Early versus late surgery of thoracic spine fractures in multiple injured patients: is early stabilization always recommendable?

Abstract:
BACKGROUND CONTEXT
Many institutions' retrospective studies investigated the effect of the timing of surgery on outcomes of polytraumatized patients with severe lesions of the thoracic spine and mainly found a better outcome for patients who were operated on less than 72 hours posttrauma.

PURPOSE
We conducted a prospective study in a Level I trauma center to validate the retrospective data and to investigate other variables, in addition to the timing of surgery that may influence patient outcomes.

STUDY DESIGN
Prospective observational clinical study.

PATIENT SAMPLE
Within this prospective study at a Level I trauma center, we enrolled 38 multiple injured patients with unstable fractures of vertebral column from Level Th1 to L1. Further inclusion criteria consisted of an injury severity score of 16 or more and an intensive care unit (ICU) stay of more than 7 days. The age of included patients was limited from 16 or more to 75 or less years.

OUTCOME MEASURES
Hospital stay, stay on ICU, and mortality.

METHODS
Twenty-two patients were operated on less than or equal to 72 hours posttrauma, and 16 received late surgery greater than or equal to 72 hours posttrauma.

RESULTS
Patients who received early surgery had a significantly higher mortality rate (p<.01) than those who received late surgery. Sixty-seven percent of our patients who had an initial hemoglobin (Hb) less than 10 mg/dL died. Seventy-five percent of those patients who had an Hb less than 10 mg/dL and received a thoracic drain died.

CONCLUSIONS
Although some reports indicate advantages for early surgery for thoracic spine trauma in the polytraumatized patient, careful patient selection should be used. Based on the results of this prospective study, early surgery for thoracic spine trauma in patients with concomitant severe thoracic trauma and low initial Hb levels may pose a risk for poor clinical outcomes.

Konieczny|Markus R|MR|
Strüwer|Johannes|J|
Jettkant|Birger|B|
Schinkel|Christian|C|
Kälicke|Thomas|T|
Muhr|Gert|G|
Frangen|Thomas M|TM|

Thoracic spine fracture
Timing of surgery
Thoracic trauma
Polytrauma
Second hit


Restoration of tissue damage, and never activity after hypoxia-ischemia by implantation of peripheral blood mononuclear cells.

Abstract: Hypoxia-ischemia (HI) encephalopathy is a frequent cause of disability and mortality with limited therapeutic options. Here, we collected peripheral blood mononuclear cells (PB-MNCs) from healthy donors and labeled them with CM-DiI before implanting these cells by tail-vein injection into rats at day 3 after hypoxia-ischemia (HI). For immune-suppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24h before cell transplantation. Then we observed the PB-MNCs by fluorescent microscopy, examined motor function of rats by rotarod and cylinder tests, measured the lesion volume using image-pro plus software, and analyzed the apoptosis of neural cells in HI rats by tunnel assay. The results showed PB-MNCs could survive in the brain of hosts, migrate to the damage area and express neural marker. In addition, The HI rats that received PB-MNCs showed a reduction in motor function impairment, lesion volume and neural cell apoptosis. To better understand the mechanism of cell migration, PB-MNCs were also injected into normal rats via tail-vein. The expression of stromal cell-derived factor-1 (SDF-1) in the brain of normal and HI rats was measured by RT- PCR and western-blot, while the response of PB-MNCs in vitro to HI or normal brain extracts were measured by cell migration assay. Collectively these data suggest that the migration of PB-MNCs is directed to the damaged brain through an SDF-1-dependent pathway. Our results suggest that intravenous transplantation of PB-MNCs may be a feasible candidate for HI therapy.

Liu|Yu-xiao|YX| Guo|Xiao-ming|XM| Li|Jun-feng|JF| Meng|Yu|Y| Zhang|Hai-tao|HT| Liu|Ai-jun|AJ| Li|Shou-chun|SC| Liu|Yuan-lin|YL| Zhu|Heng|H| Xue|Jing-hui|JH| Zhang|Yi|Y| Zhang|Zhi-wen|ZW|

D019650:Hematopoietic Stem Cell Mobilization

Peripheral blood mononuclear cells
Peripheral blood mononuclear cells
HI
PB-MNCs
Cell transplantation
Migration
Stromal cell-derived factor-1
Stromal cell-derived factor-1
SDF-1
ANOVA
BM-MNCs
CB-MNCs
CsA
G-CSF
GFAP
HE
Hypoxia–ischemia encephalopathy
SD
Sprague-Dawley
TTC
analysis of variance
bone marrow mononuclear
cord blood mononuclear
cyclosporine A
glial fibrillary acidic protein
granulocyte colony-stimulating factor
hematoxylin and eosin
hypoxia–ischemia
peripheral blood mononuclear cells
stromal cell-derived factor-1
triphenyltetrazolium chloride

P P P P P P P P P U U U U U U U M U U U M M M R U U M U P P U


Regulation of bile acid receptor activity☆.

Abstract: Many receptors can be activated by bile acids (BAs) and their derivatives. These include nuclear receptors farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR), as well as membrane receptors Takeda G protein receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and cholinergic receptor muscarinic 2 (CHRM2). All of them are implicated in the development of metabolic and immunological diseases in response to endobiotic and xenobiotic exposure. Because epigenetic regulation is critical for organisms to adapt to constant environmental changes, this review article summarizes epigenetic regulation as well as post-transcriptional modification of bile acid receptors. In addition, the focus of this review is on the liver and digestive tract although these receptors may have effects on other organs. Those regulatory mechanisms are implicated in the disease process and critically important in uncovering innovative strategy for prevention and treatment of metabolic and immunological diseases.

Sphingosine-1-phosphate receptor 2 (S1PR2)


What Have We Learned from Animal Models of Endometriosis and How Can We Use the Knowledge Gained to Improve Treatment of Patients?

Abstract: Endometriosis is a complex disorder with a high socio-economic impact. Development of effective novel drug therapies which can be given to women to relieve chronic pain symptoms without side effects such as hormone suppression is urgently required, but progress has been slow. Several different rodent models of 'endometriosis' have been developed, the majority of which mimic aspects of peritoneal disease (e.g. 'lesions' in peritoneal cavity either surgically or spontaneously attached to wall, mesentery, fat). Results obtained using these models have informed our understanding of aetiology including evidence for differential expression of regulatory factors in lesions and impacts on pain perception and fertility. Refinement of these models to ensure reproducibility, extension of models to replicate ovarian and deep disease, complementary in vitro approaches and robust experimental design are all needed to ensure preclinical drug testing results in positive findings in clinical trials and translation for patient benefit.

Pain
Infertility
Menstruation
Precision Medicine
Primate


A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection.

Abstract:
AIMS
The food-born trematode Opisthorchis felineus colonizes bile ducts of the liver of fish-eating mammals including humans. There is growing evidence that this liver fluke is a risk factor for cholangiocarcinoma (CCA). Cancer cell lines are necessary for drug screening and for identifying protein markers of CCA. The aim was to establish a cell line derived from cholangiocarcinoma associated with opisthorchiasis felinea.

MAIN METHODS
Allotransplantation, immunohistochemistry, karyotype analysis, cell culture techniques, immunocytochemistry and real-time PCR.

KEY FINDINGS
Here we repot the establishment of first CCA cell line, CCA-OF, from a primary tumor of an experimental CCA in Syrian hamsters treated with low doses of dimethyl nitrosamine and associated with O. felineus infection. The cell line was found to be allotransplantable. Expression of epithelial and mesenchymal markers (cytokeratin 7, glycosyltransferase exostosin 1, Ca2+-dependent phospholipid-binding protein annexin A1 and vimentin) was demonstrated by immunostaining of the primary tumors, CCA-OF cells, and allotransplants. CCA-OF cells were found to express presumed CCA biomarkers previously detected in both human and experimental tumors associated with the liver fluke infection. The cells were diploid-like (2n = 42-46) with complex chromosomal rearrangements and have morphological features of epithelial-like cells. The usefulness of the CCA-OF cell model for antitumor activity testing was demonstrated by an analysis of effects of resveratrol treatment. It was shown that resveratrol treatment inhibited the proliferation and the migration ability of CCA-OF cells.

SIGNIFICANCE
Thus, the allotransplantable CCA-OF cell line can be used in studies on helminth-associated cholangiocarcinogenesis and for the testing of antitumor drugs.

Mordvinov|Viatcheslav A|VA|
Minkova|Galina A|GA|
Kovner|Anna V|AV|
Ponomarev|Dmitriy V|DV|
Lvova|Maria N|MN|
Zaparina|Oxana|O|
Romanenko|Svetlana A|SA|
Shilov|Alexander G|AG|
Pakharukova|Maria Y|MY|

Cell line
Hamster
Cholangiocarcinoma
Opisthorchis felineus
Experimental model


Environmentally benign synthesis of phytochemicals-capped gold nanoparticles as nanopriming agent for promoting maize seed germination.

Abstract: Application of nanotechnology in agriculture is moving towards to improve the cultivation and growth of crop plants. The present study is the first attempt to propose a simple, yet cost-effective and ecofriendly synthesis of phytochemicals-capped GNPs using rhizome extract of galanga plant at room temperature. The synthesized GNPs were characterized by various characterization techniques. To promote the green nanotechnology applications in agriculture, GNPs solution at environmentally realistic dose (5 to 15ppm) as nanopriming agent was used to activate the germination and early seedling growth of maize aged seeds. Priming with 5ppm GNPs showed the best effects on promoting emergence percentage (83%) compared to unprimed control (43%) and hydroprimed groups (56%). Seed priming at both 5 and 10ppm GNPs also enhanced seedling vigor index by 3 times over the control. Priming with GNPs at 10ppm was found to enhance the best physiological and biochemical properties of maize seedlings. Internalization studies by inductively coupled plasma atomic emission spectroscopy (ICP-OES) and transmission electron microscopy (TEM) strongly supported that GNPs can internalize into seeds. However, ICP-OES analysis revealed that GNPs were not present in both shoot and root parts, suggesting that nanopriming approach minimizes the Au translocation from seeds into plant vegetative organs. Phytosynthesized GNPs were found to be less toxic than chemically synthesized GNPs. This is the first report showing phytochemicals-capped GNPs as a promising nanopriming agent for activating the germination of naturally aged seeds of crop plant.

Mahakham|Wuttipong|W|
Theerakulpisut|Piyada|P|
Maensiri|Santi|S|
Phumying|Santi|S|
Sarmah|Ajit K|AK|

Gold nanoparticles
Nanopriming
Maize
Green nanotechnology
Aged seeds


Analysis of cancer-related mutations in extracellular vesicles RNA by Droplet Digital™ PCR.

Abstract: Extracellular vesicles (EVs) are taking their place as potential biomarkers in the field of liquid biopsy. In this study, EVs were isolated from plasma samples of 31 patients with colorectal cancer and melanoma via differential centrifugation and Droplet Digital™ PCR (Bio-Rad, CA, USA) was used to profile BRAF V600E/K, KRAS G12A/C/D/V and KRAS G13D mutations from EV-derived cDNA. The concordance rates with corresponding tissue were 54% and 44% in the colorectal cancer and melanoma cohort, respectively. Two patients displayed mutations in EVs not previously detected in tissue as evidence for emerging molecular resistance to anti-EGFR and BRAF/MEK inhibitor therapy prior to radiological evidence of tumor progression. We concluded that EV-derived nucleic acids may provide clinically relevant diagnostic information and mirror evolution of the disease.

Yap|Soo Ann|SA|0000-0002-9450-9822
Münster-Wandowski|Agnieszka|A|
Nonnenmacher|Anika|A|
Keilholz|Ulrich|U|
Liebs|Sandra|S|

extracellular vesicles
liquid biopsy
colorectal cancer
melanoma
ddPCR
exosomes


Comparison of FGFR1 expression on lens epithelial cells between adults and fetuses.

Abstract:
AIM
To study the differences of fibroblast growth factor receptor 1 (FGFR1) gene on human lens epithelial cells (HLECs) of adults and fetuses.

METHODS
Indirect in situ RT-PCR was adopted for detection of FGFR1 gene. The cDNA of the mRNA in the paraffin sections of fetus and adult HLEC was synthesized by reverse transcription reaction. After PCR amplification, in situ hybridization test was performed with synthesized oligonucleotide probe and relative quantification was carried out using image analysis.

RESULTS
HLECs of adults and fetuses expressed FGFR1 gene, the expression level was higher in fetuses than in adults. The difference between them had significance (P<0.05).

CONCLUSIONS
FGFR1 exist in HLEC and the expression is age-related, which could be one of causes of the high occurrence of post operational after-cataract in children.

fibroblast growth factor receptor 1
human lens epithelial cells
indirect in situ RT-PCR
after-cataract


Sea turtle hatchling locomotor performance: incubation moisture effects, ontogeny and species-specific patterns.

Abstract: Incubation conditions are critical in determining numerous traits in reptilian neonates. This is particularly significant in species with low offspring survival such as sea turtle species, because of the extremely high predation rates that hatchlings face during their initial dispersal from nesting beaches. Hatchlings that develop in suboptimal nest environments are likely to be smaller, slower and more susceptible to predation than hatchlings from optimal nest environments. Previous studies have focused on the effects of temperature on hatchling traits, but few have investigated the effects of moisture concentrations, despite moisture levels in nests influencing hatchling size, sex, incubation duration, and hatching success. Here, we incubated eggs of three sea turtle species at various moisture levels and tested the terrestrial and aquatic locomotor performance of the resultant hatchlings during the frenzy and post-frenzy period. We also compared and evaluated the ontogeny of early locomotor performance for each species over the first months of life. Drier incubation conditions produced hatchlings that crawled more slowly and took longer to self-right than hatchlings from wetter incubation conditions. There was no difference in swimming performance associated with moisture treatments. We suggest that moisture in the nest environment during incubation may influence hatchling performance via their initial hydration levels. Thus, nest moisture influences terrestrial performance (i.e., escaping from the nest and dispersing across the beach), although upon entering the ocean hatchlings have the opportunity to rehydrate by drinking and thus, differences in locomotor performance associated with moisture treatments cease.

Moisture
Incubation conditions
Dispersal
Crawling
Swimming
Life history


SU-E-I-58: Objective Models of Breast Shape Undergoing Mammography and Tomosynthesis Using Principal Component Analysis.

Abstract:
PURPOSE
To develop an objective model of the shape of the compressed breast undergoing mammographic or tomosynthesis acquisition.

METHODS
Automated thresholding and edge detection was performed on 984 anonymized digital mammograms (492 craniocaudal (CC) view mammograms and 492 medial lateral oblique (MLO) view mammograms), to extract the edge of each breast. Principal Component Analysis (PCA) was performed on these edge vectors to identify a limited set of parameters and eigenvectors that. These parameters and eigenvectors comprise a model that can be used to describe the breast shapes present in acquired mammograms and to generate realistic models of breasts undergoing acquisition. Sample breast shapes were then generated from this model and evaluated. The mammograms in the database were previously acquired for a separate study and authorized for use in further research.

RESULTS
The PCA successfully identified two principal components and their corresponding eigenvectors, forming the basis for the breast shape model. The simulated breast shapes generated from the model are reasonable approximations of clinically acquired mammograms.

CONCLUSIONS
Using PCA, we have obtained models of the compressed breast undergoing mammographic or tomosynthesis acquisition based on objective analysis of a large image database. Up to now, the breast in the CC view has been approximated as a semi-circular tube, while there has been no objectively-obtained model for the MLO view breast shape. Such models can be used for various breast imaging research applications, such as x-ray scatter estimation and correction, dosimetry estimates, and computer-aided detection and diagnosis.

Mammography
Edge detection
Databases
Data analysis
Digital mammography
Digital tomosynthesis mammography
Eigenvalues
Image analysis
Medical imaging
Vector calculus


Novel Two-Dimensional WO3/Bi2W2O9 Nanocomposites for Rapid H2S Detection at Low Temperatures.

Abstract: Compared with single-component metal oxides, multicomponent metal oxides show good gas sensing performance in the field of gas sensing, but they still need to be further improved in terms of rapid response. In this paper, a two-dimensional flaky WO3/Bi2W2O9 composite material with a thickness of about 32.3 nm was synthesized by a simple solvothermal method. The composite has good sensing performance and selectivity toward H2S. When the operating temperature is as low as 92 °C, the response to 100 ppm H2S reaches 84.18, and the response time is 2 s, which is extremely fast due to the open system of the two-dimensional nanosheet. A combination of gas chromatography-mass spectrometry (GC-MS) and X-ray photoelectron spectroscopy (XPS) is used to analyze the changes of H2S and the surface chemistry of WO3/Bi2W2O9 composite materials; the sensing mechanism of H2S was studied by a Kelvin probe and UV diffuse reflection. Compared with the pure phase WO3 and Bi2W2O9, good gas sensing properties of the WO3/Bi2W2O9 composite may be due to its unique heterostructure. This is the first application of WO3/Bi2W2O9 in the field of gas sensing and is of great significance for the rapid detection of H2S at low temperatures for multicomponent metal oxides.

two-dimensional
WO3/Bi2W2O9 composite
sensing mechanism
heterostructure
H2S sensing properties


Slice-to-volume medical image registration: A survey.

Abstract: During the last decades, the research community of medical imaging has witnessed continuous advances in image registration methods, which pushed the limits of the state-of-the-art and enabled the development of novel medical procedures. A particular type of image registration problem, known as slice-to-volume registration, played a fundamental role in areas like image guided surgeries and volumetric image reconstruction. However, to date, and despite the extensive literature available on this topic, no survey has been written to discuss this challenging problem. This paper introduces the first comprehensive survey of the literature about slice-to-volume registration, presenting a categorical study of the algorithms according to an ad-hoc taxonomy and analyzing advantages and disadvantages of every category. We draw some general conclusions from this analysis and present our perspectives on the future of the field.

Medical image registration
Slice-to-volume registration
Bibliographical review
Medical image analysis


miR-34a regulates HDAC1 expression to affect the proliferation and apoptosis of hepatocellular carcinoma.

Abstract: miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P<0.05), but HDAC1 expression in HCC tissues was markedly higher than in normal tissues (P<0.05). In addition, miR-34a expression was negatively related to HDAC1 expression. miR-34a mimic was transfected into HCC cell lines (HepB3 and HepG2). CCK8 assay, colony formation assay and flow cytometry showed miR-34a over-expression could inhibit the proliferation of HCC cells and induce their apoptosis. Western blotting indicated miR-34a over-expression down-regulated the expression of Bcl-2, procaspase-3, procaspase-9 and c-Myc, but up-regulate p21 expression. Bioinformatics analysis indicated HDAC1 was a target gene of miR-34a. Dual Luciferase Reporter Gene Assay and retrieval assay showed miR-34a could act at the 3'UTR of HDAC1 gene to regulate its expression. Thus, miR-34a may inhibit the proliferation of HCC cells and induce their apoptosis via regulating HDAC1 expression. Our findings provide evidence for the diagnosis and therapeutic target of HCC.

Sun|Ting-Yi|TY| Xie|Hong-Jian|HJ| Li|Zhen|Z| Kong|Ling-Fei|LF| Gou|Xiang-Nan|XN| Li|Du-Juan|DJ| Shi|Yu-Jie|YJ| Ding|Yan-Zhi|YZ|


The sialyltransferase ST3Gal3 facilitates the receptivity of the uterine endometrium in vitro and in vivo.

Abstract: The receptive uterine endometrium specifically expresses certain glycosyltransferases, and the corresponding oligosaccharides play important roles in accepting the embryo. The sialyltransferase β-galactoside-α2,3-sialyltransferase III (ST3Gal3) is the key enzyme responsible for sialyl Lewis X (sLeX) oligosaccharide biosynthesis, but the expression and function of ST3Gal3 in the receptive endometrium is still elusive. Here, we found that human endometrial tissues at secretory phase expressed a 4-fold higher ST3Gal3 level relative to the tissues at proliferative phase. Meanwhile, downregulation of ST3Gal3 or sLeX epitope blockage significantly impaired the receptive ability of human endometrial RL95-2 cells to trophoblastic cells in vitro and inhibited implantation in pregnant mice. This study suggests that ST3Gal3 facilitates endometrial receptivity through increasing sLeX oligosaccharide, which gives a better understanding of the glycobiology of implantation.

Yu|Ming|M| Wang|Hao|H| Liu|Jianwei|J| Qin|Huamin|H| Liu|Shuai|S| Yan|Qiu|Q|

ST3Gal3
sLeX
endometrial receptivity
embryo implantation


Willingness to Discuss and Screen for Pre-Exposure Prophylaxis in Pharmacies Among Men Who Have Sex With Men.

Abstract:
OBJECTIVE
To determine the willingness to discuss and be screened for pre-exposure prophylaxis (PrEP) in pharmacies among MSM.

METHODS
Led by Georgia's Fulton County Board of Health, this study surveyed individuals who attended 2 Atlanta-based Gay Pride events in 2018. This analysis was limited to those who identified as men who have sex with men (MSM) who were not HIV positive and reported never using PrEP. Multivariable regression was used to determine the correlates of willingness to discuss and be screened for PrEP in-pharmacy.

RESULTS
Most (69%) were willing to discuss PrEP with pharmacy staff and 61.35% were willing to be screened for PrEP in-pharmacy. Those who were interested in PrEP were significantly more willing to discuss PrEP in-pharmacy compared to those not interested in PrEP (prevalence ratio [PR]: 1.65; 95% confidence interval [95% CI]: 1.11-2.48). Race was not associated with willingness to discuss PrEP with pharmacy staff. However, black MSM (BMSM) were less willing to be screened in pharmacies than white MSM, until we accounted for interest in PrEP (PR: 1.27; 95% CI: 1.09-1.48).

DISCUSSION
Pharmacies may be an optimal setting to expand PrEP access to reach racial minorities who have the highest need but are not being reached. Pharmacy-based PrEP discussions and screening could improve awareness of HIV status and increase PrEP knowledge and uptake. Future studies should determine optimal pharmacy conditions under which PrEP screening and uptake are acceptable for BMSM.

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

PrEP
MSM
HIV prevention
health disparities
health inequities


The Role of the L-Type Ca2+ Channel in Altered Metabolic Activity in a Murine Model of Hypertrophic Cardiomyopathy.

Abstract: Heterozygous mice (αMHC ) expressing the human disease-causing mutation Arg403Gln exhibit cardinal features of hypertrophic cardiomyopathy (HCM) including hypertrophy, myocyte disarray, and increased myocardial fibrosis. Treatment of αMHC mice with the L-type calcium channel (ICa-L) antagonist diltiazem has been shown to decrease left ventricular anterior wall thickness, cardiac myocyte hypertrophy, disarray, and fibrosis. However, the role of the ICa-L in the development of HCM is not known. In addition to maintaining cardiac excitation and contraction in myocytes, the ICa-L also regulates mitochondrial function through transmission of movement of ICa-L via cytoskeletal proteins to mitochondrial voltage-dependent anion channel. Here, the authors investigated the role of ICa-L in regulating mitochondrial function in αMHC mice. Whole-cell patch clamp studies showed that ICa-L current inactivation kinetics were significantly increased in αMHC cardiac myocytes, but that current density and channel expression were similar to wild-type cardiac myocytes. Activation of ICa-L caused a significantly greater increase in mitochondrial membrane potential and metabolic activity in αMHC . These increases were attenuated with ICa-L antagonists and following F-actin or β-tubulin depolymerization. The authors observed increased levels of fibroblast growth factor-21 in αMHC mice, and altered mitochondrial DNA copy number consistent with altered mitochondrial activity and the development of cardiomyopathy. These studies suggest that the Arg403Gln mutation leads to altered functional communication between ICa-L and mitochondria that is associated with increased metabolic activity, which may contribute to the development of cardiomyopathy. ICa-L antagonists may be effective in reducing the cardiomyopathy in HCM by altering metabolic activity.

Viola|Helena M|HM|
Johnstone|Victoria P A|VPA|
Cserne Szappanos|Henrietta|H|
Richman|Tara R|TR|
Tsoutsman|Tatiana|T|
Filipovska|Aleksandra|A|
Semsarian|Christopher|C|
Seidman|Jonathan G|JG|
Seidman|Christine E|CE|
Hool|Livia C|LC|

cardiomyopathy
L-type calcium channel
calcium
mitochondria
HCM, hypertrophic cardiomyopathy
ICa-L, L-type Ca2+ channel
MHC, myosin heavy chain
VDAC, voltage-dependent anion channel
[Ca2+]i, intracellular calcium
Ψm, mitochondrial membrane potential


Post encroachment time threshold identification for right-turn related crashes at unsignalized intersections on intercity highways under mixed traffic.

Abstract: Unsignalized intersections in developing countries experience many serious conflicts between cross-traffic due to indiscipline traffic manoeuvrability. Historically, Post Encroachment Time (PET) has gained attention as a proximal indicator to analyze crossing conflicts. However, identifying an appropriate PET threshold to classify critical conflicts for highly heterogeneous traffic scenario is still an unexplored area. Consequently, this study proposes a novel approach of PET threshold identification with proof of application by collecting data from ten intersections located on four-lane intercity highways in the National Capital Region (NCR), India. Both crossing conflicts and right-turn related crash data (for the left-hand drive) are collected. Their correlations are thoroughly studied for each PET threshold using a quantitative technique considering all and individual vehicle categories. Finally, a qualitative analysis is done by ranking the sites based on cumulative PET and related crashes to verify the proposed quantitative technique. A PET threshold of 1 s is obtained from both the techniques which can be used to identify critical conflicts for unsignalized intersections located on four-lane intercity highways. The proposed methodology will serve as an alternative, faster and effective tool to evaluate the hazardousness of unsignalized intersections located on intercity highways under highly heterogeneous traffic condition.

post encroachment time
threshold
crash
Unsignalized intersections


Newborn signal functions in Bangladesh: identification through expert consultation and assessment of readiness among public health facilities-study protocol using Delphi technique.

Abstract:
INTRODUCTION
There is a set of globally accepted and nationally adapted signal functions for categorising health facilities for maternal services. Newborn resuscitation is the only newborn intervention which is included in the WHO recommended list of emergency obstetric care signal functions. This is not enough to comprehensively assess the readiness of a health facility for providing newborn services. In order to address the major causes of newborn death, the Government of Bangladesh has prioritised a set of newborn interventions for national scale-up, the majority of which are facility-based. Effective delivery of these interventions depends on a core set of functions (skills and services). However, there is no standardised and approved set of newborn signal functions (NSFs) based on which the service availability and readiness of a health facility can be assessed for providing newborn services. Thus, this study will be the first of its kind to identify such NSFs. These NSFs can categorise health facilities and assist policymakers and health managers to appropriately plan and adequately monitor the progress and performance of health facilities delivering newborn healthcare.

METHODS AND ANALYSIS
We will adopt the Delphi technique of consensus building for identification of NSFs and 1-2 indicator for each function while employing expert consultation from relevant experts in Bangladesh. Based on the identified NSFs and signal function indicators, the existing health facility assessment (HFA) tools will be updated, and an HFA survey will be conducted to assess service availability and readiness of public health facilities in relation to the new NSFs. Descriptive statistics (proportion) with a 95% CI will be used to report the level of service availability and readiness of public facilities regarding NSFs.

ETHICS AND DISSEMINATION
Ethical approval was obtained from Research Review and Ethical Review Committee of icddr, b (PR-17089). Results will be disseminated through meetings, seminars, conference presentations and international peer-review journal articles.


Wild longnose dace downstream of wastewater treatment plants display an obese phenotype.

Abstract: Wild fish living downstream of wastewater treatment plants (WWTPs) often have increased body condition factors or body mass indices compared to upstream fish. This observation has been largely attributed to increased nutrient loading and food availability around wastewater effluent outflows. While a higher condition factor in fish is generally considered a predictor of healthy ecosystems, the metabolic status and capacity of the animals downstream of WWTPs may be a better predictor of fitness and potential population level effects. To address this, we sampled wild longnose dace (Rhinichthys cataractae), a native species in North American waterways, from sites upstream and downstream of WWTPs. Downstream fish had higher body mass indices, which corresponded with higher nutrient (lipid, protein, and glycogen) storage in somatic tissues compared to upstream fish. Liver transcriptome analysis revealed metabolic reprogramming favoring lipid synthesis, including higher hepatic triglyceride levels and transcript abundance of targeted lipogenic genes. This suggests that effluent exposure-mediated obesity in dace is a result of changes at the transcriptional level. To determine potential ecological consequences, we subjected these fish to an acute stressor in situ to determine their stress performance. Downstream fish failed to mobilize metabolites post-stress, and showed a reduction in liver aerobic and anaerobic metabolic capacity. Taken together, fish living downstream of WWTPs exhibit a greater lipid accumulation that results in metabolic disruption and may compromise the ability of these fish to cope with subsequent environmental and/or anthropogenic stressors.

Lazaro-Côté|Analisa|A|
Faught|Erin|E|
Jackson|Leland J|LJ|
Vijayan|Mathilakath M|MM|

Transcriptomics
Cyprinidae
Lipid metabolism
Metabolic programming
Municipal wastewater effluent


Environmental and cost life cycle assessment of different alternatives for improvement of wastewater treatment plants in developing countries.

Abstract: Most of wastewater treatment plants (WWTPs) in developing countries comprised primary and secondary treatment without including any tertiary treatment or sludge processing. Decision makers think that additional treatment is costly and the gained environmental benefits are limited. This study aims to investigate the environmental and economic benefits of improving current conventional WWTPs in developing countries by adding tertiary treatment and/or anaerobic digestion of sludge. For this purpose, life cycle assessment (LCA) for four different scenarios was studied for a wastewater plant located in Gamasa, Egypt. The 1st scenario is the plant in its current state. The 2nd scenario is the addition of anaerobic digestion of sludge. The 3rd scenario is the addition of a tertiary treatment stage. The 4th scenario is the addition of anaerobic digestion of sludge and tertiary treatment stage. CML 2000 method was used for assessing the environmental impacts of the four scenarios. The 4th scenario attained maximum environmental benefits for all categories due to the energy saving and the prospect of water reuse. The application of the 4th scenario achieved environmental benefits in some important categories such as ozone layer depletion. According to the economic evaluation, the addition of tertiary treatment leads to gain financial profits due to the value of the reusable produced water. This study underlines the importance of considering LCA in development of WWTPs in developing countries.

Awad|Hamdy|H|
Gar Alalm|Mohamed|M|
El-Etriby|Hisham Kh|HK|

Life cycle assessment
Wastewater treatment
Tertiary treatment
Anaerobic digestion


Ultra-small silver nanoparticles induced ROS activated Toll-pathway against Staphylococcus aureus disease in silkworm model.

Abstract: The present study investigated the therapeutic action of flavonoids loaded silver nanoparticles (FLV-Ag NPs) on a silkworm, Bombyx mori L., larvae infected by the S. aureus, where an in vivo model system was used. FLV-Ag NPs were synthesized using a Ricinus communis L. leaf extracted flavonoid mixture in various concentrations. The reduction reaction was performed under a simple sunlight exposure condition. In the reduction process, quercetin and kaempferol loadings were also found. They were confirmed by UV-visible, TEM, XRD, XPS, DLS and FTIR spectroscopic techniques. TEM confirmed that the synthesized NPs were monodispersed and with an average size of 5.8nm±0.04. Initially, those synthesized FLV-Ag NPs were tested against S. aureus in in vitro by comparing their potential inhibitory activity with only flavonoids mixture (FLVs) and pure silver nanoparticles (Ag NPs). Furthermore, these FLV-Ag NPs were used to treat S. aureus infected B. mori larvae and the therapeutic efficacy was measured. Our results demonstrate that the FLV-Ag NPs are effective in curing the S. aureus infection through the induced expression of antimicrobial peptide genes, the enhanced oxidative enzyme levels, and the promoted phagocytosis of S. aureus by the haemocytes in silkworm larvae. On the basis of these results, it is proposed that the mechanism of the antimicrobial activity of FLV-Ag NPs involves the NPs-insect fat body cell association and a reactive oxygen species-mediated Toll-pathway.

Rajasekharreddy|Pala|P|
Rani|Pathipati Usha|PU|
Mattapally|Saidulu|S|
Banerjee|Sanjay Kumar|SK|

Nanoparticles
Toll-pathway
Staphylococcus aureus
Flavonoids
Bombyx mori
Antimicrobial peptides


Usefulness of four dimensional (4D) PET/CT imaging in the evaluation of thoracic lesions and in radiotherapy planning: Review of the literature.

Abstract: In the past decade, Positron Emission Tomography (PET) has become a routinely used methodology for the assessment of solid tumors, which can detect functional abnormalities even before they become morphologically evident on conventional imaging. PET imaging has been reported to be useful in characterizing solitary pulmonary nodules, guiding biopsy, improving lung cancer staging, guiding therapy, monitoring treatment response and predicting outcome. This review focuses on the most relevant and recent literature findings, highlighting the current role of PET/CT and the evaluation of 4D-PET/CT modality for radiation therapy planning applications. Current evidence suggests that gross tumor volume delineation based on 4D-PET/CT information may be the best approach currently available for its delineation in thoracic cancers (lung and non-lung lesions). In our opinion, its use in this clinical setting is strongly encouraged, as it may improve patient treatment outcome in the setting of radiation therapy for cancers of the thoracic region, not only involving lung, but also lymph nodes and esophageal tissue. Literature results warrants further investigation in future prospective studies, especially in the setting of dose escalation.

Sindoni|Alessandro|A| Minutoli|Fabio|F| Pontoriero|Antonio|A| Iatì|Giuseppe|G| Baldari|Sergio|S| Pergolizzi|Stefano|S|

D000072078:Positron Emission Tomography Computed Tomography

Lung cancer
Radiation therapy
Four dimensional PET/CT


Cadmium in locally grown rice (Oryza sativa) in Nigeria.

Abstract: Cadmium levels were determined in locally grown rice samples in Nigeria and any potential risk involved in their consumption was assessed. The dried samples were digested with a 1:1 HNO3:HClO4 mixture and analysed with atomic absorption spectrophotometer (AAS). Mean cadmium values (mg/kg) were: Adamawa (0.50 ± 0.02), Benue (0.63 ± 0.05), Nasarawa (0.48 ± 0.10), Taraba (0.48 ± 0.10), Anambra (0.49 ± 0.09), Ebonyi (0.60 ± 0.08) and Enugu (0.59 ± 0.10). All samples exceeded the Codex Alimentarius maximum limit for cadmium in rice. The dietary intake for a 60 kg adult ranges from 235 to 309 µg/week in the northern region and 240-294 µg/week in the south-eastern region. The target hazard quotient (THQ) ranged from 0.54 to 0.71, which is less than 1, indicating that the population will not be exposed to a potential health risk from dietary cadmium. However, the measured cadmium levels in rice should be of concern.

Ihedioha|J N|JN|
Ekere|N R|NR|
Okoye|C O B|CO|


Impact of seasonal thermal stress on physiological and blood biochemical parameters in pigs under different dietary energy levels.

Abstract: The present study was formulated to find out the status of important season related thermal stress biomarkers of pure-bred (Hampshire) and crossbred (50% Hampshire × 50% local) pigs under the agro-climatic condition of Assam State, India. The experiment was also aimed to study the role of different level of energy ration (110, 100, and 90% energy of NRC feeding standard for pig) in variation of physiological and biochemical parameters in two genetic groups of pigs in different seasons. The metabolizable energy value were 3260, 2936.5, and 3585.8 kcal/kg in grower ration and 3260.2, 2936.6, and 3587 kcal/kg in finisher ration for normal energy (NE), low energy (LE) and high energy (HE), respectively. Both the genetic group of animals were housed separately under intensive system of management. Each pen was measuring 10' × 12' along with an outer enclosure. Six weaned piglets (almost similar body weight of average 10.55 kg) of each group were kept in a separate pen. However, after attainment of 35 kg body weight, the animals of a group were divided in two pens of three animals each. The present experiment indicated that average ambient temperature during summer months (27.33-29.51 °C) was above the comfort zone for pigs (22 °C). The significantly (P < 0.01) higher relative humidity (RH) (%) was recorded in outdoor environment (87.26-91.10%) and in the morning time (86.60-91.10%). The temperature humidity index (THI) during the study period was found to be indicative of thermal stress to the experimental animals during summer (79.55-82.56). Physiological parameters viz., respiration rate (RR) and rectal temperature (RT) were significantly (P < 0.01) higher in summer season (43.75-72.12 breaths/min. and 102.29-103.23 °F) and non-significantly higher values were recorded in Hampshire pigs. It was also found that the significantly (P < 0.01) lower RR as well as RT was recorded in the pigs fed with high energy (HE) ration during summer season. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were significantly (P < 0.01) lower during summer, while both the genetic groups showed significantly (P < 0.01) higher concentration of serum cortisol during summer season. It was also observed that thyroid hormone and cortisol concentrations were maintained in groups of pig fed vegetable oil incorporated HE diet during summer. From the present study, it is found that the increasing the energy level of the ration might be helpful to minimize the effects of thermal stress during summer.

Pathak|P K|PK|
Roychoudhury|R|R|
Saharia|J|J|
Borah|M C|MC|
Dutta|D J|DJ|
Bhuyan|R|R|
Kalita|D|D|

Season
Stress
Pig
Dietary energy levels
Biomarkers
India


Distance measures and optimization spaces in quantitative fatty acid signature analysis.

Abstract: Quantitative fatty acid signature analysis has become an important method of diet estimation in ecology, especially marine ecology. Controlled feeding trials to validate the method and estimate the calibration coefficients necessary to account for differential metabolism of individual fatty acids have been conducted with several species from diverse taxa. However, research into potential refinements of the estimation method has been limited. We compared the performance of the original method of estimating diet composition with that of five variants based on different combinations of distance measures and calibration-coefficient transformations between prey and predator fatty acid signature spaces. Fatty acid signatures of pseudopredators were constructed using known diet mixtures of two prey data sets previously used to estimate the diets of polar bears Ursus maritimus and gray seals Halichoerus grypus, and their diets were then estimated using all six variants. In addition, previously published diets of Chukchi Sea polar bears were re-estimated using all six methods. Our findings reveal that the selection of an estimation method can meaningfully influence estimates of diet composition. Among the pseudopredator results, which allowed evaluation of bias and precision, differences in estimator performance were rarely large, and no one estimator was universally preferred, although estimators based on the Aitchison distance measure tended to have modestly superior properties compared to estimators based on the Kullback-Leibler distance measure. However, greater differences were observed among estimated polar bear diets, most likely due to differential estimator sensitivity to assumption violations. Our results, particularly the polar bear example, suggest that additional research into estimator performance and model diagnostics is warranted.

Bromaghin|Jeffrey F|JF|
Rode|Karyn D|KD|
Budge|Suzanne M|SM|
Thiemann|Gregory W|GW|

diet composition
polar bear
Ursus maritimus
gray seal
Halichoerus grypus
Chukchi Sea
Aitchison
Kullback–Leibler
QFASA


Possible role of rice bran extract in microglial modulation through PPAR-gamma receptors in alzheimer's disease mice model.

Abstract: Alzheimer's Disease (AD), the most prevalent neurodegenerative disorder among elderly people, is ordinarily associated with progressive cognitive decline. Peroxisome proliferator-activated receptors-gamma (PPAR-γ) agonists can be targeted as a beneficial therapeutic strategy against AD. In the present study, we aimed to investigate the preventive and therapeutic effects of rice bran extract (RBE) as a possible PPAR-γ agonist on the microglial phenotype modulation in AD in mice compared to the effects of pioglitazone. This study included 64 adult male Swiss Albino mice divided into 8 groups, each group comprised 8 mice; control group, RBE group, lipopolysaccharide-induced neurodegeneration (a) (LPSa) group, (LPSb) group, RBE-preventive group (RBE + LPSa), pioglitazone-preventive group (PG + LPSa), RBE-treated group (RBE + LPSb), and pioglitazone-treated group (PG + LPSb). Cognitive functions were assessed by Y-maze and Morris water maze tests. The expression of PPAR-γ, CD45, arginase1, CD36, and CD163 genes was assessed by real time qPCR and the estimation of NF-kβ protein level was done by Western blot technique. Moreover, the assessment of Aβ42 and P-tau levels was performed by ELISA. Histopathological examination of brain tissues was performed for all the studied groups. Our results showed that RBE and pioglitazone could modulate microglial phenotype from M1 to M2 where they significantly decreased the expression of NF-κβ and the pro-inflammatory microglial marker (CD45) in parallel with increasing the expression of the anti-inflammatory microglial and phagocytic markers (arginase1, CD163, and CD36). In addition, RBE and pioglitazone significantly increased PPAR-γ expression and reduced Aβ42 deposition as well as p-tau protein levels. In conclusion, our study identified the possible role of PPAR-γ agonistic activity of RBE as a preventive and therapeutic agent in the treatment of the neuro-inflammation associated with AD.

Rice bran extract
PPAR-γ
Pioglitazone
Neuro-inflammation
Alzheimer’s disease
Microglia


Making Markets in Long-Term Care: Or How a Market Can Work by Being Invisible.

Abstract: Many Western countries have introduced market principles in healthcare. The newly introduced financial instrument of "care-intensity packages" in the Dutch long-term care sector fit this development since they have some characteristics of a market device. However, policy makers and care providers positioned these instruments as explicitly not belonging to the general trend of marketisation in healthcare. Using a qualitative case study approach, we study the work that the two providers have done to fit these instruments to their organisations and how that enables and legitimatises market development. Both providers have done various types of work that could be classified as market development, including creating accounting systems suitable for markets, redefining public values in the context of markets, and starting commercial initiatives. Paradoxically, denying the existence of markets for long-term care and thus avoiding ideological debates on the marketisation of healthcare has made the use of market devices all the more likely. Making the market invisible seems to be an operative element in making the market work. Our findings suggest that Dutch long-term care reform points to the need to study the 'making' rather than the 'liberalising' of markets and that the study of healthcare markets should not be confined to those practices that explicitly label themselves as such.

Long-term care
Financial instruments
Market development
Health care markets
The Netherlands


COVID-19 and Food-Related Outcomes in Children with Autism Spectrum Disorder: Disparities by Income and Food Security Status.

Abstract:
Background
Limited research suggests increased adverse behavioral outcomes, such as distractibility and hyperactivity, among children with autism spectrum disorder (ASD) as a result of coronavirus 2019 (COVID-19); however, little is known about how the pandemic has impacted food-related behaviors among children with ASD.

Objective
This study characterizes the impact of the pandemic on access to preferred foods and eating behaviors among children with ASD.

Methods
Caregiver proxies (n = 200) participated in a cross-sectional, online survey investigating the impact of COVID-19 on reported food and eating behaviors of children, ages 2-17 y. Logistic regression models were used to assess the magnitude of association of a change in the child's eating behaviors and in food availability, overall and by household income and food security status.

Results
A majority of respondents reported a moderate-to-large impact on their child's eating behaviors (57%) since the onset of COVID-19, and 65% reported unavailability of their child's preferred foods. Increased risk of a moderate-to-large impact on children's eating behaviors was associated with shelter regulations compared with no regulations (OR: 2.30; 95% CI: 1.12, 4.72), food insecurity compared with security status (OR: 2.60; 95% CI: 1.45, 4.67), and household income of <$50,000 compared with ≥$100,000 (OR: 2.33; 95% CI: 1.02, 5.29). The pandemic also amplified the risk of food unavailability by household food security status (food insecure vs. secure; OR: 4.13; 95% CI: 2.12, 7.69) and across income levels (<$50,000 vs. ≥$100,000; OR: 3.48; 95% CI: 1.42, 8.55; and $50,000 to <$100,000 vs. ≥$100,000; OR: 4.00; 95% CI: 1.71, 9.34). Reported frequencies of consumption of meat, seafood, vegetables, and 100% fruit juice significantly decreased among the children post-onset of COVID-19, while frequency of consumption of sweets increased.

Conclusions
A large proportion of caregivers reported substantial COVID-19 impacts on food availability and eating behaviors of children with ASD, especially among low-resource dyads. This study highlights the added burden of existing disparities due to the pandemic on children living with ASD.

COVID-19
autism spectrum disorder
food security
coronavirus
child
feeding behavior
food supply
low income
nutrition


Scapulothoracic Muscle Strength Changes Following a Single Session of Manual Therapy and an Exercise Programme in Subjects with Neck Pain.

Abstract:
INTRODUCTION
Scapulothoracic muscle weakness has been associated with neck pain (NP). Little evidence exists regarding lower trapezius (LT), middle trapezius (MT) and serratus anterior (SA) strength in this population. LT strength changes have been observed following thoracic manipulation in healthy subjects. The purpose of the present study was to examine scapulothoracic strength changes following cervical manipulation in subjects with NP.

METHODS
Twenty-two subjects with NP and 17 asymptomatic control (AC) subjects underwent strength testing of the LT, MT and SA using a hand-held dynamometer. Subjects with NP were treated with passive intervertebral neck manipulation and neck range of motion exercises. The AC group received no intervention. Strength testing was repeated after manipulation, then 48 and 96 hours later. Change scores were calculated for strength over time. Paired t-tests were done for strength change between painful and non-painful sides in the NP group. Independent t-tests were done for strength change between the NP group and AC group.

RESULTS
There was no significant difference between groups for age, gender, hand dominance or body mass index. Mean (standard deviation) symptom duration for subjects in the NP group was 43.27 (62.71) months. There was no significant difference in strength change over time between painful and non-painful sides in the NP group for any muscle; however, there was a significant difference in strength change over time between those in the NP group and AC group for the LT (p < 0.01), SA (p < 0.01) and MT (p < 0.01).

DISCUSSION
Scapulothoracic muscle strength improvements were observed in both extremities following passive intervertebral neck manipulation and neck range of motion exercises. Improvements lasted up to 96 hours following manipulation, even though no strengthening exercises were prescribed.

CONCLUSIONS
Manipulation and range of motion should be considered as a component of intervention programmes for patients with NP and scapulothoracic muscle weakness. Future studies should compare manipulation alone to exercise alone to determine impact on strength. Copyright © 2016 The Authors Musculoskeletal Care Published by John Wiley & Sons Ltd.

Petersen|Shannon|S| Domino|Nathan|N| Postma|Christopher|C| Wells|Cody|C| Cook|Chad|C|

trapezius
serratus anterior
manipulation
Axioscapular
mobilization
scapula


A repeated-measures examination of organizational stressors, perceived psychological and physical health, and perceived performance in semi-elite athletes.

Abstract: Organizational stressors can undermine the psychological well-being and performance of athletes. Less is known, however, about how these relationships unfold over time and whether organizational stressors can impact upon perceived physical health. The current study, therefore, used a repeated-measures design to examine relationships between organizational stressors with components of perceived psychological (anxiety and depression) and physical (illness symptoms and missed training days via illness) ill-health, and perceived performance at the within-person level. Twenty-three semi-elite female rowers completed monthly measures of study variables for six-months. Multilevel models indicated that selection-related stressors positively predicted symptoms of perceived psychological and physical ill-health, and negatively predicted perceived performance. Conversely, coaching stressors negatively predicted symptoms of perceived psychological ill-health. Logistics and operations stressors positively predicted perceived performance, whereas goals and development stressors negatively predicted perceived performance. These findings demonstrate for the first time that, with a repeated-measures design, organizational stressors can predict components of perceived physical and psychological ill-health, and perceived performance at the within-person level in athletes. From a practical perspective, practitioners should incorporate these findings when diagnosing the need for, developing, and optimally implementing primary and secondary stress management interventions.

Simms|Max|M|
Arnold|Rachel|R|
Turner|James E|JE|
Hays|Kate|K|

repeated-measures
well-being
anxiety
depression
Acute illnesses
strain


Effect of hepatic iron concentration and viral factors in chronic hepatitis C-infected patients with thalassemia major, treated with interferon and ribavirin.

Abstract:
BACKGROUND
Beta thalassemia major patients are vulnerable to transfusion-transmitted infection, especially hepatitis C virus (HCV), and iron overload. These comorbidities lead to cirrhosis and hepatocellular carcinoma in these patients. In order to prevent these complications, treatment of HCV infection and regular iron chelating seems to be necessary. The aim of this study was to evaluate the effect of hepatic iron concentration (HIC) and viral factors on the sustained virological response (SVR) in chronic HCV-infected patients, with beta thalassemia major being treated with interferon and ribavirin.

MATERIALS AND METHODS
We enrolled 30 patients with thalassemia major and chronic HCV who were referred to the Hematology Clinic of Guilan University of Medical Sciences, between December 2002 and April 2006. HIC was measured by atomic absorption spectroscopy before treatment. The viral factors (viral load, genotype) and HIC were compared between those who achieved a SVR and nonresponders.

RESULTS
Mean age of the 30 thalassemic patients, was 22.56 ± 4.28 years (14-30 years). Most patients were male (56.7%). Genotype 1a was seen in 24 (80%) cases. SVR was achieved in 15 patients (50%). There were no significant correlations between HIC (P = 1.00), viral load (P = 0.414), HCV genotype (P = 0.068), and SVR. No difference was observed in viral load (P = 0.669) and HIC (P = 0.654) between responders and nonresponders.

CONCLUSION
HIC, HCV viral load, and HCV genotype were not correlated with virological response, and it seems that there is no need to postpone antiviral treatment for more vigorous iron chelating therapy.

Jafroodi|Maryam|M| Asadi|Ramin|R| Heydarzadeh|Abtin|A| Besharati|Sepiedeh|S|

hepatic iron concentration
thalassemia major
ribavirin
hepatitis C virus
combination therapy
interferon alfa


Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium-containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer.

Abstract: Biocomposite scaffolds of lithium (Li)-containing mesoporous bioglass and monomethoxy poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-b-PLL) copolymer were fabricated in this study. The results showed that the water absorption and degradability of Li-containing mesoporous bioglass/mPEG-PLGA-b-PLL composite (l-MBPC) scaffolds were obviously higher than Li-containing bioglass/mPEG-PLGA-b-PLL composite (l-BPC) scaffolds. Moreover, the apatite-formation ability of l-MBPC scaffolds was markedly enhanced as compared with l-BPC scaffolds, indicating that l-MBPC scaffolds containing mesoporous bioglass exhibited good bioactivity. The cell experimental results showed that cell attachment, proliferation, and alkaline phosphatase activity of MC3T3-E1 cells on l-MBPC scaffolds were remarkably improved as compared to l-BPC scaffolds. In animal experiments, the histological elevation results revealed that l-MBPC scaffolds significantly promoted new bone formation, indicating good osteogenesis. l-MBPC scaffolds with improved properties would be an excellent candidate for bone tissue repair.

Cai|Yanrong|Y| Guo|Lieping|L| Shen|Hongxing|H| An|Xiaofei|X| Jiang|Hong|H| Ji|Fang|F| Niu|Yunfei|Y|

degradability
bioactivity
osteogenesis
copolymer
MBG
bone repair
cell proliferation


Quantitative SPECT/CT imaging for medication-related osteonecrosis of the jaw: a preliminary study using volume-based parameters, comparison with chronic osteomyelitis.

Abstract:
OBJECTIVE
To investigate the quantitative SPECT/CT imaging for medication-related osteonecrosis of the jaw (MRONJ) using volume-based parameters.

METHODS
Thirteen patients with mandibular lesions (nine MRONJ and four chronic osteomyelitis) underwent SPECT/CT acquisition at 4 h after injection of technetium 99m hydroxymethylene diphosphonate. Then, reconstruction of the acquired data and underwent voxel-based quantitative analysis using GI-BONE software. The parameters of the quantitative manner, such as maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV) and total bone uptake (TBU), were compared for the mandibular lesions. Statistical analyses for the quantitative parameters of mandibular lesions were performed by Mann-Whitney U test. A p value lower than 0.05 was considered as statistically significant.

RESULTS
Then, reconstruction of these quantitative parameters, SUVmax (10.16 ± 0.96), SUVpeak (7.95 ± 0.88), SUVmean (5.90 ± 0.86) and TBU (94.22 ± 57.44) for chronic osteomyelitis were significantly higher than those for MRONJ [5.50 ± 2.47 (p = 0.020), 4.10 ± 1.85 (p = 0.011), 2.74 ± 1.07 (p = 0.006) and 29.88 ± 15.46 (p = 0.034), respectively].

CONCLUSIONS
SUVmax, SUVpeak, SUVmean and TBU derived from bone SPECT/CT and voxel-based quantitative parameters may be useful for the evaluation of mandibular lesions, such as MRONJ and chronic osteomyelitis.

D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw

D000072098:Single Photon Emission Computed Tomography Computed Tomography

Medication-related osteonecrosis of the jaw (MRONJ)

Single-photon emission computed tomography


Led by the Holy Spirit.

Abstract: The vocational call to being a physician has been one of the greatest honors and blessings of my life. As a Catholic physician, being a direct extension of the healing hands of our Lord is something this is not easily translated into words. I reflect on two cases that remind me of this great calling.

Vocational call
Catholic physician
Faith
Ministry
Primary care


The effect of a family intervention on primary caregivers psychological outcomes: Findings from the integrative literature review.

Abstract:
AIMS
This literature review examines the effectiveness of the family interventions (FIs) targeted at the primary caregivers of people diagnosed with schizophrenia on improving the knowledge level of schizophrenia and health-related outcomes.

METHODS
A total of nine studies were reviewed from December 1999 to May 2017. The methods described by the Center for Reviews and Dissemination were used to guide this review.

RESULTS
The FIs showed consistent improvement in the knowledge level of schizophrenia among participants for various follow-up intervals. In addition, FIs were found to be superior to treatment as usual in influencing health-related outcomes.

CONCLUSIONS
Implications of the findings for mental healthcare practice to include primary caregivers with the patient in the treatment process.

D016032:Randomized Controlled Trials as Topic

family intervention
psychological outcomes
schizophrenia


Recent Trends in Photoacoustic Imaging Techniques for 2D Nanomaterial-Based Phototherapy.

Abstract: A variety of 2D materials have been developed for therapeutic biomedical studies. Because of their excellent physicochemical properties, 2D materials can be used as carriers for delivering therapeutic agents into a lesion, leading to phototherapy. Various optical imaging techniques have been used for the monitoring of the treatment process. Among these, photoacoustic imaging has unique advantages including relatively deep imaging depth and large field of view with high spatial resolution. In this review article, we summarize the types of photoacoustic imaging systems used for phototherapy monitoring, then we explore contrast-enhanced photoacoustic images using 2D materials. Finally, photoacoustic image-guided phototherapies are discussed. We conclude that 2D material-based phototherapy can be efficiently monitored by photoacoustic imaging techniques.

Jeong|Woo Yeup|WY|
Kang|Moon Sung|MS|
Lee|Haeni|H|
Lee|Jong Hun|JH|
Kim|Jeesu|J|0000-0002-2542-0234
Han|Dong-Wook|DW|0000-0001-8314-1981
Kim|Ki Su|KS|0000-0002-6289-9467

photoacoustic imaging
phototherapy
2D materials
image-guided therapy


Comparative evaluation of the efficacy of wound healing with and without dehydrated human amniotic/chorionic membrane in alveoloplasty: a pilot study.

Abstract:
Objectives
Wound healing is an integral part of any surgical procedure. Appropriate wound closure is critical to any successful surgical procedure, especially intraoral procedures. Various factors aid in wound healing, both pharmacological and non-pharmacological. Dehydrated human amniotic/chorionic membrane (dHACM) is an emerging bioinert material that contains anti-inflammatory properties, angiogenetic properties, osteogenic potential, and various growth factors. The purpose of this study was to evaluate the efficacy of wound healing properties of dHACM in bilateral alveoloplasty patients.

Materials and Methods
A prospective split-mouth study was conducted on 10 patients. Site A received sutures with dHACM and site B was sutured without dHACM. Wound healing was assessed with the Landry, Turnbull, and Howley Index.

Results
Sites A and site B were compared. A P<0.05 and a test value of 22 was obtained, indicating a statistical difference between the two sites.

Conclusion
Our study showed better healing with dHACM than without.

Wound Healing
Alveoloplasty
Amnion
Biological dressings


Phytochemical Profiles and Antioxidant Activity of Grasses Used in South African Traditional Medicine.

Abstract: Grasses are a valuable group of monocotyledonous plants, used as nourishing foods and as remedies against diseases for both humans and livestock. Phytochemical profiles of 13 medicinal grasses were quantified, using spectrophotometric methods and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), while the antioxidant activity was done using DPPH and ferric-reducing-power assays. The phytochemical analysis included the total soluble phenolic content, flavonoids, proanthocyanidins, iridoids and phenolic acids. Among the 13 grasses, the root methanolic extracts of Cymbopogon spp., Cymbopogon nardus and Cenchrus ciliaris contained the highest concentrations of total soluble phenolics (27-31 mg GAE/g DW) and flavonoids (4-13 mg CE/g DW). Condensed tannins and total iridoid content were highest (2.3 mg CCE/g DW and 3.2 mg HE/g DW, respectively) in Cymbopogon nardus. The most common phenolic compounds in the grass species included ρ-coumaric, ferulic, salicylic and vanillic acids. In the DPPH radical scavenging assay, the EC50 values ranged from 0.02 to 0.11 mg/mL for the different grasses. The best EC50 activity (lowest) was exhibited by Cymbopogon nardus roots (0.02 mg/mL) and inflorescences (0.04 mg/mL), Cymbopogon spp. roots (0.04 mg/mL) and Vetiveria zizanioides leaves (0.06 mg/mL). The highest ferric-reducing power was detected in the whole plant extract of Cynodon dactylon (0.085 ± 0.45; r2 = 0.898). The observed antioxidant activity in the various parts of the grasses may be due to their rich pool of phytochemicals. Thus, some of these grasses provide a source of natural antioxidants and phytochemicals that can be explored for their therapeutic purposes.

Gebashe|Fikisiwe|F|
Aremu|Adeyemi O|AO|0000-0002-6602-246X
Gruz|Jiri|J|
Finnie|Jeffrey F|JF|
Van Staden|Johannes|J|

flavonoids
phenolic acids
Poaceae
UHPLC
medicinal plants
secondary metabolites


The Role of Peripheral Myelin Protein 2 in Remyelination.

Abstract: The protein component of the myelin layer is essential for all aspects of peripheral nerves, and its deficiency can lead to structural and functional impairment. The presence of peripheral myelin protein 2 (P2, PMP2, FABP8, M-FABP) in Schwann cells has been known for decades and shown recently to be involved in the lipid homeostasis in the peripheral neural system. However, its precise role during de- and remyelination has yet to be elucidated. To this end, we assessed remyelination after sciatic nerve crush injury in vivo, and in an experimental de/remyelination ex vivo myelinating culture model in P2-deficient (P2 -/- ) and wild-type (WT) animals. In vivo, the nerve crush paradigm revealed temporal structural and functional changes in P2 -/- mice as compared to WT animals. Concomitantly, P2 -/- DRG cultures demonstrated the presence of shorter internodes and enlarged nodes after ex vivo de/remyelination. Together, these data indicate that P2 may play a role in remyelination of the injured peripheral nervous system, presumably by affecting the nodal and internodal configuration.

Stettner|Mark|M|
Zenker|Jennifer|J|
Klingler|Fabian|F|
Szepanowski|Fabian|F|
Hartung|Hans-P|HP|
Mausberg|Anne K|AK|
Kleinschnitz|Christoph|C|
Chrast|Roman|R|
Kieseier|Bernd C|BC|

D000818:Animals
D018920:Coculture Techniques
D051379:Mice
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D018996:Myelin P2 Protein
D009431:Neural Conduction
D000074586:Remyelination
D012583:Schwann Cells
D020426:Sciatic Neuropathy

Chronic inflammatory demyelinating neuropathy


Establishing a novel lens opacities classification system based on ultrasound biomicroscopy (UBM) for pediatric cataracts: reliability and availability.

Abstract:
Background
This study sought to develop and validate a lens opacities classification system based on ultrasound biomicroscopy (UBM) imaging to grade pediatric cataracts.

Methods
The study was conducted at Guangzhou Children's Hospital, Guangzhou Women and Children's Medical Center. UBM images of patients at the hospital from September 2013 to November 2014 were used in this study. We summarized the characteristics of lenticular opacification in each of the following 4 zones: the anterior capsule (A); the cortex (C); the nucleus (N); and the posterior capsule (P). The UBM data and intraoperative videos were compared, and sensitivity, specificity, accuracy, and positive and negative predictive values were determined for our Lens Opacities Classification System based on UBM for Pediatric Cataracts (LOCS-UP) detection. Two physicians classified pediatric cataracts (anterior capsule, cortex, and posterior capsule) by extracting 146 images from the UBM database. Patients' data were recorded to calculate the kappa coefficients. The LOCS-UP was developed.

Results
Under this standard, all types of pediatric cataracts can be classified and acquired a code by the LOCS-UP. The LOCS-UP had the highest sensitivity (100%) and specificity (98.96%) in naming the anterior capsule and the lowest sensitivity (50%) and specificity (89.59%) in naming the posterior capsule. Its consistency at naming the anterior capsule was satisfactory (Kappa coefficient: 0.70), and it was also able to name the nucleus, cortex, and posterior capsule (0.56, 0.58, and 0.48, respectively).

Conclusions
LOCS-UP could name pediatric cataracts by providing an unique digital encoding, which could reflect characteristics exactly for different local lens anomalies to all kinds of pediatric cataract patients. This method provides detailed and accurate information about Patients' lenses.

Xiang|Dao-Man|DM| Jiang|Nan|N| Chen|Li-Hong|LH| Chen|Wen-Si|WS| Yu|Ying|Y| Wang|Jian-Xun|JX| He|Ping|P| Xie|Wan-Hua|WH|

lens opacity
ultrasound biomicroscopy (UBM)
Pediatric cataracts
diagnosis


Molecular Bases for the Regulation of NKG2D Ligands in Cancer.

Abstract: NKG2D is an activating receptor expressed by NK and T cells primarily involved in the elimination of transformed and infected cells. NKG2D ligands are self-proteins restrictedly expressed in healthy tissues, but induced in response to signaling pathways commonly associated with transformation. Proliferative, tumor suppressor, and stress signaling pathways linked to the tumorigenic process induce the expression of NKG2D ligands, initiating an immune response against the incipient tumor. Nevertheless, the activity of NKG2D ligands is counter-regulated in vivo by the immunoediting of cancer cells, resulting in the expression of multiple mechanisms of immune evasion in advanced tumors. The redundancy of NKG2D ligands, besides increasing the complexity of their regulation, may impair the generation of these immune evasion mechanisms. In this review, we attempt to integrate the mechanisms and pathways involved in the regulation of NKG2D ligand expression in cancer.

Huergo-Zapico|Leticia|L|
Acebes-Huerta|Andrea|A|
López-Soto|Alejandro|A|
Villa-Álvarez|Mónica|M|
Gonzalez-Rodriguez|Ana Pilar|AP|
Gonzalez|Segundo|S|

regulation
NKG2D
T cells
signaling pathways
MICA
MICB
NK cell
ULBP


In vitro response of human osteoblasts to multi-step sol-gel derived bioactive glass nanoparticles for bone tissue engineering.

Abstract: A multi-step sol-gel process was employed to synthesize bioactive glass (BG) nanoparticles. Transmission electron microscopy (TEM) revealed that the BG nanoparticles were spherical and ranged from 30 to 60 nm in diameter. In vitro reactivity of the BG nanoparticles was tested in phosphate buffer saline (PBS), Tris-buffer (TRIS), simulated body fluid (SBF), and Dulbecco's modified Eagle's medium (DMEM), in comparison with similar sized hydroxyapatite (HA) and silicon substituted HA (SiHA) nanoparticles. Bioactivity of the BG nanoparticles was confirmed through Fourier transform infrared spectroscopy (FTIR) analysis. It was found that bone-like apatite was formed after immersion in SBF at 7 days. Solutions containing BG nanoparticles were slightly more alkaline than HA and SiHA, suggesting that a more rapid apatite formation on BG was related to solution-mediated dissolution. Primary human osteoblast (HOB) cell model was used to evaluate biological responses to BG nanoparticles. Lactate dehydrogenase (LDH) cytotoxicity assay showed that HOB cells were not adversely affected by the BG nanoparticles throughout the 7day test period. Interestingly, MTS assay results showed an enhancement in cell proliferation in the presence of BG when compared to HA and SiHA nanoparticles. Particularly, statistically significant (p<0.05) alkaline phosphatase (ALP) activity of HOB cells was found on the culture containing BG nanoparticles, suggesting that the cell differentiation might be promoted by BG. Real-time quantitative PCR analysis (qPCR) further confirmed this finding, as a significantly higher level of RUNX2 gene expression was recorded on the cells cultured in the presence of BG nanoparticles when compared to those with HA and SiHA.

Fan|Jian Ping|JP|
Kalia|Priya|P|
Di Silvio|Lucy|L|
Huang|Jie|J|

D060888:Real-Time Polymerase Chain Reaction

D017550:Spectroscopy, Fourier Transform Infrared

Osteoblast
Bioactive glass
Nanoparticles
Tissue engineering
Hydroxyapatite
Sol–gel


Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

Abstract:
AIMS
Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke.

METHODS
Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure.

RESULTS
The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke.

CONCLUSIONS
Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Joshi|Roshni|R|
Wannamethee|S Goya|SG|
Engmann|Jorgen|J|
Gaunt|Tom|T|
Lawlor|Deborah A|DA|
Price|Jackie|J|
Papacosta|Olia|O|
Shah|Tina|T|
Tillin|Therese|T|
Chaturvedi|Nishi|N|
Kivimaki|Mika|M|
Kuh|Diana|D|
Kumari|Meena|M|
Hughes|Alun D|AD|
Casas|Juan P|JP|
Humphries|Steve|S|
Hingorani|Aroon D|AD|
Schmidt|A Floriaan|AF|

lipoproteins
coronary heart disease
stroke
triglycerides
Epidemiology
metabolomics


Predictive effect of GIPR SNP rs10423928 on glucose metabolism liver fat and adiposity in prediabetic and diabetic subjects.

Abstract: The gastric inhibitory polypeptide receptor (GIPR) regulates postprandial metabolism. In this context GIPR SNP rs10423928 seems toplay an important role in modulating glucose metabolism and insulinsensitivity. However, evidence regarding thisparticular SNP is still vague. In this study, we collected baseline data from four different dietaryintervention studies. We genotyped 424 subjects with prediabetes and 73with diabetes for GIPR SNP rs10423928 and examined its impact on glucosemetabolism, insulin sensitivity and body fat accumulation. We extended previous data by showing that carriers of the A allele withprediabetes displayed increased fasting glucose (p = 0.015). Unexpectedly,A allele carriers showed lower glucose levels 2 h (p = 0.021) after anoral glucose challenge compared to T/T homozygous individuals. A allelecarriers also showed significantly higher insulin sensitivity (p < 0.001)(assessed by Cederholm Index), indicating an enhanced ß-cell response. This study points to a potential protective role for rs10423928 inglucose metabolism and insulin sensitivity in subjects with prediabetes.Further studies are necessary to confirm these results.

Barbosa-Yañez|Renate Luzía|RL|
Markova|Mariya|M|
Dambeck|Ulrike|U|
Honsek|Caroline|C|
Machann|Jürgen|J|
Schüler|Rita|R|
Kabisch|Stefan|S|
Pfeiffer|Andreas F H|AFH|


Protected Blend of Organic Acids and Essential Oils Improves Growth Performance, Nutrient Digestibility, and Intestinal Health of Broiler Chickens Undergoing an Intestinal Challenge.

Abstract: The growing restriction of antibiotic growth promoters (AGP) use in farming animals has raised a concern regarding the viability of the animal production system. In this new context, feed additives with proven positive impact on intestinal health may be used as strategy to avoid losses on performance. The aim of this study was to evaluate the effects of a protected blend of organic acids and essential oils [P(OA+EO)] on growth performance, nutrient digestibility, and intestinal health of broiler chickens. A total of 1,080 Cobb × Cobb 500 male broilers were randomly distributed in four treatments with 10 replicates (27 birds/each). Treatments were as follow: non-challenged control; challenged control; AGP (enramycin at 10 g/t); and P(OA+EO) at 300 g/t. All birds on challenged groups were challenged with Eimeria spp. at 1 day and with Clostridium perfringens at 11, 12, and 13 days. Body weight gain (BWG), feed intake and feed conversion ratio (FCR) were evaluated until 42 days. At 17 days, one bird per pen was orally gavaged with fluorescein isothiocyanate-dextran (FITC-d) and blood samples were collected for FITC-d detection to assess intestinal permeability. At 21 days, apparent ileal nutrient and energy (IDE) digestibility, intestinal macroscopic and histologic alterations (ISI) and, expression of mucin2 (MUC2), claudin1 (CLDN1), and occludin (OCLN) genes in the jejunum were evaluated. From 1 to 42 days, birds from the non-challenged and P(OA+EO) groups had greater (P < 0.001) BWG compared to challenged control and AGP groups. The challenged control group presented the worst FCR (P < 0.001). IDE was 106 kcal/kg greater when broilers were fed P(OA+EO) compared to the challenged control group. Broilers supplemented with P(OA+EO) had improved intestinal integrity with lower blood FITC-d concentration and ISI scores, and greater expression of MUC2, CLDN1, and OCLN genes compared to the challenged control group (P < 0.05). In conclusion, the P(OA+EO) and the AGP led to increased growth performance, nutrient digestibility and intestinal health of challenged broilers. A marked difference occurred in favor of the P(OA+EO), suggesting that this blend may be used to improve intestinal health and broiler growth performance in AGP free programs.

Stefanello|Catarina|C|
Rosa|Daniele P|DP|
Dalmoro|Yuri K|YK|
Segatto|Ana L|AL|
Vieira|Marcia S|MS|
Moraes|Mariana L|ML|
Santin|Elizabeth|E|

organic acid
essential oil
intestinal health
broiler
antibiotic


The First Coordination Polymers Based on 1,3-Diphosphaferrocenes and 1,1',2,3',4-Pentaphosphaferrocenes.

Abstract: Phosphaferrocenes in combination with coinage metal salts proved to be excellent building blocks in supramolecular chemistry for the buildup of oligomeric and polymeric assemblies. The synthesis of a series of novel phosphaferrocenes containing the 1,3-P2C3iPr3 and/or the 1,2,4-P3C2iPr2 ligand is described herein. The self-assembly processes of the 1,3-diphospha-, 1,2,4-triphospha-, and 1,1',2,3',4-pentaphosphaferrocenes with CuI halides led to the formation of 1D or 2D polymers. With [Cp*Fe(η5-P2C3iPr3)] (Cp* = η5-C5Me5), infinite chains are formed, whereas with [(η5-P3C2iPr2)Fe(η5-P2C3iPr3)] 1D ladderlike structures are obtained. These are the first polymers containing such a di- and pentaphosphaferrocene, respectively. On the other hand, the use of [Cp*Fe(η5-P3C2iPr2)] leads to the construction of 2D networks with intact sandwich complexes, which is uncommon for this class of complexes.

Heindl|Claudia|C|
Reisinger|Sabine|S|
Schwarzmaier|Christoph|C|
Rummel|Lena|L|
Virovets|Alexander V|AV|
Peresypkina|Eugenia V|EV|
Scheer|Manfred|M|

Polymers
Phosphaferrocenes
Supramolecular chemistry
Copper
Self‐assembly


AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions.

Abstract: AMP-activated protein kinase (AMPK) and its yeast homolog, Snf1, are critical regulators in the maintenance of energy metabolic balance not only stimulating energy production but also inhibiting energy-consuming processes. The AMPK/Snf1 signaling controls energy metabolism by specific phosphorylation of many metabolic enzymes and transcription factors, enhancing or suppressing their functions. The AMPK/Snf1 complexes can be translocated from cytoplasm into nuclei where they are involved in the regulation of transcription. Recent studies have indicated that AMPK/Snf1 activation can control histone acetylation through different mechanisms affecting not only gene transcription but also many other epigenetic functions. For instance, AMPK/Snf1 enzymes can phosphorylate the histone H3S10 (yeast) and H2BS36 (mammalian) sites which activate specific histone acetyltransferases (HAT), consequently enhancing histone acetylation. Moreover, nuclear AMPK can phosphorylate type 2A histone deacetylases (HDAC), e.g. HDAC4 and HDAC5, triggering their export from nuclei thus promoting histone acetylation reactions. AMPK activation can also increase the level of acetyl CoA, e.g. by inhibiting fatty acid and cholesterol syntheses. Acetyl CoA is a substrate for HATs, thus increasing their capacity for histone acetylation. On the other hand, AMPK can stimulate the activity of nicotinamide phosphoribosyltransferase (NAMPT) which increases the level of NAD(+). NAD(+) is a substrate for nuclear sirtuins, especially for SIRT1 and SIRT6, which deacetylate histones and transcription factors, e.g. those regulating ribosome synthesis and circadian clocks. Histone acetylation is an important epigenetic modification which subsequently can affect chromatin remodeling, e.g. via bromodomain proteins. We will review the signaling mechanisms of AMPK/Snf1 in the control of histone acetylation and subsequently clarify their role in the epigenetic regulation of ribosome synthesis and circadian clocks.

AMPK/Snf1
Histone acetylation
Epigenetic
Acetyl CoA
Chromatin
Aging


Therapeutic management of ventricular arrhythmias in Andersen-Tawil syndrome.

Abstract: Andersen-Tawil Syndrome (ATS) is a rare periodic paralysis with typical skeletal and neuromuscular features. Cardiac involvement may range from asymptomatic ventricular arrhythmias to sudden death. Its management remains challenging and the choice between antiarrhythmic drug therapy and implantable cardioverter defibrillator (ICD) is not simple. We present a case of ATS patient with episodes of bidirectional ventricular tachycardia, well controlled by flecainide therapy initially, which in particular conditions of fever and hypokaliemia had a cardiac arrest with ventricular fibrillation, with neurological sequelae and need of an ICD implant. A review of the therapeutic management of this disease is presented.

Maffè|Stefano|S|
Paffoni|Paola|P|
Bergamasco|Luca|L|
Dellavesa|Pierfranco|P|
Zenone|Franco|F|
Baduena|Lara|L|
Franchetti Pardo|Nicolò|N|
Careri|Giulia|G|
Facchini|Emanuela|E|
Sansone|Valeria|V|
Parravicini|Umberto|U|

Subcutaneous implantable cardioverter defibrillator


Age-specific predictors of cervical dysplasia recurrence after primary conization: analysis of 3,212 women.

Abstract:
OBJECTIVE
This study aimed to identify predictors of recurrence/persistence of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesion (r-CIN2+) after primary conization.

METHODS
Retrospective analysis involving all consecutive women having conization for CIN2+ between 1998 and 2018. The risk of r-CIN2+ was assessed using Kaplan-Meier and Cox models.

RESULTS
Data of 3,212 women were retrospectively identified. After a mean follow-up of 47 (±22.2) months, 112 (3.5%) patients developed r-CIN2+. Mean time interval between prior conization and diagnosis of r-CIN2+ was 26.2 (±13.2) months. Via multivariate analysis, presence of high-risk human papillomavirus (HPV) types at the time of CIN2+ diagnosis, hazard ratio (HR)=3.40 (95% confidence interval [CI]=1.66-6.95) for HPV16/18 and HR=2.59 (95% CI=1.21-5.55) for HPV types other than 16/18, positive margins at primary conization, HR=4.11 (95% CI=2.04-8.26) and HPV persistence after conization, HR=16.69 (95% CI=8.20-33.9), correlated with r-CIN2+, independently. Considering age-specific HPV types distribution, we observed that HPV16/18 infection correlated to an increased risk of r-CIN2+ only in young women (aged ≤25 years; p=0.031, log-rank test); while in the older population (>25 years) HPV type(s) involved had not impact on r-CIN2+ risk (p>0.200, log-rank test).

CONCLUSION
HPV persistence is the main factor predicting r-CIN2+. Infection from HPV16/18 has a detrimental effect in young women, thus highlighting the need of implementing vaccination against HPV in this population. Further prospective studies are warranted for tailoring clinical decision-making for post-conization follow-up on the basis of risk factors.

Squamous Intraepithelial Lesions of the Cervix


Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-specific Factors in Patient-centered Care.

Abstract:
OBJECTIVE
Health equity considerations have not been incorporated into prior Canadian Rheumatology Association guidelines. Our objective was to identify the challenges and possible solutions to mitigate threats to health equity in rheumatoid arthritis (RA) care in Canada.

METHODS
A consultation process informed selection of priority populations, determined to be rural and remote, Indigenous, elderly with frailty, first-generation immigrant and refugee, low income and vulnerably housed, and diverse gender and sex populations. Semistructured interviews were completed with patients with lived experience, healthcare providers, and equity-oriented researchers. These interviews probed on population factors, initial and ongoing healthcare access issues, and therapeutic considerations influencing RA care. Known or proposed solutions to mitigate inequities during implementation of service models for the population group were requested. The research team used a phenomenological thematic analysis model and mapped the data into a logic model. Solutions applicable to several population groups were proposed.

RESULTS
Thirty-five interviews were completed to identify realities for each population in accessing RA care. Five themes emerged as primary solutions to population-based inequities, including actively improving the patient-practitioner relationship, increasing accessibility and coordination of care through alternative models of care, upholding autonomy in treatment selection while actively addressing logistical barriers and individualized therapy needs, collaborating with health supports valued by the patient, and being advocates for policy change and health system restructuring to ensure appropriate resource redistribution.

CONCLUSION
The challenges for populations facing inequities in rheumatology care and promising solutions should inform guideline development and implementation, policy change, and health system restructuring.

equity
rheumatoid arthritis
guidelines
health services


Management and weaning from mechanical ventilation in neurologic patients.

Abstract: In the early phase following severe brain injury (BI), mechanical ventilation (MV) is often needed to prevent airway from aspiration, control PaCO2 and PaO2 and avoid secondary brain insults. Although patients with BI are frequently hospitalized in the intensive care unit (ICU) without respiratory problems, they display longer durations of MV and a challenging weaning process compared to other ICU populations. Historically, the MV settings of BI patients associated high tidal volume with low or no positive end-expiratory pressure (PEEP), for neurological reasons. The extensive data about the beneficial effects of protective ventilation in patients without acute respiratory distress syndrome, have questioned the consequences of such management in BI patients. Recent studies suggest that protective ventilation is safe and could even bear significant impact on morbidity in these patients. The MV weaning process is also challenging, since these patients display a high rate of extubation failure. Recently, new clinical scales of successful extubation have been highlighted combining airway and neurologic operators. A minimal level of arousal should be achieved before extubation, but the Glasgow Coma Score has been inconsistently associated with successful extubation, probably owing to the challenging quantification in intubated patients. Early tracheostomy seems to bear positive effects on morbidity in BI patients. Nonetheless the level of evidence remains poor and no strong recommendations can be made on this topic. Overall, the respiratory bundle of care in BI patients could be readapted with the new data available in the literature. Even if they bear positive impact on morbidity in ICU, their consequences on neurological recovery have yet to be adequately assessed.

Cinotti|Raphaël|R| Bouras|Marwan|M| Roquilly|Antoine|A| Asehnoune|Karim|K|

Ventilator-induced lung injury
intra-cranial haemorrhage
subarachnoid haemorrhage (SAH)
weaning, traumatic brain injury (TBI)


Circulating endothelial-derived apoptotic microparticles in the patients with ischemic symptomatic chronic heart failure: relevance of pro-inflammatory activation and outcomes.

Abstract:
BACKGROUND
Endothelial-derived apoptotic microparticles (EMPs) play a pivotal role in endothelial dysfunction in hronic Heart Failure (CHF).

OBJECTIVES
The present study aimed to evaluate the association between EMPs and pro-inflammatory biomarkers, clinical status, and outcomes in the patients with ischemic CHF.

PATIENTS AND METHODS
This study was conducted on 154 patients with ischemic symptomatic moderate-to-severe CHF on discharge from hospital. The observation period was up to 3 years. Circulating NT-pro-BNP, TNF-alpha, sFas, and sFas ligand were determined at baseline. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-re-hospitalization rate were examined. The data were analyzed using descriptive statistics, Receive Operation Characteristic Curve (ROC), and logistic regression analysis. Besides, P < 0.05 was considered as statistically significant.

RESULTS
During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. The results showed a significant difference between the patients with a large number of EMPs (> 0.514 n/mL) and those with a low level of the biomarker (< 0.514 n/mL) regarding their survival. The number of circulating EPMs independently predicted all-cause mortality (OR = 1.58; 95% CI = 1.20 - 1.88; P = 0.001), CHF-related death (OR = 1.22; 95% CI: 1.12 - 1.36; P < 0.001), and CHF-related re-hospitalization (OR = 1.20; 95% CI: 1.11 - 1.32; P < 0.001).

CONCLUSIONS
Among the patients with symptoms of CHF, increased number of circulating EMPs was associated with increased 3-year CHF-related death, all-cause mortality, and risk of recurrent hospitalization due to CHF.

Berezin|Alexander E|AE|
Kremzer|Alexander A|AA|
Samura|Tatayna A|TA|
Martovitskaya|Yulia V|YV|

Microparticles
Heart Failure
Survival
Inflammation
Prognosis


Developing a quality and safety curriculum for fellows: lessons learned from a neonatology fellowship program.

Abstract: Formal training in health care quality and safety has become an important component of medical education at all levels, and quality and safety are core concepts within the practice-based learning and system-based practice medical education competencies. Residency and fellowship programs are rapidly attempting to incorporate quality and safety curriculum into their training programs but have encountered numerous challenges and barriers. Many program directors have questioned the feasibility and utility of quality and safety education during this stage of training. In 2010, we adopted a quality and safety educational module in our neonatal fellowship program that sought to provide a robust and practical introduction to quality improvement and patient safety through a combination of didactic and experiential activities. Our module has been successfully integrated into the fellowship program's curriculum and has been beneficial to trainees, faculty, and our clinical services, and our experience suggests that fellowship may be particularly well suited to incorporation of quality and safety training. We describe our module and share tools and lessons learned during our experience; we believe these resources will be useful to other fellowship programs seeking to improve the quality and safety education of their trainees.

Gupta|Munish|M| Ringer|Steve|S| Tess|Anjala|A| Hansen|Anne|A| Zupancic|John|J|

quality
safety
curriculum
fellowship
practice-based learning
systems-based practice


Brevilin A induces apoptosis and autophagy of colon adenocarcinoma cell CT26 via mitochondrial pathway and PI3K/AKT/mTOR inactivation.

Abstract: Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner. Apoptosis induced by Brevilin A was higher than that induced by adriamycin under the same dose. Cleaved-caspase-8, cleaved-caspase-9 and cleaved-caspase-3 were up-regulated after Brevilin A treatment, together with an increase of Bax protein expression, while Bcl-2 was reduced. Further investigation revealed that Brevilin A inhibited the phosphorylation of PI3K, AKT and mTOR and promoted the expressions of autophagy-related proteins LC3-II, Beclin1 and Atg5 and consequent formation of autophagosomes, whereas 3-methyladenine (3-MA), a type III PI3K inhibitor, inhibited autophagosomes formation induced by Brevilin A. In vivo investigation suggested that Brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues. Our results demonstrated that the anti-tumor activity of Brevilin A was mainly achieved by the induction of cell apoptosis and autophagy, suggesting a promising potential as antitumor drug against colon adenocarcinoma.

You|Pengtao|P| Wu|Hezhen|H| Deng|Meng|M| Peng|Jingling|J| Li|Fangping|F| Yang|Yanfang|Y|

Brevilin A
Apoptosis
Autophagy
CT26
Mechanism


Neural evidence that human emotions share core affective properties.

Abstract: Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

Wilson-Mendenhall|Christine D|CD|
Barrett|Lisa Feldman|LF|
Barsalou|Lawrence W|LW|