In vitro and in vivo evaluation of radiolabeled methyl N-[5-(3'-halobenzoyl)-1H-benzimidazol-2-yl]carbamate for cancer radiotherapy.

Abstract: The role of theranostics in cancer management is growing so is the selection of vectors used to deliver these modalities to cancer cells. We describe biological evaluation of a novel theranostic agent targeted to microtubules. Methyl N-[5-(3'-[131 I]iodobenzoyl)-1H-benzimidazol-2-yl]carbamate (1) and methyl N-[5-(3'-[125 I]iodobenzoyl)-1H-benzimidazol-2-yl]carbamate (2) were synthesized from a common precursor 3'-stannylated derivative (4). Antiproliferative effects and radiotoxicity of 131 I-labeled β-particle emitting 1 were examined in vitro in human neuroblastoma and glioblastoma cells lines. The therapeutic potential of 1 was also examined in a subcutaneous mouse model of human glioblastoma U-87 MG. Compound 1 at the extracellular radioactive concentration of 0.35 MBq/mL, easily achievable in vivo, kills >90% of neuroblastoma cells and >60% glioblastoma cells as measured in a clonogenic assay. D10 doses established for 1 indicate that as few as 3,000 decays are sufficient to kill 90% of BE(2)-C cells. Even U-87 MG cells, the least sensitive of the tested cell lines, require <20,000 decays of intracellular 131 I to reduce number of clonogenic cells by 90%. Biodistribution studies of 2 delivered either intratumorally or intraperitoneally show a similar tissue distribution for both routes of the drug administration. The whole body clearance half-lives were on average 6 hr. Intratumor administration of 1 produces significant tumor growth delay. After a single dose of 8.4 ± 0.3 MBq of compound 1, the tumor doubling times were 3.2 ± 0.1 and 7.9 ± 0.6 days in control and treated mice, respectively. Methyl N-[5-(3'-radiohalobenzoyl)-1H-benzimidazol-2-yl]carbamates have properties compatible with a theranostic approach to cancer management.

D023041:Xenograft Model Antitumor Assays

theranostics
microtubules
β-particles
benzimidazole carbamates
cancer therapy


Incidence, characteristics, and management of recently diagnosed, microscopically invasive breast cancer by receptor status: Iowa SEER 2000 to 2013.

Abstract:
BACKGROUND
Recent incidence, treatment patterns, and outcomes for node negative microscopically invasive breast cancer (MIBC) have not been reported.

METHODS
State Health Registry of Iowa data identified women with ductal carcinoma in situ (DCIS), MIBC, and stage I breast cancer excluding MIBC (stage 1BC).

RESULTS
From 2000 to 2013, 1,706, 193, and 4,514 women were diagnosed with DCIS, MIBC, and stage 1BC, respectively. MIBC increased at an annual percentage change of 2.1 (P = .041). MIBC was more frequently human epidermal growth factor receptor 2 positive than stage 1BC (39.7% vs 9.6%, P < .001). Mastectomy was performed more frequently in MIBC than DCIS (40.9% vs 30.6%, P = .014) or stage 1BC (40.9% vs 33.8%, P = .119). Chemotherapy was given to 4.1% of women with MIBC. Survival for women with MIBC was intermediate between DCIS and stage 1BC.

CONCLUSIONS
Management of MIBC is an increasingly frequent clinical scenario. Women with MIBC receive more aggressive local and systemic therapy than women with DCIS.

Thomas|Alexandra|A|
Weigel|Ronald J|RJ|
Lynch|Charles F|CF|
Spanheimer|Philip M|PM|
Breitbach|Elizabeth K|EK|
Schroeder|Mary C|MC|

Mastectomy
Breast neoplasms
Cancer incidence
Microinvasive tumor
SEER program


Determination of the effects of innovativeness levels of the elderly on their psychological resilience.

Abstract:
PURPOSE
This study was conducted to determine the rate at which the individual levels of innovativeness of the elderly explain their psychological resilience.

DESIGN AND METHODS
This study was conducted with 313 elderly people. The data of the study were collected using the Individual Innovativeness Scale and Psychological Resilience Scale for Adults.

FINDINGS
In this study, a significant relationship was found between individual innovativeness and psychological resilience in the elderly. Demographic variables were related to psychological resilience.

PRACTICE IMPLICATIONS
Within the scope of these results, increasing the individual innovativeness levels of older adults will enable them to be psychologically more resilient.

resilience
individual innovation
older adults
aging
regression analysis


High-yield synthesis of sub-10 nm Pt nanotetrahedra with bare ⟨111⟩ facets for efficient electrocatalytic applications.

Abstract: Unlike other shapes, the design of tetrahedral Pt nanocrystals (Pt-NTd), which have the largest number of Pt(111) surface atoms and highest catalytic activities toward the electron transfer reactions, has widely been considered a synthetic challenge due to their thermodynamic instability. Here, we show that, by inducing their nucleation on functionalized carbon, Pt NTds can be obtained with tunable sizes and high yields. The carbon support anchors the nanocrystals early and prevents their oriented attachment leading to nanowire formation. Therein, an in situ generated amine is crucial for stabilization of Pt-NTds, which can later be removed to expose the Pt(111) facets for higher catalytic efficiency. The bare nanocrystals exhibit much improved stability and electrocatalytic activity characteristic of Pt(111) toward oxygen reduction reaction (ORR) and methanol and formic acid oxidation reactions. For example, ∼90% of their activity was retained after 5000 potential cycles, while the ORR onset potential was recorded to be very high, 1.01 V vs reversible hydrogen electrode (RHE).

Rana|Moumita|M|
Chhetri|Manjeet|M|
Loukya|B|B|
Patil|Pramod K|PK|
Datta|Ranjan|R|
Gautam|Ujjal K|UK|

Pt(111)
oxygen reduction reaction
electrocatalysis
fuel cell
metal nanocrystals
methanol oxidation


Interdependencies among Selected Pro-Inflammatory Markers of Endothelial Dysfunction, C-Peptide, Anti-Inflammatory Interleukin-10 and Glucose Metabolism Disturbance in Obese Women.

Abstract:
BACKGROUND
Currently increasing importance is attributed to the inflammatory process as a crucial factor responsible for the progressive damage to vascular walls and progression of atherosclerosis in obese people. We have studied the relationship between clinical and biochemical parameters and C-peptide and anti-inflammatory IL-10, as well as selected markers of inflammation and endothelial dysfunction such as: CCL2, CRP, sICAM-1, sVCAM-1 and E-selectin in obese women with various degree of glucose metabolism disturbance.

MATERIAL AND METHODS
The studied group consisted of 61 obese women, and 20 normal weight, healthy volunteers. Obese patients were spited in subgroups based on the degree of glucose metabolism disorder. Serum samples were analyzed using ELISA kits.

RESULTS
Increased concentrations of sICAM-1, sVCAM-1, E-selectin, CCL2 and CRP were found in all obese groups compared to the normal weight subjects. In patients with Type 2 diabetes mellitus (T2DM) parameters characterizing the degree of obesity significantly positively correlated with levels of CRP and CCL2. Significant relationships were found between levels of glucose and sICAM-1and also E-selectin and HOMA-IR. C-peptide levels are positively associated with CCL2, E-selectin, triglycerides levels, and inversely with IL-10 levels in newly diagnosed T2DM group (p<0.05). Concentrations of IL-10 correlated negatively with E-selectin, CCL2, C-peptide levels, and HOMA-IR in T2DM group (p<0.05).

CONCLUSION
Disturbed lipid and carbohydrate metabolism are manifested by enhanced inflammation and endothelial dysfunction in patients with simply obesity. These disturbances are associates with an increase of adhesion molecules. The results suggest the probable active participation of higher concentrations of C-peptide in the intensification of inflammatory and atherogenic processes in obese patients with type 2 diabetes. In patients with obesity and type 2 diabetes, altered serum concentrations of Il-10 seems to be dependent on the degree of insulin resistance and proinflammatory status.

Janowska|Joanna|J| Chudek|Jerzy|J| Olszanecka-Glinianowicz|Magdalena|M| Semik-Grabarczyk|Elżbieta|E| Zahorska-Markiewicz|Barbara|B|

D019010:Vascular Cell Adhesion Molecule-1

endothelial dysfunction
C-peptide
glucose metabolism disturbance
Obesity
adhesion molecules
chemokine (C-C motif) ligand 2
interleukin-10.


The nuchal translucency examination leading to early diagnosis of structural fetal anomalies.

Abstract:
OBJECTIVE
To evaluate the ability to diagnose structural fetal anomalies during or soon after an extended nuchal translucency (NT) examination.

METHODS
The study population included all women who had a routine NT examination in the ultrasound division of one of three centers. Also included in the study were women referred to these centers following an abnormal NT examination. The sonographers were instructed to pay attention to fetal anomalies while performing the NT examination. Each examination was initially attempted transabdominally. Failure to obtain adequate views transabdominally was an indication for a transvaginal examination. When a structural fetal anomaly was detected or suspected, a full fetal anomaly scan was performed. When a diagnosis could not be established, fetal anatomy scan was repeated after 14 weeks of gestation. Fetal cardiac scanning was performed transvaginally, immediately or within 3 days after an increased NT was observed. When fetal anomalies were diagnosed the patients were informed about the possibilities of terminating the pregnancy or continuing the work-up and follow-up. Overall, ascertainment of fetal outcome was available in 85% of the study population.

RESULTS
We performed 4467 NT examinations during the study period and additional 123 fetal cardiac scanning following an abnormal NT examination. Overall, we performed 365 fetal cardiac scanning between 11 and 14 weeks of gestation. The fetal anomalies detected included the following: three skeletal anomalies, seven brain anomalies, four urinary system anomalies, four abdominal anomalies, two facial anomalies, and 13 cardiac anomalies. Six of the 13 cardiac anomalies were found in the atrioventricular canal. One third of the patients (11/33) elected to discontinue the pregnancy a short time after the detection of the congenital anomaly (until 14 weeks of gestation) and half of the patients (16\33) asked for termination of pregnancy later. More than 60% of the patients (20/33) with congenital anomalies detected following the NT examination refused to have chorionic villous sampling (CVS) or amniocentesis.

CONCLUSION
The opportunity to scan the fetal anatomy in the early stages of pregnancy, when the NT examination is performed, justifies the approach of extended NT examination.

Goldstein|Israel|I| Weizman|Boris|B| Nizar|Khatib|K| Weiner|Zeev|Z|

Nuchal translucency
Structural fetal anomalies


The flicker Pupil Light Response (fPLR).

Abstract:
Purpose
The photoreceptor classes driving the flicker pupil light response (fPLR) to monochromatic sinusoidal temporal modulation are largely unknown. Here, we determine the photoreceptor inputs to the fPLR.

Methods
The 0.5-Hz fPLR was measured in healthy observers using a Maxwellian view (41° diameter) pupillometer at five narrowband wavelengths (short: 409 nm; intermediate: 462, 507, 530 nm; and long: 592 nm) over ∼10 log units of irradiance spanning scotopic to photopic levels (5.6 to 15.6 log quanta·cm-2·s-1; -6.9 to 3.6 log cd·m-2). The relative photoreceptor contributions to the fPLR were then derived from these amplitude-irradiance functions using a criterion fPLR.

Results
The fPLR amplitude is small (≤ 3.9 ± 3.1%; mean ± SEM) below 8.0 log quanta·cm-2·s-1 then increases with retinal irradiance in accordance with a Hill function that asymptotes between 13.0 to 15.0 log quanta·cm-2·s-1 (wavelength dependent). The Hill slope is steepest for the intermediate wavelengths. Further increases in irradiance (>15.0 log quanta·cm-2·s-1) produce a distinct suppression of the fPLR for the intermediate wavelengths. The fPLR phase delay shows a linear decrease with increasing irradiance. The spectral sensitivity of the fPLR is dominated by inner retinal melanopsin ganglion cell and outer retinal rod photoreceptor inputs to the afferent pupil control pathway; the relative melanopsin : rhodopsin weighting decreases with the transition from photopic to scotopic lighting.

Conclusions
The fPLR can be used as a marker of melanopsin and rod interactions during the flicker stimulation and to quantify their contributions to the post-illumination pupil response (PIPR).

Translational Relevance
These irradiance and wavelength responses will be useful in standardizing the measurements of the fPLR using chromatic pupillometry.

Adhikari|Prakash|P|
Feigl|Beatrix|B|
Zele|Andrew J|AJ|

flicker pupil light response
photoreceptor
spectral sensitivity
melanopsin
rod
cone


Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model.

Abstract: The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.

Shin|Jung Hyun|JH|
Ryu|Chae-Min|CM|
Ju|Hyein|H|
Yu|Hwan Yeul|HY|
Song|Sujin|S|
Shin|Dong-Myung|DM|0000-0002-0511-5750
Choo|Myung-Soo|MS|

D045164:Mesenchymal Stem Cell Transplantation

N-acetylcysteine
mesenchymal stem cell
interstitial cystitis
combination therapy


EXPERIENCIAS Y PROCESO DE DUELO ENTRE PROFESIONALES DE ENFERMERÍA ONCOLÓGICA PEDIÁTRICA: EXPERIENCES AND GRIEVING PROCESS AMONG PEDIATRIC CANCER NURSES.

Abstract: Explore how nursing professionals handle the death of a pediatric patient with cancer under their care and identify needs that they face in the workplace. An exploratory qualitative design was used, under the phenomenological framework and the Model of Information, Motivation and Behavioral Skills (IMHB). The data was obtained through semi-structured interviews with a sample of ten pediatric oncology nursing professionals. Each interview was transcribed and analyzed to identify thematic axes in the narrative of the participants. The findings revealed four categories that alluded to professional experiences in the face of the death of a patient and their handling of the grieving process. These were: Perception of nursing professionals about cancer; management of the pediatric patient in the terminal phase, coping strategies and areas of professional need. According to the findings, limitations were identified in knowledge about the subject of death and the grieving process of these health professionals. These limitations reflect being an obstacle in their clinical skills and in their capacity for assertive management. It is essential to educate these professionals about Thanatology and its benefits; as well as, to enable them access to psychological interventions for emotional management.

Duelo
enfermería
nursing
pediatric patients
oncology
Bereavement
investigación cualitativa
oncología
pacientes pediátricos
qualitative research


An open trial of equine-assisted therapy for children exposed to problematic parental substance use.

Abstract: Children exposed to problematic parental substance use (PPSU) often face a number of deleterious developmental outcomes, yet these children are less likely to become known to child protection and welfare services. Although there is a growing evidence base for equine-assisted therapy (EAT) as an effective treatment modality for atypically developing children and adolescents, scant research has explored the benefit of EAT for children exposed to PPSU. The current study is the first to explore the benefit of EAT for children exposed to PPSU in Victoria, Australia. Five 12-week EAT programmes were delivered from 2012 to 2015 with a total of 41 children (mean age of 10.26 years) taking part. Children's parents (n = 41) and schoolteachers (n = 31) completed the Strengths and Difficulties Questionnaire pre- and post-intervention. Parents reported that children's total difficult behaviour and emotional problems decreased following the 12-week EAT programme. In addition, parents and teachers observed a significant decrease in children's hyperactivity. The findings obtained highlight the benefit of EAT for children exposed to PPSU and thus, extends the existing evidence base for this treatment modality.

Tsantefski|Menka|M| Briggs|Lynne|L| Griffiths|Jessica|J| Tidyman|Anne|A|

equine-assisted therapy
problematic parental substance use
children's well-being


The Iron Curtain: Macrophages at the Interface of Systemic and Microenvironmental Iron Metabolism and Immune Response in Cancer.

Abstract: Macrophages fulfill central functions in systemic iron metabolism and immune response. Infiltration and polarization of macrophages in the tumor microenvironment is associated with differential cancer prognosis. Distinct metabolic iron and immune phenotypes in tumor associated macrophages have been observed in most cancers. While this prompts the hypothesis that macroenvironmental manifestations of dysfunctional iron metabolism have direct associations with microenvironmental tumor immune response, these functional connections are still emerging. We review our current understanding of the role of macrophages in systemic and microenvironmental immune response and iron metabolism and discuss these functions in the context of cancer and immunometabolic precision therapy approaches. Accumulation of tumor associated macrophages with distinct iron pathologies at the invasive tumor front suggests an "Iron Curtain" presenting as an innate functional interface between systemic and microenvironmental iron metabolism and immune response that can be harnessed therapeutically to further our goal of treating and eliminating cancer.

iron metabolism
tumor microenvironment
cancer systems
immunotherapy
macrophage polarization


Autophagy maintains ubiquitination-proteasomal degradation of Sirt3 to limit oxidative stress in K562 leukemia cells.

Abstract: Sirtuin protein family member 3 (Sirt3) has been suggested as a positive regulator in alleviating oxidative stress by acting on the mitochondrial antioxidant machinery in solid tumors; however, its role and regulation in hematological malignancies has been poorly understood. Here, we show that contrary to what has been reported in solid tumors, in K562 leukemia cells elevated Sirt3 was associated with mitochondrial stress, and depletion of Sirt3 decreased reactive oxygen species (ROS) generation and lipid oxidation, but increased the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), suggesting an opposite role of Sirt3 in regulating oxidative stress in the leukemia cells. Notably, loss of autophagy by deletion of autophagy essential gene or by pharmacological inhibition on autophagic degradation caused a significant accumulation of Sirt3. However, induced activation of autophagy did not cause autophagic degradation of Sirt3. Furthermore, inhibiting proteasome activity accumulated Sirt3 in autophagy-intact but not autophagy-defective cells, and disrupting functional autophagy either genetically or pharmacologically caused significantly less ubiquitination of Sirt3. Therefore, our data suggest that basal but not enhanced autophagy activity maintains ubiquitination-proteasomal degradation of Sirt3 to limit lipid oxidative stress, representing an adaptive mechanism by which autophagy, in collaboration with the ubiquitination-proteasomal system, controls oxidative stress by controlling the levels of certain proteins in K562 leukemia cells.

Fang|Yixuan|Y| Wang|Jian|J| Xu|Li|L| Cao|Yan|Y| Xu|Fei|F| Yan|Lili|L| Nie|Meilan|M| Yuan|Na|N| Zhang|Suping|S| Zhao|Ruijin|R| Wang|Hongbin|H| Wu|Mengyin|M| Zhang|Xiaoying|X| Wang|Jianrong|J|

Autophagy
Sirt3
oxidative stress
erythroleukemia cells
ubiquitination-proteasome pathway


Heavy metal contamination and ecological risk in Spartina alterniflora marsh in intertidal sediments of Bohai Bay, China.

Abstract: To investigate the effects of Spartina alterniflora on heavy metals pollution of intertidal sediments, sediment cores of a S. alterniflora salt marsh and a mudflat in Bohai Bay, China were analyzed. The results showed that S. alterniflora caused higher total C and P, but lower bulk density and electrical conductivity. The levels of Cd, Cu and Pb were higher in S. alterniflora sediment. Both Cd and Zn were higher than the probable effect level at both sites, indicating their toxicological importance. The geo-accumulation and potential ecological risk indexes revealed higher metal contamination in S. alterniflora sediment. Multivariate analysis implied that anthropogenic activities altered mobility and bioavailability of heavy metals. The percentage of mobile heavy metals was higher in S. alterniflora sediment, indicating improvement of conversion from the immobilized fraction to the mobilized fraction. These findings indicate that S. alterniflora may facilitate accumulation of heavy metals and increase their bioavailability and mobility.

Chai|Minwei|M| Shi|Fuchen|F| Li|Ruili|R| Shen|Xiaoxue|X|

Heavy metal
Ecological risk
Spartina alterniflora
Bohai Bay
Chemical speciation


A fluorescence/colorimetric dual-mode sensing strategy for miRNA based on graphene oxide.

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs, which are involved in RNA silencing and post-transcriptional regulation of gene expression. Numerous studies have determined the expression of certain miRNAs in specific tissues and cell types, and their aberrant expression is associated with a variety of serious diseases such as cancers, immune-related diseases, and many infectious diseases. This suggests that miRNAs may be attractive and promising non-invasive biomarkers of diseases. In this study, we established a graphene oxide (GO)-based fluorescence/colorimetric dual sensing platform for miRNA by using a newly designed probe. The probe was designed to form a hairpin-like configuration with a fluorescent dye-labeled long tail, possessing a guanine (G)-rich DNAzyme domain in the loop region and target binding domain over the stem region and tail. By introducing this new hairpin-like probe in a conventional GO-based fluorescence platform, we observed both the miRNA-responsive color change by direct observation and sensitive fluorescence increase even below the nanomolar levels in a single solution without an additional separation step.

Shin|Bomi|B| Park|Ji-Seon|JS| Chun|Hang-Suk|HS| Yoon|Seokjoo|S| Kim|Woo-Keun|WK| Lee|Jieon|J|

Graphene oxide
Dual sensing
Colorimetric assay
Fluorescence assay
Point of care testing
miRNA detection


Modeling and development of screen-printed impedance biosensor for cytotoxicity studies of lung carcinoma cells.

Abstract: Electrical cell-substrate impedance sensing (ECIS) is a powerful technique to monitor real-time cell behavior. In this study, an ECIS biosensor formed using two interdigitated electrode structures (IDEs) was used to monitor cell behavior and its response to toxicants. Three different sensors with varied electrode spacing were first modeled using COMSOL Multiphysics and then fabricated and tested. The silver/silver chloride IDEs were fabricated using a screen-printing technique and incorporated with polydimethylsiloxane (PDMS) cell culture wells. To study the effectiveness of the biosensor, A549 lung carcinoma cells were seeded in the culture wells together with collagen as an extracellular matrix (ECM) to promote cell attachment on electrodes. A549 cells were cultured in the chambers and impedance measurements were taken at 12-h intervals for 120 h. Cell index (CI) for both designs were calculated from the impedance measurement and plotted in comparison with the growth profile of the cells in T-flasks. To verify that the ECIS biosensor can also be used to study cell response to toxicants, the A549 cells were also treated with anti-cancer drug, paclitaxel, and its responses were monitored over 5 days. Both simulation and experimental results show better sensitivity for smaller spacing between electrodes. Graphical abstract The fabricated impedance biosensor used screen-printed silver/silver chloride IDEs. Simulation and experimental results show better sensitivity for smaller between electrodes.

Mansor|Ahmad Fairuzabadi Mohd|AFM|
Ibrahim|Irmanisha|I|
Zainuddin|Ahmad Anwar|AA|
Voiculescu|Ioana|I|
Nordin|Anis Nurashikin|AN|

D000072283:A549 Cells
D015374:Biosensing Techniques
D003198:Computer Simulation
D017097:Electric Impedance
D004566:Electrodes
D006801:Humans
D008175:Lung Neoplasms
D008954:Models, Biological
D017239:Paclitaxel

ECIS
A549
Paclitaxel
Screen-printed biosensor
Silver/silver chloride electrode


Trends in perioperative outcomes of hospitals performing major cancer surgery.

Abstract:
BACKGROUND AND OBJECTIVES
Cancer surgery outcomes at National Cancer Institute-designated cancer centers (NCI-CCs) have been shown to vary, and have not been uniformly better than outcomes among non-NCI-CCs. We aimed to assess whether NCI-CCs have improved their short-term outcomes over time and whether variation across these centers has changed.

METHODS
Patients who underwent colectomy, esophagectomy, hepatectomy, pancreatectomy, and proctectomy for cancer were identified from the 2010 to 2016 American College of Surgeons' National Surgical Quality Improvement Program registry. Hospital trends in risk-adjusted, smoothed observed-to-expected ratios were assessed to evaluate improvement and variation in perioperative complications, stratified by NCI-CC status.

RESULTS
Complications occurred in 18.8% of 204 732 patients who underwent major cancer operations at 645 hospitals, and complications occurred in 19.9% of 60,903 patients at 54 NCI-CCs studied. More NCI-CCs than non-NCI-CCs improved over the period (85.2% vs 58.4%, P < 0.001; relative risk [RR] 1.46, 95% confidence interval [CI], 1.28-1.66); this remained significant after adjusting for years of participation (RR 1.33, 95% CI, 1.17-1.51). Variation in performance remained unchanged over time.

CONCLUSION
NCI-CCs were detected to have improved over a contemporary seven-year period and to have improved more than non-NCI-CCs. However, NCI-CCs do not uniformly outperform non-NCI-CCs, and variation in perioperative outcomes remains, warranting continued quality improvement efforts targeting cancer-specific operations.

D054547:National Cancer Institute (U.S.)

National Cancer Institute Cancer Centers

National Surgical Quality Improvement Program (NSQIP)


The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins.

Abstract: Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins.

Kawada|Daiki|D|
Kobayashi|Hiromu|H|
Tomita|Tsuyoshi|T|
Nakata|Eisuke|E|
Nagano|Makoto|M|
Siekhaus|Daria Elisabeth|DE|
Toshima|Junko Y|JY|
Toshima|Jiro|J|

Arf-GAP
Intracellular trafficking
Endocytosis
Small GTPase
Vesicular trafficking


A longitudinal investigation of repressive coping and ageing.

Abstract:
OBJECTIVES
Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults.

METHOD
Study 1 compared younger adults (mean age 27.6 years) with older adults (mean age 74.2 years) on inventories of mental health and well-being and examined the prevalence of repressive coping in both samples. Study 2 re-tested a sample of older adults previously reported following an interval of 7 years.

RESULTS AND CONCLUSION
Study 1 - in line with previous research older adults demonstrated greater psychological well-being and had a higher prevalence of repressive coping than younger adults (at 30% vs. 12% respectively). Study 2 - the data indicated that the prevalence of repressive coping rose from 41% at the first time of testing (2002) to 56.4% at the second testing interval (2009). These results suggest that repressive coping may increase across the lifespan in certain individuals and continue to increase throughout older adulthood. Furthermore, this increase in repressive coping with age appears to result in better well-being in those older adults who become repressive copers.

Erskine|James|J| Kvavilashvili|Lia|L| Myers|Lynn|L| Leggett|Sarah|S| Davies|Steve|S| Hiskey|Syd|S| Hogg|Joanna|J| Yeo|Sophia|S| Georgiou|George|G|

repressive coping
ageing
well-being
psychopathology
thought suppression


Characteristics of resveratrol and serotonin on antioxidant capacity and susceptibility to oxidation of red blood cells in stored human blood in a time-dependent manner.

Abstract: Objective In stored red blood cells (RBCs), which are used in diseases (e.g., acute blood loss and leukaemia), storage lesions arise by oxidative stress and other factors over time. This study investigated the protective effects of resveratrol and serotonin on stored RBCs. Methods Blood from each donor (n = 10) was placed in different bags containing 70 mL of citrate phosphate dextrose (total volume: 500 mL) and divided into three groups (n = 30): control, 60 µg/mL resveratrol, and 60 µg/mL serotonin. Malondialdehyde (MDA) and glutathione (GSH) levels, activity of glutathione peroxidase (GSH-Px), catalase, and carbonic anhydrase (CA), and susceptibility to oxidation in RBCs, and pH in whole blood were measured at baseline and on days 7, 14, 21, and 28. Results MDA levels and susceptibility to oxidation were increased in all three groups time-dependently, but this increase was greater in the serotonin group than in the other groups. Activity of GSH-Px, CAT, and CA, as well as GSH levels, were decreased in the control and serotonin groups time-dependently, but were significantly preserved in the resveratrol group. The pH was decreased in all groups time-dependently. Conclusion Our study shows that resveratrol attenuates susceptibility to oxidation of RBCs and protects their antioxidant capacity, and partially preserves CA activity time-dependently.

Huyut|Zübeyir|Z|
Şekeroğlu|Mehmet Ramazan|MR|
Balahoroğlu|Ragıp|R|
Huyut|Mehmet Tahir|MT|

resveratrol
serotonin
Antioxidants
oxidation
storage lesions
stored RBCs
chronic storage


First report of Demodex bovis infestation in bovine besnoitiosis co-infected dairy cattle in Italy.

Abstract: A form of generalized demodectic mange in two dairy cows infected with Besnoitia besnoiti is described. The herd was endemically infected with bovine besnoitiosis; an overall seroprevalence of B. besnoiti antibodies of 23.5%, that increased up to 43.5% considering only cows, was reported. Two out of the cows seropositive to B. besnoiti, at clinical examination presented skin nodules, widespread all over the body, and in particular in anterior regions. Skin biopsies from the region of the neck were collected and the nodules were microscopically examined through compression method. B. besnoiti tissue cysts were not revealed but a semi-solid yellowish content was evidenced with the presence of several mites, morphologically identified as Demodex bovis. Histological examination of skin biopsies evidenced slight acanthosis and hyperkeratosis of the epidermis and superficial dermatitis with oedema and macrophagic and eosinophilic infiltration. Cystic formations located in the deep dermis were lined by metaplastic squamous epithelium and severe cellular infiltration. A treatment with eprinomectin was attempted and clinical improvement of both cows was observed, particularly at the fifteenth day after treatment, with nodules reduced in size and mites in there degenerated. This is the first report of the co-infection of D. bovis infestation and bovine besnoitiosis in cattle. Furthermore, it was demonstrated that D. bovis circulates in the Italian cattle population, but subclinical forms could be underdiagnosed.

Villa|Luca|L|
Gazzonis|Alessia Libera|AL|
Perlotti|Chiara|C|
Zanzani|Sergio Aurelio|SA|
Sironi|Giuseppe|G|
Manfredi|Maria Teresa|MT|

Demodex bovis
Co-infection
Dairy cows
Besnoitia besnoiti
Histology
Eprinomectin


Comparison of Kt/V and urea reduction ratio in measuring dialysis adequacy in paediatric haemodialysis in England.

Abstract:
BACKGROUND
The National Kidney Foundation-Dialysis Outcomes Quality Initiative (KDOQI) guidelines and the Renal Association recommend the use of either Kt/V or urea reduction ratio (URR) to measure haemodialysis adequacy.

OBJECTIVES
To determine the methods used to measure paediatric haemodialysis adequacy and to assess consistency between calculations of single pool Kt/V (spKt/V) and URR.

DESIGN
A service evaluation was conducted to establish current practices in measuring dialysis adequacy. A prospective longitudinal study was conducted to compare spKt/V and URR.

PARTICIPANTS
Thirty-two children were recruited consisting of 13 males and 19 females in five paediatric dialysis centres.

RESULTS
Inconsistencies were reported of the method of post-urea sampling with 4 of the 10 centres using the KDOQI recommended sampling method. Five dialysis centres reported using URR and five reported using spKt/V. There were substantial differences between the two measures. Using URR suggested that up to 44% of children did not receive adequate dialysis, whereas measurement by spKt/V suggested no more than 6% of the same dialysis sessions were not adequate.

CONCLUSION
One standard measure should be used to assess dialysis adequacy in paediatric centres in England. KDOQI guidelines were not consistently followed in obtaining a post-urea blood sample and this procedure should be standardised.

Dunne|Nina|N| Campbell|Malcolm|M| Fitzpatrick|Maggie|M| Callery|Peter|P|


Establishment and validation of a novel droplet digital PCR assay for ultrasensitive detection and dynamic monitoring of EGFR mutations in peripheral blood samples of non-small-cell lung cancer patients.

Abstract:
BACKGROUND
Droplet digital PCR (ddPCR)-based blood detection of EGFR mutations plays significant roles in the individualized therapy of non-small-cell lung cancer (NSCLC) patients. However, a standard assay that is approved by health authorities is still lacking. Additionally, the proper application of this method in clinical settings also needs further investigation.

METHODS
The performance of a newly established ddPCR assay was first evaluated using reference samples and then validated by comparing this method with the amplification refractory mutation system (ARMS) using cell-free DNA (cfDNA) in patients' peripheral blood. Further, the correlation between dynamic quantification of EGFR mutation in the patients and their clinical outcome of tyrosine kinase inhibitors (TKIs) therapy was investigated.

RESULTS
A total of 77 patients were included, with 50 in the test group and 27 in the validation group. According to the results of the reference samples and the blood samples in the test group, the cut-off value for patient detection was proposed as mutation rate ≥ 0.1% (total copy number of cfDNA ≥ 1000) or at least one copy of mutation DNA was detected (total copy number of cfDNA < 1000). With this criterion, superior sensitivity of our assay to that of ARMS was observed (P = 0.002 for Ex19Del & L858R and P < 0.001 for T790M). The dynamic quantification of EGFR mutations during TKI therapy indicated that an increase in mutation abundance was correlated with resistance, while a decline was associated with response. Notably, a rebound in mutation abundance during chemotherapy may indicate a desirable chance for TKI re-treatment.

CONCLUSION
The novel ddPCR assay showed superior sensitivity in the detection of EGFR mutation in blood. The dynamic quantification of EGFR mutations by this assay would greatly facilitate the administration of TKI therapy, including the monitoring of resistance and response, as well as cohort screening for retreatment.

Tang|Chuanhao|C| Zhu|Lingxiang|L| Zhang|Lijuan|L| Tan|Chianru|C| Peng|Zhiyong|Z| Liu|Baoxia|B| Liu|Wenjing|W| Hu|Haixu|H| Bai|Yu|Y| Wang|Bo|B| Lin|Li|L| Liang|Jun|J| Li|Xiaoyan|X| Guo|Yong|Y| Liu|Yi|Y|

D002289:Carcinoma, Non-Small-Cell Lung
D019008:Drug Resistance, Neoplasm
D066246:ErbB Receptors
D006801:Humans
D008175:Lung Neoplasms
D009154:Mutation
D016133:Polymerase Chain Reaction
D047428:Protein Kinase Inhibitors

Amplification refractory mutation system (ARMS)


'I'm not in GP pain, I'm in hospital pain': Qualitative study regarding patient decision-making factors in seeking care in the emergency department with non-specific low back pain.

Abstract:
OBJECTIVE
To investigate factors contributing to the decision for a working age adult experiencing non-specific low back pain (NSLBP) to seek care at an Australian metropolitan tertiary ED.

METHODS
Participants triaged with NSLBP were recruited from one metropolitan tertiary Australian ED. We employed a qualitative descriptive methodology using semi-structured interviews to collect data. The short-form Orebro musculoskeletal pain screening questionnaire was administered pre-interview and used to inform discussion of psychosocial factors in the interview.

RESULTS
Patient perception and interpretation of their low back pain symptoms was the most important participant decision-making factor. This was part of the care-seeking decision for all participants. Convenience of care accessed in the ED was also important with many participants aiming to avoid multiple appointments in primary care settings while in pain or attending ED because it was close to home. Participants expected high-quality care in the ED and often did not identify an alternative in primary care they believed could provide an equivalent standard of care. Few participants were advised to attend ED by a GP or physiotherapist, but when given, this advice was a critical factor.

CONCLUSIONS
Patient beliefs about NSLBP are important drivers of ED care seeking. Evidence-based guidelines recommend screening for red flags and then addressing pain and disability through engagement with patient concerns and providing a management plan/pathway. In the ED setting, addressing the anxieties of these patients and re-interpreting the significance of their pain may be a path to providing time efficient high-value care.

emergency department
low back pain
decision making
low-value care
qualitative research


Prostaglandin E2/EP2 receptor signalling pathway promotes diabetic retinopathy in a rat model of diabetes.

Abstract:
AIMS/HYPOTHESIS
Diabetic retinopathy is a common microvascular complication of diabetes mellitus and is initiated by inflammation and apoptosis-associated retinal endothelial cell damage. Prostaglandin E2 (PGE2) has emerged as a critical regulator of these biological processes. We hypothesised that modulating PGE2 and its E-prostanoid receptor (EP2R) would prevent diabetes mellitus-induced inflammation and microvascular dysfunction.

METHODS
In a streptozotocin (STZ)-induced rat model of diabetes, rats received intravitreal injection of PGE2, butaprost (a PGE2/EP2R agonist) or AH6809 (an EP2R antagonist). Retinal histology, optical coherence tomography, ultrastructure of the retinal vascular and biochemical markers were assessed.

RESULTS
Intravitreal injection of PGE2 and butaprost significantly accelerated retinal vascular leakage, leucostasis and endothelial cell apoptosis in STZ-induced diabetic rats. This response was ameliorated in diabetic rats pre-treated with AH6809. In addition, pre-treatment of human retinal microvascular endothelial cells with AH6809 attenuated PGE2- and butaprost-induced activation of caspase 1, activation of the complex containing nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a C-terminal caspase-activation and recruitment domain (ASC), and activation of the EP2R-coupled cAMP/protein kinase A/cAMP response element-binding protein signalling pathway.

CONCLUSIONS/INTERPRETATION
The PGE2/EP2R signalling pathway is involved in STZ-induced diabetic retinopathy and could be considered as a potential target for diabetic retinopathy prevention and treatment.

Wang|Man|M| Wang|Yangningzhi|Y| Xie|Tianhua|T| Zhan|Pengfei|P| Zou|Jian|J| Nie|Xiaowei|X| Shao|Jun|J| Zhuang|Miao|M| Tan|Chengye|C| Tan|Jianxin|J| Dai|Youai|Y| Sun|Jie|J| Li|Jiantao|J| Li|Yuehua|Y| Shi|Qian|Q| Leng|Jing|J| Wang|Xiaolu|X| Yao|Yong|Y|0000-0002-5506-7101

D058307:Receptors, Prostaglandin E, EP2 Subtype

Diabetic retinopathy
Inflammation
Endothelial cell
PGE2
Microvascular disease


In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative.

Abstract:
BACKGROUND
Thiadiazole not only acts as "hydrogen binding domain" and "two-electron donor system" but also as constrained pharmacophore.

METHODS
The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involves preparation of 4-morpholino-1, 2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1, 2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol- 3-yl) morpholine. Oxirane ring of this compound was opened by treating with 2-amino-2-methyl propan-1- ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy.

RESULTS
The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S. aureus, Bacillus sps, K. Pneumoniae and E. coli species.

CONCLUSION
In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field.

Mali|Suraj N|SN|
Sawant|Sudhir|S|
Chaudhari|Hemchandra K|HK|
Mandewale|Mustapha C|MC|

D000900:Anti-Bacterial Agents
D001419:Bacteria
D001424:Bacterial Infections
D018938:Caco-2 Cells
D053837:DNA Cleavage
D006801:Humans
D062105:Molecular Docking Simulation
D013329:Structure-Activity Relationship
D013830:Thiadiazoles

antibacterial
DNA cleavage
thiadiazole
molecular docking
Heterocycle
tuberculosis.


Growth and Photoelectrochemical Energy Conversion of Wurtzite Indium Phosphide Nanowire Arrays.

Abstract: Photoelectrochemical (PEC) water splitting into hydrogen and oxygen is a promising strategy to absorb solar energy and directly convert it into a dense storage medium in the form of chemical bonds. The continual development and improvement of individual components of PEC systems is critical toward increasing the solar to fuel efficiency of prototype devices. Within this context, we describe a study on the growth of wurtzite indium phosphide (InP) nanowire (NW) arrays on silicon substrates and their subsequent implementation as light-absorbing photocathodes in PEC cells. The high onset potential (0.6 V vs the reversible hydrogen electrode) and photocurrent (18 mA/cm(2)) of the InP photocathodes render them as promising building blocks for high performance PEC cells. As a proof of concept for overall system integration, InP photocathodes were combined with a nanoporous bismuth vanadate (BiVO4) photoanode to generate an unassisted solar water splitting efficiency of 0.5%.

Kornienko|Nikolay|N|
Gibson|Natalie A|NA|
Zhang|Hao|H|
Eaton|Samuel W|SW|
Yu|Yi|Y|
Aloni|Shaul|S|
Leone|Stephen R|SR|
Yang|Peidong|P|

energy conversion
catalysis
chemical vapor deposition
nanowire synthesis
photoelectrochemistry


How brain imaging provides predictive biomarkers for therapeutic success in the context of virtual reality cognitive training.

Abstract: As Virtual reality (VR) is increasingly used in neurological disorders such as stroke, traumatic brain injury, or attention deficit disorder, the question of how it impacts the brain's neuronal activity and function becomes essential. VR can be combined with neuroimaging to offer invaluable insight into how the targeted brain areas respond to stimulation during neurorehabilitation training. That, in turn, could eventually serve as a predictive marker for therapeutic success. Functional magnetic resonance imaging (fMRI) identified neuronal activity related to blood flow to reveal with a high spatial resolution how activation patterns change, and restructuring occurs after VR training. Portable and quiet, electroencephalography (EEG) conveniently allows the clinician to track spontaneous electrical brain activity in high temporal resolution. Then, functional near-infrared spectroscopy (fNIRS) combines the spatial precision level of fMRIs with the portability and high temporal resolution of EEG to constitute an ideal measuring tool in virtual environments (VEs). This narrative review explores the role of VR and concurrent neuroimaging in cognitive rehabilitation.

Ansado|Jennyfer|J| Chasen|Clelia|C| Bouchard|Stéphane|S| Northoff|Georg|G|

Virtual reality
Neurorehabilitation
fMRI
EEG
NIRS


Pathways to precision medicine in smoking cessation treatments.

Abstract: Cigarette smoking is highly addictive and modern genetic research has identified robust genetic influences on nicotine dependence. An important step in translating these genetic findings to clinical practice is identifying the genetic factors affecting smoking cessation in order to enhance current smoking cessation treatments. We reviewed the significant genetic variants that predict nicotine dependence, smoking cessation, and response to cessation pharmacotherapy. These data suggest that genetic risks can predict smoking cessation outcomes and moderate the effect of pharmacological treatments. Some pharmacogenetic findings have been replicated in meta-analyses or in multiple smoking cessation trials. The variation in efficacy between smokers with different genetic markers supports the notion that personalized smoking cessation intervention based upon genotype could maximize the efficiency of such treatment while minimizing side effects, thus influencing the number needed to treat (NNT) and the number needed to harm. In summary, as precision medicine is revolutionizing healthcare, smoking cessation may be one of the first areas where genetic variants may identify individuals at increased risk. Current evidence strongly suggests that genetic variants predict cessation failure and that cessation pharmacotherapy effectiveness is modulated by biomarkers such as nicotinic cholinergic receptor α5 subunit (CHRNA5) genotypes or nicotine metabolism ratio (NMR). These findings strengthen the case for the development and rigorous testing of treatments that target patients with different biological risk profiles.

Precision medicine
Smoking cessation
Pharmacogenetics


Transorbital Approach for Improved Access in the Management of Paranasal Sinus Mucoceles.

Abstract: Introduction  Paranasal sinus mucoceles result from obstruction of mucous glands resulting in a cystic fluid collection that expands and encroaches upon surrounding structures. Transnasal endoscopic marsupialization has largely replaced open resection. However, mucoceles located in the orbital region or the lateral frontal sinus continue to be difficult to approach via the transnasal approach alone and often require additional approaches, such as the frontal trephine. This study sought to investigate the feasibility of the transorbital technique as an adjunct to traditional transnasal approaches in the management of paranasal sinus mucoceles. Methods  A retrospective case series of paranasal sinus mucoceles approached with a transorbital technique from a tertiary care center. Results  From 2008 to 2016, 17 patients were treated with a transorbital approach for 20 mucoceles. Of note, 24% of the patients in our series had undergone previous surgical management of the mucocele (nontransorbital approach), representing revision cases. Most mucoceles involved the frontal sinus (82%). The total complication rate was 6%. We observed no new or worsened diplopia, ptosis, or permanent visual loss. Recurrence rate was 6%. Conclusions  The endoscopic transorbital approach is a feasible complement to transnasal approaches for treatment of mucoceles located in technically challenging locations. We have demonstrated that transorbital approaches can be performed with no resultant orbital damage, visual change, ptosis, or permanent diplopia. While most patients can be treated with a standard transnasal approach, the transorbital approach can be used as part of a multiportal strategy for those with difficult to access mucoceles. Future prospective studies are needed to further characterize patient selection and outcomes.

Miller|Craig|C|
Berens|Angelique|A|
Patel|Sapna A|SA|
Humphreys|Ian M|IM|
Moe|Kris S|KS|

mucocele
anterior skull base
computer assisted surgery
endoscopic sinus surgery
orbital/ocular


Influence of probiotics on biofilm formation and diversity of bacteria colonising crop sorghum ensiled with unsalable vegetables.

Abstract: The objective of this study was to characterise in situ digestion kinetics and bacterial colonisation of crop sorghum ensiled with unsalable carrot or pumpkin at 0, 20 or 40% dry matter (DM). Silages with or without the application of a commercial probiotic were incubated in situ for 0, 3, 6, 9, 24 and 48 h. Calculation of in situ digestion kinetics was conducted for DM, organic matter and neutral detergent fibre (aNDF). The V4 region of the 16S rRNA gene was sequenced to determine the composition and diversity of bacteria colonising the silage. Organic matter and DM digestion kinetics indicated that greater vegetable inclusion increased (P < 0.05) the soluble fraction and effective degradability. Bacterial richness at 48 h incubation was greater (P = 0.02) in 20% carrot and 40% pumpkin treatments, compared with the control. An effect of level × probiotic was observed with increased Shannon diversity (P = 0.01) for 40% carrot and 20% pumpkin probiotic treatments, respectively. Primary colonising bacteria were members of the Prevotella genus, dominating after 3 and 6 h of incubation. The abundance of Prevotella increased by 4.1% at 3 h (P < 0.01) and by 4.7% at 9 h incubation with probiotics, compared with the control. Secondary biofilm colonisers included members of Treponema, Saccharofermentans, Fibrobacter, Ruminobacter and Anaerosporobacter genera, dominant from 9 h incubation onward. This study demonstrated that including unsalable vegetables at 20 or 40% DM increases the soluble fraction and effective degradability of sorghum silage during in situ digestion and increases diversity of bacteria colonising ensiled vegetables within the rumen. KEY POINTS: • Ensiling unsalable vegetables is a viable strategy to reduce food waste. • Ensiled vegetables increased in situ soluble fraction and effective degradability. • Bacterial richness at 48 h incubation improved with 20% carrot or 40% pumpkin. • Diversity of colonising rumen bacteria increased with carrot or pumpkin inclusion.

Probiotics
Biofilm
In situ technique
Rumen bacterial community
Unsalable vegetable silage


Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells.

Abstract: Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling.

Yang|Bin|B|
Li|Wei|W|
Zheng|Qichang|Q|
Qin|Tao|T|
Wang|Kun|K|
Li|Jinjin|J|
Guo|Bing|B|
Yu|Qihong|Q|
Wu|Yuzhe|Y|
Gao|Yang|Y|
Cheng|Xiang|X|
Hu|Shaobo|S|
Kumar|Stanley Naveen|SN|
Liu|Sanguang|S|
Song|Zifang|Z|

D048051:p38 Mitogen-Activated Protein Kinases

Nuclear factor erythroid 2-related factor 2


Effects of dietary vitamin D3 on growth performance, antioxidant capacities and innate immune responses in juvenile black carp Mylopharyngodon piceus.

Abstract: The aim of this experiment was used to investigate the effects of different contents of dietary vitamin D3 on the growth performance and antioxidant and innate immune responses in juvenile black carp Mylopharyngodon piceus. Black carp juveniles were fed six levels of dietary vitamin D3 (VD3) (96, 220, 412, 840, 1480, and 3008 IU/Kg) for 9 weeks. Results showed that highest weight gain (WG) and special growth ratio (SGR) were obtained at 534.2 IU/Kg dietary VD3 according to the second-order polynomial regression model. The protein efficiency ratio (PER) of black carp could be significantly increased by 412, 840, and 1480 IU/Kg dietary VD3 (p < 0.05), while the feed conversion ratio (FCR) were reduced by 412, 840, and 1480 IU/Kg dietary VD3 (p < 0.05). Adequate dietary VD3 content (412, 840, and 1480 IU/Kg) could significantly upregulate expression levels of lipoxygenase 5 (LPO 5); increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR); and improve GSH contents and total antioxidant capacities (T-AOC) in the liver of black carp. However, glutathione S-transferase (GST) activities and malondialdehyde (MDA) levels were significantly reduced by adequate dietary VD3 content (412, 840, and 1480 IU/Kg) in the fish liver. In addition, 412, 840, and 1480 IU/Kg dietary VD3 could significantly upregulate the mRNA expression levels of interferon-α (IFN-α), lysozyme (LYZ), hepcidin (HEPC), natural resistance-associated macrophage protein (NRAMP), and complement component 3 (C3) and C9 in the hemocytes and liver of black carp juveniles compared with the VD3-deficient diet (96 IU/Kg). Meanwhile, higher contents of dietary VD3 could increase serum LYZ and ACP activities and C3 and C4 contents in black carp juveniles compared with the groups fed VD3-deficient diet. In conclusion, these results suggest that adequate dietary VD3 could increase growth performances, improve antioxidant capacities, and then enhance innate immune parameters in black carp juveniles.

Vitamin D3
Growth performance
Antioxidant capacities
Innate immune responses
Mylopharyngodon piceus


Facile Formation of 2D-3D Heterojunctions on Perovskite Thin Film Surfaces for Efficient Solar Cells.

Abstract: The interfaces between perovskite and charge transport layers greatly impact the device efficiency and stability of perovskite solar cells (PSCs). Inserting an ultrathin wide-band-gap layer between perovskite and hole transport layers (HTLs) has recently been shown as an effective strategy to enhance device performance. Herein, a small amount of an organic halide salt, N,N'-dimethylethylene-1,2-diammonium iodide, is used to create two-dimensional (2D)-three-dimensional (3D) heterojunctions on MAPbI3 thin film surfaces by facile solution processing. The formation of an ultrathin wide-band-gap 2D perovskite layer on top of 3D MAPbI3 changes the morphological and photophysical properties of perovskite thin films, effectively reduces the surface defects, and suppresses the charge recombination in the interfaces between perovskite and HTL. As a result, a power conversion efficiency of ∼20.2%, with an open-circuit voltage of 1.14 V, a short-circuit current density of 22.57 mA cm-2, and a fill factor of 0.78, is achieved for PSCs with enhanced stability.

stability
perovskite solar cells
2D−3D heterojunctions
interface engineering
surface passivation


The practical significance of perinatal cardiology based on own experience.

Abstract: The article underlined the role of perinatal cardiology in contributing to the medical care of the pregnant woman taking into consideration the technical and medical progress which has made it possible to save not only human life but also its quality. The role of correct early diagnosis, as well as correct treatment was discussed and the results of such procedure demonstrated.

classification of fetal heart defects
cardiac surgery of the newborn
fetal heart defect
fetal surgery
fetal treatment


Mortality data 2004-2019: an audit of the Royal Adelaide Hospital Adult Burn Service.

Abstract:
BACKGROUND
Burns are complex, multifaceted injuries that can pose significant challenges to the treating team. The Royal Adelaide Hospital (RAH) Burns Service has undergone a major evolution over the past two decades, with perceived improvement in outcomes. We present here a longitudinal audit of the RAH Burns Service Mortality Data between 2004 and 2019.

METHODS
An audit was conducted of all index admissions to the RAH Burns Unit from 1 January 2004 to 31 December 2019. Age at admission, total body surface area, burn depth, presence of inhalation injury and outcome were recorded. Baux and revised Baux Scores were calculated. Lethal Area 50% for different time points and age groups, Baux50/100 and Revised Baux50/100 values were then calculated using logistical regression.

RESULTS
During 2004-2019, there were 5653 index admissions to the RAH Burns Unit. The mean total body surface area of burn injuries admitted was 5.1% and the survival rate was 99.17%. The Lethal Area 50% for the study period was 74%, with an improvement from 70% (2004-2011) to 80% (2012-2019). The Baux50 score for the time period was 120 and the Revised Baux50 was 129.

CONCLUSION
The RAH results are comparable with other high-income country Burn Services and demonstrated significant improvement across the study period. The data also highlight areas for ongoing focus such as the elderly burns patient.

Stefani|Kristian|K|0000-0001-9470-2924
Wagstaff|Marcus J D|MJD|
Damkat|Ivo|I|
Greenwood|John E|JE|

mortality
Baux Score
Adult burn care
LA50


Adolescent and young adult male health: a review.

Abstract: Adolescent and young adult male health receives little attention, despite the potential for positive effects on adult quality and length of life and reduction of health disparities and social inequalities. Pediatric providers, as the medical home for adolescents, are well positioned to address young men's health needs. This review has 2 primary objectives. The first is to review the literature on young men's health, focusing on morbidity and mortality in key areas of health and well-being. The second is to provide a clinically relevant review of the best practices in young men's health. This review covers male health issues related to health care access and the Centers for Disease Control and Prevention's Healthy 2020 objectives for adolescents and young adults, focusing on the objectives for chronic illness, mortality, unintentional injury and violence, mental health and substance use, and reproductive and sexual health. We focus, in particular, on gender-specific issues, particularly in reproductive and sexual health. The review provides recommendations for the overall care of adolescent and young adult males.

Bell|David L|DL|
Breland|David J|DJ|
Ott|Mary A|MA|

D000293:Adolescent
D016497:Adolescent Health Services
D002423:Cause of Death
D002908:Chronic Disease
D006285:Health Planning
D006297:Health Services Accessibility
D006801:Humans
D008297:Male
D054526:Men's Health
D008603:Mental Health
D020380:Needs Assessment
D018802:Patient-Centered Care
D010372:Pediatrics
D017410:Practice Guidelines as Topic
D060728:Reproductive Health
D019966:Substance-Related Disorders
D014481:United States
D014754:Violence
D014947:Wounds and Injuries
D055815:Young Adult

young adult
male
adolescent health
gender
sexual and reproductive health


The rubber hand illusion in complex regional pain syndrome: preserved ability to integrate a rubber hand indicates intact multisensory integration.

Abstract: In patients with complex regional pain syndrome (CRPS) type 1, processing of static tactile stimuli is impaired, whereas more complex sensory integration functions appear preserved. This study investigated higher order multisensory integration of body-relevant stimuli using the rubber hand illusion in CRPS patients. Subjective self-reports and skin conductance responses to watching the rubber hand being harmed were compared among CRPS patients (N=24), patients with upper limb pain of other origin (N=21, clinical control group), and healthy subjects (N=24). Additionally, the influence of body representation (body plasticity [Trinity Assessment of Body Plasticity], neglect-like severity symptoms), and clinical signs of illusion strength were investigated. For statistical analysis, 1-way analysis of variance, t test, Pearson correlation, with α=0.05 were used. CRPS patients did not differ from healthy subjects and the control group with regard to their illusion strength as assessed by subjective reports or skin conductance response values. Stronger left-sided rubber hand illusions were reported by healthy subjects and left-side-affected CRPS patients. Moreover, for this subgroup, illness duration and illusion strength were negatively correlated. Overall, severity of neglect-like symptoms and clinical signs were not related to illusion strength. However, patients with CRPS of the right hand reported significantly stronger neglect-like symptoms and significantly lower illusion strength of the affected hand than patients with CRPS of the left hand. The weaker illusion of CRPS patients with strong neglect-like symptoms on the affected hand supports the role of top-down processes modulating body ownership. Moreover, the intact ability to perceive illusory ownership confirms the notion that, despite impaired processing of proprioceptive or tactile input, higher order multisensory integration is unaffected in CRPS.

Reinersmann|Annika|A|
Landwehrt|Julia|J|
Krumova|Elena K|EK|
Peterburs|Jutta|J|
Ocklenburg|Sebastian|S|
Güntürkün|Onur|O|
Maier|Christoph|C|

Rubber hand illusion
Complex regional pain syndrome
Body image
Cortical reorganization
Sense of ownership


Biological effects of mixed-ion beams. Part 2: The relative biological effectiveness of CHO-K1 cells irradiated by mixed- and single-ion beams.

Abstract: The relative biological effectiveness (RBE) values were determined for single- and mixed-ion beams containing carbon and oxygen ions. The CHO-K1 cells were irradiated with beams with the linear energy transfer (LET) values of 236-300 and 461-470 keV/μm for 12C and 16O ions, respectively. The RBE was estimated as a function of dose, survival fraction (SF) and LET. The SF was not affected by varying contributions of the constituent ions to the total mixed dose. The RBE has the same value for single-ion exposures with ions with LET 300 (12C) and 470 keV/μm (16O).

Czub|Joanna|J| Banaś|Dariusz|D| Braziewicz|Janusz|J| Buraczewska|Iwona|I| Jaskóła|Marian|M| Kaźmierczak|Urszula|U| Korman|Andrzej|A| Lankoff|Anna|A| Lisowska|Halina|H| Szefliński|Zygmunt|Z| Wojewódzka|Maria|M| Wójcik|Andrzej|A|

Relative biological effectiveness
CHO-K1 cells
Ions beams


Evaluation of No-Touch Technologies for Decontamination of Toys in Pediatric Healthcare Settings.

Abstract: No-touch technologies could be useful to decontaminate shared toys in healthcare settings. A high-level disinfection cabinet and electrostatic sprayer were effective against methicillin-resistant Staphylococcus aureus (MRSA), bacteriophage MS2, and Clostridioides difficile spores on toys. An ultraviolet-C light box was less effective but reduced MRSA and bacteriophage MS2 by >2 log10.

Haydar|Hanan|H|
Kumar|Jessica A|JA|
Cadnum|Jennifer L|JL|
Zangla|Emily|E|
Hoyen|Claudia K|CK|
Donskey|Curtis J|CJ|

electrostatic sprayer
Staphylococcus aureus
Clostridium difficile


The Evolutionary Forces Shaping Cis- and Trans-Regulation of Gene Expression within a Population of Outcrossing Plants.

Abstract: Understanding the persistence of genetic variation within populations has long been a goal of evolutionary biology. One promising route toward achieving this goal is using population genetic approaches to describe how selection acts on the loci associated with trait variation. Gene expression provides a model trait for addressing the challenge of the maintenance of variation because it can be measured genome-wide without information about how gene expression affects traits. Previous work has shown that loci affecting the expression of nearby genes (local or cis-eQTLs) are under negative selection, but we lack a clear understanding of the selective forces acting on variants that affect the expression of genes in trans. Here, we identify loci that affect gene expression in trans using genomic and transcriptomic data from one population of the obligately outcrossing plant, Capsella grandiflora. The allele frequencies of trans-eQTLs are consistent with stronger negative selection acting on trans-eQTLs than cis-eQTLs, and stronger negative selection acting on trans-eQTLs associated with the expression of multiple genes. However, despite this general pattern, we still observe the presence of a trans-eQTL at intermediate frequency that affects the expression of a large number of genes in the same coexpression module. Overall, our work highlights the different selective pressures shaping variation in cis- and trans-regulation.

Josephs|Emily B|EB|
Lee|Young Wha|YW|
Wood|Corlett W|CW|
Schoen|Daniel J|DJ|
Wright|Stephen I|SI|
Stinchcombe|John R|JR|

D018506:Gene Expression Regulation, Plant

population genetics
trans-regulatory variation
coexpression networks
eQTLs


The functional networks of a novel environment: Neural activity mapping in awake unrestrained rats using positron emission tomography.

Abstract:
INTRODUCTION
Novel environment stimulation is thought to have an important role in cognitive development and has been shown to encourage exploratory behavior in rats. However, psychopathology or perceived danger or stress can impede this exploratory drive. The balance between brain circuits controlling the exploratory drive elicited by a novel environment, and the avoidance response to stressors, is not well understood.

METHODS
Using positron emission tomography (PET) and the glucose analog [18 F]fluorodeoxyglucose (18F-FDG), we assessed awake brain glucose metabolism (BGluM) in rats while in a novel environment (cage of an unfamiliar male rat) and non-novel environment (the animal's home cage).

RESULTS
Exposure to the novel environment increased BGluM in regions associated with vision (visual cortex), motor function and motivated behavior (striatum and motor cortex), and anxiety (stria terminalis), and decreased BGluM in regions associated with auditory processing (auditory cortex, insular cortex, inferior colliculus), locomotor activity (globus pallidus, striatum, motor cortex, ventral thalamic nucleus), spatial navigation (retrosplenial cortex), and working memory (hippocampus, cingulate cortex, prelimbic cortex, orbitofrontal cortex).

CONCLUSION
These results suggest that the novel cage is a stressful environment that inhibits activity in brain regions associated with exploratory behavior. Patterns of inhibition in the novel cage also support the proposed rat default mode network, indicating that animals are more cognitively engaged in this environment. Additionally, these data support the unique capability of combining FDG-PET with psychopharmacology experiments to examine novelty seeking and brain activation in the context of decision making, risk taking, and cognitive function more generally, along with response to environmental or stress challenges.

novel environment
brain glucose metabolism
FDG
functional connectivity
imaging
olfaction


Promoting Occupational Health through Gamification and E-Coaching: A 5-Month User Engagement Study.

Abstract: Social gamification systems have shown potential for promoting healthy lifestyles, but applying them to occupational settings faces unique design challenges. While occupational settings offer natural communities for social interaction, fairness issues due to heterogeneous personal goals and privacy concerns increase the difficulty of designing engaging games. We explored a two-level game-design, where the first level related to achieving personal goals and the second level was a privacy-protected social competition to maximize goal compliance among colleagues. The solution was strengthened by employing occupational physicians who personalized users' goals and coached them remotely. The design was evaluated in a 5-month study with 53 employees from a Dutch university. Results suggested that the application helped half of the participants to improve their lifestyles, and most appreciated the role of the physician in goal-setting. However, long-term user engagement was undermined by the scalability-motivated design choice of one-way communication between employees and their physician. Implications for social gamification design in occupational health are discussed.

occupational health
E-coaching
user engagement
social gamification
behavior change
health informatics
user study


Classification of geographical origin of kimchi by volatile compounds analysis using an electronic nose.

Abstract: Food authenticity is one of the largest concerns in recent days. As kimchi has been a global food, its production origin has been important issue, particularly due to the large import from China. Among the potential methods, electronic nose which can measure volatile compounds in foods is considered to be a powerful device for identifying country of production. This study is to classify 69 kinds of kimchi produced in South Korea (39) and China (30) by analyzing volatile compounds in kimchi using electronic nose-mass spectrometry. Two widely used multivariate analyses, discriminant function analysis and principal component analysis, were used. Results showed that both multivariate analyses can completely separate Korean and Chinese kimchi using 10 kinds of molecular weights among 10-160 amu. The results indicate that the volatile compounds in kimchi are a suitable target to determine the geographical origin of kimchi.

Lee|Wang-Hee|WH| Oh|Il-Nam|IN| Choi|Seunghyun|S| Park|Jong-Tae|JT|

Kimchi
Electronic nose
Food authenticity
Discriminant function analysis
Principal component analysis


Medicaid Utilization among Middle-age and Older Adults: A Health and Retirement Study Longitudinal Analysis (1998 to 2014).

Abstract: With over fifteen million older adults in the United States relying on the means-tested Medicaid program for healthcare coverage, there has been concern over rising Medicaid costs among this rapidly growing age group. Few studies have longitudinally examined trends among older beneficiaries over time to identify factors related to Medicaid utilization and to better understand how potential coverage changes might impact this group. This study used the 1998 to 2014 waves of the Health and Retirement Study (N = 8,162) to analyze a representative sample of those aged 50 and older to ascertain demographic, health, and economic factors associated with Medicaid utilization over a sixteen-year period. The analyses showed stable probabilities of accessing the program over time and observed that the most vulnerable older adults make up the pool of Medicaid beneficiaries. There is no evidence of significant asset divestment in order to qualify for benefits. Multivariate analyses further revealed those who were older, female, minority race/ethnicity, less educated, in poorer health, below the federal poverty line, and with lower net wealth had a higher risk of utilizing Medicaid during the observed time period than their counterparts. Findings highlight the importance of monitoring changes in the documented risk factors over time in terms of their impact on Medicaid utilization and underscore the need to consider how these factors may be interrelated.

Tavares|Jane|J|
Cohen|Marc A|MA|
Silberman|Susan|S|
Popham|Lauren|L|

Medicaid utilization
health and retirement study
medicaid beneficiaries
medicaid spend-down


Prostaglandin Transporter OATP2A1/SLCO2A1 Is Essential for Body Temperature Regulation during Fever.

Abstract: Prostaglandin E2 (PGE2) in the hypothalamus is a principal mediator of the febrile response. However, the role of organic anion transporting polypeptide 2A1 (OATP2A1/SLCO2A1), a prostaglandin transporter, in facilitating this response is unknown. Here, we investigated the effect of Slco2a1 deficiency on the body core temperature (Tc) and on the PGE2 concentration in hypothalamus interstitial fluid (Cisf) and CSF (Ccsf) of lipopolysaccharide (LPS; 100 μg/kg, i.p.)-treated mice of both sexes. Slco2a1-/- mice did not develop a febrile response. Ccsf was increased in Slco2a1+/+ and Slco2a1-/- mice, and Ccsf of Slco2a1-/- mice was well maintained at 5 h after LPS injection (1160 pg/ml) compared with Slco2a1+/+ mice (316 pg/ml). A microdialysis study revealed that Cisf peaked at 2 h after LPS injection in Slco2a1+/+ mice (841 pg/ml), whereas the increase in Cisf was negligible in Slco2a1-/- mice. The PGE2 plasma concentration in Slco2a1-/- mice (201 pg/ml) was significantly higher than that in Slco2a1+/+ mice (54 pg/ml) at 1 h after LPS injection, whereas the two groups showed similar PGE2 concentrations in the hypothalamus. Strong Oatp2a1 immunoreactivity was observed in F4/80-positive microglia and perivascular cells and in brain capillary endothelial cells. The changes in Tc and Cisf seen in LPS-injected Slco2a1+/+ mice were partially attenuated in monocyte-/macrophage-specific Slco2a1-/- (Slco2a1Fl/Fl/LysMCre/+) mice. Thus, OATP2A1 facilitates the LPS-induced febrile response by maintaining a high level of Cisf, possibly by regulating PGE2 secretion from F4/80-positive glial cells and/or facilitating PGE2 transport across the blood-brain barrier. These findings suggest that OATP2A1 is a useful therapeutic target for neuroinflammation.SIGNIFICANCE STATEMENT Fever is a physiological response caused by pyrogen-induced release of prostaglandin E2 (PGE2) in the hypothalamus, which plays a central role in regulating the set-point of body temperature. However, it is unclear whether the prostaglandin transporter OATP2A1/SLCO2A1 is involved in this response. We show here that LPS-induced fever is associated with increased PGE2 concentration in hypothalamus interstitial fluid (Cisf), but not in CSF (Ccsf), by means of a microdialysis study in global Slco2a1-knock-out mice and monocyte-/macrophage-specific Slco2a1-knock-out mice. The results suggest that OATP2A1 serves as a regulator of Cisf in F4/80-positive glial cells. OATP2A1 was detected immunohistochemically in brain capillary endothelial cells and, therefore, may also play a role in PGE2 transport across the blood-brain barrier.

Nakamura|Yoshinobu|Y| Nakanishi|Takeo|T|0000-0002-6561-7138 Shimada|Hiroaki|H| Shimizu|Junya|J| Aotani|Rika|R| Maruyama|Shio|S| Higuchi|Kei|K| Okura|Takashi|T| Deguchi|Yoshiharu|Y| Tamai|Ikumi|I|

transporter
OATP2A1
fever
prostaglandin E2
hypothalamus
macrophage


Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Abstract: : Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10-15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring.

Fattizzo|Bruno|B|0000-0003-0857-8379 Serpenti|Fabio|F| Barcellini|Wilma|W| Caprioli|Chiara|C|

hypoplastic myelodysplastic syndrome
aplastic anemia
genomic and molecular landscape
immunological aspects
immunosuppressive therapy


Pathways involved in the spread of buccal carcinoma on contrast-enhanced multislice CT.

Abstract:
OBJECTIVES
To explore how buccal carcinoma spread, using contrast-enhanced multislice CT (CEMSCT).

METHODS
We retrospectively analysed the extent of lesions in 56 patients with primary buccal squamous cell carcinoma (SCCA). Abnormal manifestations on CEMSCT at oral subsites and involved adjacent structures were documented and evaluated, which were compared with the results of surgery and histopathology.

RESULTS
Infiltration and spread to oral subsites and/or adjacent structures was confirmed in 33 patients (58.9%). The opening of the Stensen duct was the most commonly invaded oral subsite (72.7%); other sites included the gingivobuccal sulcus (60.6%), pterygomandibular raphe (54.5%), gingiva (24.2%), retromolar trigone (24.2%), orbicularis oris (18.2%) and the floor of mouth (15.2%). Of the involved adjacent structures, the buccal space was the most common site of spread (69.7%), followed by the masticatory muscles and spaces (57.6%), bone (54.5%), skin and subcutaneous fat (39.4%), pharynx (30.3%), investing fascia (15.2%) and the base of the skull (6.1%). CEMSCT manifestations of the involvement in buccal SCCAs had correlations with pathological findings (p < 0.05). The sensitivities, specificities and accuracies of two radiologists' evaluation on buccal carcinoma involvement were 50.00%, 23.21% and 73.21%; and 51.79%, 32.14% and 83.93%, respectively.

CONCLUSIONS
Buccal SCCAs could superficially and deeply spread to multiple oral subsites and/or adjacent structures. CEMSCT could delineate their spread pathways and extents.

Xu|S-S|SS| Li|D|D| Zhou|Y|Y| Sheng|B|B| Zeng|C|C| Zhong|S-X|SX|

contrast-enhanced multislice computed tomography


There ain't nothing like a Dame: a commentary on Lonsdale (1947) 'Divergent beam X-ray photography of crystals'.

Abstract: Prof. Dame Kathleen Lonsdale was one of the two first female Fellows of the Royal Society, having originally been a student of that great British scientist and Nobel Laureate William Henry Bragg. She came to fame initially for her solution of the crystal structure of hexamethyl benzene, thus demonstrating that the benzene ring was flat, of considerable importance to organic chemistry, where it had been proposed before but without proof. This was at a time when the solution of crystal structures was in its infancy, and in its day this work was considered a triumph. As a rare example then of a female physicist, Lonsdale became interested in various aspects of the diffraction of X-rays, and in particular published an important paper on a form of diffraction in which a strongly divergent source was used rather than the usual highly collimated beam. The photographs thus obtained showed a series of arcs and circles, whose positions were so sensitive that they could be used to determine the quality of crystals such as diamond, and even to calculate their lattice dimensions, and hence carbon-carbon bond lengths, to hitherto extraordinary precision. Lonsdale also became known not just as a scientist but as a peace activist and an active member of the Society of Friends. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

divergent beam
diamond
Kossel patterns
X-ray diffraction


Identification and validation of a novel eight mutant-derived long non-coding RNAs signature as a prognostic biomarker for genome instability in low-grade glioma.

Abstract: Long non-coding RNAs (lncRNAs) comprise an integral part of the eukaryotic transcriptome. Alongside proteins, lncRNAs modulate lncRNA-based gene signatures of unstable transcripts, play a crucial role as antisense lncRNAs to control intracellular homeostasis and are implicated in tumorigenesis. However, the role of genomic instability-associated lncRNAs in low-grade gliomas (LGG) has not been fully explored. In this study, lncRNAs expression and somatic mutation profiles in low-grade glioma genome were used to identify eight novel mutant-derived genomic instability-associated lncRNAs including H19, FLG-AS1, AC091932.1, AC064875.1, AL138767.3, AC010273.2, AC131097.4 and ISX-AS1. Patients from the LGG gene mutagenome atlas were grouped into training and validation sets to test the performance of the signature. The genomic instability-associated lncRNAs signature (GILncSig) was then validated using multiple external cohorts. A total of 59 novel genomic instability-associated lncRNAs in LGG were used for least absolute shrinkage and selection operator (Lasso), single and multifactor Cox regression analysis using the training set. Furthermore, the independent predictive role of risk features in the training and validation sets were evaluated through survival analysis, receiver operating feature analysis and construction of a nomogram. Patients with IDH1 mutation status were grouped into two different risk groups based on the GILncSig score. The low-risk group showed a relatively higher rate of IDH1 mutations compared with patients in the high-risk group. Furthermore, patients in the low-risk group had better prognosis compared with patients in the high-risk group. In summary, this study reports a reliable prognostic prediction signature and provides a basis for further investigation of the role of lncRNAs on genomic instability. In addition, lncRNAs in the signature can be used as new targets for treatment of LGG.

Maimaiti|Aierpati|A| Wang|Xixian|X| Pei|Yinan|Y| Nuermaimaiti|Nuerbiye|N| Tuersunniyazi|Abudireheman|A| Abula|Yaeraili|Y| Feng|Zhaohai|Z| Jiang|Lei|L| Shi|Xin|X| Kasimu|Maimaitijiang|M|

D015972:Gene Expression Regulation, Neoplastic


Impairment of decision-making in multiple sclerosis: A neuroeconomic approach.

Abstract:
OBJECTIVE
To assess the decision-making impairment in patients with multiple sclerosis (MS) and how they relate to other cognitive domains.

METHODS
We performed a cross-sectional analysis in 84 patients with MS, and 21 matched healthy controls using four tasks taken from behavioral economics: (1) risk preferences, (2) choice consistency, (3) delay of gratification, and (4) rate of learning. All tasks were conducted using real-world reward outcomes (food or money) in different real-life conditions. Participants underwent cognitive examination using the Brief Repeatable Battery-Neuropsychology.

RESULTS
Patients showed higher risk aversion (general propensity to choose the lottery was 0.51 vs 0.64, p = 0.009), a trend to choose more immediate rewards over larger but delayed rewards ( p = 0.108), and had longer reactions times ( p = 0.033). Choice consistency and learning rates were not different between groups. Progressive patients chose slower than relapsing patients. In relation to general cognitive impairments, we found correlations between impaired decision-making and impaired verbal memory ( r = 0.29, p = 0.009), visual memory ( r = -0.37, p = 0.001), and reduced processing speed ( r = -0.32, p = 0.001). Normalized gray matter volume correlated with deliberation time ( r = -0.32, p = 0.005).

CONCLUSION
Patients with MS suffer significant decision-making impairments, even at the early stages of the disease, and may affect patients' quality and social life.

Sepúlveda|Maria|M|
Fernández-Diez|Begoña|B|
Martínez-Lapiscina|Elena H|EH|
Llufriu|Sara|S|
Sola-Valls|Nuria|N|
Zubizarreta|Irati|I|
Blanco|Yolanda|Y|
Saiz|Albert|A|
Levy|Dino|D|
Glimcher|Paul|P|
Villoslada|Pablo|P|

decision-making
Multiple sclerosis
neuroeconomics
cognitive impairment


Anti-citrullinated protein antibodies are associated with osteopenia but not with pain at diagnosis of rheumatoid arthritis: data from the BARFOT cohort.

Abstract:
BACKGROUND
Anti-citrullinated protein antibodies (ACPA) have been suggested to have a potential role in both bone loss and pain in rheumatoid arthritis (RA), based on studies in vitro and in animal models. Here we addressed if anti-cyclic citrullinated (anti-CCP) antibodies were associated with osteopenia or pain in patients with RA, at the time for diagnosis.

METHODS
Baseline data from the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort, which consists of patients with RA with a disease duration of 1 year or less, were analyzed. To be included, they should have been assessed by anti-CCP, dual-energy X-ray absorptiometry (DEXA) of lumbar spine and hip, and/or digital X-ray radiogrammetry (DXR) of the metacarpal bones. Osteopenia was defined as a z-score < - 1 SD. Pain VAS > 40 mm, was defined as patient unacceptable pain. Multiple logistic regression analyses were performed to assess whether anti-CCP was independently associated with osteopenia or unacceptable pain.

RESULTS
Of the 657 patients, 65% were women, 58% were anti-CCP positive, 37% had osteopenia in the lumbar spine, and 29% had osteopenia in the hip. Sixty-one percent had unacceptable pain at diagnosis. Patients positive for anti-CCP had significantly more frequently osteopenia in the femoral neck and Ward's triangle compared with anti-CCP-negative patients (p = 0.016 and 0.003, respectively). This difference was found in men at any anti-CCP titer, but in women, osteopenia in these hip locations was found only in those with high anti-CCP titers (> 500 IU/ml). Anti-CCP was not associated with osteopenia in the lumbar spine or the metacarpal bones. In multiple logistic regression analyses, anti-CCP was independently associated with osteopenia in the femoral neck and/or Ward's triangle but not with unacceptable pain. Instead, inflammatory variables were independently associated with unacceptable pain.

CONCLUSION
These data show that in patients with early RA, anti-CCP positivity was independently associated with osteopenia in the femoral neck and/or Ward, but not in the lumbar spine. In our patients, we could not confirm a recently suggested association between anti-CCP antibodies and pain. Further studies are necessary to explore the possible clinical relevance of interactions between ACPA, bone, and pain found in vitro and in animal models.

Hafström|Ingiäld|I| Ajeganova|Sofia|S| Forslind|Kristina|K| Svensson|Björn|B|

Anti-citrullinated protein antibodies
Pain
Rheumatoid arthritis
Bone mineral density


Quantitative Analysis of Tissue Samples by Combining iTRAQ Isobaric Labeling with Selected/Multiple Reaction Monitoring (SRM/MRM).

Abstract: Mass spectrometry-based phosphoproteomics is an indispensible technique used in the discovery and quantification of phosphorylation events on proteins in biological samples. The application of this technique to tissue samples is especially useful for the discovery of biomarkers as well as biological studies. We herein describe the application of a large-scale phosphoproteome analysis and SRM/MRM-based quantitation to develop a strategy for the systematic discovery and validation of biomarkers using tissue samples.

D002851:Chromatography, High Pressure Liquid


Circulating T cell subsets are associated with clinical outcome of anti-VEGF-based 1st-line treatment of metastatic colorectal cancer patients: a prospective study with focus on primary tumor sidedness.

Abstract:
BACKGROUND
In a prospective study with long-term follow-up, we analyzed circulating T cell subsets in patients with metastatic colorectal cancer (mCRC) in the context of primary tumor sidedness, KRAS status, and clinical outcome. Our primary goal was to investigate whether baseline levels of circulating T cell subsets serve as a potential biomarker of clinical outcome of mCRC patients treated with an anti-VEGF-based regimen.

METHODS
The study group consisted of 36 patients with colorectal adenocarcinoma who started first-line chemotherapy with bevacizumab for metastatic disease. We quantified T cell subsets including Tregs and CD8+ T cells in the peripheral blood prior to therapy initiation. Clinical outcome was evaluated as progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

RESULTS
1) mCRC patients with KRAS wt tumors had higher proportions of circulating CD8+ cytotoxic T cells among all T cells but also higher measures of T regulatory (Treg) cells such as absolute count and a higher proportion of Tregs in the CD4+ subset. 2) A low proportion of circulating Tregs among CD4+ cells, and a high CD8:Treg ratio at initiation of VEGF-targeting therapy, were associated with favorable clinical outcome. 3) In a subset of patients with primarily right-sided mCRC, superior PFS and OS were observed when the CD8:Treg ratio was high.

CONCLUSIONS
The baseline level of circulating immune cells predicts clinical outcome of 1st-line treatment with the anti-VEGF angio/immunomodulatory agent bevacizumab. Circulating immune biomarkers, namely the CD8:Treg ratio, identified patients in the right-sided mCRC subgroup with favorable outcome following treatment with 1st-line anti-VEGF treatment.

D042461:Vascular Endothelial Growth Factor A

T cell subsets
Metastatic colorectal cancer
Anti-VEGF
Antitumor immune response
Primary colorectal carcinoma sidedness
Regulatory T cells


Discontinued in 2013: diabetic drugs.

Abstract:
INTRODUCTION
The increasing prevalence of diabetes, with no cure on the horizon, continues to provide biopharmaceutical companies with an incentive to develop novel therapies and improve existing compounds.

AREAS COVERED
The following paper provides a summary of the experimental drug projects targeted for diabetes and associated complications that were discontinued in 2013. The discontinued projects, highlighted in this article, were identified via biopharmaceutical company pipelines, annual reports, and press releases. The authors also used other sources including: Google, ClinicalTrials.gov, and PubMed. Compounds were in various stages of development at termination and many of them had been associated with favorable effects in earlier studies.

EXPERT OPINION
There were two main reasons for the termination of anti-diabetic compounds that dominated 2013: concerns about safety and efficacy. Attempts to discover a novel mechanism that is both safe and effective in human disease present many challenges, not least is the cost for developing new treatments.

Hedrington|Maka S|MS|
Davis|Stephen N|SN|

D000818:Animals
D003920:Diabetes Mellitus
D015507:Drugs, Investigational
D006801:Humans
D007004:Hypoglycemic Agents
D016896:Treatment Outcome

diabetes
aleglitazar
diabetic nephropathy
discontinued drugs
fasiglifam


Characterization of gut microbial structural variations as determinants of human bile acid metabolism.

Abstract: Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

Wang|Daoming|D|
Doestzada|Marwah|M|
Chen|Lianmin|L|
Andreu-Sánchez|Sergio|S|
van den Munckhof|Inge C L|ICL|
Augustijn|Hannah E|HE|
Koehorst|Martijn|M|
Ruiz-Moreno|Angel J|AJ|
Bloks|Vincent W|VW|
Riksen|Niels P|NP|
Rutten|Joost H W|JHW|
Joosten|Leo A B|LAB|
Netea|Mihai G|MG|
Wijmenga|Cisca|C|
Zhernakova|Alexandra|A|
Kuipers|Folkert|F|
Fu|Jingyuan|J|

structural variation
bile acid metabolism
bacterial genetics
human gut microbiome
metagenome
population-based cohort study


Complete chloroplast genome of Lycoris sprengeri (Amaryllidaceae) and genetic comparison.

Abstract: Lycoris sprengeri is native to China and has various variations. It belongs to the Amaryllidaceae family, which contains abundant alkaloids for medical use and also was planted as garden bulbous flowers. In this study, we assembled the complete chloroplast (cp) genome of L. sprengeri by DNA sequencing, which will improve the complete cp genomic information for analysis of phylogenetic relationships and germplasm identification in Lycoris. The whole cp genome is 158,687 bp, which contained a large single-copy region (LSC) of 86,489 bp, a small single-copy region (SSC) of 18,540 bp, and a pair of inverted repeats (IRs) of 26,829 bp. A total of 137 genes were annotated, including 87 protein coding genes (PCGs), 42 tRNA, and 8 rRNA genes. Phylogenetic tree analysis revealed that the close relationship of three species of Lycoris (L. sprengeri, L. radiate, and L. squamigera) in the Amaryllidaceae family.

complete chloroplast genome
Lycoris sprengeri
genetic comparison