.

Abstract:
OBJECTIVE
To analyze the role of stakeholders to three alternative strategies to improve processes and practices regarding the regulation, assessment, and management of orthopaedic medical devices in Mexico.

MATERIALS AND METHODS
The study was based on document analysis and 17 structured interviews with multiple key actors within the Mexican health system to inform a stakeholder analysis aiming at assessing the political feasibility of these strategies.

RESULTS
Central level government agencies, those with a relation to quality of care, were identified as most relevant stakeholders to influence the adaption and application of the strategies. Major barriers identified are financial and human resources, and organisational culture towards reform.

CONCLUSIONS
Discussed strategies are political feasible. However, solving identified barriers is crucial to achieve changes directed to improve outputs and outcomes of medical device life cycle and positively influence the quality of health care and the health system's performance.

Lingg|Myriam|M| Dreser|Anahi|A| Durán-Arenas|Luis|L| Wyss|Kaspar|K|

regulation
assessment
management
health technology
medical device.


Lower Incidence of Esophagitis in the Elderly Undergoing Definitive Radiation Therapy for Lung Cancer.

Abstract:
INTRODUCTION
Most patients with lung cancer are elderly and poorly represented in randomized clinical trials. They are often undertreated because of concerns about their ability to tolerate aggressive treatment. We tested the hypothesis that elderly patients undergoing definitive lung radiation might tolerate treatment differently than younger patients.

METHODS
A total of 125 patients who underwent definitive lung radiotherapy were identified from a prospective institutional database (University of Michigan cohort). Logistic regression modeling was performed to assess the impact of age on esophagitis grade 2 or higher or grade 2 or higher and pneumonitis grade 3 or higher or grade 2 or higher, with adjustment for esophageal and lung dose, respectively, as well as for chemotherapy utilization, smoking status, and performance status. The analysis was validated in a large cohort of 691 patients from the Michigan Radiation Oncology Quality Consortium registry, an independent statewide prospective database.

RESULTS
In the University of Michigan cohort, multivariable regression models revealed a significant inverse correlation between age and rate of esophagitis for both toxicity levels, (adjusted OR = 0.93 for both models and 95% confidence intervals of 0.88-0.98 and 0.87-0.99), with areas under the curve of 0.747 and 0.721, respectively, demonstrating good fit. This same association was noted in the Michigan Radiation Oncology Quality Consortium cohort. There was no significant association between age and pneumonitis.

CONCLUSIONS
There is a lower incidence of esophagitis with increasing age even after adjustment for use of chemotherapy. This is a novel finding in thoracic oncology. No age dependence was noted for pulmonary toxicity. The elderly are able to tolerate definitive thoracic radiation well and should be offered this option when clinically warranted.

Soni|Payal D|PD|
Boonstra|Philip S|PS|
Schipper|Matthew J|MJ|
Bazzi|Latifa|L|
Dess|Robert T|RT|
Matuszak|Martha M|MM|
Kong|Feng-Ming|FM|
Hayman|James A|JA|
Ten Haken|Randall K|RK|
Lawrence|Theodore S|TS|
Kalemkerian|Gregory P|GP|
Jolly|Shruti|S|

Esophagitis
Elderly
Radiation
Lung Cancer
Toxicity


Are Temporal Differences in GDNF and NOS Isoform Induction Contributors to Neurodegeneration? A Fluorescence Microscopy-Based Study.

Abstract:
BACKGROUND
Specific factors in Parkinson's disease have become targets as to their protective and degenerative effects. We have demonstrated that cytokines and PD-CSF detrimentally affect microglia and astrocyte growth. While glial cell-derived neurotrophic factor (GDNF) has been recognized as a possible neuron-rescue agent, nitric oxide synthase (NOS) has been implicated in neurodegenerative processes.

OBJECTIVE
To demonstrate that glial cell activation, cytokine production, and NOS induction, play an intimate role in the loss of dopaminergic signaling, via mechanisms that are a result of inflammation and inflammatory stimuli.

METHODS
Study animals were sacrificed following endotoxin treatment and tissue sections were harvested and probed for GDNF and NOS isomers by fluorescence deconvolution microscopy. Fluorescence was mapped and quantified for each probe.

RESULTS
An immune cell influx into 'vulnerable' areas of the brain was seen, and three NOS isomers, inducible (iNOS), neuronal (nNOS) and endothelial (eNOS), were synthesized in the brains, a finding which suggests that each isomer has a role in neurodegeneration. eNOS was found associated with blood vessels, while iNOS was associated with glial and matrix cells and nNOS was located with both glia and neurons. Following endotoxin treatment, serum levels of nitric oxide were higher at 6-8 hours, while tissue levels of NOS were elevated for much longer. Thus, induction of NOS occurred earlier than the induction of GDNF.

CONCLUSION
Our findings suggest that the protective abilities of GDNF to combat neural destruction are not available rapidly enough, and do not remain at sufficiently high levels long enough to assert its protective effects. (250).

Doursout|Marie-Francoise|MF|
Liang|Yangyan|Y|
Schiess|Mya C|MC|
Padilla|Angelica|A|
Poindexter|Brian J|BJ|
Hickson-Bick|Diane L M|DL|
Bick|Roger J|RJ|

Neurodegeneration
Nitric oxide
Endotoxin
Fluorescence microscopy
Glial derived neurotrophic factor


Patterns of Care and Treatment Target Success among Persons with Type 2 Diabetes Mellitus in Dubai: A Retrospective Cohort Study.

Abstract:
OBJECTIVES
Despite the high prevalence of type 2 diabetes mellitus (T2DM), few data exist describing its management in Dubai. This study characterized the treatment and estimated levels of glycemic, lipid, and blood pressure control among a sample with T2DM at a large Dubai Hospital.

METHODS
This retrospective cohort study systematically sampled charts from adults seeking care for T2DM from October 2009 to March 2010 until the target (N = 250) was reached. Data on patient characteristics, pharmacotherapy, complications, and laboratory testing were abstracted until September 2011. The frequency of treatments and modifications over the period was calculated, and measures of glycosylated hemoglobin A1c, low-density lipoprotein, and blood pressure control were compared with guideline targets. Frequencies of complications were compared according to treatment type.

RESULTS
One-third of the cohort comprised men, and the mean age was 58 years. At enrolment, the mean time from T2DM diagnosis was nearly 15 years and 74% had received insulin. During the study period, the most common regimens were insulin + oral combinations (55%) and oral combination therapy (39%). Overall, 67% received any insulin therapy during the study; and by study end, 78% had received insulin at any time. At the most recent assessment, guideline targets for glycosylated hemoglobin A1c, blood pressure, and low-density lipoprotein were met by 23%, 29%, and 71%, respectively. Complications were more frequent among those treated with combination or insulin therapies.

CONCLUSIONS
This study provides baseline data from Dubai for future comparisons of the effectiveness of new treatments, and to better understand the humanistic and economic burden of T2DM and its complications.

Osenenko|Katherine M|KM|
Szabo|Shelagh M|SM|
Qatami|Lara|L|
Korenblat Donato|Bonnie M|BM|
Al Madani|Abdulrazzak Ali|AA|
Al Awadi|Fatheya Fardallah|FF|
Al-Ansari|Jaber|J|
Maclean|Ross|R|
Levy|Adrian R|AR|

treatment
diabetes
United Arab Emirates
glycemic control


Fractional-Pixel CO2 Laser Treatment in Patients With Urodynamic Stress Urinary Incontinence: 1-Year Follow-Up.

Abstract:
BACKGROUND AND OBJECTIVES
Vaginal pixelated low power and long pulses (LPLP) CO2 laser has been suggested as an optional treatment for stress urinary incontinence (SUI) with many studies reporting short-term improvements. The objective of this study was to assess the 1-year subjective and objective efficacy of vaginal CO2 laser in women with urodynamic SUI.

STUDY DESIGN/MATERIALS AND METHODS
This was a prospective multicenter study. Patients with confirmed urodynamic SUI graded as mild or moderate were included. We used three sessions of fractional pixelated CO2 laser for vaginal application and followed up the patients at 6 and 12 months. We used the following measures at follow-up: 1-hour pad test (ICS protocol), questionnaires including Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ), Patient Global Impression of Improvement (PGI-I), and a 3-day urinary diary. The urodynamic assessment was repeated at 6 months.

RESULTS
Fifty-two patients with SUI had three laser treatments, of whom 48 completed a 6-month follow-up and 42 patients completed 12-month follow-up. No serious adverse events were recorded during the study period. A significant reduction on the 1-hour pad test was found from baseline (6.3 ± 1.6 g) to the 12-month follow-up (3.7 ± 1.4 g, P < 0.05) was found. PGI-I showed 75.0%, 61.9%, and 64.3% improvements at 3, 6, and 12 months, respectively. PFDI improved significantly and consistently from baseline until 12 months (37.2 ± 3.89 to 16.1 ± 3.7, P < 0.05). Similarly, PFIQ showed significant improvements from the first treatment up to 12 months. Urodynamic assessment at 6 months showed that 41.4% of patients had no stress incontinence.

CONCLUSION
The vaginal CO2 laser was found to be effective for mild-to-moderate SUI over a follow-up period of 1 year, according to a variety of objective and subjective parameters. The wide range of parameters enables optimal patient consultation and subsequent treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Alcalay|Menachem|M|0000-0002-8970-3516
Ben Ami|Moshe|M|
Greenshpun|Anatoly|A|
Hagay|Zion|Z|
Schiff|Eyal|E|

vaginal CO2 laser
urodynamic assessment
bladder symptoms
quality of life
urinary stress incontinence


Methylglyoxal Causes Cell Death in Neural Progenitor Cells and Impairs Adult Hippocampal Neurogenesis.

Abstract: Methylglyoxal (MG) is formed during normal metabolism by processes like glycolysis, lipid peroxidation, and threonine catabolism, and its accumulation is associated with various degenerative diseases, such as diabetes and arterial atherogenesis. Furthermore, MG has also been reported to have toxic effects on hippocampal neurons. However, these effects have not been studied in the context of neurogenesis. Here, we report that MG adversely affects hippocampal neurogenesis and induces neural progenitor cell (NPC) death. MG significantly reduced C17.2 NPC proliferation, and high concentration of MG (500 μM) induced cell death and elevated oxidative stress. Further, MG was found to activate the ERK signaling pathway, indicating elevated stress response. To determine the effects of MG in vivo, mice were administrated with vehicle or MG (0.5 or 1 % in drinking water) for 4 weeks. The numbers of BrdU-positive cells in hippocampi were significantly lower in MG-treated mice, indicating impaired neurogenesis, but MG did not induce neuronal damage or glial activations. Interestingly, MG reduced memory retention when administered to mice at 1 % but not at 0.5 %. In addition, the levels of hippocampal BDNF and synaptophysin were significantly lower in the hippocampi of mice treated with MG at 1 %. Collectively, our findings suggest MG could be harmful to NPCs and to hippocampal neurogenesis.

Chun|Hye Jeong|HJ|
Lee|Yujeong|Y|
Kim|Ah Hyun|AH|
Lee|Jaewon|J|

Methylglyoxal
Neural progenitor cells
Hippocampal neurogenesis
Memory retention
Brain-derived neurotropic factor


Long-term trends in pancreatic cancer mortality in Spain (1952-2012).

Abstract:
BACKGROUND
Pancreatic cancer is acquiring increasing prominence as a cause of cancer death in the population. The purpose of this study was to analyze long-term pancreatic cancer mortality trends in Spain and evaluate the independent effects of age, death period and birth cohort on these trends.

METHODS
Population and mortality data for the period 1952-2012 were obtained from the Spanish National Statistics Institute. Pancreatic cancer deaths were identified using the International Classification of Diseases ICD-6 to ICD-9 (157 code) and ICD-10 (C25 code). Age-specific and age-adjusted mortality rates were computed by sex, region and five-year period. Changes in pancreatic cancer mortality trends were evaluated using joinpoint regression analyses by sex and region. Age-period-cohort log-linear models were fitted separately for each sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures.

RESULTS
In men, rates increased by 4.1% per annum from 1975 until the mid-1980s and by 1.1% thereafter. In women, there was an increase of 3.6% per annum until the late 1980s, and 1.4% per annum from 1987 to 2012. With reference to the cohort effects, there was an increase in mortality until the generations born in the 1950s in men and a subsequent decline detected by the change point in 1960. A similar trend was observed in women, but the change point occurred 10 years later than in men.

CONCLUSIONS
Pancreatic cancer mortality increased over the study period in both sexes and all regions. An important rise in rates -around 4% annually- was registered until the 1980s, and upward trends were more moderate subsequently. The differences among sexes in trends in younger generations may be linked to different past prevalence of exposure to some risk factors, particularly tobacco, which underwent an earlier decrease in men than in women.

Pancreatic cancer
Mortality
Spain
Age-period-cohort analysis
Change-points
Time trends
Tobacco smoking


Fibrinolysin production by Alcaligenes faecalis strain 26 isolated from environment.

Abstract:
Background and Objectives
Fibrinolytic drugs are commonly used for fibrin clot lysis but due to their inappropriate side effects, as well as their high costs, using fibrinolytic enzymes has been paid attention. Bacterial sources of this enzyme are a good alternative for this purpose. The aim was fibrinolysin production through screening of fibrinolysin producing bacteria from environmental samples.

Materials and Methods
Bacterial isolation was performed from different environmental samples and was screened based on sheep blood clot digestion and culture on plasma plate. The most potent isolate was optimized for different growth parameters including temperature, pH and fibrinolysin production at optimum growth conditions. The stability of produced enzyme at various temperatures and pH and treatment with MgSO4, NiSO4, SDS and EDTA was then investigated. Finally this isolate was identified based on the 16S rRNA sequencing.

Results
As a result, from 79 different isolates, the most potent fibrinolysin producer was identified as Alcaligenes faecalis strain 26. This isolate produced 12 mm halo zone on plasma plate. Its optimum growth temperature and pH was 43°C and 7, respectively. The produced enzyme had the best stability at pH 7 and was also active up to 60°C. The fibrinolytic activity of this isolate was reduced following treatment with MgSO4, NiSO4 and also with protease inhibitors, such as SDS and EDTA.

Conclusion
Based on the obtained results it can be suggested that Alcaligenes faecalis strain 26 has appropriate efficiency for fibrinolysin production that can be used in food industry and medicine.

Fibrinolysin
Alcaligenes faecalis
Blood clot


Incidence and risk factors of skin rashes and hepatotoxicity in HIV-infected patients receiving nevirapine-containing combination antiretroviral therapy in Taiwan.

Abstract:
OBJECTIVES
To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors.

METHODS
The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed.

RESULTS
Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence interval (CI) 1.56-8.96); higher CD4 counts (aOR for per 50 cells/μl increase 1.51, 95% CI 1.12-2.03) and the concurrent use of trimethoprim/sulfamethoxazole (aOR 14.01, 95% CI 1.98-98.95) were associated with hepatotoxicity.

CONCLUSIONS
Abnormal liver function at baseline was significantly associated with skin rashes, while a higher CD4 count and the concurrent use of trimethoprim/sulfamethoxazole were associated with hepatotoxicity after the initiation of nevirapine-containing cART in HIV-infected Taiwanese patients.

Tseng|Yu-Tzu|YT| Yang|Chia-Jui|CJ| Chang|Sui-Yuan|SY| Lin|Shu-Wen|SW| Tsai|Mao-Song|MS| Liu|Wen-Chun|WC| Wu|Pei-Ying|PY| Su|Yi-Ching|YC| Luo|Yu-Zhen|YZ| Yang|Shang-Ping|SP| Hung|Chien-Ching|CC| Chang|Shan-Chwen|SC|


Liver resection combined with inferior vena cava resection and reconstruction using artificial vascular graft: A literature review.

Abstract: In cases where liver tumors invade the inferior vena cava (IVC), IVC resection along with liver resection may be needed to effect a cure. Furthermore, if the IVC defect is large, IVC reconstruction with vascular graft after resection is required. There are limited reports of cases of IVC reconstruction using a graft. By reviewing data from the literature of previous studies, the present study was aimed at investigating the surgical outcomes of liver resection with IVC resection and reconstruction using an artificial vascular graft. PubMed was searched for previous articles reporting cases with the combined surgery. The search was limited to articles in English, and cases with exceptional surgeries such as in situ cold perfusion, and ante situm and ex vivo techniques were excluded from this study. Surgical outcomes of the extracted cases were investigated. Cases dealt only with primary closure after IVC resection, and those in which the IVC tumor thrombus was treated by opening the IVC wall, removing the thrombus and then closing the IVC without wall excision were not included in this study. The literature search identified 13 studies, including 111 cases. Operative mortality in the reported cases was 8.1% (9 out of 111 cases). Thrombus in the artificial vascular graft was observed in two cases, and patency of the graft during the follow-up period was confirmed in 109 of the 111 cases (98.2%). These results suggested that the surgical outcomes of liver resection combined with IVC resection and reconstruction using the artificial vascular graft were favorable.

Tomimaru|Yoshito|Y|0000-0002-4432-060X Eguchi|Hidetoshi|H| Wada|Hiroshi|H| Doki|Yuichiro|Y| Mori|Masaki|M| Nagano|Hiroaki|H|

liver resection
inferior vena cava
reconstruction
artificial vascular graft


POLYMERIC BIOMATERIALS AND NANOMEDICINES.

Abstract: This overview intends to demonstrate the close relationship between the design of smart biomaterials and water-soluble polymer-drug conjugates. First, the discovery and systematic studies of hydrogels based on crosslinked poly(meth)acrylic acid esters and substituted amides is described. Then, the lessons learned for the design of water-soluble polymers as drug carriers are highlighted. The current state-of-the-art in water-soluble, mainly poly[N-(2-hydroxypropyl)methacylamide (HPMA), polymer-drug conjugates is shown including the design of backbone degradable HPMA copolymer carriers. In the second part, the modern design of hybrid hydrogels focuses on the self-assembly of hybrid copolymers composed from the synthetic part (backbone) and biorecognizable grafts (coiled-coil forming peptides or morpholino oligonucleotides) is shown. The research of self-assembling hydrogels inspired the invention and design of drug-free macromolecular therapeutics - a new paradigm in drug delivery where crosslinking of non-internalizating CD20 receptors results in apoptosis in vitro and in vivo. The latter is mediated by biorecognition of complementary motifs; no low molecular weight drug is needed.

Nanomedicines
Polymer-drug conjugates
Hydrogels
Drug-free macromolecular therapeutics
Cancer
Self-assembly of macromolecules


Effect of Aggregation on the Hydrodynamic Properties of Bovine Serum Albumin.

Abstract:
PURPOSE
To systematically analyze shape and size of soluble irreversible aggregates and the effect of aggregate formation on viscosity.

METHODS
Online light scattering, refractive index and viscosity detectors attached to HPLC (Viscotek®) were used to study aggregation, molecular weight and intrinsic viscosity of bovine serum albumin (BSA). Irreversible aggregates were generated by heat stress. Bulk viscosity was measured by an oscillating piston viscometer.

RESULTS
As BSA was heated at a higher concentration or for a longer time, the relative contribution, molecular weight and intrinsic viscosity of aggregate species increased. Molecular shape was evaluated from intrinsic viscosity values, and aggregates were estimated to be more asymmetric than monomer species. The presence of aggregates resulted in an increase in bulk viscosity when relative contribution of very high molecular weight species exceeded 10%.

CONCLUSIONS
For model system and conditions studied, generation of higher order aggregate species was concluded to be associated with an increase in molecular asymmetry. Elevated viscosity in the presence of aggregated species points to molecular asymmetry being a critical parameter affecting solution viscosity of BSA.

Pindrus|Mariya A|MA|
Cole|James L|JL|
Kaur|Japneet|J|
Shire|Steven J|SJ|
Yadav|Sandeep|S|
Kalonia|Devendra S|DS|

D002851:Chromatography, High Pressure Liquid

aggregation
intrinsic viscosity
effective molecular shape


Motor hysteresis in a sequential grasping and pointing task is absent in task-critical joints.

Abstract: In a prior study (Schütz et al. in Exp Brain Res 2016. doi: 10.1007/s00221-016-4608-6 ), we demonstrated that the cognitive cost of motor planning did not differ in a vertical pointing and grasping task. It was unclear whether the similar cost implied that both tasks required the same number of independent degrees of freedom (IDOFs) or that the number of IDOFs did not affect motor planning. To differentiate between both cases, a reanalysis of the prior data was conducted. The number of IDOFs in the pointing and grasping tasks was computed by factor analysis. In both tasks, two IDOFs were used, which was the minimum number required for position control. This indicates that hand alignment in the grasping task did not require an additional IDOF. No conclusions regarding the link between the cognitive cost of motor planning and the number of IDOFs could be drawn. A subset of task-critical joint angles was not affected by motor hysteresis. This indicates that a joint's susceptibility to motor hysteresis depends on its relevance to the task goal. In task-critical joints, planning cost minimization by motor plan reuse is suppressed in favor of the task goal.

Motor hysteresis
Grasping
Pointing
Motor planning
Factor analysis


Comparative morphology of the hemolymph vascular system in Uropygi and Amblypygi (Arachnida): Complex correspondences support Arachnopulmonata.

Abstract: Although the circulatory system of arthropods has long been considered as rather simple, recent studies have demonstrated that in certain arthropod taxa, such as Malacostraca, some Chilopoda and also many Chelicerata, the vascular systems in particular are rather complex. Furthermore, a recent study has revealed that the prosomal ganglion of scorpions and spiders is supplied by an intricate network of arteries, the complexity of which bears a close resemblance to that of vertebrate capillary systems. In this study, we analyzed the hemolymph vascular systems of various species of Pedipalpi (i.e., Amblypygi and Uropygi). By combining modern techniques, such as MicroCT and cLSM, with computer-based 3D-reconstruction, we were able to produce comprehensive visualizations and descriptions of the vascular systems. Despite the lack of well-corroborated phylogenetic hypotheses on arachnid relationships and the controversial assertion of relationships between the pulmonate arachnids, we aim to elucidate the evolution of complex vascular systems in Arachnida. By comparing these highly complex vascular systems not only with each other, but also with other pulmonate arachnids, we found numerous detailed correspondences in the general branching pattern as well as in the supply patterns of the prosomal ganglion. We argue that these numerous and detailed correspondences by their absence in other arachnids i.e. aplumonates, support Arachnopulmonata. J. Morphol. 277:1084-1103, 2016. © 2016 Wiley Periodicals, Inc.

morphology
Uropygi
Amblypygi
Arachnopulmonata
circulatory system


Functional reorganization of brain networks across the human menstrual cycle.

Abstract: The brain is an endocrine organ, sensitive to the rhythmic changes in sex hormone production that occurs in most mammalian species. In rodents and nonhuman primates, estrogen and progesterone's impact on the brain is evident across a range of spatiotemporal scales. Yet, the influence of sex hormones on the functional architecture of the human brain is largely unknown. In this dense-sampling, deep phenotyping study, we examine the extent to which endogenous fluctuations in sex hormones alter intrinsic brain networks at rest in a woman who underwent brain imaging and venipuncture for 30 consecutive days. Standardized regression analyses illustrate estrogen and progesterone's widespread associations with functional connectivity. Time-lagged analyses examined the temporal directionality of these relationships and suggest that cortical network dynamics (particularly in the Default Mode and Dorsal Attention Networks, whose hubs are densely populated with estrogen receptors) are preceded-and perhaps driven-by hormonal fluctuations. A similar pattern of associations was observed in a follow-up study one year later. Together, these results reveal the rhythmic nature in which brain networks reorganize across the human menstrual cycle. Neuroimaging studies that densely sample the individual connectome have begun to transform our understanding of the brain's functional organization. As these results indicate, taking endocrine factors into account is critical for fully understanding the intrinsic dynamics of the human brain.

Pritschet|Laura|L|
Santander|Tyler|T|
Taylor|Caitlin M|CM|
Layher|Evan|E|
Yu|Shuying|S|
Miller|Michael B|MB|
Grafton|Scott T|ST|
Jacobs|Emily G|EG|

Sex hormones
Estrogen
Progesterone
Functional connectivity
Resting-state


Hygroscopic expansion of self-adhesive resin cements and the integrity of all-ceramic crowns.

Abstract:
OBJECTIVE
Low pH neutralization and subsequent remnant hydrophilicity can lead to hygroscopic expansion of self-adhesive resin cements (SARCs) after water storage. The aim of this in vitro study was to investigate the effects of hygroscopic expansion of SARCs, used as luting and partial core build-up material, on integrity and cement gap thickness increase of all-ceramic CAD/CAM crowns.

METHODS
Human third molars (n=48) were prepared and anatomical all-ceramic CAD/CAM crowns were manufactured (VITABLOCS Mark II, VITA Zahnfabrik). Crowns internal surfaces were HF etched and silanized. The prepared teeth with their respective crowns were divided into 6 groups (n=8). In groups 1, 3 and 5 the coronal dentin was removed to simulate a partial core build-up. Groups 1 and 2 were luted with iCEM (Heraeus Kulzer), 3 and 4 with RelyX Unicem 2 Automix (3M), 5 and 6 with Variolink Esthetic DC (Ivoclar Vivadent). All specimens were dual cured and stored in distilled water at 37°C. Crown integrity was controlled at baseline and in regular intervals until 180 days. Cement gap thickness was measured using an optical 3D scanner (ATOS Triple scan, GOM) at baseline and after 180 days. Crown integrity was statistically analysed using Kaplan-Meier survival analysis and cement gap thickness increase using two-way ANOVA (α=0.05).

RESULTS
After 180 days storage, crack formation was observed in all specimens of group 1 (mean survival time of 85.5 days), in one specimen of group 2 and in two specimens of group 4. Two-way ANOVA analysis revealed a statistically significant interaction between material type and build-up on cement gap size increase for iCEM.

SIGNIFICANCE
Within the limits of this study, the application of SARCs with low pH neutralization as partial build-up material under CAD/CAM crowns is not recommended for clinical use.

Kirsten|Magdalena|M|
Matta|Ragai Edward|RE|
Belli|Renan|R|
Lohbauer|Ulrich|U|
Wichmann|Manfred|M|
Petschelt|Anselm|A|
Zorzin|José|J|

D000134:Acid Etching, Dental
D000180:Acrylic Resins
D002516:Ceramics
D003188:Composite Resins
D017076:Computer-Aided Design
D003442:Crowns
D003738:Dental Cements
D003776:Dental Porcelain
D017267:Dental Prosthesis Design
D006801:Humans
D006863:Hydrogen-Ion Concentration
D066298:In Vitro Techniques
D008422:Materials Testing
D008964:Molar, Third
D011140:Polyurethanes
D019279:Resin Cements
D014867:Water
D017155:Wettability

Hygroscopic expansion
Self-adhesive resin cements
All-ceramic crowns
pH neutralization
CAD/CAM
Fractography


Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells.

Abstract: The aim of this study was to develop anti-EGFR antibody conjugated poly(lactide-co-glycolide) nanoparticles (NPs) to target epidermal growth factor receptor, highly expressed on non-small cell lung cancer cells to improve cytotoxicity and site specificity. Cetuximab was conjugated to docetaxel (DTX) loaded PLGA NPs by known EDC/NHS chemistry and characterised for size, zeta potential, conjugation efficiency and the results were 128.4 ± 3.6 nm, -31.0 ± 0.8 mV, and 39.77 ± 3.4%, respectively. In vitro release study demonstrated sustained release of drug from NPs with 25% release at pH 5.5 after 48 h. In vitro cytotoxicity studies demonstrated higher anti-proliferative activity of NPs than unconjugated NPs. Cell cycle analysis and apoptosis study were performed to evaluate extent of cell arrest at different phases and apoptotic potential for the formulations, respectively. In vivo efficacy study showed significant reduction in tumour growth and so antibody conjugated NPs present a promising active targeting carrier for tumour selective therapeutic treatment.

Patel|Jitendrakumar|J| Amrutiya|Jitendra|J| Bhatt|Priyanka|P| Javia|Ankit|A| Jain|Mukul|M| Misra|Ambikanandan|A|

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

Antibody
docetaxel
poly(lactide-co-glycolide)
epidermal growth factor receptor
cetuximab


BNIP3-mediated Autophagy Induced Inflammatory Response and Inhibited VEGF Expression in Cultured Retinal Pigment Epithelium Cells Under Hypoxia.

Abstract:
BACKGROUND
Bcl-2/adenovirus E1B-19kDa-interacting protein (BNIP3), an important target of hypoxia-inducible factors-1 alpha (HIF-1α), was reported to be overexpressed under hypoxic condition. Our previous study demonstrated the protective effect on detached retina by BNIP3-mediated autophagy. The study investigated the role of BNIP3-mediated autophagy in retinal pigment epithelial (RPE) cells under hypoxia, and observed the relationship between BNIP3, vascular endothelial growth factor (VEGF) and inflammatory response in hypoxic RPE cells.

METHODS
BNIP3 knock down in retinal pigment epithelial cells was performed by small interfering RNA (siRNA) technology in ARPE-19 cells, a human RPE cell line. Both control and BNIP3-knockdown ARPE-19 cells were then subjected to a hypoxic challenge using cobalt (II) chloride (CoCl2). The expression of autophagy-related genes, VEGF and inflammatory factors (IL-18, IL-8, MMP-2, MMP-9, NLRP3, TNF-α) in RPE cells was examined using quantitative Polymerase Chain Reaction (qPCR). The protein levels of HIF-1α, BNIP3, the maker proteins (ATG5, LC3,p62, Beclin-1) of autophagy and the component proteins (p-p70S6K, p70S6K, mTOR, p-mTOR) of the mTORC1 pathway were analyzed by Western blot. BNIP3 subcellualr localization was detected by immunofluorescence. Cell viability was measured with Cell Counting kit-8. Cell apoptosis was examined by TUNEL staining and caspase-3 activity assay.

RESULTS
The expression levels of BNIP3, HIF-1α and marker genes of autophagy were upregulated in ARPE-19 cells in response to hypoxia. Importantly, hypoxia-induced autophagy was mediated by the mTORC1 pathway, and was blocked upon BNIP3 knockdown. Additionally, hypoxia reduced cell viability, which was relieved by an mTORC1 inhibitor. Also, autophagy protected ARPE-19 cells from CoCl2-induced cell apoptosis. Moreover, inhibition of autophagy upregulated the expression of VEGF and IL-18, and downregulated the expression of other inflammatory factors in the hypoxic ARPE-19 cells.

CONCLUSION
BNIP3-mediated autophagy under hypoxia is involved in regulating inflammatory response and VEGF expression, which consequently affects the cell viability of RPE cells.

Chen|Yuhong|Y| Yan|Quan|Q| Xu|Yihua|Y| Ye|Fuxiang|F| Sun|Xiaodong|X| Zhu|Hong|H| Wang|Hong|H|

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D042461:Vascular Endothelial Growth Factor A

autophagy VEGF hypoxia BNIP3 RPEs inflammation.


Thrombospondin 1 in Metabolic Diseases.

Abstract: The thrombospondin family comprises of five multifunctional glycoproteins, whose best-studied member is thrombospondin 1 (TSP1). This matricellular protein is a potent antiangiogenic agent that inhibits endothelial migration and proliferation, and induces endothelial apoptosis. Studies have demonstrated a regulatory role of TSP1 in cell migration and in activation of the latent transforming growth factor beta 1 (TGFβ1). These functions of TSP1 translate into its broad modulation of immune processes. Further, imbalances in immune regulation have been increasingly linked to pathological conditions such as obesity and diabetes mellitus. While most studies in the past have focused on the role of TSP1 in cancer and inflammation, recently published data have revealed new insights about the role of TSP1 in physiological and metabolic disorders. Here, we highlight recent findings that associate TSP1 and its receptors to obesity, diabetes, and cardiovascular diseases. TSP1 regulates nitric oxide, activates latent TGFβ1, and interacts with receptors CD36 and CD47, to play an important role in cell metabolism. Thus, TSP1 and its major receptors may be considered a potential therapeutic target for metabolic diseases.

TGFβ1
obesity
diabetes
cardiovascular disease
nitric oxide
angiogenesis
atherosclerosis


Staphylococcus aureus and Host Immunity in Recurrent Furunculosis.

Abstract: Staphylococcus aureus is one of the severest and most persistent bacterial pathogens. The most frequent S. aureus infections include impetigo, folliculitis, furuncles, furunculosis, abscesses, hidradenitis suppurativa, and mastitis. S. aureus produces a great variety of cellular and extracellular factors responsible for its invasiveness and ability to cause pathological lesions. Their expression depends on the growth phase, environmental factors, and location of the infection. Susceptibility to staphylococcal infections is rooted in multiple mechanisms of host immune responses and reactions to bacterial colonization. Immunological and inflammatory processes of chronic furunculosis are based on the pathogenicity of S. aureus as well as innate and acquired immunity. In-depth knowledge about them may help to discover the whole pathomechanism of the disease and to develop effective therapeutic options. In this review, we focus on the S. aureus-host immune interactions in the pathogenesis of recurrent furunculosis according to the most recent experimental and clinical findings.

Staphylococcus aureus
Furunculosis
Infection
Staphylococcal infections
Acquired immunity
Innate immunity


Application of Chaos Theory in the Assessment of Emotional Vulnerability and Emotion Dysregulation in Adults.

Abstract: In this work, we propose an interdisciplinary chaos analysis of emotion dysregulation (ED) and emotional vulnerability in adults. One of the main goals was the assessment of incongruences that occur in the evaluation of one's own emotional dysregulation mechanisms in the presence of an extremely weak stimulus (Butterfly Effect). Thus, we considered a "flavor" of the Lyapunov Function method based on the assumption that the effort of answering to the test is itself a small perturbation. In this context, we calculated the "instability coefficient" Δ defined as the Euclidean distance between the pairs of vectors that include similar and reverted items of a test. The relationship between Δ, ED, and emotional characteristics as quality (positive/negative) and type (trait/state) was highlighted. We hypothesized that a higher level of Δ should be significantly related with a higher ED and with the type and the quality of emotions. The results suggest that Δ is significantly correlated with trait emotions (positively with negative emotions, and negatively with positive ones) and with ED. Moreover, Δ significantly predicts ED in adults. Thus, we consider that this approach is promising with respect to the evolution of emotional mechanisms across time. The presence of an initial instability to a weak perturbation might predict future abnormal emotional functioning, which could put at risk the mental or psychosomatic systems.

Chaos theory
emotions
Butterfly Effect
Lyapunov Function
emotion regulation


Concepts and Physiological Aspects of the Otolith Organ in Relation to Electrical Stimulation.

Abstract:
BACKGROUND
This paper discusses some of the concepts and major physiological issues in developing a means of electrically stimulating the otolithic system, with the final goal being the electrical stimulation of the otoliths in human patients. It contrasts the challenges of electrical stimulation of the otolith organs as compared to stimulation of the semicircular canals. Electrical stimulation may consist of trains of short-duration pulses (e.g., 0.1 ms duration at 400 Hz) by selective electrodes on otolith maculae or otolithic afferents, or unselective maintained DC stimulation by large surface electrodes on the mastoids - surface galvanic stimulation.

SUMMARY
Recent anatomical and physiological results are summarized in order to introduce some of the unique issues in electrical stimulation of the otoliths. The first challenge is that each otolithic macula contains receptors with opposite polarization (opposing preferred directions of stimulation), unlike the uniform polarization of receptors in each semicircular canal crista. The puzzle is that in response to the one linear acceleration in the one macula, some otolithic afferents have an increased activation whereas others have decreased activation. Key Messages: At the vestibular nucleus this opposite receptor hair cell polarization and consequent opposite afferent input allow enhanced response to the one linear acceleration, via a "push-pull" neural mechanism in a manner analogous to the enhancement of semicircular canal responses to angular acceleration. Within each otolithic macula there is not just one uniform otolithic neural input to the brain - there are very distinctly different channels of otolithic neural inputs transferring the neural data to the brainstem. As a simplification these channels are characterized as the sustained and transient systems. Afferents in each system have different responses to stimulus onset and maintained stimulation and likely different projections, and most importantly different thresholds for activation by electrical stimulation and different adaptation rates to maintained stimulation. The implications of these differences are considered.

D000818:Animals
D004558:Electric Stimulation
D006801:Humans
D009475:Neurons, Afferent
D010037:Otolithic Membrane
D012665:Semicircular Canals

Galvanic stimulation
Balance
Saccule
Utricle
Vestibular labyrinth


Development of modified HCH-1 kinetic model for long-term enzymatic cellulose hydrolysis and comparison with literature models.

Abstract:
Background
Enzymatic hydrolysis is a major step for cellulosic ethanol production. A thorough understanding of enzymatic hydrolysis is necessary to help design optimal conditions and economical systems. The original HCH-1 (Holtzapple-Caram-Humphrey-1) model is a generalized mechanistic model for enzymatic cellulose hydrolysis, but was previously applied only to the initial rates. In this study, the original HCH-1 model was modified to describe integrated enzymatic cellulose hydrolysis. The relationships between parameters in the HCH-1 model and substrate conversion were investigated. Literature models for long-term (> 48 h) enzymatic hydrolysis were summarized and compared to the modified HCH-1 model.

Results
A modified HCH-1 model was developed for long-term (> 48 h) enzymatic cellulose hydrolysis. This modified HCH-1 model includes the following additional considerations: (1) relationships between coefficients and substrate conversion, and (2) enzyme stability. Parameter estimation was performed with 10-day experimental data using α-cellulose as substrate. The developed model satisfactorily describes integrated cellulose hydrolysis data taken with various reaction conditions (initial substrate concentration, initial product concentration, enzyme loading, time). Mechanistic (and semi-mechanistic) literature models for long-term enzymatic hydrolysis were compared with the modified HCH-1 model and evaluated by the corrected version of the Akaike information criterion. Comparison results show that the modified HCH-1 model provides the best fit for enzymatic cellulose hydrolysis.

Conclusions
The HCH-1 model was modified to extend its application to integrated enzymatic hydrolysis; it performed well when predicting 10-day cellulose hydrolysis at various experimental conditions. Comparison with the literature models showed that the modified HCH-1 model provided the best fit.

Liang|Chao|C|
Gu|Chao|C|
Raftery|Jonathan|J|
Karim|M Nazmul|MN|
Holtzapple|Mark|M|

HCH-1
Enzymatic cellulose hydrolysis
Model comparison
Sensitivity analysis
Simulation


Interdisciplinary promises versus practices in medicine: the decoupled experiences of social sciences and humanities scholars.

Abstract: This paper explores social scientists' and humanities (SSH) scholars' integration within the academic medical research environment. Three questions guided our investigation: Do SSH scholars adapt to the medical research environment? How do they navigate their career within a culture that may be inconsistent with their own? What strategies do they use to gain legitimacy? The study builds on three concepts: decoupling, doxa, and epistemic habitus. Twenty-nine semi-structured interviews were conducted with SSH scholars working in 11 faculties of medicine across Canada. Participants were selected through purposeful and snowball sampling. The data were analyzed by thematic content analysis. For most of our participants, moving into medicine has been a challenging experience, as their research practices and views of academic excellence collided with those of medicine. In order to achieve some level of legitimacy more than half of our participants altered their research practices. This resulted in a dissonance between their internalized appreciation of academic excellence and their new, altered, research practices. Only six participants experienced no form of challenge or dissonance after moving into medicine, while three decided to break with their social science and humanities past and make the medical research community their new home. We conclude that the work environment for SSH scholars in faculties of medicine does not deliver on the promise of inclusiveness made by calls for interdisciplinarity in Canadian health research.

Medicine
Decoupling
Social sciences
Humanities
Research
Canada
Interdisciplinarity
Bourdieu


The effects of inbreeding on covering success, gestation length and foal sex ratio in Australian thoroughbred horses.

Abstract:
BACKGROUND
Horses produce only one foal from an eleven-month gestation period, making the maintenance of high reproductive rates essential. Genetic bottlenecks and inbreeding can increase the frequency of deleterious variants, resulting in reduced reproductive levels in a population. In this study we examined the influence of inbreeding levels on foaling rate, gestation length and secondary sex ratio in Australian Thoroughbred mares. We also investigated the genetic change in these traits throughout the history of the breed. Phenotypic data were obtained from 27,262 breeding records of Thoroughbred mares provided by three Australian stud farms. Inbreeding was estimated using the pedigree of each individual dating back to the foundation of the breed in the eighteenth century.

RESULTS
While both gestation length and foaling rate were heritable, no measurable effect of inbreeding on either trait was found. However, we did find that the genetic value for both traits had decreased within recent generations. A number of environmental factors also had significant effects on foaling rate and gestation length. Secondary sex ratio had only an extremely small paternal heritable effect and was not susceptible to environmental influences.

CONCLUSIONS
In contrast to racing performance, inbreeding had no measurable effect on foaling rate or gestation length in Australian Thoroughbred horses. This could be because the level of inbreeding in the population examined is not high enough to show a discernible effect on reproductive traits. Populations that experience higher levels of inbreeding due to use of artificial reproductive technologies or extremely small population sizes may show a more pronounced reduction in natural foaling rate or gestation length. It is also possible that the intensive management techniques used in the Thoroughbred population masks any negative effects of inbreeding. The decrease in the genetic value of foaling rate is likely to be because horses with unfavourable genetic potential have not yet been selected out of the population. The change in genetic value of gestation length may be due to selective breeding favouring horses with shorter pregnancies. We also found that prioritising the mating of older mares, and avoiding out of season mating could lead to an increased breeding success.

Todd|Evelyn T|ET|
Hamilton|Natasha A|NA|
Velie|Brandon D|BD|
Thomson|Peter C|PC|

Inbreeding
Thoroughbred horse
Fertility
Genetic diversity


Establishment and validation of a nomogram model for periprosthetic infection after megaprosthetic replacement around the knee following bone tumor resection: A retrospective analysis.

Abstract:
BACKGROUND
Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model, which can provide a reference for clinicians, and patients to reduce the occurrence of periprosthetic infection (2) explore the risk factors for deep infection of megaprosthesis.

HYPOTHESIS
A prediction model can be established and has favorable predictive accuracy.

PATIENTS AND METHODS
One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model.

RESULTS
Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy.

DISCUSSION
This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients.

LEVEL OF EVIDENCE
IV, retrospective, cohort study.

Zhang|Hao-Ran|HR| Zhao|Yun-Long|YL| Wang|Feng|F| Yang|Xiong-Gang|XG| Xu|Ming-You|MY| Qiao|Rui-Qi|RQ| Li|Ji-Kai|JK| Pang|Cheng-Gang|CG| Yu|Xiu-Chun|XC| Hu|Yong-Cheng|YC|

Nomogram model
Periprosthetic infection
Knee
Risk factor
Megaprosthesis


PMv Neuronal Firing May Be Driven by a Movement Command Trajectory within Multidimensional Gaussian Fields.

Abstract: The premotor cortex (PM) is known to be a site of visuo-somatosensory integration for the production of movement. We sought to better understand the ventral PM (PMv) by modeling its signal encoding in greater detail. Neuronal firing data was obtained from 110 PMv neurons in two male rhesus macaques executing four reach-grasp-manipulate tasks. We found that in the large majority of neurons (∼90%) the firing patterns across the four tasks could be explained by assuming that a high-dimensional position/configuration trajectory-like signal evolving ∼250 ms before movement was encoded within a multidimensional Gaussian field (MGF). Our findings are consistent with the possibility that PMv neurons process a visually specified reference command for the intended arm/hand position trajectory with respect to a proprioceptively or visually sensed initial configuration. The estimated MGF were (hyper) disc-like, such that each neuron's firing modulated strongly only with commands that evolved along a single direction within position/configuration space. Thus, many neurons appeared to be tuned to slices of this input signal space that as a collection appeared to well cover the space. The MGF encoding models appear to be consistent with the arm-referent, bell-shaped, visual target tuning curves and target selectivity patterns observed in PMV visual-motor neurons. These findings suggest that PMv may implement a lookup table-like mechanism that helps translate intended movement trajectory into time-varying patterns of activation in motor cortex and spinal cord. MGFs provide an improved nonlinear framework for potentially decoding visually specified, intended multijoint arm/hand trajectories well in advance of movement.

movement command
premotor cortex
position/configuration
MGF
brain machine interface
reach and grasp


Effectiveness of Breastfeeding Support Packages in Low- and Middle-Income Countries for Infants under Six Months: A Systematic Review.

Abstract: Small and nutritionally at-risk infants under six months, defined as those with wasting, underweight, or other forms of growth failure, are at high-risk of mortality and morbidity. The World Health Organisation 2013 guidelines on severe acute malnutrition highlight the need to effectively manage this vulnerable group, but programmatic challenges are widely reported. This review aims to inform future management strategies for small and nutritionally at-risk infants under six months in low- and middle-income countries (LMICs) by synthesising evidence on existing breastfeeding support packages for all infants under six months. We searched PubMed, CINAHL, Cochrane Library, EMBASE, and Global Health databases from inception to 18 July 2018. Intervention of interest were breastfeeding support packages. Studies reporting breastfeeding practices and/or caregivers'/healthcare staffs' knowledge/skills/practices for infants under six months from LMICs were included. Study quality was assessed using NICE quality appraisal checklist for intervention studies. A narrative data synthesis using the Synthesis Without Meta-analysis (SWiM) reporting guideline was conducted and key features of successful programmes identified. Of 15,256 studies initially identified, 41 were eligible for inclusion. They were geographically diverse, representing 22 LMICs. Interventions were mainly targeted at mother-infant pairs and only 7% (n = 3) studies included at-risk infants. Studies were rated to be of good or adequate quality. Twenty studies focused on hospital-based interventions, another 20 on community-based and one study compared both. Among all interventions, breastfeeding counselling (n = 6) and education (n = 6) support packages showed the most positive effect on breastfeeding practices followed by breastfeeding training (n = 4), promotion (n = 4) and peer support (n = 3). Breastfeeding education support (n = 3) also improved caregivers' knowledge/skills/practices. Identified breastfeeding support packages can serve as "primary prevention" interventions for all infants under six months in LMICs. For at-risk infants, these packages need to be adapted and formally tested in future studies. Future work should also examine impacts of breastfeeding support on anthropometry and morbidity outcomes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018102795).

breastfeeding
infant
review
nutritionally at-risk
malnutrition