Concentration Polarization in Ultrafiltration/Nanofiltration for the Recovery of Polyphenols from Winery Wastewaters.

Abstract: Concentration polarization is intrinsically associated with the selective character of membranes and often means flux decline and which causes a subsequent decrease of ultrafiltration and nanofiltration performance. More important is the fact that it acts as a precursor of membrane fouling and creates severe fouling problems in the longer times range. The quantification of its dependence on the operating parameters of cross-flow velocities and transmembrane pressures makes recourse to the film theory to introduce mass-transfer coefficients that generally are calculated by dimensionless correlations of the Sherwood number as a function of the Reynolds and Schmidt numbers. In the present work, the mass-transfer coefficients are obtained through the fitting of experimental results by the pressure variation method. The ultrafiltration/nanofiltration of the winery wastewaters from the racking operation is carried out with the membranes ETNA 01PP (Alfa Laval) and NF 270 (Dow Filmtec) under a wide range of cross-flow velocities and transmembrane pressures up to 15 bar.

concentration polarization
ultrafiltration
nanofiltration
winery wastewater
polyphenols recovery


The stochastic association of nanoparticles with algae at the cellular level: Effects of NOM, particle size and particle shape.

Abstract: Association of nanoparticles (NPs) with algae likely plays a critical role in their transfer in aquatic food chains. Although our understanding of the ecotoxicity and fate of NPs in the environment is increasing, it is still unclear how the physicochemical properties of NPs influence their interaction with algae at cellular levels and how this is reflected at a population level. This is due to the limitation in the existing analytical techniques to quantify the association of NPs with cells. To fill this data gap, we applied the novel technique of single-cell inductively coupled plasma mass spectrometry to quantify the cellular association of gold (Au)-NPs with algal cells (Pseudokirchneriella subcapitata) as a function of particle size, shape (spherical 10 nm, spherical 60 nm, spherical 100 nm, rod-shaped 10 × 40 nm, and rod-shaped 50 × 100 nm), and surface chemistry [citrate and natural organic matter (NOM) coating] on a cell-by-cell basis. The association of Au-NPs with algal cells was found to be a random probability following a so-called stochastic process; after 72 h of exposure, less than 45% of the cell population accumulated NPs on their surface. The number of Au-NPs per cell was found to be heterogeneously distributed as some cells were associated with a significantly higher number (e.g. up to 600 spherical 10 nm particles per cell) of Au-NPs than other cells present in the medium. The presence of NOM on the surface of the particles decreased the percentage of cells containing NPs except for the spherical 60 nm Au-NPs. We conclude that some algae within a population can accumulate NPs on their surface and this accumulation is influenced by the size, shape, and surface chemistry of NPs. It is important to understand how NPs may enter aquatic food chains to assess the possible risk.

Abdolahpur Monikh|Fazel|F|
Chupani|Latifeh|L|
Guo|Zhiling|Z|
Zhang|Peng|P|
Darbha|Gopala Krishna|GK|
Vijver|Martina G|MG|
Valsami-Jones|Eugenia|E|
Peijnenburg|Willie J G M|WJGM|

Nanoparticle
Natural organic matter
Extracellular polymeric substances
Particle number
ScICP-MS


Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

Abstract:
PURPOSE
Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk.

METHODS
This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status.

RESULTS
Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years).

CONCLUSION
Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.

Xhaard|Constance|C|
Lence-Anta|Juan J|JJ|
Ren|Yan|Y|
Borson-Chazot|Françoise|F|
Sassolas|Geneviève|G|
Schvartz|Claire|C|
Colonna|Marc|M|
Lacour|Brigitte|B|
Danzon|Arlette|A|
Velten|Michel|M|
Clero|Enora|E|
Maillard|Stéphane|S|
Marrer|Emilie|E|
Bailly|Laurent|L|
Mariné Barjoan|Eugènia|E|
Schlumberger|Martin|M|
Orgiazzi|Jacques|J|
Adjadj|Elisabeth|E|
Pereda|Celia M|CM|
Turcios|Silvia|S|
Velasco|Milagros|M|
Chappe|Mae|M|
Infante|Idalmis|I|
Bustillo|Marlene|M|
García|Anabel|A|
Salazar|Sirced|S|
Rodriguez|Regla|R|
Benadjaoud|Mohamed Amine|MA|
Ortiz|Rosa M|RM|
Rubino|Carole|C|
de Vathaire|Florent|F|

Recreational physical activity
Thyroid cancer
Risk factors
Pooled case-control study


Modeling, instrumentation, automation, and optimization of water resource recovery facilities (2019) DIRECT.

Abstract: A review of the literature published in 2019 on topics relating to water resource recovery facilities (WRRFs) in the areas of modeling, automation, measurement and sensors, and optimization of wastewater treatment (or water resource reclamation) is presented.

D001331:Automation
D014865:Waste Disposal, Fluid
D062065:Waste Water
D018508:Water Purification
D062066:Water Resources

modeling
automation
optimization
energy efficiency
machine learning
neural networks
soft sensors


Ciprofloxacin-intercalated layered double hydroxide-in-hybrid films as composite dressings for controlled antimicrobial topical delivery.

Abstract: Films based on biopolymers and loaded with antimicrobial agents are convenient pharmaceutical dosage forms for topical application. Inorganic carriers loaded with these agents lead to composite materials, which combined with polymers produce further functionality. Here, hybrid composite films based on layered double hydroxide (LDH) and hyaluronan (HS) as ciprofloxacin (Cip) delivery systems were studied as an alternative for prophylaxis and treatment of opportunistic infections in wounds. Cip-intercalated Zn-Al LDH (LDH-Cip), with high drug loading and crystallinity, were obtained by a precipitation at variable pH method, and then included in a HS dispersion for obtaining the hybrid composite films by solvent casting. Physicochemical characterization of films showed that a composite material where the HS acted as matrix and LDH-Cip aggregates acted as filler were obtained. LDH-Cip were uniformly dispersed along the (LDH-Cip)/HS films, which exhibited roughness in their surface, increasing their swelling capacity in PBS pH = 5.8. Controlled releases of Cip toward PBS at pH = 5.8 and 7.4 were obtained, and the best fits for the release profiles were found with Higuchi and Korsmeyer-Peppas models, respectively. (LDH-Cip)/HS films exhibited antimicrobial activity against S. aureus. These films would then provide sustained release of Cip after topical administration, maintaining a suitable level of antibacterial activity, combined with the wound healing properties of the HS. The interesting properties shown by the (LDH-Cip)/HS films make them a promising alternative for application in skin wounds.

Salguero|Yadira|Y|
Valenti|Laura|L|
Rojas|Ricardo|R|
García|Mónica C|MC|

D017550:Spectroscopy, Fourier Transform Infrared

Topical delivery
Inorganic carriers
Hybrid composite films
Ciprofloxacin
Controlled drug delivery


Semiconducting graphitic carbon nitride integrated membranes for sustainable production of clean water: A review.

Abstract: Semiconducting membranes integrated with nanomaterials have placed themselves in new emerging researches tremendously for seawater desalination, oil-water separation, disinfection, removal of inorganic as well as organic pollutants. Howbeit, only nanoparticles unified membranes show quite a lot lags in their performance, although some of these particles associated with the demerits of high cost. In contrast, graphitic carbon nitride incorporated membranes offered improved aforementioned properties corresponding to absolute essential qualities such as cost-effective, environmentally friendly, easy-to-operate, green manufacturing, anti-fouling, and low energy consumption. Moreover, their high mechanical strength, high stability against harsh environment and long-term utilization without flux reduction are strong plus. Even though there are some undeniable downsides of these membranes in real world applications as bulk synthesis, consistent dispersion of graphitic carbon nitride, low photocatalytic efficiency etc. Accordingly, in the present article, these frailties of the membranes having graphitic carbon nitride as a filler and their respective synthesis procedures and properties are discussed. A comprehensive analysis over the application of semiconducting graphitic carbon nitride incorporated membranes with and without special surface modification; and exploration of the future challenges and difficulties associated to these membranes are also reviewed. Consequently, the current article provides brief overview about graphitic carbon nitride integrated composite membranes as well as their applications, and it finished up with new thoughts of further improvements/modifications to overcome their shortcomings in actual environmental conditions.

Graphitic carbon nitride
Membranes
Desalination
Antifouling
Photo-catalytic membranes
Water purification


Protective Effect of Se-Methylselenocysteine on Elaidic Acid-Induced Inflammation in Human Arterial Endothelial Cells.

Abstract: This study was designed to investigate the anti-inflammatory effect of Se-methylselenocysteine (MSC) on elaidic acid (9t18:1, EA) induced human arterial endothelial cells (HAECs). MTT and flow cytometry were used to determine cell viability and cell apoptosis respectively. Western blotting was used to assess protein expression of intercellular adhesion molecular 1 (ICAM-1), E-selectin, interleukin-8 (IL-8), endothelial nitric oxide synthase (e-NOS) and phospholipases A2 (PLA2), while enzyme-linked immunosorbent assay (ELISA) was performed to examine the secretion level of nitric oxide (NO). In the cell viability assay, EA significantly decreased cell viability when compared with negative control (NC) group, and MSC effectively reversed this adverse effect, especially at the concentration of 200 μmol/L with 24 h incubation. Also, the same concentration of MSC prevented HAECs cell apoptosis induced by EA. In addition, we found that the expression of ICAM-1, E-selectin, IL-8 and PLA2 were significantly increased and e-NOS decreased in EA group compared with NC group. Inhibition of PLA2 promoted ICAM-1, E-slectin and IL-8 expression in HAECs induced by EA. And MSC down-regulated the secretion of NO level in EA-induced HAECs. Based on these results, we concluded that MSC activated PLA2 which regulated the expression of ICAM-1, E-selectin and IL-8 to protect inflammation induced by EA in HEACs.

Xia|Jizhu|J| Xia|Xiaorong|X| Wang|Wenyuan|W| Xia|Jiyi|J| Li|Mingxing|M|

Se-methylselenocysteine
inflammation
endothelial cell
elaidic acid
PLA2


Anti-inflammatory effect of Phellinus linteus grown on germinated brown rice on dextran sodium sulfate-induced acute colitis in mice and LPS-activated macrophages.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY
Phellinus linteus is a herb used in traditional Asian medicine to treat stomachache, inflammation, and tumors. Recent studies show that the extract of Phellinus linteus has anti-inflammatory and antitumor activities. However, Phellinus linteus extract has limitation of high cost and limited availability because of supply shortage. Here, we grew Phellinus linteus on germinated brown rice to address the issue of supply shortage and investigated anti-inflammatory effect in vivo as well as in vitro.

MATERIALS AND METHODS
Phellinus linteus grown on germinated brown rice (PBR) were extracted using filtration steps, which included γ-aminobutyric acid (GABA). The PBR (200, 500mg/kg/day) was applied into the mouse model of dextran sodium sulfate (DSS)-induced colitis and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. We used sulfasalazine as a reference drug. In addition, mechanism related to anti-inflammatory was investigated by Western blotting.

RESULTS
In the mouse model of DSS-induced colitis, PBR ameliorated the pathological characteristics of colitis such as shortening of colon length and improved the disease activity index score. In addition, we showed that PBR reduced the expression of nuclear factor-kappa B (NF-κB) in colitis. Western blotting showed that PBR decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins. Further, PBR treatment reduced the expression of mitogen-activated protein kinases (MAPKs) (e.g., extracellular signal-regulated protein kinase (ERK) and p38) in the mouse model of DSS-induced colitis.

CONCLUSIONS
Treatment of RAW 264.7 macrophages with a combination of PBR and LPS showed a significant concentration-dependent inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production. In addition, we determined the ability of PBR to reduce the iNOS and tumor necrosis factor (TNF)-α expression. PBR inhibited the expression of iNOS, NF-κB, and Cox-2 proteins in LPS-stimulated RAW264.7 macrophages. This study presents the potential use of PBR as a drug candidate against colitis.


Ecologically sustainable weed management: How do we get from proof-of-concept to adoption?

Abstract: Weed management is a critically important activity on both agricultural and non-agricultural lands, but it is faced with a daunting set of challenges: environmental damage caused by control practices, weed resistance to herbicides, accelerated rates of weed dispersal through global trade, and greater weed impacts due to changes in climate and land use. Broad-scale use of new approaches is needed if weed management is to be successful in the coming era. We examine three approaches likely to prove useful for addressing current and future challenges from weeds: diversifying weed management strategies with multiple complementary tactics, developing crop genotypes for enhanced weed suppression, and tailoring management strategies to better accommodate variability in weed spatial distributions. In all three cases, proof-of-concept has long been demonstrated and considerable scientific innovations have been made, but uptake by farmers and land managers has been extremely limited. Impediments to employing these and other ecologically based approaches include inadequate or inappropriate government policy instruments, a lack of market mechanisms, and a paucity of social infrastructure with which to influence learning, decision-making, and actions by farmers and land managers. We offer examples of how these impediments are being addressed in different parts of the world, but note that there is no clear formula for determining which sets of policies, market mechanisms, and educational activities will be effective in various locations. Implementing new approaches for weed management will require multidisciplinary teams comprised of scientists, engineers, economists, sociologists, educators, farmers, land managers, industry personnel, policy makers, and others willing to focus on weeds within whole farming systems and land management units.

Liebman|Matt|M| Baraibar|Bàrbara|B| Buckley|Yvonne|Y| Childs|Dylan|D| Christensen|Svend|S| Cousens|Roger|R| Eizenberg|Hanan|H| Heijting|Sanne|S| Loddo|Donato|D| Merotto|Aldo|A| Renton|Michael|M| Riemens|Marleen|M|

D003247:Conservation of Natural Resources

diversified weed management strategies
herbicide resistance
multidisciplinary research
outreach
site-specific weed management
weed ecology
weed-suppressive crop genotypes


Frequency and Impact of Cerebral Infarctions in Patients With Tuberculous Meningitis.

Abstract: Background and Purpose- Cerebral infarctions complicate a variable proportion of tuberculous meningitis (TBM) cases and adversely affect outcomes. The objective of this study was to evaluate the predictors of cerebral infarcts in patients with TBM and to assess their impact on mortality. Methods- The study was based on a retrospective chart review of all patients with TBM admitted to a tertiary care hospital between 2002 and 2013. Data were collected on basic demographics, conventional vascular risk factors, radiological findings, severity of TBM, and neurological outcomes. Data were analyzed using SPSS version 19.0. Binary logistic regression was done to determine the factors predictive of cerebral infarcts and of mortality in patients with TBM. Results- A total of 559 patients were admitted with TBM during the study period. Mean age was 41.9 years (SD, 17.7 years), and 47% were women. A quarter of the patients had stage III disease. One hundred forty-four (25.8%) patients had cerebral infarcts on brain imaging of which 3 quarters were acute or subacute. Those with cerebral infarcts were more likely to be >40 years of age (adjusted odds ratio [AOR], 1.7; 95% CI, 1.1-2.7) and to have hypertension (AOR, 1.8; 95% CI, 1.1-2.8), dyslipidemia (AOR, 9.7; 95% CI, 3.8-24.8), and diabetes mellitus (AOR, 2.2; 95% CI, 1.3-3.6). Presence of cerebral infarction was an independent predictor of mortality among patients with TBM (AOR, 2.1; 95% CI, 1.22-3.5). Conclusions- Cerebral infarcts complicate a substantial proportion of TBM cases. Conventional vascular risk factors are the most important predictors of infarction, and future efforts need to focus on these high-risk patients with TBM to reduce morbidity and mortality.

Wasay|Mohammad|M|
Khan|Maria|M|
Farooq|Salman|S|
Khowaja|Zubair Ali|ZA|
Bawa|Zeeshan Ali|ZA|
Mansoor Ali|Shehzad|S|
Awan|Safia|S|
Beg|M Asim|MA|

cerebral infarction
risk factors
diabetes mellitus
stroke
tuberculosis, meningeal


Spinal cord compression as initial presentation of metastatic occult follicular thyroid carcinoma.

Abstract: Metastatic tumors are the most common tumors of the spine, accounting for 98% of all spine lesions. But spinal cord compression as the initial presentation of metastatic occult follicular carcinoma without any thyroid enlargement is unusual and relatively rare. This report describes a 35-years-old female patient presenting with paraplegia and urinary incontinence for the last two months. She had no thyroid enlargement; no thyroid related symptoms and her biochemical thyroid profile was normal. Magnetic resonance imaging (MRI) of spine shows a huge mass compressing the spinal cord at D11-D12 involving both the spinal and paraspinal areas. The patient was treated by surgery and radioiodine ablation as the histopathology showed metastatic follicular thyroid carcinoma. This case was reported because of the rarity of the disease. Early diagnosis and initiation of the treatment should promise a good prognosis for a patient with metastatic spinal cord compression.

Khan|Md Nuruzzaman|MN|
Sharfuzzaman|Amsm|A|
Mostafa|Md Golam|MG|

spinal cord compression
Occult follicular thyroid carcinoma
spinal metastasis


Analysis of emerging contaminants in water and solid samples using high resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic activity with YES-assay.

Abstract: Trace emerging contaminants (ECs) occur in both waste and surface waters that are rich in particulates that have been found to sorb several organic contaminants. An analytical method based on off-line solid-phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS) analysis was developed for the detection and quantification of 31 ECs from surface water, wastewater, suspended particulate matter (SPM) as well as sediments. Lyophilized sediments and air-dried SPM were subjected to ultrasonic extraction. Water samples and extracts were then concentrated and cleaned-up by off-line SPE. Quantification was realized using a Q Exactive mass spectrometer in both full scan (FS) and MS2 modes. These two modes were optimized and compared to determine which one was the most suitable for each matrix studied. Yeast estrogen screen assay (YES-assay) adapted from the direct measurement of estrogenic activity without sample extraction was tested on filtered wastewater samples. An endocrine disrupting effect was detected in all effluent samples analyzed with estradiol equivalent concentrations ranging from 4.4 to 720 ng eq E2 L-1 for the WWTP-1 and 6.5-42 ng eq E2 L-1 for the WWTP-2. The analytical methods were also applied on six samples of surface water, the corresponding SPM, the sediments and thirty-nine effluent samples from two wastewater treatment plants (WWTPs) sampled over a period of five months (February to June 2014).

Comtois-Marotte|Simon|S|
Chappuis|Thomas|T|
Vo Duy|Sung|S|
Gilbert|Nicolas|N|
Lajeunesse|André|A|
Taktek|Salma|S|
Desrosiers|Mélanie|M|
Veilleux|Éloïse|É|
Sauvé|Sébastien|S|

D001681:Biological Assay
D002853:Chromatography, Liquid
D052244:Endocrine Disruptors
D004784:Environmental Monitoring
D004967:Estrogens
D012441:Saccharomyces cerevisiae
D052616:Solid Phase Extraction
D053719:Tandem Mass Spectrometry
D014874:Water Pollutants, Chemical

Emerging contaminants
YES-assay
High-resolution mass spectrometry
Liquid chromatography
Multi-residue analysis


Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells.

Abstract: In this study, we investigated the ability of a phenolic extract from extra virgin olive oil (OPE) to modulate the inflammatory response in intestinal epithelial cells. Undifferentiated and differentiated Caco-2 cells were challenged with LPS (50 μg/mL) or IL-1β (5 ng/mL) to mimic the early and intermediate phase of intestinal inflammation, respectively. The effects of OPE on nuclear factor-κB-driven transcription and IL-8 promoter activity were evaluated in transfection assays, coupled to p65 nuclear translocation. Modulation of IL-8 mRNA levels by OPE was measured by quantitative RT-PCR while effects on protein levels by ELISA. Specific mitogen activated protein kinases inhibitors were used to investigate mRNA stability and the involvement of related signaling pathways. OPE prevented IL-8 expression and secretion in LPS-treated Caco-2 cells. In the presence of IL-1β OPE exhibited opposing effects on IL-8 gene transcription and mRNA/protein levels. While in IL-1β-treated cells IL-8 promoter activity was inhibited by treatment with OPE, IL-8 mRNA stability was strongly enhanced, leading to increased protein expression. Inhibitors of p38 and extracellular signal-regulated kinases partly prevented OPE effect on IL-8 mRNA levels. Intestinal epithelial cells represent a direct target of the action of olive oil phenols where they regulate IL-8 expression by transcriptional and posttranscriptional mechanisms.

Muto|Eri|E|
Dell'Agli|Mario|M|
Sangiovanni|Enrico|E|
Mitro|Nico|N|
Fumagalli|Marco|M|
Crestani|Maurizio|M|
De Fabiani|Emma|E|
Caruso|Donatella|D|

D048049:Extracellular Signal-Regulated MAP Kinases

Phenols
Intestine
Inflammation
IL-8
Extra-virgin olive oil


The influence of leaf size and shape on leaf thermal dynamics: does theory hold up under natural conditions?

Abstract: Laboratory studies on artificial leaves suggest that leaf thermal dynamics are strongly influenced by the two-dimensional size and shape of leaves and associated boundary layer thickness. Hot environments are therefore said to favour selection for small, narrow or dissected leaves. Empirical evidence from real leaves under field conditions is scant and traditionally based on point measurements that do not capture spatial variation in heat load. We used thermal imagery under field conditions to measure the leaf thermal time constant (τ) in summer and the leaf-to-air temperature difference (∆T) and temperature range across laminae (Trange ) during winter, autumn and summer for 68 Proteaceae species. We investigated the influence of leaf area and margin complexity relative to effective leaf width (we ), the latter being a more direct indicator of boundary layer thickness. Normalized difference of margin complexity had no or weak effects on thermal dynamics, but we strongly predicted τ and ∆T, whereas leaf area influenced Trange . Unlike artificial leaves, however, spatial temperature distribution in large leaves appeared to be governed largely by structural variation. Therefore, we agree that small size, specifically we , has adaptive value in hot environments but not with the idea that thermal regulation is the primary evolutionary driver of leaf dissection.

Leigh|A|A|
Sevanto|S|S|
Close|J D|JD|
Nicotra|A B|AB|

leaf size
thermal dynamics
boundary layer
effective leaf width
leaf dissection
cooling time constant
infrared imagery
leaf shape
leaf temperature


Involvement of RNA granule proteins in meiotic silencing by unpaired DNA.

Abstract: In Neurospora crassa, expression from an unpaired gene is suppressed by a mechanism known as meiotic silencing by unpaired DNA (MSUD). MSUD utilizes common RNA interference (RNAi) factors to silence target mRNAs. Here, we report that Neurospora CAR-1 and CGH-1, homologs of two Caenorhabditis elegans RNA granule components, are involved in MSUD. These fungal proteins are found in the perinuclear region and P-bodies, much like their worm counterparts. They interact with components of the meiotic silencing complex (MSC), including the SMS-2 Argonaute. This is the first time MSUD has been linked to RNA granule proteins.

Xiao|Hua|H|
Vierling|Michael M|MM|
Kennedy|Rana F|RF|
Boone|Erin C|EC|
Decker|Logan M|LM|
Sy|Victor T|VT|
Haynes|Jackson B|JB|
Williams|Michelle A|MA|
Shiu|Patrick K T|PKT|

D004271:DNA, Fungal
D020868:Gene Silencing
D008540:Meiosis
D009492:Neurospora crassa
D012313:RNA
D034622:RNA Interference


Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist Radiotracer in Schizophrenia.

Abstract:
BACKGROUND
Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH.

METHODS
D2/3 agonist positron emission tomography radiotracer [11C]N-propyl-norapomorphine ([11C]NPA) binding potential (BPND) was measured in 14 off-medication subjects with SCH and 14 matched HCs at baseline and after the administration of 0.5 mg kg-1 oral D-amphetamine. The amphetamine-induced change in BPND (ΔBPND) was calculated as the difference between BPND in the postamphetamine condition and BPND in the baseline condition and was expressed as a percentage of BPND at baseline.

RESULTS
A trend-level increase was observed in comparing baseline [11C]NPA BPND (repeated-measures analysis of variance, F1,26 = 3.34, p = .08) between the SCH and HC groups. Amphetamine administration significantly decreased BPND in all striatal regions across all subjects in both groups. No differences were observed in [11C]NPA ΔBPND (repeated-measures analysis of variance, F1,26 = 1.9, p = .18) between HCs and subjects with SCH. Amphetamine significantly increased positive symptoms in subjects with SCH (19.5 ± 5.3 vs. 23.7 ± 4.1, paired t test, p < .0001); however, no correlations were noted with [11C]NPA BPND or ΔBPND.

CONCLUSIONS
This study provides in vivo indication of a role for postsynaptic factors in amphetamine-induced psychosis in SCH.

Frankle|W Gordon|WG|
Paris|Jennifer|J|
Himes|Michael|M|
Mason|N Scott|NS|
Mathis|Chester A|CA|
Narendran|Rajesh|R|

Dopamine
Schizophrenia
High affinity
Amphetamine
Positron emission tomography (PET)
[(11)C]N-propyl-norapomorphine (NPA)


The Impact of State Level Public Policy, Prescriber Education, and Patient Factors on Opioid Prescribing in Elective Orthopedic Surgery: Findings From a Tertiary, Academic Setting.

Abstract:
Background
The United States is in the midst of an opioid misuse epidemic. There have been recent changes to North Carolina's public policy leading to institutional education attempting to reduce high-risk opioid prescribing. This study investigated whether state-level and institutional efforts were associated with provider-level changes in opioid prescriptions after common orthopedic surgeries.

Patients and Methods
Six-week post-operative opioid prescribing in patients 18 years or older undergoing high-volume elective surgeries were reviewed retrospectively. Three patient cohorts from equivalent calendar year periods were included in this analysis; preceding policy implementation (January 1, 2017, to March 31, 2017), immediately after policy implementation (January 1, 2018, to March 31, 2018), and 1 year after policy implementation (January 1, 2019, to March 31, 2019). Multivariable models were constructed to evaluate the effects of public policy and institutional education on postoperative opioid prescribing.

Results
The mean (standard deviation) amount of oxycodone 5-mg equivalents prescribed at discharge decreased from 75.6 (53.2) in 2017 to 55.7 (36.2) in 2018 and then 45.6 (32.6) in 2019 (P < .05). Similarly, 6-week postoperative cumulative oxycodone 5-mg equivalents prescribed also significantly decreased from 123.3 (145.8) in 2017 to 84.1 (90.3) in 2018 and to 80.2 (150.1) in 2019. Other outcomes including prescription duration and rates of outlier prescribing showed similar trends.

Conclusion
In a North Carolina tertiary academic hospital, opioid prescribing decreased after public policy implementation and an institutional response of education for prescribers within a national context of changing practices in opioid prescribing. State-level public policy and prescriber education could be important avenues for decreasing postoperative opioid prescription in orthopedic settings.

Cunningham|Daniel J|DJ|
George|Steven Z|SZ|
Lewis|Brian D|BD|

ACDF, anterior cervical discectomy and fusion

ACLR, anterior cruciate ligament reconstruction

CSRS, Controlled Substances Reporting System

NSAID, nonsteroidal anti-inflammatory drug

STOP, Strengthen Opioid Misuse and Prevention

STROBE, Strengthen the Reporting of Observational Studies in Epidemiology


Attributing discrimination to weight: associations with well-being, self-care, and disease status in patients with type 2 diabetes mellitus.

Abstract: This study examined the association between attributing self-reported discrimination to weight and diabetes outcomes (glycemic control, diabetes-related distress, and diabetes self-care). A community dwelling sample of 185 adults (mean age 55.4; 80 % White/Caucasian 65 % female) with poorly controlled type 2 diabetes (HbA1c level ≥ 7.5 %) provided demographic and several self-report measures (including diabetes-related distress, diabetes self-care activities, discrimination, and attributions of discrimination), and had height, weight, and glycated hemoglobin (HbA1c) assessed by trained research staff as part of a larger research study. Individuals who attributed self-reported discrimination to weight had significantly higher HbA1c levels, higher levels of diabetes-related distress, and worse diabetes-related self-care behaviors (general diet, exercise, and glucose testing). These relationships persisted even when controlling for BMI, overall discrimination, depressive symptoms, and demographic characteristics. Results indicate that the perception of weight stigma among individuals with type 2 diabetes is strongly associated with a range of poor diabetes outcomes. Efforts to reduce exposure to and/or teach adaptive coping for weight stigma may benefit patients with type 2 diabetes.

Potter|Lindsey|L| Wallston|Kenneth|K| Trief|Paula|P| Ulbrecht|Jan|J| Juth|Vanessa|V| Smyth|Joshua|J|

Discrimination
Weight
Diabetes
Distress
Self-care behavior
Obese


Psychometric evaluation of the Orofacial Pain Scale for Non-Verbal Individuals as a screening tool for orofacial pain in people with dementia.

Abstract:
OBJECTIVE
The aim of this study was to describe the psychometric evaluation of the Orofacial Pain Scale for Non-Verbal Individuals (OPS-NVI) as a screening tool for orofacial pain in people with dementia.

BACKGROUND
The OPS-NVI has recently been developed and needs psychometric evaluation for clinical use in people with dementia. The pain self-report is imperative as a reference standard and can be provided by people with mild-to-moderate cognitive impairment.

METHODS
The presence of orofacial pain during rest, drinking, chewing and oral hygiene care was observed in people with mild cognitive impairment (MCI) and dementia using the OPS-NVI. Participants who were considered to present a reliable self-report were asked about pain presence, and in all participants, the oral health was examined by a dentist for the presence of potential painful conditions. After item-reduction, inter-rater reliability and criterion validity were determined.

RESULTS
The presence of orofacial pain in this population was low (0%-10%), resulting in an average Positive Agreement of 0%-100%, an average Negative Agreement of 77%-100%, a sensitivity of 0%-100% and a specificity of 66%-100% for the individual items of the OPS-NVI. At the same time, the presence of oral problems, such as ulcers, tooth root remnants and caries was high (64.5%).

CONCLUSION
The orofacial pain presence in this MCI and dementia population was low, resulting in low scores for average Positive Agreement and sensitivity and high scores for average Negative Agreement and specificity. Therefore, the OPS-NVI in its current form cannot be recommended as a screening tool for orofacial pain in people with MCI and dementia. However, the inter-rater reliability and criterion validity of the individual items in this study provide more insight for the further adjustment of the OPS-NVI for diagnostic use. Notably, oral health problems were frequently present, although no pain was reported or observed, indicating that oral health problems cannot be used as a new reference standard for orofacial pain, and a regular oral examination by care providers and oral hygiene care professionals remains indispensable.

orofacial pain
dementia
cognitive impairment
dentistry
pain assessment


Dual recovery among people with serious mental illnesses and substance problems: a qualitative analysis.

Abstract:
OBJECTIVE
Individuals with serious mental illnesses are more likely to have substance-related problems than those without mental health problems. They also face more difficult recovery trajectories as they cope with dual disorders. Nevertheless, little is known about individuals' perspectives regarding their dual recovery experiences.

METHODS
This qualitative analysis was conducted as part of an exploratory mixed-methods study of mental health recovery. Members of Kaiser Permanente Northwest (a group-model, not-for-profit, integrated health plan) who had serious mental illness diagnoses were interviewed four times over two years about factors affecting their mental health recovery. Interviews were recorded, transcribed, and coded with inductively derived codes. Themes were identified by reviewing text coded "alcohol or other drugs."

RESULTS
Participants (N = 177) had diagnosed schizophrenia/schizoaffective disorder (n = 75, 42%), bipolar I/II disorder (n = 84, 48%), or affective psychosis (n = 18, 10%). At baseline, 63% (n = 112) spontaneously described addressing substance use as part of their mental health recovery. When asked at follow-up, 97% (n = 171) provided codeable answers about substances and mental health. We identified differing pathways to recovery, including through formal treatment, self-help groups or peer support, "natural" recovery (without the help of others), and continued but controlled use of alcohol. We found three overarching themes in participants' experiences of recovering from serious mental illnesses and substance-related problems: Learning about the effects of alcohol and drugs provided motivation and a foundation for sobriety; achieving sobriety helped people to initiate their mental health recovery processes; and achieving and maintaining sobriety built self-efficacy, self-confidence, improved functioning and a sense of personal growth. Non-judgmental support from clinicians adopting chronic disease approaches also facilitated recovery.

CONCLUSIONS
Irrespective of how people achieved sobriety, quitting or severely limiting use of substances was important to initiating and continuing mental health recovery processes. Substance abuse treatment approaches that are flexible, reduce barriers to engagement, support learning about effects of substances on mental health and quality of life, and adopt a chronic disease model of addiction may increase engagement and success. Peer-based support like Alcoholics or Narcotics Anonymous can be helpful for people with serious mental illnesses, particularly when programs accept use of mental health medications.

Green|Carla A|CA|
Yarborough|Micah T|MT|
Polen|Michael R|MR|
Janoff|Shannon L|SL|
Yarborough|Bobbi Jo H|BJ|

Dual recovery
serious mental illnesses
schizophrenia
schizoaffective disorder
affective psychosis
substance use
biopolar disorder


Molecular regulation of cellular iron balance.

Abstract: Handling a life-supporting yet redox-active metal like iron represents a significant challenge to cells and organisms that must not only tightly balance intra- and extracellular iron concentrations but also chaperone it during its journey from its point of entry to final destinations, to prevent inappropriate generation of damaging reactive oxygen species. Accordingly, regulatory mechanisms have been developed to maintain appropriate cellular and body iron levels. In intracellular compartments, about 95% of iron is protein-bound and the expression of the major proteins of iron metabolism is controlled by an integrated and dynamic system involving multilayered levels of regulation. However, dysregulation of iron homeostasis, which could result from both iron-related and unrelated effectors, may occur and have important pathological consequences in a number of human disorders. In this review, we describe the current understanding of the mechanisms that keep cellular iron balance and outline recent advances that increased our knowledge of the molecular physiology of iron metabolism. © 2017 IUBMB Life, 69(6):389-398, 2017.

Recalcati|Stefania|S| Gammella|Elena|E| Buratti|Paolo|P| Cairo|Gaetano|G|0000-0002-8147-4720

D051792:Basic Helix-Loop-Helix Transcription Factors

iron
ferritin
ferroportin
hepcidin
iron regulatory proteins
transferrin receptor


Intracellular trafficking and cellular uptake mechanism of mPEG-PLGA-PLL and mPEG-PLGA-PLL-Gal nanoparticles for targeted delivery to hepatomas.

Abstract: The lysosomal escape of nanoparticles is crucial to enhancing their delivery and therapeutic efficiency. Here, we report the cellular uptake mechanism, lysosomal escape, and organelle morphology effect of monomethoxy (polyethylene glycol)-poly (D,L-lactide-co-glycolide)-poly (L-lysine) (mPEG-PLGA-PLL, PEAL) and 4-O-beta-D-Galactopyranosyl-D-gluconic acid (Gal)-modified PEAL (PEAL-Gal) for intracellular delivery to HepG2, Huh7, and PLC hepatoma cells. These results indicate that PEAL is taken up by clathrin-mediated endocytosis of HepG2, Huh7 and PLC cells. For PEAL-Gal, sialic acid receptor-mediated endocytosis and clathrin-mediated endocytosis are the primary uptake pathways in HepG2 cells, respectively, whereas PEAL-Gal is internalized by sag vesicle- and clathrin-mediated endocytosis in Huh7 cells. In the case of PLC cells, clathrin-mediated endocytosis and sialic acid receptor play a primary role in the uptake of PEAL-Gal. TEM results verify that PEAL and PEAL-Gal lead to a different influence on organelle morphology of HepG2, Huh7 and PLC cells. In addition, the results of intracellular distribution reveal that PEAL and PEAL-Gal are less entrapped in the lysosomes of HepG2 and Huh7 cells, demonstrating that they effectively escape from lysosomes and contribute to enhance the efficiency of intracellular delivery and tumor therapy. In vivo tumor targeting image results demonstrate that PEAL-Gal specifically delivers Rhodamine B (Rb) to the tumor tissue of mice with HepG2, Huh7, and PLC hepatomas and remains at a high concentration in tumor tissue until 48 h, properties that will greatly contribute to enhanced antitumor efficiency.

Liu|Peifeng|P| Sun|Yanming|Y| Wang|Qi|Q| Sun|Ying|Y| Li|He|H| Duan|Yourong|Y|

Intracellular trafficking
Nanoparticles
Hepatoma
Organelle morphology
Cell uptake


Efficacy and safety of 308-nm excimer lamp in the treatment of scalp psoriasis: a retrospective study.

Abstract:
BACKGROUND
Scalp psoriasis is a major therapeutic challenge due to the hindrance caused by hair. Treatment with the 308-nm excimer lamp is purported to provide many benefits over conventional phototherapy. This retrospective study evaluates the efficacy, safety, and effective dosage of 308-nm excimer light in the treatment of scalp psoriasis.

METHODS
We retrospectively reviewed the medical records of patients with scalp psoriasis who received treatment with 308-nm excimer light. Clinical and epidemiological data as well as details regarding treatment were statistically analyzed to determine the treatment outcomes.

RESULTS
Twenty patients with scalp psoriasis were included in the study. Their mean age was 47.45 ± 17.93 years. Eleven patients responded to treatment at the end of 10 sessions. The median baseline Psoriatic Scalp Severity Index (PSSI) was 12 (range, 3-32). At the end of the protocol, the median PSSI was 4.5 (range, 0-24), indicating a statistically significant reduction (P < 0.001). Common adverse effects included erythema, irritation, and desquamation.

CONCLUSION
The 308-nm excimer light appears to be an effective and safe modality that requires short treatment time. The modality could be considered as an alternative or adjuvant treatment for scalp psoriasis.

excimer lamp
scalp psoriasis
phototherapy
excimer light
excimer laser


Portable fluoride-selective electrode as signal transducer for sensitive and selective detection of trace antibiotics in complex samples.

Abstract: Ion-selective electrodes (ISE) can rapidly, sensitively detect their corresponding ions and are suitable for field testing. However, most ISE methods cannot detect other targets directly which limits their practice application. Herein, we established an aptamer-sensing platform to detect organic small molecule using a portable fluoride-selective electrode (FSE). To achieve the purpose, novel signal tags were fabricated based on nano metal-organic frameworks (NMOF) encapsulating F- and labeling aptamers. They were then immobilized on one stir-bar. Subsequently, a double stir-bars (bar-a and b) assisted target recycling strategy was designed to convert organic small molecular target to F- for signal development and amplification. The movement of tags from bar-a to b can be triggered by the analytes. After reaction, the transferred signal tags in bar-b were washed and released F- which can be measured by FSE for qualification of the target. The assay was evaluated to detect kanamycin or chloramphenicol which was employed as the representatives of organic small molecular with a low detection limit of 0.35 nmol L-1 or 0.46 nmol L-1, respectively. Satisfactory performance was observed in complex sample analysis of kanamycin (milk, fish, urine and serum) with a recovery of 91-108% and an RSD (n = 6) <5%. The proposed method broadens the application of traditional FSE to the detection of organic small molecule. And the employment of NMOF which has higher encapsulating capacity of F- for preparing signal tags can be extended to FSE based aptasensors.

Huang|Shengfeng|S| Gan|Ning|N| Zhang|Xinyu|X| Wu|Yongxiang|Y| Shao|Yong|Y| Jiang|Zhengjin|Z| Wang|Qiqin|Q|


Modification of footed pajamas to confirm arthropod bites: The Modified Onesie Biting Bug Assessment suit.

Abstract: When children present with features of bed bug bites, many parents are reluctant to accept the diagnosis. Furthermore, standard methods to detect arthropods in or around one's home can be expensive, time-consuming, and frustrating. We developed a simple, inexpensive way to provide evidence that the lesions are in fact due to arthropod bites. The Modified Onesie Biting Bug Assessment (MOBBA) suit utilizes simple alterations to a full-body onesie-type footed pajama, exposing some body surfaces to insect predators while protecting other areas.

bed bugs
bites and stings
infestations
insect bite/bite reactions


Improved respiratory self-navigation for 3D radial acquisitions through the use of a pencil-beam 2D-T2 -prep for free-breathing, whole-heart coronary MRA.

Abstract:
PURPOSE
In respiratory self-navigation (SN), signal from static structures, such as the chest wall, may complicate motion detection or introduce post-correction artefacts. Suppressing signal from superfluous tissues may therefore improve image quality. We thus test the hypothesis that SN whole-heart coronary magnetic resonance angiography (MRA) will benefit from an outer-volume suppressing 2D-T2 -Prep and present both phantom and in vivo results.

METHODS
A 2D-T2 -Prep and a conventional T2 -Prep were used prior to a free-breathing 3D-radial SN sequence. Both techniques were compared by imaging a home-built moving cardiac phantom and by performing coronary MRA in nine healthy volunteers. Reconstructions were performed using both a reference-based and a reference-independent approach to motion tracking, along with several coil combinations. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared, along with vessel sharpness (VS).

RESULTS
In phantoms, using the 2D-T2 -Prep increased SNR by 16% to 53% and mean VS by 8%; improved motion tracking precision was also achieved. In volunteers, SNR increased by an average of 29% to 33% in the blood pool and by 15% to 25% in the myocardium, depending on the choice of reconstruction coils and algorithm, and VS increased by 34%.

CONCLUSION
A 2D-T2 -Prep significantly improves image quality in both phantoms and volunteers when performing SN coronary MRA. Magn Reson Med 79:1293-1303, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Coristine|Andrew J|AJ|
Chaptinel|Jerome|J|
Ginami|Giulia|G|0000-0003-4669-0572
Bonanno|Gabriele|G|
Coppo|Simone|S|
van Heeswijk|Ruud B|RB|
Piccini|Davide|D|
Stuber|Matthias|M|

self-navigation
coronary
2D
T2-Prep
adiabatic
inner volume
iterative


Acute Necrotizing Pancreatitis Following Olanzapine Treatment and 759C/T Polymorphism of HTR2C Gene: A Case Report.

Abstract: Acute pancreatitis can be attributed to numerous potential causes, such as alcohol abuse, chololithiasis, infection, lesions, tumors, hypercalcemia, hyperlipidemia, and medications. Among psychotropic medications, the use of some atypical antipsychotics, such as clozapine, olanzapine, quetiapine and risperidone, has been implicated in the development of acute pancreatitis, although the underlying mechanism has not been clarified. We describe the case of a young man with no other major medical problems, alcohol abuse or predisposing factors, who developed acute necrotizing pancreatitis following olanzapine administration, possibly through severe elevation of serum triglycerides. A pharmacogenomic analysis revealed the presence of the 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled (HTR2C) -759C genotype which is related to increased risk for metabolic syndrome.

Rizos|Emmanouil|E| Tournikioti|Kalliopi|K| Alevyzakis|Evangelos|E| Peppa|Melpomeni|M| Papazaxos|Konstantinos|K| Zorbas|Georgios|G| Michopoulos|Ioannis|I| Liappas|Ioannis|I| Papageorgiou|Charalampos|C| Douzenis|Athanasios|A|

olanzapine
Acute pancreatitis
-759C/T HTR2C genetic polymorphism


Addition of hydrophobic side chains improve the apoptosis inducibility of the human glyoxalase I inhibitor, TLSC702.

Abstract: Glyoxalase I (GLO I) is a known therapeutic target in cancer. Even though TLSC702, a GLO I inhibitor that we discovered, induces apoptosis in tumor cells, exceptionally higher doses are required compared with those needed to inhibit GLO I activity in vitro. In this work, structure-activity optimization studies were conducted on four sections of the TLSC702 molecule to determine the partial structural features necessary for the inhibition of GLO I. Herein, we found that the carboxy group in TLSC702 was critical for binding with the divalent zinc at the active site of GLO I. In contrast, the side chain substituents in the meta- and para- positions of the benzene ring had little influence on the in vitro inhibition of GLO I. The CLogP values of the TLSC702 derivatives showed a positive correlation with the antiproliferative effects on NCI-H522 cells. Thus, two derivatives of TLSC702, which displayed either high or low lipophilicity due to the types of substituents at the phenyl position, were selected. Even though both derivatives showed comparable inhibitory effects as that of their parent compound, the derivative with the high CLogP value was distinctly more antiproliferative than TLSC702. In contrast, the derivative with the low CLogP value did not decrease cell viability in NCI-H522 and HL-60 cells. These findings suggested that structural improvements, such as the addition of hydrophobic moieties to the phenyl group, enhanced the ability of TLSC702 to induce apoptosis by increasing cell membrane permeability.

Azuma|Miku|M| Inoue|Manami|M| Nishida|Aya|A| Akahane|Haruka|H| Kitajima|Masataka|M| Natani|Shunsuke|S| Chimori|Ryusei|R| Yoshimori|Atsushi|A| Mano|Yasunari|Y| Uchiro|Hiromi|H| Tanuma|Sei-Ichi|SI| Takasawa|Ryoko|R|

D057927:Hydrophobic and Hydrophilic Interactions

Apoptosis
Glyoxalase I
Inhibitor
Anticancer
Methylglyoxal


Supporting research readiness in social enterprise health services.

Abstract: Health-based social enterprises are spun out of the NHS, yet continue to provide NHS-funded services. With the spin-out, however, formal processes for research governance were lost. Patients have a right to take part in research, regardless of where they access healthcare. This paper discusses the barriers to social enterprises undertaking applied health research and makes recommendations to address the need for equivalence of governance processes with NHS trusts.

D016520:Entrepreneurship
D006302:Health Services Research
D006801:Humans
D020380:Needs Assessment
D010358:Patient Participation
D013222:State Medicine
D006113:United Kingdom

Social enterprises
Research governance
Applied Health Research
Research infrastructure


Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway.

Abstract: Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0.027), positive regional lymph node metastasis ( p = 0.002), and poor overall survival ( p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.

Zhang|Xiupeng|X| Zhang|Yong|Y| Fan|Chuifeng|C| Wang|Liang|L| Liu|Yang|Y| Li|Ailin|A| Jiang|Guiyang|G| Zhou|Haijing|H| Cai|Lin|L| Miao|Yuan|Y|

D051698:Activating Transcription Factor 2

D015972:Gene Expression Regulation, Neoplastic

D048051:p38 Mitogen-Activated Protein Kinases

Noxin
proliferation
breast cancer
P38
prognosis


Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201.

Abstract:
OBJECTIVE
We previously reported the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy (Jpn J Clin Oncol 2013). We sought to determine the clinical usefulness of a more convenient hydration method, evaluating the safety and efficacy of shorter-term and lower-volume hydration.

METHOD
Chemonaïve patients with advanced lung cancer who were ≤ 75 years and reserved an adequate renal function for cisplatin use (≥ 60 mg/m(2)) were eligible. An intravenously administered hydration of 1700 ml in ~3.5 h with 1500 ml of orally administered hydration was investigated. The primary endpoint was the proportion of patients without grade 2 or worse renal toxicity in the first cycle.

RESULTS
A total of 45 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl, and the median cisplatin dose on day 1 was 75 mg/m(2). In the first cycle, one patient (2 %) developed grade 2 creatinine toxicity, and thus, the proportion of patients with less than grade 2 was 98 % (the lower limit of 95 % confidence interval; 93 %), which met the primary endpoint. Five patients (11 %) had grade 1 or greater nephrotoxicity, three of whom successfully recovered. The objective response rate was 24 % and median progression-free survival 5.8 months.

CONCLUSION
This prospective study demonstrated the safety and efficacy of shorter-term lower-volume hydration.

Ninomiya|Kiichiro|K| Hotta|Katsuyuki|K| Hisamoto-Sato|Akiko|A| Ichihara|Eiki|E| Gotoda|Hiroko|H| Morichika|Daisuke|D| Tamura|Tomoki|T| Kayatani|Hiroe|H| Minami|Daisuke|D| Kubo|Toshio|T| Tabata|Masahiro|M| Tanimoto|Mitsune|M| Kiura|Katsuyuki|K|

D000971:Antineoplastic Combined Chemotherapy Protocols

D066066:Response Evaluation Criteria in Solid Tumors


Usefulness of a single-parameter tool for the prediction of large vessel occlusion in acute stroke.

Abstract:
BACKGROUND
In acute stroke, large vessel occlusion (LVO) should be promptly identified to guide patient's transportation directly to comprehensive stroke centers (CSC) for mechanical thrombectomy (MT). In many cases, prehospital multi-parameter scores are used by trained emergency teams to identify patients with high probability of LVO. However, in several countries, the first aid organization without intervention of skilled staff precludes the on-site use of such scores. Here, we assessed the accuracy of LVO prediction using a single parameter (i.e. complete hemiplegia) obtained by bystander's telephone-based witnessing.

PATIENTS AND METHODS
This observational, single-center study included consecutive patients who underwent intravenous thrombolysis at the primary stroke center and/or were directly transferred to a CSC for MT, from January 1, 2015 to March 1, 2020. We defined two groups: patients with initial hemiplegia (no movement in one arm and leg and facial palsy) and patients without initial hemiplegia, on the basis of a bystander's witnessing.

RESULTS
During the study time, 874 patients were included [mean age 73 years (SD 13.8), 56.7% men], 320 with initial hemiplegia and 554 without. The specificity of the hemiplegia criterion to predict LVO was 0.88, but its sensitivity was only 0.53.

CONCLUSION
Our results suggest that the presence of hemiplegia as witnessed by a bystander can predict LVO with high specificity. This single criterion could be used for decision-making about direct transfer to CSC for MT when the absence of emergency skilled staff precludes the patient's on-site assessment, especially in regions distant from a CSC.

Thrombectomy
Pre-hospital triage
Stroke management
Stroke unit


Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial.

Abstract:
BACKGROUND
Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS).

OBJECTIVE
To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit.

METHODS
Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634).

RESULTS
There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr.

CONCLUSION
This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Deep brain stimulation
Spasmodic dysphonia
Quality of life
Randomized control trial


Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test.

Abstract: An outbreak of human leishmaniasis was confirmed in the southwest of the province of Madrid, Spain, between July 2009 and December 2012. Incidence of Leishmania infection in dogs was unchanged in this period, prompting a search for alternative sylvatic infection reservoirs. We evaluated exposure to Leishmania in serum samples from animals in the area with an indirect immunofluorescence test (IFAT). Using promastigotes from six culture passages and a 1/25 threshold titer, we found anti-Leishmania infantum seroreactivity in 9.3% of cats (4 of 43), 45.7% of rabbits (16/35) and 74.1% of hares (63/85). Use of promastigotes from >10 in vitro passages resulted in a notably IFAT lower titer, suggesting antigenic changes during extended culture. Postmortem inspection of seropositive animals showed no clinical signs of infection. The results clearly suggest that asymptomatic hares were the main reservoir in the outbreak, and corroborate IFAT as a sensitive serological surveillance method to detect such cryptic Leishmania infections.

Moreno|Inmaculada|I|
Álvarez|Julio|J|
García|Nerea|N|
de la Fuente|Santiago|S|
Martínez|Irene|I|
Marino|Eloy|E|
Toraño|Alfredo|A|
Goyache|Joaquin|J|
Vilas|Felipe|F|
Domínguez|Lucas|L|
Domínguez|Mercedes|M|

D019084:Fluorescent Antibody Technique, Indirect

Immunofluorescence
Hare
Anti-Leishmania antibodies
Incidental reservoirs
Leishmaniosis
Promastigote epitope expression


Nanoamorphous drug products - Design and development.

Abstract: Most of the recent drug compounds coming out of the drug discovery pipeline are labile (multiple polymorphs), and need to be developed into robust marketed oral drug formulations. There are only 22 oral macroamorphous drug products approved by FDA and till date none approved oral nanoamorphous drug products. However, there are several oral nanoamorphous drug formulations (including both labile and non-labile drugs) being researched and a few of these are in the clinical trials. Due to the labile nature of these drug compounds, there is a need to utilize a controlled strategy for design and development of robust nanoamorphous drug formulations in order to prevent any physicochemical instability. The present research focuses on the use of a novel integrated critical process parameters and critical formulation parameters (iCPP-CFPs) DoE approach for the design and development of stable nanoamorphous spironolactone (BCS class II compound with eight polymorphic forms). There are possibilities of the interconversion of these polymorphic forms during processing (manufacturing nanoamorphous particles) and during storage. In the present study, polymorphic transitions (amorphous to crystalline and anhydrous to hydrate) were carefully monitored via orthogonal solid-state characterization tools. Significant polymorphic transitions were observed in the formulations stored at 40 °C/75% RH over six months, however the formulations stored at 4 °C were stable. The significant iCPP-CFPs (solvent-to-antisolvent ratio, drug concentration and inlet temperature of the spray dryer) were critically investigated for their influence on different CQAs (critical quality attributes). Solvent-to-antisolvent ratio and inlet temperature were identified to be the significant iCPP-CFPs. Particle size and total product yield were identified to be the significant CQAs. Lab-scale manufacturing of the spray dried nanoamorphous spironolactone resulted in a remarkably high total product yield (82.4 ± 3.91% w/w) with a uniform and homogenous particle size (244.2 ± 23.32 nm). Furthermore, the physicochemical attributes and the drug release criteria of the nanoamorphous spironolactone were compared with two marketed products (spironolactone tablets, USP 100 mg (Pfizer and Mylan)) and other in-house formulations. In addition, nanoamorphous spironolactone showed a significantly superior kinetic solubility/dissolution rate (10-fold) with a longer supersaturation time (∼6h) compared to the in-house formulations.

Amorphous
Solid-state
Spray drying
Design of experiments
In vitro dissolution testing
Nanoparticles
Quality by design
Sonoprecipitation


The nurse's role in preventing cervical cancer: A cultural framework.

Abstract: This article proposes an innovative, theoretically-driven intervention to reduce risk from human papillomavirus (HPV). This lessening of HPV risk would lead to a reduction in the rate of cervical cancer. Aims of this article are to introduce a culturally appropriate model (PEN-3) that may facilitate vaccine uptake among vulnerable populations and to ascertain whether culturally appropriate health education delivered by nurses could be included in vaccine education programs.

Johnson-Mallard|Versie|V|
Thomas|Tami L|TL|
Kostas-Polston|Elizabeth A|EA|
Barta|Michelle|M|
Lengacher|Cecile A|CA|
Rivers|Desiree|D|

Nurses
Cultural
Health Education
Immunization
Schools


The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat cells, a model of CD4⁺ T cells.

Abstract: CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in association with deregulated growth and resistance to apoptosis. The janus kinase (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The present study aimed to explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell proliferation was determined using WST-1 assay after curcumol treatment. The cell cycle distribution and Bcl-2 protein expression were assessed by flow cytometry. The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2 stimulation were determined by western blot analysis. The Electrophoretic Mobility Shift Assay was used to detect the DNA binding activities of transcription factors STAT3 and STAT5. The study results showed that curcumol could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose-dependent manner. Curcumol at 50μg/mL and Jak3 inhibitor ZM39923 could inhibit the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis might partly be mediated by inhibition of Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively; further studies are required in vivo to test the use of curcumol as a promising therapeutic option for RA.

Wang|Heng|H| Wang|Yong|Y| Jiang|Xiaoji|X| Wang|Zhizhong|Z| Zhong|Bing|B| Fang|Yongfei|Y|

D017209:Apoptosis
D015496:CD4-Positive T-Lymphocytes
D059447:Cell Cycle Checkpoints
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D004268:DNA-Binding Proteins
D004365:Drugs, Chinese Herbal
D006801:Humans
D007376:Interleukin-2
D053616:Janus Kinase 3
D019169:Jurkat Cells
D008213:Lymphocyte Activation
D010766:Phosphorylation
D019253:Proto-Oncogene Proteins c-bcl-2
D016196:S Phase
D050796:STAT3 Transcription Factor
D050799:STAT5 Transcription Factor
D012717:Sesquiterpenes
D025521:Tumor Suppressor Proteins

Mechanism
Curcumol
Jurkat cells
Rheumatoid arthritis
Jak3–STAT


The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study.

Abstract:
BACKGROUND
Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)].

METHODS
A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) parameters were computed from satellite sensors. Brachial FMD and carotid IMT were measured by ultrasound.

RESULTS
Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P < 0.001) and low-density cholesterol (LDL-C) was lower in the top PM2.5 tertile (P < 0.001). Brachial FMD [7.84 ± 1.77, 95% confidence interval (CI) 7.59-8.10%, vs 8.50 ± 2.52, 95% CI 8.23-8.77%, P < 0.0001) was significantly lower and carotid IMT (0.68 ± 0.13 mm, 95% CI 0.67-0.69 mm vs 0.63 mm ± 0.15 mm 95% CI 0.62-0.64 mm; P < 0.0001) was significantly thicker in the top PM2.5 tertile compared with the lowest tertile. On multiple regression, FMD was inversely related to PM2.5 (beta = 0.134, P = 0.015) independent of gender, age and blood pressure (model R2 = 0.156, F-value = 7.6, P < 0.0001). Carotid IMT was significantly correlated with PM2.5 exposure (beta = 0.381, P < 0.0001) independent of age, location, gender, WHR, blood pressure and LDL-C (model R2 = 0.408, F-value = 51.4, P-value <0.0001).

CONCLUSIONS
Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

Woo|K S|KS|0000-0002-5953-0386
Chook|P|P|
Hu|Y J|YJ|
Lao|X Q|XQ|
Lin|C Q|CQ|
Lee|Pwa|P|
Kwok|Cyt|C|
Wei|A N|AN|
Guo|D S|DS|
Yin|Y H|YH|
Lau|Kha|K|
Leung|K S|KS|
Leung|Y|Y|
Celermajer|D S|DS|

air pollution (PM2.5)
modernizing China
Flow-mediated dilation
carotid intima-media thickness


Epidemiological Study on Metal Pollution of Ningbo in China.

Abstract: Background: In order to search for effective control and prevention measures, the status of metal pollution in Ningbo, China was investigated. Methods: Nine of the most common contaminating metals including lead (Pb), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), chromium (Cr), nickel (Ni), zinc (Zn), and mercury (Hg) in samples of vegetables, rice, soil, irrigation water, and human hair were detected using inductively coupled plasma-mass spectrometry (ICP-MS). Three different districts including industrial, suburban and rural areas in Ningbo were studied through a stratified random sample method. Results: (1) Among all of the detected vegetable samples, Cd exceeded the standard limit rates in industrial, suburban and rural areas as high as 43.9%, 27.5% and 5.0%, respectively; indicating the severity of Cd pollution in Ningbo. (2) The pollution index (PI) of Cd and Zn in soil (1.069, 1.584, respectively) suggests that soil is slightly polluted by Cd and Zn. Among all samples, metal contamination levels in soil were all relatively high. (3) A positive correlation was found between the concentrations of Pb, Cd and Cu in vegetables and soil; Pb, Cu, Cr and Ni in vegetables and irrigation water, as well as, Cu and Ni in rice and irrigation water; and, (4) Higher Pb and Cd concentrations were found in student scalp hair in both industrial and suburban areas compared to rural areas. (5) Hg and Pb that are found in human scalp hair may be more easily absorbed from food than any of the other metals. Conclusions: In general, certain harmful metal pollutions were detected in both industrial and suburban areas of Ningbo in China.

metal pollution
vegetable
rice
irrigation water
human hair


Tamsulosin-Induced Priapism: Report of Two Cases and Review of Literature.

Abstract: Tamsulosin in a widely used drug in urology practice in treating lower urinary tract symptoms of benign prostatic hyperplasia, distal ureteral stones, and ureteral stent-related symptoms. Ischemic priapism is a rare but serious adverse effect of tamsulosin. We report two cases of tamsulosin-induced priapism and reviewed available literature citing priapism as a complication of tamsulosin. We also reviewed the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to identify reported cases of tamsulosin-induced priapism.  First patient was a 61-year-old African American male with paraplegia of 30-year duration. He developed priapism after taking first dose of tamsulosin for lower urinary tract symptoms. He presented with 18 hours of painful erection and was treated with aspiration and irrigation, followed by phenylephrine injection. The patient maintained potency after treatment. The second patient was a 24-year-old male who received tamsulosin in the emergency department as medical expulsive therapy for 11 mm distal ureteral stone. Since he had intractable pain, he underwent emergency primary ureteroscopy with laser lithotripsy as definitive treatment of his ureteral calculus. He developed intraoperative priapism that subsided postoperatively. However, he was discharged with tamsulosin to reduce stent-related urinary symptoms. He returned back to the emergency department after 3 days with persistent priapism for 3 days and needed penoscrotal corporeal decompression to treat his priapism. At 6 weeks follow-up visit, the patient has lost his potency. Although there were only 4 case reports on review of the literature, we were able to identify 46 cases reported in the U.S. FAERS database.  Priapism can be an adverse reaction to tamsulosin. Providers and patients should be aware about this complication to ensure early seeking of management to avoid devastating outcomes, particularly in young patients when tamsulosin is given as medical expulsive therapy for ureteral stone and stent-related symptoms.

Khater|Usama|U|
Ramasamy|Ranjith|R|
Shah|Hemendra N|HN|

priapism
tamsulosin
ureteral stone
BPH
ureteral stent


Thyroid Incidentalomas in Association With Low-Dose Computed Tomography in the National Lung Screening Trial.

Abstract: Advances in cancer screening methods have opened avenues for incidental findings and cancer overdiagnosis. We performed a secondary analysis of the National Lung Screening Trial (enrollment from 2002-2004), a randomized controlled trial comparing low-dose computed tomography (LDCT; n = 26,722) with chest radiography (CXR; n = 26,732) for lung cancer detection, to examine incidental findings related to thyroid cancer (ThCa). Three screening rounds were included, and median follow-up was 6.6 years for LDCT and 6.5 years for CXR. Radiologists reported lung and non-lung-related abnormalities. In the LDCT arm, 5.7%, 4.7%, and 4.5% of participants had abnormalities above the diaphragm (AADs) detected at baseline, year 1, and year 2, respectively, compared with 2.3%, 1.5%, and 1.3% in the CXR arm. In the LDCT arm, 205 AADs (7.0%) were thyroid-related. Overall, 60 ThCas were reported, 35 in the LDCT arm and 25 in the CXR arm (P = 0.2). In the LDCT arm, participants with a prior AAD had a 7.8-fold increased risk (95% confidence interval: 4.0, 15.1) of ThCa compared with those who did not have an AAD. Early and persistent excess of ThCas diagnosed earlier in the LDCT arm suggests overdiagnosis. The use of sensitive screening modalities for early detection of lung cancer might result in the discovery of thyroid incidentalomas.

Loomans-Kropp|Holli A|HA|
Dunn|Barbara K|BK|
Kramer|Barnett S|BS|
Pinsky|Paul|P|

D000368:Aged
D055088:Early Detection of Cancer
D005260:Female
D006801:Humans
D033162:Incidental Findings
D008175:Lung Neoplasms
D008297:Male
D000069342:Medical Overuse
D008875:Middle Aged
D011446:Prospective Studies
D013902:Radiography, Thoracic
D012907:Smoking
D013964:Thyroid Neoplasms
D014057:Tomography, X-Ray Computed
D014481:United States

incidentaloma
screening
overdiagnosis
thyroid cancer


Recent advances on mycotic keratitis caused by dematiaceous hyphomycetes.

Abstract: Dematiaceous hyphomycetes (DH) are darkly pigmented fungi ubiquitously found all over the world as plant pathogens and saprophytes, and many of the members of this group have emerged as opportunistic pathogens. These fungi are responsible for a wide variety of infections including mycotic keratitis, which is considered as one of the major causes of corneal blindness, particularly in tropical and subtropical countries with an annual global burden of about 1 000 000 patients. The infection is more common in workers working in an outdoor environment. Moreover, trauma is found to be the most important predisposing cause of mycotic keratitis. Considerable delay in diagnosis and scarcity of effective pharmacological drugs are the major factors responsible for increased morbidity and visual impairment. Considering the crucial role of DH in mycotic keratitis, in the present review, we have focused on major DH with special emphasis on their pathogenicity, diagnosis and treatment strategies.

mycotic keratitis
dematiaceous hyphomycetes
fungi
diagnosis
treatment
cornea


Colonization of Clostridium butyricum in Rats and Its Effect on Intestinal Microbial Composition.

Abstract: Gut microorganisms participate in many physiological processes. In particular, Clostridium butyricum can modulate gut microorganisms and treat diseases. The colonization and persistence of strains in the gut contribute to beneficial effects, and the colonization by C. butyricum in the gut is currently unknown. We investigated the total intestinal contents of C. butyricum at 12 h, 24 h, 48 h, and four and six days using real-time reverse transcription-PCR, after oral administration of C. butyricum to rats for seven consecutive days. We assessed the bacterial community structure using Illumina MiSeq sequencing. The results showed that C. butyricum was mainly colonized in the colon. The total content of C. butyricum in the gut increased significantly at 12 h after administration. Exogenous C. butyricum could still be detected in the gut six days after administration. Administration of C. butyricum significantly enhanced gut microbial diversity. The relative abundance of short-chain fatty acid-producing bacterial genera was shown to be higher than that of the control group, and treatment with C. butyricum elevated Firmicutes and diminished Bacteroidetes phyla compared with to the control group. These findings laid the foundation for the study of probiotic colonization capacity and the improvement of microflora for the prevention of gut diseases.

Luo|Xianshu|X| Kong|Qing|Q|0000-0002-5147-7832 Wang|Yuming|Y| Duan|Xuefeng|X| Wang|Peng|P| Li|Chenman|C| Huan|Yuchen|Y|

colonization
Clostridium butyricum
gut microorganisms
real-time quantitative PCR


Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses.

Abstract: Inflammatory responses play critical roles in carbon monoxide (CO) poisoning-induced cerebral injury. The present study investigated whether erythropoietin (EPO) modulates the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) inflammatory signaling pathways in brain injury after acute CO poisoning. EPO (2500 and 5000 U/kg) was injected subcutaneously twice a day after acute CO poisoning for 2 days. At 48 h after treatment, the expression levels of TLR4 and NF-κB as well as the levels of inflammatory cytokines in the hippocampal tissues were measured. Our results showed that CO poisoning induced a significant upregulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat hippocampal tissues. Treatment with EPO remarkably suppressed the gene and protein expression levels of TLR4 and NF-κB, as well as the concentrations of TNF-α, IL-1β, and IL-6 in the hippocampal tissues. EPO treatment ameliorated CO poisoning-induced histological edema and neuronal necrosis. These results suggested that EPO protected against CO poisoning-induced brain damage by inhibiting the TLR4-NF-κB inflammatory signaling pathway.

Pang|Li|L| Zhang|Nan|N| Dong|Ning|N| Wang|Da-Wei|DW| Xu|Da-Hai|DH| Zhang|Ping|P| Meng|Xiang-Wei|XW|

erythropoietin
carbon monoxide poisoning
toll-like receptor 4
nuclear factor-kappa B
inflammatory cytokine


Food synergies for improving bioavailability of micronutrients from plant foods.

Abstract: Plant foods are endowed with micronutrients but an understanding of bioavailability is essential in countries primarily dependent on plant based foods. Bioavailability depends majorly on food synergies. This review examines the nature of certain food synergies and methods to screen and establish it as a strategy to control micronutrient deficiency in the populations. Strong evidence on the synergistic effect of inclusion of vitamin C rich fruits and non-vegetarian foods in enhancing the bioavailability of iron has been demonstrated. Fat is found to be synergistic for vitamin A absorption. Red wine and protein have been explored for zinc absorption and effect of fat has been studied for vitamin D. Methods for screening of bioavailability, and biomarkers to demonstrate the synergistic effects of foods are required. Translation of food synergy as a strategy requires adaptation to the context and popularization of intelligent food synergies.

Nair|K Madhavan|KM|
Augustine|Little Flower|LF|

Food synergy
Bioavailability
Micronutrients
Plant foods


Is there evidence for the impact of poor oral health on school performance?

Abstract: As part of our study, we reviewed the report published in BMC-Oral Health, titled "An assessment of the impacts of child oral health in Indonesia and associations with self-esteem, school performance and perceived employability" by Maharani et.al, 2017. We noted a plausible error in the interpretation of results in the report and re-examined the published data. Contradictory to the published report, our analysis showed no evidence for the relationship between toothache and poor school performance. Significant relationship was only found between plaque accumulation and school performance. We argued that the error may have originated from an unclear objective and misclassification of school performance variable before applying statistical test to address the objective of this study.

Oral health
School performance
Child
Appraisal
Study design


Where's Waldo? A new commensal species, Waldo arthuri (Mollusca, Bivalvia, Galeommatidae), from the Northeastern Pacific Ocean.

Abstract: A galeommatid bivalve mollusk, representing a new species, is described from off the coasts of California and Vancouver Island, British Columbia. The new bivalve has a commensal relationship with the heart urchin, Brisaster latifrons. It has been observed crawling between the oral spines of this urchin, frequently near the peristome. The bivalve has been recorded from 80 (Vancouver Island) to 444 (southern California) meters depth, in muddy sediments. In common with other galeommatoideans, the new species broods its young; however it differs from the large majority of commensal members in lacking planktotrophic larval development. Waldo arthuri, new species, has multiple morphological, ecological and developmental similarities to other members of the genus Waldo Nicol, 1966, from the southern Atlantic and Antarctic Oceans. This is most pronounced for the Argentine species, Waldo paucitentaculatus Zelaya & Ituarte, 2013, Waldo arthuri's sister speciesin nuclear and mitochondrial gene trees. Despite this close relationship, Waldo arthuri is phylogentically distinct and possesses several hinge, shell sculpture, foot, and mantle tentacle characteristics that merit its description as new.

Valentich-Scott|Paul|P|
O Foighil|Diarmaid|D|
Li|Jingchun|J|

Waldo
Bivalvia
Galeommatidae
Commensal relationships
urchin
Echinodea
taxonomy


Complement System: a Neglected Pathway in Immunotherapy.

Abstract: Approved for the treatment of autoimmune diseases, hematological malignancies, and solid cancers, several monoclonal antibodies (mAb) make use of complement in their mechanism of action. Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. Accordingly, new approaches can now be developed with the final objective of increasing the clinical efficacy of mAb. These improvements include (i) the concurrent administration of fresh frozen plasma during mAb therapy; (ii) mAb modifications such as immunoglobulin G subclass switching, Fc mutation, or IgG hexamerization to improve the fixation and activation of C1q; (iii) optimization of the target recognition to induce a higher complement-dependent cytotoxicity (CDC) and/or complement-dependant cellular cytotoxicity (CDCC); and (iv) the control of soluble and cellular complement inhibitors.

Complement
Monoclonal antibody
Autoimmunity cancer


Expression, purification and antibody preparation using different constructs of PCV2 capsid protein.

Abstract: Capsid protein (Cap) of porcine circovirus 2 (PCV2) contained critical epitopes for inducing a protective immune response. Here, different fragments of PCV2 Cap protein were cloned, expressed, purified and used to raise polyclonal antibodies. The result showed the recombinant plasmids expressed efficiently in the prokaryotic system. Western blot and ELISA showed the recombinant protein had antigenicity and immunogenicity. Furthermore, efficiency of different constructs to produce antibody against PCV2 was compared. Reactivity and specificity of the polyclonal antibody were characterized by Western blot and indirect immunofluorescent assays. The results indicated that polyclonal antiserum prepared from protein ΔCap17-233 had better reactivity and specificity against PCV2 in comparison to that of protein ΔCap51-233 and the inactivated vaccine. These results will contribute to further studies focusing on the gene and vaccine development against PCV2.

Chen|Fuwang|F| Yang|Xin|X| Pang|Daxing|D| Peng|Zhiyuan|Z| Dong|Meichen|M| Liu|Xiaoyun|X| Ouyang|Hongsheng|H| Ren|Linzhu|L|

D015967:Gene Expression Regulation, Viral

Antibody
Porcine circovirus 2
Capsid protein (Cap protein)


Comparison of the prevalence and features of inner ear malformations in congenital unilateral and bilateral hearing loss.

Abstract:
OBJECTIVES
The aim of the study was to clarify differences in the prevalence and features of bony malformations in inner ear between congenital unilateral sensorineural hearing loss (USNHL) and congenital bilateral sensorineural hearing loss (BSNHL).

METHODS
We conducted a retrospective study of 378 consecutive infants referred from routine newborn hearing screening in the past 18 years. Clinical background, audiological data, and temporal bone computed tomography (CT) findings were analyzed. The prevalence of malformations between USNHL and BSNHL groups were compared using the Chi-square test.

RESULTS
The proportion of family history of hearing loss was significantly higher in infants with BSNHL than in those with USNHL (26/107 [24.3%] vs. 4/105 [3.7%]; p = 0.0001). Temporal bone CT scanning revealed significantly a higher prevalence of inner ear malformations in infants with USNHL than in those with BSNHL (93/109 [85.3%] vs. 4/107 [3.7%]; p < 0.0001). The most frequent anomaly in USNHL was cochlear nerve canal stenosis (69.7%), followed by cochlear malformations (20.2%), and narrow internal auditory canal (17.4%). Four infants with BSNHL accompanied by inner ear anomaly had complications such as Down's syndrome, developmental delay, or epilepsy.

CONCLUSIONS
The prevalence of bony malformations in inner ear and/or IAC was markedly higher in infants with congenital USNHL than in infants with BSNHL. Temporal bone CT scanning may help to clarify the etiology of congenital hearing loss, especially in USNHL.

D020022:Genetic Predisposition to Disease

Inner ear
Bilateral hearing loss
Infants
Etiology
Congenital abnormalities
Unilateral hearing loss


Detecting self-produced speech errors before and after articulation: an ERP investigation.

Abstract: It has been argued that speech production errors are monitored by the same neural system involved in monitoring other types of action errors. Behavioral evidence has shown that speech errors can be detected and corrected prior to articulation, yet the neural basis for such pre-articulatory speech error monitoring is poorly understood. The current study investigated speech error monitoring using a phoneme-substitution task known to elicit speech errors. Stimulus-locked event-related potential (ERP) analyses comparing correct and incorrect utterances were used to assess pre-articulatory error monitoring and response-locked ERP analyses were used to assess post-articulatory monitoring. Our novel finding in the stimulus-locked analysis revealed that words that ultimately led to a speech error were associated with a larger P2 component at midline sites (FCz, Cz, and CPz). This early positivity may reflect the detection of an error in speech formulation, or a predictive mechanism to signal the potential for an upcoming speech error. The data also revealed that general conflict monitoring mechanisms are involved during this task as both correct and incorrect responses elicited an anterior N2 component typically associated with conflict monitoring. The response-locked analyses corroborated previous observations that self-produced speech errors led to a fronto-central error-related negativity (ERN). These results demonstrate that speech errors can be detected prior to articulation, and that speech error monitoring relies on a central error monitoring mechanism.

Trewartha|Kevin M|KM|
Phillips|Natalie A|NA|

speech errors
speech production
event-related potentials
conflict monitoring
error-related negativity


A normalization method for combination of laboratory test results from different electronic healthcare databases in a distributed research network.

Abstract:
PURPOSE
Distributed research networks (DRNs) afford statistical power by integrating observational data from multiple partners for retrospective studies. However, laboratory test results across care sites are derived using different assays from varying patient populations, making it difficult to simply combine data for analysis. Additionally, existing normalization methods are not suitable for retrospective studies. We normalized laboratory results from different data sources by adjusting for heterogeneous clinico-epidemiologic characteristics of the data and called this the subgroup-adjusted normalization (SAN) method.

METHODS
Subgroup-adjusted normalization renders the means and standard deviations of distributions identical under population structure-adjusted conditions. To evaluate its performance, we compared SAN with existing methods for simulated and real datasets consisting of blood urea nitrogen, serum creatinine, hematocrit, hemoglobin, serum potassium, and total bilirubin. Various clinico-epidemiologic characteristics can be applied together in SAN. For simplicity of comparison, age and gender were used to adjust population heterogeneity in this study.

RESULTS
In simulations, SAN had the lowest standardized difference in means (SDM) and Kolmogorov-Smirnov values for all tests (p < 0.05). In a real dataset, SAN had the lowest SDM and Kolmogorov-Smirnov values for blood urea nitrogen, hematocrit, hemoglobin, and serum potassium, and the lowest SDM for serum creatinine (p < 0.05).

CONCLUSION
Subgroup-adjusted normalization performed better than normalization using other methods. The SAN method is applicable in a DRN environment and should facilitate analysis of data integrated across DRN partners for retrospective observational studies.

Yoon|Dukyong|D|
Schuemie|Martijn J|MJ|
Kim|Ju Han|JH|
Kim|Dong Ki|DK|
Park|Man Young|MY|
Ahn|Eun Kyoung|EK|
Jung|Eun-Young|EY|
Park|Dong Kyun|DK|
Cho|Soo Yeon|SY|
Shin|Dahye|D|
Hwang|Yeonsoo|Y|
Park|Rae Woong|RW|

D002984:Clinical Laboratory Information Systems

normalization
laboratory test
distributed research networks
electronic health records
pharmacoepidemiology


Western herbal medicines in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

Abstract:
OBJECTIVE
To evaluate the efficacy of Western herbal medicines in the treatment of irritable bowel syndrome (IBS).

DESIGN
A computer-based search of MEDLINE, EMBASE, CINAHL, AMED, GreenFILE, Health Source: Nursing/Academic Edition, and the Cochrane Library was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses and reviews was also undertaken. Trials were included in the review if they were double-blind and placebo-controlled investigating the effects of Western herbal medicines on IBS-related symptoms or quality of life. There were no language restrictions. Eligibility assessment and data extraction were performed by two independent researchers. For herbal medicines where there was more than 1 trial of similar design, data were synthesised using relative risk of symptoms improving using the random effects model.

RESULTS
Thirty-three trials were identified that met all eligibility criteria. Seventeen of these evaluated peppermint essential oil, fifteen other Western herbal medicines, and one trial evaluated peppermint oil in one arm and aniseed essential oil in the other arm. Eighteen different herbal preparations were evaluated in these trials. Data suggests that a number of Western herbal medicines may provide relief of IBS symptoms. Meta-analyses suggest that peppermint essential oil is both efficacious and well-tolerated in the short-term management of IBS. Aloe vera and asafoetida also demonstrated efficacy in reducing global IBS symptoms in meta-analyses. The herbal formulas STW 5, STW 5-II and Carmint, along with Ferula assa-foetida, Pimpenella anisum oil, the combination of Curcumin and Foeniculum vulgare oil, and the blend of Schinopsis lorentzii, Aesculus hippocastanum, and peppermint essential oil also demonstrated efficacy in rigorously-designed clinical trials.

CONCLUSION
A number of Western herbal medicines show promise in the treatment of IBS. With the exception of peppermint essential oil, Aloe vera, and asafoetida, however, none of the positive trials have been replicated. This lack of replication limits the capacity to make definitive statements of efficacy for these herbal medicines.

Hawrelak|Jason A|JA|
Wohlmuth|Hans|H|
Pattinson|Martina|M|
Myers|Stephen P|SP|
Goldenberg|Joshua Z|JZ|
Harnett|Joanna|J|
Cooley|Kieran|K|
Van De Venter|Claudine|C|
Reid|Rebecca|R|
Whitten|Dawn L|DL|

D000529:Complementary Therapies
D029001:Herbal Medicine
D006801:Humans
D043183:Irritable Bowel Syndrome
D009822:Oils, Volatile
D028321:Plant Preparations

Herbal medicine
Irritable bowel syndrome
Systematic review
Peppermint oil
Aloe vera
Asafetida
Complementary medicine


Using propensity score adjustment method in genetic association studies.

Abstract:
BACKGROUND
The statistical tests for single locus disease association are mostly under-powered. If a disease associated causal single nucleotide polymorphism (SNP) operates essentially through a complex mechanism that involves multiple SNPs or possible environmental factors, its effect might be missed if the causal SNP is studied in isolation without accounting for these unknown genetic influences. In this study, we attempt to address the issue of reduced power that is inherent in single point association studies by accounting for genetic influences that negatively impact the detection of causal variant in single point association analysis. In our method we use propensity score (PS) to adjust for the effect of SNPs that influence the marginal association of a candidate marker. These SNPs might be in linkage disequilibrium (LD) and/or epistatic with the target-SNP and have a joint interactive influence on the disease under study. We therefore propose a propensity score adjustment method (PSAM) as a tool for dimension reduction to improve the power for single locus studies through an estimated PS to adjust for influence from these SNPs while regressing disease status on the target-genetic locus. The degree of freedom of such a test is therefore always restricted to 1.

RESULTS
We assess PSAM under the null hypothesis of no disease association to affirm that it correctly controls for the type-I-error rate (<0.05). PSAM displays reasonable power (>70%) and shows an average of 15% improvement in power as compared with commonly-used logistic regression method and PLINK under most simulated scenarios. Using the open-access multifactor dimensionality reduction dataset, PSAM displays improved significance for all disease loci. Through a whole genome study, PSAM was able to identify 21 SNPs from the GAW16 NARAC dataset by reducing their original trend-test p-values from within 0.001 and 0.05 to p-values less than 0.0009, and among which 6 SNPs were further found to be associated with immunity and inflammation.

CONCLUSIONS
PSAM improves the significance of single-locus association of causal SNPs which have had marginal single point association by adjusting for influence from other SNPs in a dataset. This would explain part of the missing heritability without increasing the complexity of the model due to huge multiple testing scenarios. The newly reported SNPs from GAW16 data would provide evidences for further research to elucidate the etiology of rheumatoid arthritis. PSAM is proposed as an exploratory tool that would be complementary to other existing methods. A downloadable user friendly program, PSAM, written in SAS, is available for public use.

Sengupta Chattopadhyay|Amrita|A|
Lin|Ying-Chao|YC|
Hsieh|Ai-Ru|AR|
Chang|Chien-Ching|CC|
Lian|Ie-Bin|IeB|
Fann|Cathy S J|CS|

D001172:Arthritis, Rheumatoid
D056726:Genetic Association Studies
D006801:Humans
D020641:Polymorphism, Single Nucleotide
D057216:Propensity Score
D012044:Regression Analysis

Propensity score
Single nucleotide polymorphism
Logistic regression
Rheumatoid arthritis
Gene–gene interaction
Single-point association test