CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer.

Abstract:
OBJECTIVE
Olaparib (O), a polyADPribose polymerase (PARP) inhibitor, and cediranib (C), a VEGF receptor (VEGFR)1-3 inhibitor together had greater activity than O alone in women with recurrent platinum-sensitive ovarian cancer (OvCa). The objective of this study is to identify potential lead biomarker candidates for response to O + C in the setting of a multi-institutional phase II study of O with and without C in recurrent platinum-sensitive OvCa.

METHODS
A self-selected group of patients participated in a prospectively planned exploratory biomarker substudy of the randomized phase II study of O versus O + C. Whole blood for peripheral blood mononuclear cell (PBMC) and plasma isolation was collected prior to and on day 3 of treatment. Quantitation of circulating endothelial cells (CEC), IL-6, IL-8, VEGF, and soluble VEGFR-2 plasma concentrations, and polyADPribose (PAR) incorporation were performed. Single nucleotide polymorphism analysis of XRCC1 280H, R194W, and Q399R was done. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) was performed at baseline and day 3 of treatment. Parameter changes were compared between the two arms using an exact Wilcoxon rank sum test. Kaplan-Meier and log-rank tests were used to examine survival outcome.

RESULTS
Thirteen patients elected to participate in the translational substudy, seven patients on O and six patients on O + C. Patients on O + C had a greater decrease in IL-8 concentration and larger CEC fold increase compared with those on O alone (p = 0.026, p = 0.032). The fold increase in CEC on day 3 was associated with duration of progression-free survival (PFS) (R (2) = 0.77, 95% CI 0.55-0.97, p < 0.001). IL-8 post-pretreatment changes correlate with PFS (p = 0.028). XRCC1 DNA polymorphisms were not related to PFS. All patients had reduction in PAR incorporation, and all except one had reduction in vascular flow on DCE-MRI.

CONCLUSION
Our exploratory correlative studies indicate that CEC and IL-8 changes may be predictive for response to O + C and prognostic in recurrent platinum-sensitive OvCa, requiring prospective validation.

Lee|Jung-Min|JM|
Trepel|Jane B|JB|
Choyke|Peter|P|
Cao|Liang|L|
Sissung|Tristan|T|
Houston|Nicole|N|
Yu|Minshu|M|
Figg|William D|WD|
Turkbey|Ismail Baris|IB|
Steinberg|Seth M|SM|
Lee|Min-Jung|MJ|
Ivy|S Percy|SP|
Liu|Joyce F|JF|
Matulonis|Ursula A|UA|
Kohn|Elise C|EC|

CEC
IL-8
ovarian cancer
biomarkers
olaparib
cediranib


Removal of H3K27me3 by JMJ Proteins Controls Plant Development and Environmental Responses in Arabidopsis.

Abstract: Trimethylation of histone H3 lysine 27 (H3K27me3) is a highly conserved repressive histone modification that signifies transcriptional repression in plants and animals. In Arabidopsis thaliana, the demethylation of H3K27 is regulated by a group of JUMONJI DOMAIN-CONTANING PROTEIN (JMJ) genes. Transcription of JMJ genes is spatiotemporally regulated during plant development and in response to the environment. Once JMJ genes are transcribed, recruitment of JMJs to target genes, followed by demethylation of H3K27, is critically important for the precise control of gene expression. JMJs function synergistically and antagonistically with transcription factors and/or other epigenetic regulators on chromatin. This review summarizes the latest advances in our understanding of Arabidopsis H3K27me3 demethylases that provide robust and flexible epigenetic regulation of gene expression to direct appropriate development and environmental responses in plants.

H3K27me3
development
environmental response
Arabidopsis
histone modification
JUMONJI
epigenetics
demethylases


Identification of Arterial Hyperenhancement in CT and MRI in Patients with Hepatocellular Carcinoma: Value of Unenhanced Images.

Abstract:
OBJECTIVE
According to the current guidelines, arterial hyperenhancement for diagnosis of hepatocellular carcinoma (HCC) is determined using the arterial phase only. We investigated the optimal definition of arterial hyperenhancement in patients with HCC using computed tomography (CT) and magnetic resonance imaging (MRI).

MATERIALS AND METHODS
The Institutional Review Board approved this retrospective study. The requirement for informed consent was waived. Between January 2011 and September 2013, 147 consecutive patients with surgically proven HCCs with both pre-operative CT and MRI were included. Identification rates of arterial hyperenhancement on CT and magnetic resonance (MR) images using arterial phase only, dual phase (unenhanced and arterial phases), and also subtraction MR images were assessed qualitatively.

RESULTS
The identification rates for arterial hyperenhancement on CT were significantly different between arterial phase and dual phase (72.8% vs. 90.5%; p < 0.001), whereas the rates were similar on MRI (91.8% vs. 93.9%; p = 0.257). The identification rate of arterial hyperenhancement in MRI increased to 98.6% using subtraction MR images.

CONCLUSION
Visual comparison of arterial and unenhanced phases could be recommended instead of conventional qualitative arterial phase alone assessment to determine arterial hyperenhancement of HCCs, especially when using CT.

Kim|Mimi|M|0000-0002-8266-0226
Kang|Tae Wook|TW|0000-0002-0725-8317
Cha|Dong Ik|DI|
Jang|Kyoung Mi|KM|
Kim|Young Kon|YK|
Kim|Seong Hyun|SH|
Sinn|Dong Hyun|DH|
Kim|Kyunga|K|

Hepatocellular carcinoma
Diagnosis
Computed tomography
Magnetic resonance imaging
Arterial enhancement
Contrast
Dynamic imaging


Reliability of the Single-Leg, Medial Countermovement Jump in Youth Ice Hockey Players.

Abstract: Appropriate performance tests are critical for documenting training, fatigue and injury-related changes. Functional performance testing can provide quantitative information on specialized sport movements. The single-leg, medial countermovement jump is an objective measure of frontal plane force, velocity and power, and is particularly applicable for ice hockey players given that ice skating involves applying lateral forces. This study assessed the short-term reliability (10 days) of the single-leg, medial countermovement jump performed by ten competitive male youth ice hockey players. Each participant performed three right and three left maximal single-leg, medial countermovement jumps from force plates. Measured variables included lateral and vertical takeoff velocity, lateral and vertical maximal force, maximal force above bodyweight, lateral and vertical peak concentric power, average concentric power, and average concentric power during the last 100 ms of push-off. Relative reliability was quantified by intraclass correlations. Absolute reliability and the smallest real difference were also calculated. The single-leg, medial countermovement jump had moderate-to-excellent test-retest reliability (ICC: 0.50-0.98) for all twelve variables of interest. These results suggest that the single-leg, medial countermovement jump is a reliable test for assessing frontal plane force, velocity and power in ice hockey players, and is a valid functional performance test for this population given the similarity to ice skating.

reliability
youth ice hockey
force plates


Subdiuretic dose of furosemide enhances albuterol effects in asthmatic mice rather than bumetanide.

Abstract:
BACKGROUND
One of the loop diuretics, furosemide, was found useful in bronchial asthma. It enhanced anti-asthmatic effects of albuterol. The underlying mechanism is still unclear.

OBJECTIVE
This study was planned to investigate whether the enhancing effect of furosemide for albuterol in ovalbumin-induced asthmatic BALB/c mice is diuretic-related or not.

METHODS
Two sets of experiments were performed. In the first, effects of inhaled subdiuretic doses of furosemide and bumetanide (another loop diuretic) were compared. Treatments (mg/mL) were given as 15 minute-inhalation before final ovalbumin provocation as follows: albuterol (2.5), furosemide (0.08), bumetanide (0.005), (albuterol+furosemide, 2.5+0.08), and (albuterol+bumetanide, 2.5+0.005). Airway hyperreactivity (AHR) to inhaled methacholine, levels of IL-6, TNF-α, and differential white blood cells in bronchoalveolar lavage fluid (BALF), and lung histopathology were evaluated. In the second set, effects of oral diuretic doses (mg/kg) of furosemide (10) and bumetanide (0.25) were given before final ovalbumin provocation. Urine volume and asthma parameters were measured.

RESULTS
Ovalbumin-asthmatic mice showed significant increases in AHR, levels of IL-6, TNF-α, and inflammatory cells in BALF, and lung inflammatory cell infiltration. Inhaled furosemide significantly decreased these changes while inhaled bumetanide failed. Albuterol and albuterol+bumetanide significantly decreased these changes more than furosemide while albuterol+furosemide produced the most significant decreases. Both oral furosemide and bumetanide exerted equivalent diuretic effects but failed to improve asthma.

CONCLUSIONS
Inhaled subdiuretic dose of furosemide enhanced effects of albuterol more in ovalbumin-asthmatic mice rather than bumetanide, while oral diuretic doses of both drugs failed to improve asthma, indicating that this enhancing effect is not diuretic-related.

Murad|H|H| Ghabrah|T|T| Rafeeq|M|M| Ali|S|S|

Furosemide Albuterol Bumetanide Asthma Inhalation Diuresis


Enantioselective Biosynthesis of l-Phenyllactic Acid by Whole Cells of Recombinant Escherichia coli.

Abstract:
BACKGROUND
l-Phenyllactic acid (l-PLA)-a valuable building block in the pharmaceutical and chemical industry-has recently emerged as an important monomer in the composition of the novel degradable biocompatible material of polyphenyllactic acid. However, both normally chemically synthesized and naturally occurring phenyllactic acid are racemic, and the product yields of reported l-PLA synthesis processes remain unsatisfactory.

METHODS
We developed a novel recombinant Escherichia coli strain, co-expressing l-lactate dehydrogenase (l-LDH) from Lactobacillus plantarum subsp. plantarum and glucose dehydrogenase (GDH) from Bacillus megaterium, to construct a recombinant oxidation/reduction cycle for whole-cell biotransformation of phenylpyruvic acid (PPA) into chiral l-PLA in an enantioselective and continuous manner.

RESULTS
During fed-batch bioconversion with intermittent PPA feeding, l-PLA yield reached 103.8 mM, with an excellent enantiomeric excess of 99.7%. The productivity of l-PLA was as high as 5.2 mM·h-1 per OD600 (optical density at 600 nm) of whole cells. These results demonstrate the efficient production of l-PLA by the one-pot biotransformation system. Therefore, this stereoselective biocatalytic process might be a promising alternative for l-PLA production.

Zhu|Yibo|Y| Wang|Ying|Y| Xu|Jiayuzi|J| Chen|Jiahao|J| Wang|Limei|L| Qi|Bin|B|

D001410:Bacillus megaterium
D001426:Bacterial Proteins
D061249:Batch Cell Culture Techniques
D001711:Biotransformation
D004926:Escherichia coli
D005818:Genetic Engineering
D042843:Glucose 1-Dehydrogenase
D006863:Hydrogen-Ion Concentration
D007770:L-Lactate Dehydrogenase
D007773:Lactates
D019344:Lactic Acid
D048191:Lactobacillus plantarum
D010667:Phenylpyruvic Acids

glucose dehydrogenase
">l-Lactate dehydrogenase
">l-Phenyllactic acid
NADH regeneration
whole-cell transformation


Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach.

Abstract: Dioxins and dioxin-like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects. In the present study, a total of 100 dioxins and DLCs were taken and their binding pattern was assessed with the ketosteroid receptors, i.e. androgen (hAR), glucocorticoid (hGR), progesterone (hPR) and mineralocorticoid (hMR) in comparison to the corresponding natural steroids and a known endocrine disrupting xenobiotic, Bisphenol A (BPA). Most of the DLCs, particularly those bearing hydroxyl (-OH) group showed considerable affinities with ketosteroid receptors. On comparing D scores of all the dioxins and DLCs against all four receptors, compound 8-hydroxy-3,4-dichlorodibenzofuran(8-OH-DCDF) exhibited least D score of -9.549 kcal mol-1 against hAR. 3,8-Dihydroxy-2-chlorodibenzofuran(3,8-DiOH-CDF), 4'-hydroxy-2,3,4,5-tetrachlorobiphenyl (4'-OH-TCB) and 4-hydroxy-2,2',5'-trichlorobiphenyl(4-OH-TCB) also showed comparable molecular interactions with the ketosteroid receptors. These interactions mainly include H-bonding, π-π stacking, hydrophobic, polar and van der Waals' interactions. In contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, i.e. certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health.

Khan|Mohemmed Faraz|MF|
Alam|Mohammad Mumtaz|MM|
Verma|Garima|G|
Akhtar|Wasim|W|
Rizvi|Moshahid Alam|MA|
Ali|Asif|A|
Akhter|Mymoona|M|
Shaquiquzzaman|Mohammad|M|

D057927:Hydrophobic and Hydrophilic Interactions

dioxins
ketosteroid receptors
risk assessment
Molecular docking
endocrine disruptors


The effects of elimination diet on nutritional status in subjects with atopic dermatitis.

Abstract: A food allergy is an adverse health effect arising from a specific immune response that occurs reproducibly upon exposure to a given food. In those with food allergies that are thought to cause aggravation of eczema, food avoidance is important. The objective of this study was to research the nutritional status of patients with food allergies. A total of 225 subjects diagnosed with atopic dermatitis underwent a skin prick test as well as measurement of serum immunoglobulin E. Food challenge tests were conducted using seven food items: milk, eggs, wheat, soybeans, beef, pork, and chicken. At post-food challenge visits to the test clinic, participants completed a three-day dietary record, which included two week days and one weekend day, in order to evaluate energy intake and diet quality during the challenge. We analyzed nutrient intake based on differential food allergens. Subjects with a food allergy to milk showed lower intake of Ca, Zn, and vitamin B2, and subjects with a food allergy to egg showed lower intake of vitamin A, B1, B2, niacin, and cholesterol. Subjects with a food allergy to wheat and soybean showed lower intake of Ca, P, Fe, K, Zn, vitamin B2, vitamin B6, and niacin; and subjects with a food allergy to beef, pork, and chicken showed lower intake of Fe and higher intake of K, vitamin A, B2. Subjects with atopic dermatitis were lacking in several nutrients, including vitamin A and vitamin C. A greater number of food allergies showed an association with a greater number of nutrient intake deficiencies. Allergen avoidance is the basic treatment for atopic dermatitis. However, when the allergen is food, excessive restriction can lead to nutrition deficiency. Findings of this study suggest the necessity for enhanced nutritional education in order to provide substitute foods for patients with food allergies who practice food restriction.

Kim|Jungyun|J|
Kwon|Jaryoung|J|
Noh|Geunwoong|G|
Lee|Sang Sun|SS|

atopic dermatitis
Food allergy
food restriction


Long-term outcome of totally thoracoscopic surgical ablation in atrial fibrillation: A single-center experience.

Abstract:
Background
Totally thoracoscopic ablation (TTA) is a minimally invasive and safe alternative to radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF). It has evolved over the last decades, but data are limited. The aim of this study was to report the long-term efficacy and safety of TTA through a single center experience.

Methods
We retrospectively analyzed all consecutive patients who underwent TTA for AF from February 2012 to December 2018. All patients were followed every 3 months after operation with 12-lead ECG and 24-hour Holter ECG monitoring. The late recurrence of AF was defined as any atrial tachyarrhythmia (ATa) sustained more than 30 s from 3 months after surgery.

Results
Of the total 408 patients undergoing TTA, 265 were analyzed in this study (17% paroxysmal, persistent or long standing persistent 83%, mean age 56 ± 9 years). During the mean follow-up duration 23 ± 18 months, ATa-free survival rate was 74%, 64%, 58%, 51% and 51% at 1,2,3,4 and 5 years, respectively. At the last follow-up, 75% of patients had sinus rhythm with or without additional intervention. The overall complication rate was 4.5% (12 events) and four patients (1.5%) had a stroke during follow-up.

Conclusions
TTA could be effective treatment option for AF. It had a very low risk of complication and could reduce stroke incidence. Further studies are needed to improve treatment strategy.

Kwon|Hee-Jin|HJ|
Jeong|Dong Seop|DS|
Park|Seung-Jung|SJ|
Park|Kyoung-Min|KM|
Kim|June Soo|JS|
On|Young Keun|YK|

Surgical ablation
Atrial fibrillation
Thoracoscopic ablation


Fosfomycin for bacterial prostatitis: a review.

Abstract: There has been growing interest in fosfomycin for the treatment of bacterial prostatitis due to evidence suggesting that it achieves adequate prostatic concentrations for antimicrobial effect, has activity against resistant micro-organisms, and has a low-toxicity profile. This review evaluated the current clinical evidence for fosfomycin in acute and chronic bacterial prostatitis to elucidate the clinical implications of fosfomycin in an era of increasing antimicrobial resistance. PubMed, Scopus, EMBASE, Web of Science, Google Scholar and ClinicalTrials.gov were searched for studies published in the English language from January 1984 to November 2019. The inclusion criteria were met if the study reported the use of fosfomycin (more than one dose) to treat bacterial prostatitis. Ten observational studies were identified that met the inclusion criteria. The evidence for the use of fosfomycin in acute bacterial prostatitis is sparse. The majority of the available evidence is for chronic bacterial prostatitis caused by Escherichia coli. Despite the implementation of variable dosing regimens, extended courses of fosfomycin appear to be safe and effective in achieving clinical and microbiological cure. In these studies, the use of fosfomycin was restricted to cases of treatment failure, intolerance to first-line therapy, or multi-resistant organisms. However, given the development of resistant organisms and the undesirable adverse effects of many first-line therapeutic options, fosfomycin has the potential to be considered as an effective first-line alternative for acute and chronic bacterial prostatitis in the future. Further studies, including randomized controlled trials, would be helpful to firmly establish its optimal dosing regimen, efficacy and place in therapy.

Fosfomycin
Bacterial prostatitis
Prostatitis
Chronic bacterial prostatitis
Acute bacterial prostatitis
Antimicrobial stewardship


Chemical constituents of hybrids of Ligularia cyathiceps and L. lamarum/L. subspicata collected in China: Structures of subspicatins M, N, O1, and O2, and related compounds.

Abstract: Three natural hybrids and an introgressed individual of Ligularia were evaluated based on a combination of morphology, root chemicals, and nucleotide sequences of evolutionally neutral regions to understand the chemical outcomes of hybridization and introgression. Six previously undescribed eremophilane sesquiterpenes were isolated from hybrids between L. cyathiceps and L. lamarum/L. subspicata, and benzofurans were isolated from L. subspicata for the first time. Their structures were elucidated based on spectroscopic analyses. Some compounds produced by hybrids have not been detected in either parental species, indicating that the metabolic profile was altered by hybridization and introgression.

Saito|Yoshinori|Y| Ichihara|Mayu|M| Takashima|Yuriko|Y| Okamoto|Yasuko|Y| Gong|Xun|X| Hanai|Ryo|R| Kuroda|Chiaki|C| Tori|Motoo|M|

Ligularia cyathiceps
Subspicatin
Eremophilane
Asteraceae
Chemical diversity
Internal transcribed spacer (ITS)
Ligularia lamarum
Ligularia subspicata
Structure elucidation
Subspicatol


Using a Transdisciplinary Interpretive Lens to Broaden Reflections on Alleviating Poverty and Promoting Decent Work.

Abstract: This article aims to broaden current reflections on definitions of decent work and poverty using a transdisciplinary interpretive lens comprising philosophical, juridical, economic, sociological, and psychological understandings. We (the authors) undertook an adapted systematic qualitative review to gather data on different perspectives on decent work and poverty. The article summarizes and compares reflections on the two constructs and proposes an enhancement of the current definition of decent work. The aim is to facilitate the identification and development of new research and intervention projects that can be implemented to promote fair and sustainable economic development, the provision of decent work, and the reduction of poverty globally. We believe that challenges should be dealt with pro-actively rather than reactively and that intervening at the level of primary prevention should lie at the heart of any strategy to promote decent work and alleviate poverty. Radical intervention is needed to ensure that future generations not only survive but develop, grow, and express themselves meaningfully through decent work.

Di Fabio|Annamaria|A|
Maree|Jacobus G|JG|

new responsibility for decent work agenda


Pathological lesions and global DNA methylation in rat prostate under streptozotocin-induced diabetes and melatonin supplementation.

Abstract: Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 μg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemical assays of α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTPI), and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short-term diabetes-and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long-term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.

Gobbo|Marina Guimarães|MG|
Tamarindo|Guilherme Henrique|GH|
Ribeiro|Daniele Lisboa|DL|
de Campos|Silvana Gisele Pegorin|SGP|
Taboga|Sebastião Roberto|SR|
Góes|Rejane Maira|RM|

rat
prostate
diabetes
melatonin
prostate cancer


The use of an intensive physical exertion test as a final return to play measure in concussed athletes: a prospective cohort.

Abstract:
OBJECTIVES
To examine the utility of a novel physical exertion test developed by the Chicago Blackhawks medical staff as a final return to play (RTP) clearance test in youth and young adult athletes, and to determine the relationship between participant and test variables on RTP within asymptomatic athletes diagnosed with concussion.

METHODS
Once asymptomatic and following completion of all RTP steps, concussed athletes underwent the Gapski-Goodman Test (GGT) or modified GGT (mGGT) at partnered Complete Concussion Management Inc. (CCMI) clinics as part of RTP decision-making. Prospective data was collected electronically by trained CCMI clinicians utilizing the CCMI Concussion Database System. A review was conducted to examine data collected between January 2016 and February 2017. Participant and test variables were analyzed to determine relationships with pass/fail rate of the GGT/mGGT.

RESULTS
A total of 759 athletes performed the GGT/mGGT in the study period. Although all asymptomatic, 14.6% of concussed athletes failed the GGT/mGGT while attempting to achieve RTP clearance. Statistically significant relationships were found between failure of the test and symptom severity score on initial presentation and self-reported history of pre-morbid anxiety. When taken together, sex, age, and pre-morbid anxiety significantly predicted the length of time between injury and RTP clearance.

CONCLUSION
The GGT may identify individuals who are not ready to RTP despite a self-reported asymptomatic status and completion of all RTP steps. These results illustrate that RTP clearance decisions based on self-reported asymptomatic status at rest may be inadequate. Instead, monitored, intensive, sport-specific, physical exertion testing should be utilized to inform clinical RTP decisions.

Marshall|Cameron M|CM|
Chan|Nicole|N|
Tran|Pauline|P|
DeMatteo|Carol|C|

D000293:Adolescent
D000328:Adult
D000367:Age Factors
D001007:Anxiety
D001265:Athletic Injuries
D001924:Brain Concussion
D000066491:Clinical Decision-Making
D005080:Exercise Test
D005260:Female
D006801:Humans
D008297:Male
D005082:Physical Exertion
D011446:Prospective Studies
D000068958:Return to Sport
D057566:Self Report
D012720:Severity of Illness Index
D012737:Sex Factors
D055815:Young Adult

physical exertion
Brain concussion
brain injuries
return to sport
secondary prevention
symptom flare up
traumatic


Long-term outcomes and predictors of morbi-mortality according to age in stemi patients with multivessel disease: Impact of an incomplete revascularization.

Abstract:
BACKGROUND
Optimal management strategy for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains unclear, especially in the elderly population. The aim of this study was to assess long-term outcomes and predictors of morbi-mortality according to age in patients with a STEMI and MVD.

METHODS
We prospectively included 381 consecutive patients with a STEMI who underwent primary angioplasty and showed MVD in the angiogram. 111 (29.1%) patients were older than 75 (≥75) years and 270 (70.9%) were younger than 75 (<75) years. The co-primary outcomes were the incidence of all-cause mortality and major adverse cardiac events (MACE) during follow-up.

RESULTS
During a median follow-up of 22 months, patients ≥75 years showed a higher incidence of all-cause mortality and MACE, as compared to younger patients. On multivariate analysis, incomplete revascularization (IR) was only an independent predictor of MACE (HR = 3.1, CI 95%:1.9-4.7; P = .02) in younger patients; whereas in the elderly group severely depressed ejection fraction was the unique independent predictor of MACE (HR = 2.7, CI 95%:1.5-4.8; P = .001). IR was not associated with the risk of all-cause mortality in any group.

CONCLUSION
This study confirms the relevant prevalence of MVD in STEMI patients, as well as the difference in outcomes of an IR strategy between both age-groups, being only independently associated with MACE in younger patients. This finding supports that a routine complete revascularization (CR) strategy seems to be the best therapeutic option in younguer patients, whereas in the elderly population may not confer a clear clinical benefit during a long-term follow-up.

Rumiz|Eva|E|0000-0001-6860-0801
Berenguer|Alberto|A|
Vilar|Juan Vicente|JV|
Valero|Ernesto|E|
Facila|Lorenzo|L|
Cubillos|Andres|A|
Sanmiguel|Dario|D|
Almela|Pablo|P|
Morell|Salvador|S|

D000072657:ST Elevation Myocardial Infarction

primary percutaneous coronary intervention


Overexpression of enolase 2 is associated with worsened prognosis and increased glycikolysis in papillary renal cell carcinoma.

Abstract: Papillary renal cell carcinoma (pRCC) is characterized with underlying genetic disorders and the role enolase 2 (ENO2) in ccRCC is unknown. An in silico exploratory analysis using multiple public genetic datasets was used to establish association between ENO2 expression and clinicopathological parameters. Associations of interest were validated using 49 pRCC samples using immunohistochemistry. In vitro and in vivo assays were carried out to validate findings in tissue. ENO2 was overexpressed and prognostic in pRCC. ENO2 expression was significantly higher in younger patients and in CpG island methylator phenotype subtype. ENO2-overexpressed cases showed significant enrichment in glycolysis. Overexpression of ENO2 significantly increased proliferation and silencing of ENO2 significantly inhibited growth of ACHN cells. Glycolytic genes HK1, HK 2, and lactate dehydrogenase A were decreased when ENO2 was silenced in ACHN. Glycolytic inhibitor TT-232 showed minimal inhibitory effect on ACHN cells yet showed synergistic effect in the presence of ENO2 silencing. ENO2 significantly increased and decreased extracellular glucose, respectively in ACHN cells. Xenograft mouse model showed ENO2 silencing and TT-232 combination treatment showed synergistic effect in ACHN tumors. ENO2 is associated with worsened prognosis in pRCC and is related to glycolysis. ENO2-targeted therapy can be of therapeutic potential.

Sun|Chenmin|C| Liu|Min|M| Zhang|Wenyi|W| Wang|Shuyan|S| Qian|Gang|G| Wang|Mi|M| Zhang|Guangming|G|0000-0001-5190-7364

D015972:Gene Expression Regulation, Neoplastic

papillary renal cell carcinoma
ENO2
glycolysis


Cell glycosaminoglycans content modulates human voltage-gated proton channel (HV 1) gating.

Abstract: Voltage-gated proton channels (HV 1) have been found in many mammalian cells and play a crucial role in the immune system, male fertility, and cancer progression. Glycosaminoglycans play a significant role in various aspects of cell physiology, including the modulation of membrane receptors and ion channel function. We present here evidence that mechanosensitivity of the dimeric HV 1 channel transduce changes on cell membrane fluidity related to the defective biosynthesis of chondroitin sulfate and heparan sulfate in Chinese Hamster Ovary (CHO-745) cells into a leftward shift in the activation voltage dependence. This effect was accompanied by an increase in the H+ current, and an acceleration of the activation kinetics, under symmetrical or asymmetrical pH gradient (ΔpH) conditions. Similar gating alterations were evoked by two naturally occurring HV 1 N-terminal truncated isoforms expressed in wild-type CHO-K1 and CHO-745 cells. On three different monomeric HV 1 constructs, no alterations in the biophysical parameters were observed. Moreover, we have shown that HV 1 gating can be modulated by manipulating CHO-K1 cell membrane fluidity. Our results suggest that the defective biosynthesis of chondroitin sulfate and heparan sulfate on CHO-745 cell increases membrane fluidity and allosterically modulates the coupling between voltage- and ΔpH-sensing through the dimeric HV 1 channel.

glycosaminoglycans
voltage-gated proton channels
membrane fluidity
gating modulation
gradient pH-sensing


Designing an Elusive C•G→G•C CRISPR Base Editor.

Abstract: Protein engineering advances, including DNA repair manipulation of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) machinery, have paved the way for the first set of DNA precision base editors (C•G→T•A and A•T→G•C), with wide-ranging implications for treating many human genetic diseases. By utilizing the latest protein evolution advances, a hypothetical model for the first transversion (C•G→G•C) base editor can now be proposed.

D064113:CRISPR-Cas Systems
D003564:Cytidine Deaminase
D004247:DNA
D045647:DNA Glycosylases
D000072669:Gene Editing
D006801:Humans

CRISPR
DNA repair
base editing
directed evolution


A study protocol for a cluster randomised trial for the prevention of chronic suppurative otitis media in children in Jumla, Nepal.

Abstract:
BACKGROUND
Chronic Suppurative Otitis Media (CSOM) is the commonest cause of preventable deafness, affecting 164 million people worldwide, 90 % of whom live in low resource countries, such as Nepal. Simple, inexpensive treatment of acute otitis media can prevent the development of CSOM and its sequelae: deafness, abscess, encephalitis, and, rarely, death. CSOM is a disease of poverty and its social determinants: low parental education, overcrowding, poor hygiene and malnutrition. Previous studies have established economic, socio-cultural and geographic barriers to care seeking for childhood illness in the developing world and, in particular, in Nepal. The ultimate aim of this research is to improve the ear health of the children in Jumla, Nepal. The primary outcome is an increase in mother's knowledge, attitude and practice regarding ear disease in their children. The secondary outcome is a reduction in the prevalence of CSOM in their children.

METHODS/DESIGN
Using 56 existing women's self-help groups, sample size, adjusting for clustering and data analysis, is set at 15 groups per arm. A baseline survey of 30 randomly selected groups will be performed, consisting of a knowledge, attitude and practice questionnaire aimed at women who participate in self-help groups, as well as examination of their children's ears. This will be followed by random allocation, stratified by geography, into 15 intervention and 15 control groups. The intervention groups will participate in three interactive educational sessions at their regular monthly meetings based on World Health Organisation Primary Ear and Hearing Resource, Basic Level. The control groups will continue their usual monthly group meetings. At 12 months, a follow-up assessment of both control and intervention groups will be performed, with a repeat women's survey and repeat ear examination of the children. Data analysis will be by intention to treat and clustering will be considered at every stage. Cluster level data will be analysed using t-test and individual level data using mixed effects linear regression and logistic regression random effects model as appropriate.

DISCUSSION
Despite its remote location, Jumla has a vibrant network of health posts and community workers. This project uses existing, local resources and will be undertaken in a way that is consistent with the cultural understanding of the local community in Jumla and acceptable to local care-givers.

TRIAL REGISTRATION
Australia and New Zealand Clinical Trials Register, ACTRN12614000231640.

Clarke|Susan|S|
Richmond|Robyn|R|
Worth|Heather|H|
Wagle|Rajendra Raj|RR|

Otitis Media
Hearing
Community intervention
Women’s groups


Characterization of the behavior of carotenoids from pitanga (Eugenia uniflora) and buriti (Mauritia flexuosa) during microemulsion production and in a dynamic gastrointestinal system.

Abstract: Uncommon tropical fruits are emerging as raw-material for new food products with health benefits. This work aimed at formulating and processing microemulsions from pitanga (Eugenia uniflora) and buriti (Mauritia flexuosa) fruits, since they are very rich in carotenoids (particularly lycopene and β-carotene), in order to encapsulate and increase carotenoids' bioaccessibility. Pitanga and buriti microemulsions were produced by applying a direct processing (high-speed homogenization at 15,000 rpm and ultrasound with 20 kHz probe at 40% amplitude) of the whole pulp together with surfactant (Tween 80 or Whey Protein Isolate at 2%) and corn oil (5%). All treatments (HSH-US for 0-4, 4-0, 4-4, 4-8 min-min) applied were able to increase the amount of carotenoid released. However, the processing also decreased the total amount of carotenoids in the whole pulp of studied fruits. The impact of processing during microemulsion production was not severe. The overall data suggest that the presence of surfactant and oil during processing may protect the carotenoids in fruits and microemulsions. Final recovery of total carotenoids, after passing the samples through a dynamic gastrointestinal system that simulates the human digestion, was higher for microemulsions than for whole pulps. High losses of total carotenoids in buriti and β-carotene and lycopene in pitanga occurred during jejunum and ileum phases. The present work confirms that it is possible to increase β-carotene and lycopene bioaccessibility from fruits by directly processing microemulsions (p < 0.01).

Berni|Paulo|P|0000-0003-4824-7961
Pinheiro|Ana Cristina|AC|
Bourbon|Ana Isabel|AI|
Guimarães|Maura|M|
Canniatti-Brazaca|Solange G|SG|
Vicente|Antonio A|AA|

Tropical fruits
Lycopene
Beta-carotene
Bioavailability
Dynamic digestive system
Structure design


Hepatitis E antibodies in laboratory rabbits from 2 US vendors.

Abstract: We tested laboratory rabbits from 2 US vendors for antibodies against hepatitis E virus (HEV); Seroprevalences were 40% and 50%. Retrospective analysis of an ocular herpes simplex 1 experiment demonstrated that HEV seropositivity had no effect on experiment outcome. HEV probably is widespread in research rabbits, but effects on research remain unknown.

Birke|Leslie|L|
Cormier|Stephania A|SA|
You|Dahui|D|
Stout|Rhett W|RW|
Clement|Christian|C|
Johnson|Merlin|M|
Thompson|Hilary|H|

D000818:Animals
D000914:Antibodies, Viral
D005838:Genotype
D016751:Hepatitis E
D016752:Hepatitis E virus
D006561:Herpes Simplex
D018259:Herpesvirus 1, Human
D012367:RNA, Viral
D011817:Rabbits
D012189:Retrospective Studies
D016036:Seroepidemiologic Studies

rabbits
Hepatitis E virus
HEV
herpes simplex 1 virus
viruses
zoonoses


The kidney stone and increased water intake trial in steel workers: results from a pilot study.

Abstract: Preventing dehydration in subjects at risk may provide a means of primary prevention of kidney stones. The purpose of this pilot study was to assess the hydration status of an at-risk group of steel plant workers based on end-of-shift ('post-shift') spot urine osmolality and 24-h urinary stone risk parameters. 100 volunteers were recruited from Gerdau Midlothian steel mill in Texas on 11/14/14 and 12/5/14. Clinical data were recorded and post-shift spot urine sample was used to measure urine osmolality. Participants were invited to submit a 24-h urine sample within 4 weeks of enrollment. The mean age was 41 years and 95 % were men. The majority of subjects were white (75 %), followed by 10 % Hispanic and 9 % black. The mean body mass index was 30.1 kg/m2 and overall 16 % had a past history of stone disease. Mean post-shift urine spot osmolality was 704.5 mOsm (169-1165 mOsm) and was >800 and >700 mOsm in 39 and 57 %, respectively. Among 59 24-h urines samples, the mean volume was 1.89 ± 0.92 l/day, with 56 % < 2 L and 17 % < 1 L. Elevated levels of urinary analytes were found in 29 % of subjects for calcium (>250 mg/TV), 39 % for uric acid (>700 mg/TV), 25 % for oxalate (>45 mg/TV) and 50 % for sodium (>200 meq/TV). The prevalence of stone disease in this population of steel workers was higher than the published prevalence of stone disease in the general population. A significant number of workers had concentrated post-shift and 24-h urines and elevated levels of urinary analytes.

Lotan|Yair|Y|
Antonelli|Jodi|J|
Jiménez|Inmaculada Buendia|IB|
Gharbi|Hakam|H|
Herring|Ron|R|
Beaver|Allison|A|
Dennis|Aphrihl|A|
Von Merveldt|Dendra|D|
Carter|Suzie|S|
Cohen|Adam|A|
Poindexter|John|J|
Moe|Orson W|OW|
Pearle|Margaret S|MS|

Kidney stones
Steel workers
Prevention
Hydration


Concurrent split cord malformation and teratoma: dysembryology, presentation, and treatment.

Abstract: Split cord malformation (SCM) is a rare form of spinal dysraphism in which the spinal cord is divided in the sagittal plane, forming a double neural tube. In addition to being associated with a variety of malformations, SCM may occur with spinal cord tumors, with only exceptional cases involving teratomas. As only eight patients with a teratoma associated with SCM have been reported, their presentation characteristics and treatment are currently unclear. We review the literature of all patients with SCM with concurrent spinal teratoma, discuss the potential dysembryology, and report the first case of SCM with concurrent spinal teratoma in an elderly patient. The mean age of those with concurrent SCM and teratomas was 39.4 years, with 55.6% occurring in females. The lumbar spine was the most frequent location for teratomas (66.7%), with the Type II malformation more commonly occurring with these tumors (75%). The duration of symptoms varied widely, ranging from 1 month to 5 years, with the average duration being nearly 2 years. Back pain (87.5%) and lower extremity weakness (75%) were the most common presenting symptoms. As SCM may be associated with progressive neurological deterioration and teratomas can contain immature or malignant components, surgery should be attempted with the goal of gross total resection. Nonetheless, in patients with a concurrent tumor and spinal dysraphism, spinal teratomas should be considered in the differential diagnosis. Gross total resection of these lesions may be safely achieved even in the presence of SCM using intraoperative electrophysiologic monitoring.

Babu|Ranjith|R|
Reynolds|Renee|R|
Moreno|Jessica R|JR|
Cummings|Thomas J|TJ|
Bagley|Carlos A|CA|

Split cord malformation
Teratoma
Treatment
Dysraphism
Embryology


Treatment recommendations for elderly patients with newly diagnosed glioblastoma lack worldwide consensus.

Abstract:
BACKGROUND
Glioblastoma predominantly occurs in the 6th and 7th decades of life. The optimal treatment paradigm for elderly patients is not well established. We sampled current worldwide management strategies for elderly patients with newly diagnosed glioblastoma.

METHODS
A web-based survey was developed and distributed to 168 radiation oncologists, neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American, European and Asian Organizations. Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset.

RESULTS
There were 68 (40%) respondents. Across respondents, the most important factors directing treatment were KPS (94%) and MGMT methylation status (71%). Only 37% of respondents strictly factor in age when making treatment recommendations with 59% defining elderly as greater than 70 years-old. The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows: standard chemoRT (49%), short course chemoRT (39%), and temozolomide alone (30%). The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows: short course RT alone (51%), standard chemoRT (38%), and short course chemoRT (28%). Treatment recommendations for patients with KPS < 50 were short course RT alone (40%), best supportive care (57%), or TMZ alone (17%). Individuals practicing in North America were significantly more likely to recommend standard chemoradiation for patients compared to their European counterparts.

CONCLUSION
Worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are needed to elucidate the optimal treatment strategy for this subset of patients.

Palmer|Joshua D|JD|
Bhamidipati|Deepak|D|
Mehta|Minesh|M|
Williams|Noelle L|NL|
Dicker|Adam P|AP|
Werner-Wasik|Maria|M|
Shi|Wenyin|W|

Treatment recommendations
Elderly
Glioblastoma


Risk factors of clinical dysimmune manifestations in a cohort of 86 children with 22q11.2 deletion syndrome: A retrospective study in France.

Abstract: In this study, we describe the biological immune profiles and clinical dysimmune manifestations (infections, autoimmune diseases, and allergies) of patients with 22q11.2 deletion syndrome with the aim of determining risk factors for clinical events. This retrospective study concerned all the patients with 22q11 deletion syndrome attending the Montpellier University Hospital from January 1, 1992, to December 31, 2014 who had at least one immune investigation before the age of 18. We analyzed the clinical features, biological tests and the course of infections, autoimmunity, and allergy of 86 children. Among these 86 children, 48 (59%) had a low T lymphocyte level. Twenty-nine patients (34%) had a severe infection. The only risk factor for severe infection was the low level of CD4+ T-cells (OR: 3.3; 95% confidence interval (CI) [1.020-11.108]). Eleven patients (13%) developed an autoimmune disease; the only risk factor was an antecedent of severe infection (OR: 4.1; 95% CI [1.099-15.573]). Twenty-three patients (27%) had allergic episodes. A low level of CD8+ T-cells (OR: 3.2; 95% CI [1.07-9.409]) was significantly associated with allergy manifestations. Patients with 22q11 deletion syndrome have a high rate of dysimmune manifestations. We found statistic correlations among CD4+ T-cell count, infectious manifestations, and autoimmunity.

Mahé|Perrine|P|0000-0001-8487-1628 Nagot|Nicolas|N| Portales|Pierre|P| Lozano|Claire|C| Vincent|Thierry|T| Sarda|Pierre|P| Perez|Marie-Jose|MJ| Amedro|Pascal|P| Marin|Gregory|G| Jeziorski|Eric|E|

dysimmunity
infections
autoimmunity
22q11 deletion syndrome
lymphocytes


Survival rates and the occurrence of larval malformations, including Siamese twins, following fertilization of post-ovulatory aged oocytes in ide Leuciscus idus.

Abstract: Embryonic development of lower vertebrates can be influenced by many factors, especially when outside of the mother's body and under the influence of variable abiotic and biotic factors. In this study, the effects of fertilization of post-ovulatory aged (overmature) oocytes of ide Leuciscus idus on the risk of developing anomalies in ide larvae were assessed under controlled conditions. There was a negative effect of delayed fertilization of post-ovulatory aged (overmature) oocytes in the ovary on the quality of offspring, which caused reduced survival 3 days post-fertilization and at the hatching stage (68.3 vs. 81.2% and 47.2 vs. 79.7% for the overmature and mature groups, respectively). It also increased the occurrence of numerous developmental defects (19.3 vs. 0.8% for the overmature and mature groups, respectively), including the development of Siamese twins. This is the first reported case of the occurrence of Siamese twins in ide. The ide Siamese twins look like hen eggs with 2 heads and are different from 'typical' Siamese twins in fish.

Siamese twins
Fertilization
Ide
Anomalies
Artificial reproduction


Prognostic information for people with MS: Impossible or inevitable?

Abstract: Delivering prognostic information is a challenging issue in medicine and has been largely neglected in the past. A major reason has been a suspected nocebo effect of pessimistic estimates, although this is largely unproven. Among people with multiple sclerosis (MS), there is a strong unmet need to receive long-term prognostic information. This viewpoint discusses reasons for this blind spot in physicians' attitude, foremost among which is the uncertainty of prognostic estimates. Possible strategies to move forward include tools to identify matching patients from large well-defined databases, to deliver an evidence-based individualized estimate of long-term prognosis, and its confidence interval, in a clinical setting.

D000328:Adult
D002908:Chronic Disease
D058015:Health Communication
D006801:Humans
D009103:Multiple Sclerosis
D010817:Physician-Patient Relations
D011379:Prognosis
D013997:Time Factors
D014342:Truth Disclosure

Prognosis
patient information
risk communication


Identifying Abuse and Neglect in Hospitalized Children With Burn Injuries.

Abstract:
BACKGROUND
The purpose of this study was to identify the pattern of injuries that relates to abuse and neglect in children with burn injuries.

METHODS
The Nationwide Readmissions Database for 2010-2014 was queried for all patients aged less than 18 y admitted with burn injuries. The primary outcome was child maltreatment identified at the index admission. The secondary outcome was readmission for maltreatment. A subgroup analysis was performed on patients without a diagnosis of maltreatment during the index admission. Multivariable logistic regression was performed for each outcome.

RESULTS
There were 57,939 admissions identified and 1960 (3.4%) involved maltreatment at the index admission. Maltreatment was associated with total body surface area burned >20% (odds ratio (OR) 2.79, P < 0.001) and burn of the lower limbs (OR 1.37, P < 0.001). Readmission for maltreatment was found in 120 (0.2%), and the strongest risk factor was maltreatment identified at the index admission (OR 5.11, P < 0.001). After excluding the patients with maltreatment identified at the index admission, 96 (0.17%) children were found to have a readmission for maltreatment that may have been present on the index admission and subsequently missed. The strongest risk factor was burn of the eye or ocular adnexa (OR 3.79, P = 0.001).

CONCLUSIONS
This study demonstrates that a portion of admissions for burn injuries in children could involve maltreatment that was undiagnosed. Identifying these at-risk individuals is critical to prevention efforts.

Quiroz|Hallie J|HJ|
Parreco|Joshua P|JP|
Khosravani|Nima|N|
Thorson|Chad|C|
Perez|Eduardo A|EA|
Sola|Juan E|JE|
Rattan|Rishi|R|
Pizano|Louis R|LR|


Hepatitis C Virus Clearance by Direct-acting Antiviral Results in Rapid Resolution of Hepatocytic Injury as Indicated by Both Alanine Aminotransferase and Aspartate Aminotransferase Normalization.

Abstract: Hepatitis C virus (HCV) infection results in hepatocytic injury with elevation of both alanine aminotransferase (ALT) and aspartate aminotransferase (AST). It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following virologic response. To this end, we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks (SVR12).  Single-center retrospective study on 115 HCV-infected patients who achieved SVR12 was performed.  At treatment week 2, 100% and 45.9% showed decline in HCV RNA to <700 IU/mL and undetectable levels, respectively, and this was associated with 85.5%, 83.9% and 77.4% ALT normalization, AST normalization and ALT and AST normalization. At end of treatment, 85.6% of patients with baseline elevation of both ALT and AST had normalization of both ALT and AST. At posttreatment weeks 12 and 24, 90.8% and 94.8% had normalization of both ALT and AST. HCV clearance also resulted in further decline of both ALT and AST in those with baseline <40 IU. Univariate analysis showed baseline Child-Pugh score of <6, model for end-stage liver disease score of <10, HCV genotype 1, and HCV RNA of <500 IU/mL at treatment week 2 were associated with sustained normalization of both ALT and AST at posttreatment week 12. On multivariate analysis, baseline model for end-stage liver disease score of <10 was significantly associated with normalization of both ALT and AST at posttreatment week 12, independent of baseline Child-Pugh score <6, HCV genotype 1, and HCV RNA of <500 IU/mL at treatment week 2.  During direct-acting antiviral therapy, 85.5% and 83.9% had normalization of both ALT and AST as early as in week 2, providing biochemical evidence of hepatocytic injury resolution. Sustained normalization of both ALT and AST was seen in 90.8% at posttreatment weeks 12, and was independently associated with baseline model for end-stage liver disease score of <10.

Hepatocytic injury
ALT and AST normalization
Chronic hepatitis C
Direct acting antiviral


Vitamin A status and its relationship with serum zinc concentrations among pregnant women who have previously undergone Roux-en-Y gastric bypass.

Abstract:
OBJECTIVE
To evaluate vitamin A status and its relationship with serum zinc concentrations among pregnant women who had previously undergone Roux-en-Y gastric bypass (RYGB), correlating these measures with anthropometric maternal characteristics and perinatal outcomes.

METHODS
An analytical prospective longitudinal study was conducted at a clinic in Rio de Janeiro, Brazil, between March 3, 2008, and March 30, 2012, among women with singleton pregnancies who had previously undergone RYGB. Participants received daily oral supplementation with 5000 IU retinol and 15 mg zinc. Variables assessed included vitamin A status (serum retinol and β-carotene; gestational night blindness), serum zinc concentration, maternal anthropometry, complications during pregnancy, and perinatal outcomes.

RESULTS
Overall, 30 women participated. In all trimesters, more than 60% had inadequate serum levels of retinol or β-carotene. Night blindness was reported by 17 (57%) women in each trimester. Only 6 (20%) women had zinc inadequacy in the first and third trimesters. No significant association was observed between serum retinol or zinc and maternal anthropometry and birth weight. Vitamin A deficiency was associated with urinary tract infection (first trimester, P=0.020) and dumping syndrome (third trimester, P=0.013).

CONCLUSION
Despite RYGB and nutritional deficiencies (especially of vitamin A and zinc) increasing risks during pregnancy, there was no apparent fetal compromise when considering the analysis of birth weight and length of pregnancy at birth.

Chagas|Cristiane|C| Saunders|Cláudia|C| Pereira|Silvia|S| Silva|Jacqueline|J| Saboya|Carlos|C| Ramalho|Andréa|A|

Vitamin A
Zinc
Roux-en-Y gastric bypass
Perinatal outcomes
Pregnancy
Obesity


Consistency and variation of protein subcellular location annotations.

Abstract: A major challenge for protein databases is reconciling information from diverse sources. This is especially difficult when some information consists of secondary, human-interpreted rather than primary data. For example, the Swiss-Prot database contains curated annotations of subcellular location that are based on predictions from protein sequence, statements in scientific articles, and published experimental evidence. The Human Protein Atlas (HPA) consists of millions of high-resolution microscopic images that show protein spatial distribution on a cellular and subcellular level. These images are manually annotated with protein subcellular locations by trained experts. The image annotations in HPA can capture the variation of subcellular location across different cell lines, tissues, or tissue states. Systematic investigation of the consistency between HPA and Swiss-Prot assignments of subcellular location, which is important for understanding and utilizing protein location data from the two databases, has not been described previously. In this paper, we quantitatively evaluate the consistency of subcellular location annotations between HPA and Swiss-Prot at multiple levels, as well as variation of protein locations across cell lines and tissues. Our results show that annotations of these two databases differ significantly in many cases, leading to proposed procedures for deriving and integrating the protein subcellular location data. We also find that proteins having highly variable locations are more likely to be biomarkers of diseases, providing support for incorporating analysis of subcellular location in protein biomarker identification and screening.

Xu|Ying-Ying|YY|0000-0002-3185-811X
Zhou|Hang|H|
Murphy|Robert F|RF|
Shen|Hong-Bin|HB|

D001271:Atlases as Topic
D002451:Cell Compartmentation
D002460:Cell Line
D030562:Databases, Protein
D005057:Eukaryotic Cells
D006801:Humans
D058977:Molecular Sequence Annotation
D015588:Observer Variation
D011506:Proteins
D015203:Reproducibility of Results
D035501:Uncertainty

protein subcellular location
Swiss-Prot database
human protein atlas
annotation consistency
location biomarker


Towards the theoretical limitations of X-ray nanocrystallography at high intensity: the validity of the effective-form-factor description.

Abstract: X-ray free-electron lasers (XFELs) broaden horizons in X-ray crystallography. Facilitated by the unprecedented high intensity and ultrashort duration of the XFEL pulses, they enable us to investigate the structure and dynamics of macromolecules with nano-sized crystals. A limitation is the extent of radiation damage in the nanocrystal target. A large degree of ionization initiated by the incident high-intensity XFEL pulse alters the scattering properties of the atoms leading to perturbed measured patterns. In this article, the effective-form-factor approximation applied to capture this phenomenon is discussed. Additionally, the importance of temporal configurational fluctuations at high intensities, shaping these quantities besides the average electron loss, is shown. An analysis regarding the applicability of the approach to targets consisting of several atomic species is made, both theoretically and via realistic radiation-damage simulations. It is concluded that, up to intensities relevant for XFEL-based nanocrystallography, the effective-form-factor description is sufficiently accurate. This work justifies treating measured scattering patterns using conventional structure-reconstruction algorithms.

Abdullah|Malik Muhammad|MM|
Son|Sang-Kil|SK|
Jurek|Zoltan|Z|
Santra|Robin|R|

X-ray nanocrystallography
XFELs
radiation damage
ionization
effective form factor


Effects of patient-tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low-density lipoprotein cholesterol in patients with type 2 diabetes.

Abstract:
AIMS/INTRODUCTION
Recently, patient-tailored statin therapy was proven effective for achieving target low-density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes.

MATERIALS AND METHODS
The present study was an 8-week, multicenter, single-step titration trial of patient-tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high-sensitivity C-reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation.

RESULTS
In the intention-to-treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6 mmol/L) at week 8. There were significant reductions at week 8 in total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose-dependent manner over the study period. In addition, the hsCRP levels were decreased in those high-risk patients with baseline hsCRP levels over 3 mg/L (P < 0.001), and the adiponectin levels tended to increase with all of the doses (P = 0.004) at 8 weeks.

CONCLUSIONS
Patient-tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).

Son|Jang Won|JW|
Kim|Dong Jun|DJ|
Lee|Chang Beom|CB|
Oh|Seungjoon|S|
Song|Kee-Ho|KH|
Jung|Chan Hee|CH|
Mok|Ji Oh|JO|
Kim|Jong Hwa|JH|
Moon|Min Kyong|MK|
Choi|Kyung Mook|KM|
Cho|Jae Hyoung|JH|
Choi|Sung Hee|SH|
Kim|Soo Kyung|SK|
Park|Kang Seo|KS|
Kim|Hye Soon|HS|
Kim|In Joo|IJ|
Kim|Young Il|YI|
Kim|Hae Jin|HJ|
Kim|Sang Yong|SY|
Kim|Sungrae|S|

Atorvastatin
Low‐density lipoprotein cholesterol
Type 2 diabetes mellitus


Do home pregnancy tests bring women to community health workers for antenatal care counselling? A randomized controlled trial in Madagascar.

Abstract: Task-shifting the provision of pregnancy tests to community health workers (CHWs) in low-resource settings has the potential to reach significantly more underserved women at risk of pregnancy with essential reproductive health services. This study assessed whether an intervention to supply CHWs with home pregnancy tests brought more clients for antenatal care (ANC) counselling. We implemented a randomized controlled trial among CHWs providing reproductive health services to women in Eastern Madagascar. We used ordinary least squares regressions to estimate the effect of the intervention, with district- and month-fixed effects and CHW baseline characteristics as control variables. Our outcomes of interest included whether the intervention increased: (1) the number of women at risk of pregnancy who sought services from CHWs; (2) the number of these women who knew they were pregnant by the end of visit; and (3) the number of these women who received ANC counselling during visit. We found that providing pregnancy tests to CHWs to distribute to their clients for free significantly increased the number of women at risk of pregnancy who sought services from CHWs. At follow-up, treatment-group CHWs provided services to 6.3 clients compared with 4.2 clients among control-group CHWs, which represents a 50% relative increase from the control-group mean. A significantly higher number of these clients knew they were pregnant by the end of the visit, with a mean of 0.95 in treatment compared with 0.10 in control (Coeff. 0.86; 95% CI 0.59-1.13). A significantly higher number of these clients received antenatal counselling at the visit (Coeff. 0.4; 95% CI 0.14-0.64). Introducing free home pregnancy tests as part of community-based health services can improve pregnancy care by attracting more clients at risk of pregnancy to services at the community level, enabling more women to confirm they are pregnant and receive antenatal counselling.

Comfort|Alison B|AB|
Juras|Randall C|RC|
Bradley|Sarah E K|SEK|
Ranjalahy Rasolofomanana|Justin|J|
Noeliarivelo Ranjalahy|Anja|A|
Harper|Cynthia C|CC|

Pregnancy tests
community health workers
antenatal care
task-shifting
reproductive health
sub-Saharan Africa


Knowledge, attitude and experience of episiotomy practice among obstetricians and midwives: a cross-sectional study from China.

Abstract:
OBJECTIVE
Episiotomy is still performed widely by obstetricians and midwives in some Chinese maternity units, but the reasons are unknown. This study aims to determine the knowledge, attitude and experience towards the practice of episiotomy among obstetricians and midwives in China's public hospitals and consider strategies to reduce its practice.

METHODS
A cross-sectional web survey using a self-administered questionnaire was conducted among obstetricians and midwives in 90 public hospitals in Henan Province, China.

RESULTS
900 (82.21%) participants completed the questionnaire. Average knowledge level (4.15, SD=1.10) on complications and overuse was identified among participants. Episiotomy was performed more frequently in secondary hospitals than in tertiary hospitals (p<0.05). Senior clinicians were more likely to perform episiotomy than younger ones (p<0.05). Almost half of the clinicians (42.11%) considered the current rate of episiotomy (45%) to be right or too low. The most common reason for performing episiotomy identified by obstetricians (83.94%) and midwives (79.69%) was to reduce third-degree or fourth-degree perineal laceration. Both obstetricians (80.29%) and midwives (82.57%) agreed that the most significant obstacle to reducing the rate of episiotomy was lack of training on reducing perineal tears.

CONCLUSION
In sum, episiotomy was driven by previous training, practitioners' experience and local norms rather than the latest medical evidence. Clinicians in secondary hospitals and senior clinicians are key training targets. It is urgent to improve current clinical policies and surgical procedure guidelines for obstetricians and midwives regarding episiotomy.

D007722:Health Knowledge, Attitudes, Practice

education & training (see medical education & training)


Feasibility study of 3D time-reversal reconstruction of proton-induced acoustic signals for dose verification in the head and the liver: A simulation study.

Abstract:
PURPOSE
In vivo range and dose verification based on proton-induced acoustics (protoacoustics) is potentially a useful tool for proton therapy. Built upon our previous study with two-dimensional reconstruction, the time reversal (TR) method was extended to three-dimensional (3D) and evaluated at two treatment sites (head and liver) through simulation, with the emphasis on a number of aspects such as increased spatial coverage, computational workload, and signal interference among slices.

METHODS
Two mono-energetic pencil beams were modeled in each site. The k-Wave toolbox was used to investigate the propagation and TR reconstruction of acoustic waves. The performance was quantitatively assessed based on mean square error (MSE) for dose verification and Bragg peak localization error (ΔBP ) for range verification, with regard to five parameters: number of sensors, sampling duration, sampling timestep, spill time, and noise level.

RESULTS
The respective impacts of five parameters are examined. Under the optimum setting, the achievable ΔBP can be limited within 1 voxel (voxel size: 3 × 3 × 3 mm3 ) and the achievable MSE can be limited below 0.02, for the head case (56 sensors) and the liver case (204 sensors), respectively.

CONCLUSIONS
The feasibility of range and dose verification utilizing the 3D TR method is demonstrated, as the very first step. In spite of several challenges unique to the 3D case (spatial coverage, computational workload, and signal interference among slices, etc.), promising performance is found and can be further improved through optimizing the deployment of sensors. The proposed approach may find potential use in several applications: beam diagnostics, in vivo dosimetry, and treatment monitoring.

time-reversal
dose verification
protoacoustics
proton therapy
range verification


Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury.

Abstract: Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that cells may undergo differentiation towards a neuronal cell lineage, which supports their potential use for cell-based therapy for TBI.

Schomann|Timo|T|
Iljas|Juvita D|JD|
Que|Ivo|I|
Li|Yuedan|Y|
Suidgeest|Ernst|E|
Cruz|Luis J|LJ|
Frijns|Johan H M|JHM|
Chan|Alan|A|
Löwik|Clemens M W G|CMWG|
Huisman|Margriet A|MA|
Mezzanotte|Laura|L|

D000818:Animals
D000070642:Brain Injuries, Traumatic
D002454:Cell Differentiation
D005260:Female
D018859:Hair Follicle
D008279:Magnetic Resonance Imaging
D008297:Male
D051379:Mice
D008810:Mice, Inbred C57BL
D008819:Mice, Nude
D033581:Stem Cell Transplantation
D013234:Stem Cells

Hair follicle bulge-derived stem cells
Brain injury
Magnetic resonance imaging
Bioluminescence imaging
Stem cell treatment
Tracking


Secondary immune thrombocytopenia in children: Characteristics and outcome of a large cohort from two Spanish centres.

Abstract:
AIM
To evaluate the incidence and outcome of secondary immune thrombocytopenia (ITP) in a large cohort of paediatric Spanish patients.

METHODS
A retrospective observational study was conducted in two paediatric University hospitals in Spain between 2009 and 2019, which included children from 4 months to 18 years old diagnosed with ITP. Data were recorded from clinical charts: gender, age at diagnosis, coexisting condition and associated characteristics, outcome and treatment.

RESULTS
Secondary ITP was diagnosed in 87 out of 442 patients (19.6%). Post-immunisation ITP was seen in younger children. The onset of secondary ITP to autoimmune diseases (AD) and immunodeficiencies (ID) was at an older age and had more tendency to be insidious, and platelet level was higher than primary ITP. Mean time from ITP onset to AD diseases or ID diagnosis was 1.2 and 2.6 years, respectively. Whereas the cumulative incidence of remission was significantly higher in post-immunisation and post-viral infection (compared with primary ITP patients), it was worse in AD and ID patients.

CONCLUSIONS
Identification of secondary ITP is important as it predicts outcome. Most of them are diagnosed at ITP onset, but AD diseases and ID should be ruled out periodically as they are usually identified later.

Berrueco|Rubén|R|0000-0002-1068-7489
Sebastián|Elena|E|
Solsona|María|M|
González de Pablo|Jesús|J|
Ruiz-Llobet|Anna|A|
Mesegué|Montse|M|
Gálvez|Eva|E|
Sevilla|Julián|J|

immune thrombocytopenia
children
paediatric
autoimmune diseases
immunodeficiency
vaccines


Occurrence and fate of pharmaceuticals in effluent and sludge from a wastewater treatment plant in Brazil.

Abstract: A wide variety of pharmaceuticals are discharged in water courses on a daily basis due to their incomplete removal from effluent in treatment plants. The aim of the current study was to assess the occurrence, fate and removal of pharmaceuticals from effluent and sludge samples collected in the biggest sanitary sewer plant in Southern Brazil. In total, 13 pharmaceuticals were detected in the influent through UHPLC-MS/M - paracetamol and caffeine recorded the highest concentrations, 137.98 and 35.29 µg L-1, respectively. The treated effluent presented 11 compounds. Antibiotics were the class recording the widest diversity; metronidazole showed the lowest concentration (0.023 µg L-1) and sulfamethoxazole presented the highest concentration (1.374 µg L-1) in influent samples. Seven pharmaceuticals were absorbed by the sludge; among them, one finds caffeine, ciprofloxacin and ofloxacin, which were quantified both in the effluent and in the sludge. On the other hand, doxycycline, fenbendazole, norfloxacin and tetracycline were only detected in sludge samples - their concentrations ranged from 0.026 to 5.034 mg kg-1. Clindamycin, oxytetracycline, sulfathiazole and trimethoprim concentrations increased throughout the treatment. There were high paracetamol and caffeine removal rates (>97%), and it may have happened due to degradation, photodegradation or chemical reaction. Ciprofloxacin and ofloxacin removal rate exceeded 83% mainly due to their sorption by sludge. Finally, the mass balance analysis highlighted high pharmaceutical loads (511.466 g d-1) discharged into recipient waterbodies. This outcome demands broadening the removal of these pharmaceuticals from sewage.

D001938:Brazil
D004364:Pharmaceutical Preparations
D012722:Sewage
D014865:Waste Disposal, Fluid
D062065:Waste Water
D014874:Water Pollutants, Chemical
D018508:Water Purification

pharmaceuticals
Wastewater treatment plant
mass balance analysis
adsorption onto sludge
liquid chromatography


WNT inhibition creates a BRCA-like state in Wnt-addicted cancer.

Abstract: Wnt signaling maintains diverse adult stem cell compartments and is implicated in chemotherapy resistance in cancer. PORCN inhibitors that block Wnt secretion have proven effective in Wnt-addicted preclinical cancer models and are in clinical trials. In a survey for potential combination therapies, we found that Wnt inhibition synergizes with the PARP inhibitor olaparib in Wnt-addicted cancers. Mechanistically, we find that multiple genes in the homologous recombination and Fanconi anemia repair pathways, including BRCA1, FANCD2, and RAD51, are dependent on Wnt/β-catenin signaling in Wnt-high cancers, and treatment with a PORCN inhibitor creates a BRCA-like state. This coherent regulation of DNA repair genes occurs in part via a Wnt/β-catenin/MYBL2 axis. Importantly, this pathway also functions in intestinal crypts, where high expression of BRCA and Fanconi anemia genes is seen in intestinal stem cells, with further upregulation in Wnt-high APCmin mutant polyps. Our findings suggest a general paradigm that Wnt/β-catenin signaling enhances DNA repair in stem cells and cancers to maintain genomic integrity. Conversely, interventions that block Wnt signaling may sensitize cancers to radiation and other DNA damaging agents.

Kaur|Amanpreet|A|
Lim|Jun Yi Stanley|JYS|
Sepramaniam|Sugunavathi|S|
Patnaik|Siddhi|S|
Harmston|Nathan|N|
Lee|May Ann|MA|
Petretto|Enrico|E|
Virshup|David M|DM|0000-0001-6976-850X
Madan|Babita|B|0000-0003-1065-8589


Outcomes of a two-visit protocol for long acting reversible contraception for adolescents and young adults.

Abstract:
PURPOSE
To examine outcomes of a 2-visit protocol for placement of intrauterine or subdermal contraception.

METHODS
We identified all women ages 15 to 27 who received an order for an intrauterine or subdermal contraceptive between January 2014-December 2016. We examined time from order to contraceptive placement and reasons for incomplete orders.

RESULTS
We identified 1,192 unique patients who received 1,323 orders for intrauterine or subdermal contraceptives; 68% were completed at a second visit. The median time from order to placement was 22 days (interquartile range = 15-35). Of incomplete orders, 41% were related to logistics of a subsequent visit. Twenty-eight percent of patients had a subsequent pregnancy within the study period.

CONCLUSIONS
Efforts to provide same-day access for all contraceptive methods are needed.

Wilkinson|Tracey A|TA|
Edmonds|Brownsyne Tucker|BT|
Cheng|Erika R|ER|

Contraception
Adolescent
Young Adults
Pregnancy
Access
Federally Qualified Health Center
Long-Acting Reversible Contraception


Mediating burden and stress over time: Caregivers of patients with primary brain tumor.

Abstract:
There is a growing literature on the effects of cancer caregiving on the well-being of informal family caregivers. However, there has been little longitudinal research on caregivers of patients with the complex, rapidly-changing disease of primary malignant brain tumor.

OBJECTIVE
Our objective was to model longitudinal relationships between caregiver burden, social support, and distress within caregivers of patients with primary brain tumor.

METHODS
Caregiver participants were recruited from a neuro-oncology clinic. Caregiver questionnaire data, including sociodemographics, social support, depression, anxiety, and caregiving burden, were collected at 4 time points (diagnosis, +4, +8, and +12 mo). Using the stress process model as a guide, we hypothesized that early burden would predict later depression and anxiety, and this would be mediated by social support.

RESULTS
Using data from 147 participants, we found support for the stress process model in caregivers of patients with primary brain tumor. Greater burden at diagnosis was associated with lower social support at 4 months, and lower social support was related to higher depression and anxiety at 8 months, as well as to changes in anxiety between 8 and 12 months.

CONCLUSION
We found evidence of the stress process model in caregivers of primary brain tumor patients unfolding over the course of a year after diagnosis. Our findings emphasize the potential importance of early programs for caregivers to ensure low initial levels of burden, which may have a positive effect on social support, depression, and anxiety.

Reblin|Maija|M|0000-0003-3108-465X Small|Brent|B| Jim|Heather|H| Weimer|Jason|J| Sherwood|Paula|P|

burden
caregiver
brain tumor
longitudinal
social support
distress
oncology


Efficient AuPd@GO-based electrochemical nanoprobe for sensitive detection of histone acetylase activity and its inhibitor.

Abstract: Histone acetylase (HAT p300), which has aroused great concern in fundamental research and clinical applications, serves as one class of significant tumor markers. In our work, a sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably. The AuPd@GO-based sensing mechanisms are distributed as follows: the HAT p300 derived acetylation reaction occurs at the customized peptide-immobilized electrode; the AuPd@GO composite acts as carrier to immobilize acetyl antibody, thus constructing a sandwich-type electrochemical immunosensor via an antigen and antibody interaction; importantly, a distinct electrochemical signal could be caught due to the AuPd@GO nanomaterial with a favorable electrocatalytic property to the commercialized 3,3,5',5'-tetramethyl benzidine solution (TMB). Taking advantage of AuPd@GO composite, the established immunosensor displays a wide linear range from 1 pM to 1000 nM, and the detection limit is 0.5 pM (S/N = 3) for HAT p300. Next, the biosensor is also used to analyze the inhibitor of HAT p300 successfully, which is promising for promoting the development of electrochemical HAT-related biodetection and drug discovery. Graphical abstract A sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably.

Liu|Qiong|Q| Yang|Linfei|L| She|Yuqi|Y| Hu|Yufang|Y|

D000595:Amino Acid Sequence
D015374:Biosensing Techniques
D055664:Electrochemical Techniques
D004791:Enzyme Inhibitors
D006046:Gold
D006108:Graphite
D051548:Histone Acetyltransferases
D057230:Limit of Detection
D053768:Metal Nanoparticles
D010165:Palladium
D010455:Peptides
D015203:Reproducibility of Results

Graphene-assisted supported AuPd nanomaterial


Two new quercetin glycoside derivatives from the fruits of Gardenia jasminoides var. radicans.

Abstract: Two new quercetin glycoside derivatives named quercetin-3-O-[2-O-trans-caffeoyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside] (1) and quercetin-3-O-[2-O-trans-caffeoyl-β-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside] (2) along with three known flavonoids, 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (3), 5,7-dihydroxy-8-methoxyflavone (4) and kaempferol 3-O-β-D-glucopyranoside (5), were isolated from the fruits of Gardenia jasminoides var. radicans. The structures of the new compounds were determined by means of extensive spectroscopic analysis (1D, 2D NMR and HR-ESI-MS), glycoside hydrolysis and sugar HPLC analysis after derivatisation. This is the first report on the isolation of a pair of compounds with α or β-L-rhamnopyranosyl configuration from plant and the first detail assignment of their NMR data.

Yu|Shaofu|S| Fu|Shuna|S| Liu|Bailian|B| Zhang|Ying|Y| Zhou|Guangxiong|G|

quercetin glycosides
Gardenia jasminoides var. radicans
flavonoids


Everything Is Related and It All Leads Up to My Mental Well-Being: A Qualitative Study of the Determinants of Mental Wellness Amongst Urban Indigenous Elders.

Abstract: Indigenous peoples in Canada often experience a greater burden of poor health and wellness relative to non-Indigenous Canadians due to a legacy of colonisation and racism. However, Indigenous mental wellness outcomes vary by community, and it is essential to understand how a community has been impacted by the determinants to improve mental wellness outcomes. This article shares insight from a research partnership with the Ki-Low-Na Friendship Society, an urban Indigenous community service organisation. The study used a decolonising, qualitative methodology in which urban Indigenous Elders shared their knowledge of mental wellness and experiences of services and supports. Elders described mental wellness holistically, connected to their relationships, land, language and culture. They described several determinants of wellness including identity, poverty, transportation, abuse and trauma. Elders shared experiences of culturally unsafe care and identified colonisation as root causes of poor mental wellness. They shared how some determinants affect urban Indigenous communities uniquely. This included limited transportation to cultural activities outside urban centres, such as medicine picking, the importance of urban organisations (such as Aboriginal Friendship Centres) in developing social support networks, and the role of discrimination, racism and inequitable care as barriers to accessing services in urban centres.

Schill|Kaela|K|0000-0003-4411-3579
Terbasket|Edna|E|
Thurston|Wilfreda E|WE|
Kurtz|Donna|D|
Page|Stacey|S|
McLean|Freda|F|
Jim|Randy|R|
Oelke|Nelly|N|

Indigenous Elders
aging and older people
mental health
qualitative methods
urban issues


Getting to a Man's Heart through His Colon.

Abstract: A 69-year-old man presented with a progressively enlarging pulsatile mass in the left side of his chest. Because of a history of an ischemic cardiomyopathy, he had been randomized in 2003 to undergo coronary artery bypass grafting with a Dor procedure, as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Our patient's imaging studies, including a thoracic computed tomogram and transthoracic echocardiogram, were now of concern for left ventricular pseudoaneurysm. He was taken immediately for surgical exploration. Purulent material, with empyema, extended from the anterior chest wall through the chest cavity into the mediastinum, with communication into the pericardial space. Notably, there was no compromise of the left ventricular cavity, and there was no pseudoaneurysm. The chest was copiously irrigated before closure. The epicardial patch placed 10 years earlier in the STICH trial was not thought to be the nidus of the abscess and was therefore not removed. Three months later, the patient presented again, this time with hemorrhagic shock and bleeding from his left anterior thoracotomy site, which we then re-entered. He was found to have a left ventricular pseudoaneurysm with disruption of the ventricular apex. The epicardial felt-and-Dacron patch, placed 10 years previously during his Dor procedure, was found to be infected with Clostridium difficile and was removed. The left ventricular apex was repaired. Whereas C. difficile bacteremia is rare, the seeding of prosthetic cardiac material with delayed presentation, as in this case, is extraordinarily uncommon.

Samsky|Marc D|MD|
DeVore|Adam D|AD|
Durkin|Michael|M|
Stout|Jason E|JE|
Velazquez|Eric J|EJ|
Milano|Carmelo A|CA|

empyema
Abscess/pathology
Clostridium difficile/extraintestinal
clinical trials as topic
debridement
pericarditis
postoperative complications
reoperation
ventricular dysfunction, left/surgery
ventricular remodeling


Estimation of health risks caused by exposure to enteroviruses from agricultural application of wastewater effluents.

Abstract: Agricultural reuse of wastewater is a common practice worldwide, especially in arid and semiarid area due to the freshwater scarcity. Wastewater irrigation in the Middle East, one of the most water-stressed regions in the world, could be a key factor for socio-economic development, but the microbial contamination of untreated or partially treated wastewater is a serious public health concern. Potential transmission of enteric viral infections through wastewater reuse in agricultural activities represents a true health risk for exposed individuals. Accordingly, it is important to assess the health risks associated with wastewater reuse. A quantitative microbial risk assessment (QMRA) with Monte-Carlo simulation was used to estimate the annual risk of enterovirus (EV) infection and disease burden for farmers and consumers of wastewater-irrigated lettuce in Iran, a semiarid country in the Middle East region. Risk analysis was performed based on the measured concentrations of EV in effluent of two activated sludge wastewater treatment plants (WWTP). Wastewater effluent sampling was carried out over a nine-month period, and the presence of total and fecal coliforms and EV was determined. Fecal coliform bacteria were found at a high level exceeded the guideline limit for wastewater reuse in agriculture. EVs were detected in 40% of samples with the highest frequency in summer with a mean of 12 and 16 pfu/ml for WWTP-A and B, respectively. Statistical analysis showed no correlation between the concentration of fecal coliforms and EV. The estimated infection risk for EVs was 8.8 × 10-1 and 8.2 × 10-1 per person per year (pppy) for farmers of WWTP-A and -B, respectively which was about 2 log higher than the tolerable infection risk of 2 × 10-3 pppy. The estimated risk for lettuce consumers exhibited a lower level of infection and disease burden but higher than the guideline limits. The median disease burden for consumption of lettuce irrigated with activated sludge effluents was about 10-3 Disability Adjusted Life Years (DALY) pppy which exceeded the WHO guideline threshold of 10-4 DALY pppy. The results of study indicated that the activated sludge effluents require an additional reduction of EVs to achieve the acceptable level of risk for agricultural reuse of wastewater.

Moazeni|Malihe|M| Nikaeen|Mahnaz|M| Hadi|Mahdi|M| Moghim|Sharareh|S| Mouhebat|Leili|L| Hatamzadeh|Maryam|M| Hassanzadeh|Akbar|A|

Effluent
Irrigation
QMRA
Enterovirus
Activated sludge
Infection risk


The effect of a doubled glutathione level on parameters affecting the germinability of recalcitrant Acer saccharinum seeds during drying.

Abstract: Approximately 20% of plant species, including silver maple (Acer saccharinum L.), produce seeds that are sensitive to desiccation, which is reflected in their poor storage potential and viability. In the search for a compound that can improve seed recalcitrance, freshly harvested seeds were soaked in either 2.5 mM reduced glutathione (GSH) or water and desiccated to comparable water levels of 55-20%. We examined the impact of a doubled endogenous level of glutathione on the seed germination capacity, the activity of enzymes involved in glutathione metabolism, the cell membrane components and integrity, reactive oxygen species, and ascorbate levels. GSH treatment resulted in slower dehydration and a higher germination capacity. The increased glutathione was mainly consumed by glutathione S-transferase, leading to more efficient detoxification, and by dehydroascorbate reductase (DHAR), accelerating the ascorbate regeneration. As a result, the cellular environment became more reduced, and protection of the membrane structures was enhanced. The ameliorated membrane integrity was manifested via a lower electrolyte leakage and a lower lipid peroxide level despite the higher level of hydrogen peroxide (H2O2) detected in the GSH-treated seeds. The degradation of phospholipids (PLs) was less intense and related to the phosphatidylinositol (PI) level, which is the precursor of the phospholipase D cofactor, whereas in water-soaked seeds, PL degradation was promoted by H2O2. The germination capacity of the dehydrated seeds depended primarily on the level of H2O2, lipid hydroxyperoxides, electrolyte leakage, GSH, the half-cell reduction potential of glutathione, PI, and the activity of DHAR and γ-glutamylcysteine synthetase. Interestingly, H2O2 affected all of the parameters. The germination of GSH-boosted seeds was strongly impacted by the pool of ascorbate, the half-cell reduction potential of ascorbate, and the glutathione peroxidase activity. In general, germination was DHAR activity-dependent. A strong negative correlation was detected in the water-soaked seeds, whereas a strong positive correlation was detected in the GSH-treated seeds. The enhanced level of glutathione likely improved the efficiency of the ascorbate-glutathione cycle, confirming its effect on seed germinability after dehydration.

Germinability
Silver maple
Reduced glutathione (GSH)
Antioxidant system
Components of cell membranes


Effect of chitosan nanoparticle, QMix, and EDTA on TotalFill BC sealers' dentinal tubule penetration: a confocal laser scanning microscopy study.

Abstract: The aim of the present study was to compare the effect of chitosan nanoparticle, QMix, and 17% EDTA on the penetrability of a calcium silicate-based sealer into dentinal tubules using a confocal laser scanning microscope (CLSM). Sixty mandibular premolar teeth were selected and randomly divided into three groups (n = 20) before root canal preparation according to the solution used in the final rinse protocol: chitosan, QMix, and EDTA groups. Twenty teeth of each group were filled with a TotalFill BC sealers' single gutta-percha cone and with 0.1% rhodamine B. The specimens were horizontally sectioned at 3 and 5 mm from the apex, and the slices were analyzed in CLSM (4×). Total percentage and maximum depth of sealer penetration were measured using confocal laser scanning microscopy with using Image J analysis software. Dentinal tubule's penetration depth, percentage, and area were measured using imaging software. Kruskal-Wallis test was used for statistical analysis. The level of significance was set at 5%. Results of Kruskal-Wallis analysis showed that there was a significant difference in the percentage and depth of sealer penetration among all groups at 3 and 5 mm level sections (P < 0.05). Within the groups, the minimum sealer penetration depth was recorded for chitosan nanoparticle group. Greater depth of sealer penetration was recorded at 5 mm as compared to 3 mm in all the groups. Within the limitation of the present study, it can be concluded that QMix and EDTA promoted sealer penetration superior to that achieved by chitosan nanoparticle.

Chitosan nanoparticle
QMix
EDTA
Sealer penetration
Confocal microscopy


Mastectomy skin necrosis after microsurgical breast reconstruction.

Abstract:
BACKGROUND
Mastectomy skin necrosis represents a significant clinical morbidity after immediate breast reconstruction. In addition to aesthetic deformity, necrosis of the native mastectomy skin may require debridement, additional reconstruction, or prolonged wound care and potentially delay oncologic treatment. This study aims to evaluate patient and procedural characteristics to identify predictors of mastectomy skin necrosis after microsurgical breast reconstruction.

METHODS
A retrospective review was performed of all immediate microsurgical breast reconstructions performed at a single academic center. Patient records were queried for age, diabetes, active smoking, previous breast surgery, preoperative radiation, preoperative chemotherapy, body mass index, mastectomy type, mastectomy weight, flap type, autologous flap type, and postoperative mastectomy skin flap necrosis.

RESULTS
There were 746 immediate autologous microsurgical flaps performed by three plastic surgeons at our institution during the study period. The incidence of mastectomy skin flap necrosis was 13.4%. Univariate analysis revealed a significantly higher incidence of mastectomy skin necrosis in patients with higher mastectomy weight (P < 0.001), higher autologous flap weight (P < 0.001), higher body mass index (0.002), and diabetes (P = 0.021). No significant association was found for age, smoking, prior breast surgery, preoperative chemotherapy or radiation, or mastectomy type. Multivariate analysis demonstrated statistically significant associations between mastectomy skin necrosis and both increasing mastectomy weight (odds ratio 1.348 per quartile increase, P = 0.009) and diabetes (odds ratio 2.356, P = 0.011).

CONCLUSIONS
Increasing mastectomy weight and coexisting diabetes are significantly associated with postoperative mastectomy skin necrosis after microsurgical reconstruction. These characteristics should be considered during patient counseling, procedure selection, operative planning, and intraoperative tissue viability assessment.

Vargas|Christina R|CR|
Koolen|Pieter G|PG|
Anderson|Katarina E|KE|
Paul|Marek A|MA|
Tobias|Adam M|AM|
Lin|Samuel J|SJ|
Lee|Bernard T|BT|

Mastectomy skin necrosis
Microsurgical breast reconstruction
Autologous breast reconstruction
Breast cancer


Periprocedural use of tirofiban in elective percutaneous coronary intervention for long coronary lesions in stable patients with overlapping drug-eluting stents--the PETITION study: a prospective, randomized, multicenter study.

Abstract:
BACKGROUND AND PURPOSE
Patients are at risk of developing periprocedural myonecrosis after percutaneous coronary intervention (PCI). We investigated whether the use of the platelet glycoprotein (GP) IIb/IIIa receptor inhibitor tirofiban could reduce periprocedural myocardial infarction (PMI) in patients with stable coronary artery disease undergoing elective PCI with overlapping stent implantation for long lesions.

METHODS
A total of 748 stable angina patients with long lesions (≥ 40 mm in length) treated with overlapping stent implantation were randomly assigned to receive tirofiban (tirofiban group; n = 373) or conventional therapy (control group; n = 375). Intravenous tirofiban was initiated before PCI and maintained for 12 hr after the procedure. The primary endpoint was PMI, defined as an elevation in CK-MB > 3 times the upper limit of normal 12 hr after the index procedure. The secondary endpoint was major adverse cardiac events (MACE), including cardiac death, target vessel revascularization, and recurrent MI (re-MI), at one-year of clinical follow-up. The safety end-points included Thrombolysis in Myocardial Infarction (TIMI) major bleeding and stent thrombosis.

RESULTS
Despite comparable angiographic and procedural characteristics, in the intention-to-treatment analysis, the primary endpoint was significantly reduced in the tirofiban group (4.0% vs. 11.5%, P < 0.001). Multivariate analysis revealed that the adjunctive use of tirofiban was the only negative predictor of PMI (OR 0.41, 95% CI 0.28-0.81, P < 0.01). At one-year of clinical follow-up, the overall occurrence of MACE was significantly lower in the tirofiban group (13.4% vs. 22.7%, P = 0.001). The rate of TIMI major bleeding and stent thrombosis did not differ significantly between the two groups.

CONCLUSION
Our results show that the adjunctive use of tirofiban reduces the occurrence of PMI and MACE at one year in stable coronary artery disease patients undergoing elective PCI for long lesions with overlapping stent implantation.

Zhang|Qi|Q|
Wang|Xiao Long|XL|
Liao|Min Lei|ML|
Hu|Jian|J|
Yang|Zhen Kun|ZK|
Ding|Feng Hua|FH|
Zhang|Jian Sheng|JS|
Du|Run|R|
Zhu|Tian Qi|TQ|
Shen|Wei Feng|WF|
Zhang|Rui Yan|RY|

D019039:Platelet Glycoprotein GPIIb-IIIa Complex

percutaneous coronary intervention
myocardial infarction
coronary artery disease
stable angina
GP IIb/IIIa inhibitor


CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma.

Abstract: Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4-AMPK axis to affect metabolic profile that has a strong bearing on their survival.

Dixit|Deobrat|D|
Ahmad|Fahim|F|
Ghildiyal|Ruchi|R|
Joshi|Shanker Datt|SD|
Sen|Ellora|E|

D017362:Cyclic AMP Response Element-Binding Protein

D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase

D023041:Xenograft Model Antitumor Assays