Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers.

Abstract: The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

Kashyap|Sheetal|S|
Pal|Soumya|S|
Chandan|Gourav|G|
Saini|Vipin|V|
Chakrabarti|Sasanka|S|
Saini|Neeraj K|NK|
Mittal|Amit|A|
Thakur|Vijay Kumar|VK|
Saini|Adesh K|AK|
Saini|Reena V|RV|

Microbiota
Gastrointestinal cancer
Biomarker
Colorectal cancer
Metabolites


Synergistic aircraft and ground observations of transported wildfire smoke and its impact on air quality in New York City during the summer 2018 LISTOS campaign.

Abstract: Air pollution associated with wildfire smoke transport during the summer can significantly affect ozone (O3) and particulate matter (PM) concentrations, even in heavily populated areas like New York City (NYC). Here, we use observations from aircraft, ground-based lidar, in-situ analyzers and satellite to study and assess wildfire smoke transport, vertical distribution, optical properties, and potential impact on air quality in the NYC urban and coastal areas during the summer 2018 Long Island Sound Tropospheric Ozone Study (LISTOS). We investigate an episode of dense smoke transported and mixed into the planetary boundary layer (PBL) on August 15-17, 2018. The horizontal advection of the smoke is shown to be characterized with the prevailing northwest winds in the PBL (velocity > 10 m/s) based on Doppler wind lidar measurements. The wildfire sources and smoke transport paths from the northwest US/Canada to northeast US are identified from the NOAA hazard mapping system (HMS) fires and smoke product and NOAA-HYbrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) backward trajectory analysis. The smoke particles are distinguished from the urban aerosols by showing larger lidar-ratio (70-sr at 532-nm) and smaller depolarization ratio (0.02) at 1064-nm using the NASA High Altitude Lidar Observatory (HALO) airborne high-spectral resolution lidar (HSRL) measurements. The extinction-related angstrom exponents in the near-infrared (IR at 1020-1640 nm) and Ultraviolet (UV at 340-440 nm) from NASA-Aerosol Robotic Network (AERONET) product show a reverse variation trend along the smoke loadings, and their absolute differences indicate strong correlation with the smoke-Aerosol Optical Depth (AOD) (R > 0.94). We show that the aloft smoke plumes can contribute as much as 60-70% to the column AOD and that concurrent high-loadings of O3, carbon monoxide (CO), and black carbon (BC) were found in the elevated smoke layers from the University of Maryland (UMD) aircraft in-situ observations. Meanwhile, the surface PM2.5 (PM with diameter ≤ 2.5 μm), organic carbon (OC) and CO measurements show coincident and sharp increase (e.g., PM2.5 from 5 μg/m3 before the plume intrusion to ~30 μg/m3) with the onset of the plume intrusions into the PBL along with hourly O3 exceedances in the NYC region. We further evaluate the NOAA-National Air Quality Forecasting Capability (NAQFC) model PBL-height, PM2.5, and O3 with the observations and demonstrate good consistency near the ground during the convective PBL period, but significant bias at other times. The aloft smoke layers are sometimes missed by the model.

Wu|Yonghua|Y|
Nehrir|Amin R|AR|
Ren|Xinrong|X|
Dickerson|Russell R|RR|
Huang|Jianping|J|
Stratton|Phillip R|PR|
Gronoff|Guillaume|G|
Kooi|Susan A|SA|
Collins|James E|JE|
Berkoff|Timothy A|TA|
Lei|Liqiao|L|
Gross|Barry|B|
Moshary|Fred|F|

Wildfire smoke
Ozone
Optical properties
Black carbon
Organic carbon
PM(2.5)


Magnesium in Obesity, Metabolic Syndrome, and Type 2 Diabetes.

Abstract: Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.

magnesium
obesity
metabolic syndrome
type 2 diabetes
gut microbiota
magnesium deficiency
magnesium supplementation
vitamin D


A person-centred and thriving-promoting intervention in nursing homes - study protocol for the U-Age nursing home multi-centre, non-equivalent controlled group before-after trial.

Abstract:
BACKGROUND
The literature suggests that person-centred care can contribute to quality of life and wellbeing of nursing home residents, relatives and staff. However, there is sparse research evidence on how person-centred care can be operationalised and implemented in practice, and the extent to which it may promote wellbeing and satisfaction. Therefore, the U-Age nursing home study was initiated to deepen the understanding of how to integrate person-centred care into daily practice and to explore the effects and meanings of this.

METHODS
The study aims to evaluate effects and meanings of a person-centred and thriving-promoting intervention in nursing homes through a multi-centre, non-equivalent controlled group before-after trial design. Three nursing homes across three international sites have been allocated to a person-centred and thriving-promoting intervention group, and three nursing homes have been allocated to an inert control group. Staff at intervention sites will participate in a 12-month interactive educational programme that operationalises thriving-promoting and person-centred care three dimensions: 1) Doing a little extra, 2) Developing a caring environment, and 3) Assessing and meeting highly prioritised psychosocial needs. A pedagogical framework will guide the intervention. The primary study endpoints are; residents' thriving, relatives' satisfaction with care and staff job satisfaction. Secondary endpoints are; resident, relative and staff experiences of the caring environment, relatives' experience of visiting their relative and the nursing home, as well as staff stress of conscience and perceived person-centredness of care. Data on study endpoints will be collected pre-intervention, post-intervention, and at a six-month follow up. Interviews will be conducted with relatives and staff to explore experiences and meanings of the intervention.

DISCUSSION
The study is expected to provide evidence that can inform further research, policy and practice development on if and how person-centred care may improve wellbeing, thriving and satisfaction for people who reside in, visit or work in nursing homes. The combination of quantitative and qualitative data will illuminate the operationalisation, effects and meaning of person-centred and thriving-promoting care.

TRIAL REGISTRATION
The trial was registered at ClinicalTrials.gov March 19, 2016, identifier NCT02714452 .

Edvardsson|David|D| Sjögren|Karin|K| Lood|Qarin|Q| Bergland|Ådel|Å| Kirkevold|Marit|M| Sandman|Per-Olof|PO|

Person-centred care
Residents
Relatives
Staff
Thriving
Satisfaction with care
Job satisfaction
Intervention studies
Long-term care
Residential aged care


Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Abstract: Approximately 10% of the epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are uncommon EGFR mutations. Although the efficacy of second (2G) or third generation (3G) EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon EGFR mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon EGFR mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon EGFR mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon EGFR mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major EGFR mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8-13.5), 11.7 months (95% CI: 6.6-16.7), 7.7 months (95% CI: 4.9-17.4), and 5.0 months (95% CI: 3.7-6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9-34.2), 28.8 (95% CI: 24.4-33.4), 13.5 months (95% CI: 7.4-27.8), and 9.4 months (95% CI: 3.4-10.5) for major uncommon EGFR mutation (G719X), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6-16.9), and 37.5 months (95% CI: 35.4-39.6) for common EGFR mutation-positive NSCLC. After failing 1L EGFR-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G EGFR-TKI after failing the first-line EGFR-TKI, the ORR and PFS for 3G EGFR-TKI were 80% and 8.9 months (95% CI: 8.0-9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8-39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression.

Jung|Hyun Ae|HA|0000-0002-1583-4142
Park|Sehhoon|S|
Sun|Jong-Mu|JM|
Lee|Se-Hoon|SH|
Ahn|Jin Seok|JS|
Ahn|Myung-Ju|MJ|
Park|Keunchil|K|0000-0002-4846-7449

uncommon EGFR mutation
EGFR-TKIs
progression-free survival
overall survival
T790M


Comparison of Efficiency of Video Endoscopy and Open Inguinal Lymph Node Dissection.

Abstract:
AIMS
To compare the efficiency and complications of video endoscopy, inguinal lymphadenectomy and open inguinal lymph node dissection.

PATIENTS AND METHODS
Nineteen video endoscopy inguinal lymphadenectomies were performed on 16 patients from September 2014 to December 2015, and 21 open inguinal lymph node dissections were performed on 18 patients from September 2013 to September 2014. Surgical time, operative blood loss, incidence of complications, length of stay, lymph node harvest and suture removal time were compared between the two groups.

RESULTS
Operative time (135.5±45.52 vs. 169.8±55.19 min), lymph node harvest (10.78±5.22 vs. 12.60±5.53), and hospital stay (10.43±2.53 vs. 12.50±4.98 days) did not statistically differ between the two groups (p>0.05). However, operative blood loss (22.50±14.24 vs. 68.44±42.19 ml), drainage tube removal time (7.23±1.79 vs. 11.44±2.69 days), incidence of complications (21.05% vs. 61.9%), and suture removal time (7.52±1.24 vs. 12.81±2.04 min) were significantly reduced in the video endoscopy surgery group compared with the open surgery group (p<0.05).

CONCLUSION
Compared with open surgery, video endoscopy surgery achieved the same efficiency, and had the advantage of reduction of complications, suture removal time and in-surgery blood loss.

Wang|Shuo|S| Du|Peng|P| Tang|Xingxing|X| An|Chao|C| Zhang|Ning|N| Yang|Yong|Y|

D000328:Adult
D000368:Aged
D003131:Combined Modality Therapy
D004724:Endoscopy
D006801:Humans
D007264:Inguinal Canal
D007902:Length of Stay
D008197:Lymph Node Excision
D008198:Lymph Nodes
D008297:Male
D008875:Middle Aged
D009367:Neoplasm Staging
D061646:Operative Time
D010412:Penile Neoplasms
D011182:Postoperative Care
D011183:Postoperative Complications
D012008:Recurrence
D016896:Treatment Outcome

video endoscopy inguinal lymphadenectomy


Polymorphisms of Ionotropic Glutamate Receptor-Related Genes and the Risk of Autism Spectrum Disorder in a Chinese Population.

Abstract:
OBJECTIVE
To evaluate the association of GRIK2 and NLGN1 with autism spectrum disorder in a Chinese population.

METHODS
We performed spatio-temporal expression analysis of GRIK2 and NLGN1 in the developing prefrontal cortex, and examined the expression of the genes in ASD cases and healthy controls using the GSE38322 data set. Following, we performed a case-control study in a Chinese population.

RESULTS
The analysis using the publicly available expression data showed that GRIK2 and NLGN1 may have a role in the development of human brain and contribute to the risk of ASD. Later genetic analysis in the Chinese population showed that the GRIK2 rs6922753 for the T allele, TC genotype and dominant model played a significant protective role in ASD susceptibility (respectively: OR=0.840, p=0.023; OR=0.802, p=0.038; OR=0.791, p=0.020). The NLGN1 rs9855544 for the G allele and GG genotype played a significant protective role in ASD susceptibility (respectively: OR=0.844, p=0.019; OR=0.717, p=0.022). After adjusting p values, the statistical significance was lost (p>0.05).

CONCLUSION
Our results suggested that GRIK2 rs6922753 and NLGN1 rs9855544 might not confer susceptibility to ASD in the Chinese population.

Xie|Xinyan|X| Hou|Fang|F| Li|Li|L| Chen|Yanlin|Y| Liu|Lingfei|L| Luo|Xiu|X| Gu|Huaiting|H| Li|Xin|X| Zhang|Jiajia|J| Gong|Jianhua|J| Song|Ranran|R|


The Role of Brain Methamidophos in Acephate Poisoning in Mice.

Abstract: We gave mice a 540 mg/kg dose of LD50 acephate, followed by an assessment of acephate, methamidophos (MP), and choline esterase (ChE) activity for up to 4 hours (hr) in order to investigate the time course of acephate intoxication. At 1 hr, the blood acephate and MP levels were 428 ± 90 µg/ml (mean ± SEM) and 4.2 ± 0.4 µg/ ml, respectively. The liver acephate levels were similar to those in the blood, but the liver MP levels were approximately 3.5 times that of the blood at 1 hr. The brain MP level tended to be higher than the blood MP at 1 hr. These levels decreased gradually over 4 hr, but the brain acephate and MP levels surpassed the blood levels significantly at 4 hr, and after 2 hr, respectively. Serum, liver, cerebrum, cerebellum, and brainstem cholinesterase activity (ChE) were inhibited at 1 hr, and remained inhibited in all but the cerebellum until the end of the experiment. The obtained data were applied to previously reported autopsy cases of acephate intake. Experimental data suggest that brain MP is involved in acute acephate-induced poisoning, even after a reduction in blood acephate. In autopsy cases with suspected acephate poisoning, the MP level in the brain should be considered in addition to the ChE activity to diagnose the cause of death.

Tanaka|Toshiko|T| Sato|Hiroaki|H| Yoshida|Kosho|K| Kasai|Kentaro|K|

methamidophos
intoxication
autopsy
acetylcholine esterase
organophosphate


Rapid and amplification-free detection of fish pathogens by utilizing a molecular beacon-based microfluidic system.

Abstract: Nervous necrosis virus (NNV) and iridovirus are highly infectious pathogens that can cause lethal diseases in various species of fish. These infectious diseases have no effective treatments and the mortality rate is over 80%, which could cause dramatic economic losses in the aquaculture industry. Conventional diagnostic methods of NNV or iridovirus infected fishes, such as virus culture, enzyme-linked immunosorbent assays and nucleic acid assays usually require time-consuming and complex procedures performed by specialized technicians with delicate laboratory facilities. Rapid, simple, accurate and on-site detection of NNV and iridovirus infections would enable timely preventive measures such as immediate sacrifice of infected fishes, and is therefore critically needed for the aquaculture industry. In this study, a microfluidic-based assay that employ magnetic beads conjugated with viral deoxyribonucleic acid (DNA) capturing probes and fluorescent DNA molecular beacons were developed to rapidly detect NNV and iridovirus. Importantly, this new assay was realized in an integrated microfluidic system with a custom-made control system. With this approach, direct and automated NNV and iridovirus detection from infected fishes can be achieved in less than 30 min. Therefore, this molecular-beacon based microfluidic system presents a potentially promising tool for rapid diagnosis of fish pathogens in the field in the future.

Su|Yi-Chih|YC| Wang|Chih-Hung|CH| Chang|Wen-Hsin|WH| Chen|Tzong-Yueh|TY| Lee|Gwo-Bin|GB|

D021141:Nucleic Acid Amplification Techniques

Microfluidics
Nervous necrosis virus
Iridovirus
Molecular beacon
Probe conjugated magnetic beads


Quantitative and functional alterations of 6-sulfo LacNac dendritic cells in multiple myeloma.

Abstract: Multiple myeloma (MM) results from expansion of abnormal plasma cells in the bone marrow (BM). Previous studies have shown that monocytes play a crucial role in MM pathophysiology. A 6-sulfo LacNAc-expressing population of dendritic cells (Slan-DCs) that overlaps with intermediate and non-classical monocytes in terms of phenotype has been described. Slan-DCs represent a circulating and tissue proinflammatory myeloid population which has been shown to play a role in different cancer contexts, and which exhibits a remarkable plasticity. Herein, we studied Slan-DCs from the BM and blood of MM patients. We performed quantitative and functional analyses of these cells from 54 patients with newly diagnosed, symptomatic MM, 21 patients with MGUS and 24 responding MM patients. We found that circulating Slan-DCs were significantly decreased in MM patients as compared to those of healthy donors or patients with MGUS, while CD14+CD16+ intermediate monocytes accumulate in the BM. Moreover, after activation with TLR7/8 ligand R848, IL-12-producing Slan-DCs from the BM or peripheral blood from MM patients were decreased as compared with healthy donors. We show that MM cell lines or MM cells isolated from patients at diagnosis were able to inhibit the production of IL-12 by Slan-DCs, as well as to shift the phenotype of Slan-DCs towards an intermediate monocyte-like phenotype. Finally, Slan-DCs that have been cultured with MM cells reduced their capacity to induce T cell proliferation and Th1 polarization. We conclude that Slan-DCs represent previously unrecognized players in MM development and may represent a therapeutic target.

dendritic cells
multiple myeloma
Slan-DC
Immunosurveillance
antitumor T cell
immunotherapy


The CHADS2 and CHA2DS2-VASc scores predict atrial fibrillation in dyslipidemic individuals: Role of incorporating low high-density lipoprotein cholesterol levels.

Abstract:
AIM
To investigate the value of CHADS2 and CHA2DS2-VASc scores in predicting atrial fibrillation (AF) among dyslipidemic individuals and assess the additional value of incorporating low levels of high-density lipoprotein cholesterol (HDL-C).

METHODS
This observational study included 1241 individuals attending a lipid clinic. Models including clinical and laboratory parameters were constructed to test the predictive value of CHADS2 and CHA2DS2-VASc scores as well as low HDL-C levels for incident AF. Low HDL-C levels were defined as <40 and <50mg/dL for male and female subjects, respectively.

RESULTS
After excluding 18 patients with AF at baseline, 1223 subjects were followed-up for a median period of 6years (IQR: 4-10), and 34 (2.8%) developed AF. Baseline CHADS2 (OR: 1.71; 95% CI: 1.28-2.29, p<0.001) and CHA2DS2-VASc scores (OR: 1.56; 95% CI: 1.26-1.92, p<0.001) as well as low HDL-C levels (OR: 3.79; 95% CI: 1.85-7.75, p<0.001) were significantly associated with new-onset AF. ROC curve analyses showed that both CHADS2 and CHA2DS2-VASc scores were significant predictors for new-onset AF (C-Statistic: CHADS2 0.679, p<0.001; CHA2DS2-VASc 0.698, p<0.001). Higher CHADS2 scores were associated with reduced event-free survival from AF (log-rank=10.62, p=0.001) with differences potentiated if stratified by CHA2DS2-VASc score (log-rank=22.29, p<0.001). After incorporating low HDL-C levels, both scores achieved slightly higher C-Statistic for AF prediction (0.690 and 0.707, respectively, p<0.001).

CONCLUSIONS
CHADS2 and CHA2DS2-VASc scores predict new AF in dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels were included.

Barkas|Fotios|F| Elisaf|Moses|M| Korantzopoulos|Panagiotis|P| Tsiara|Stavroula|S| Liberopoulos|Evangelos|E|

Atrial fibrillation
High-density lipoprotein
Cholesterol
CHA(2)DS(2)-VASc
CHADS(2)
Statin


Effectiveness of Argan Oil Consumption on Knee Osteoarthritis Symptoms: A Randomized Controlled Clinical Trial.

Abstract:
BACKGROUND
Knee osteoarthritis (KOA) is a common chronic degenerative disorder. It causes joint pain, walking difficulties and a decline in general physical function. Many pain drugs and treatment modalities can be prescribed for KOA. Among traditional medicines in Morocco, Argan oil has been used in the treatment of knee osteoarthritis to reduce pain and improve physical activity, though there have been no medical-based evidence for such treatment. Argan oil is known to have anti-oxidant and lipid modulatory properties due to its content of many substances, such as tocopherols, phytosterols, saturated and unsaturated fatty acids.

OBJECTIVES
This study was undertaken in order to investigate the effect of daily consumption of culinary argan oil on KOA symptoms.

PATIENTS AND METHODS
We conducted a randomized controlled clinical trial on patients with KOA according to the American College of Rheumatology (ACR) criteria. Patients were divided into 2 groups: argan oil group who received argan oil to be consumed every morning (30 ml per day) for 8 weeks and control group with no treatment. Clinical assessment before and after 8 weeks study was performed by several tests such as the Visual Analogue Scale (VAS) for pain, walking perimeter, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and the Lequesne index.

RESULTS
The study included 100 patients. 51 patients were randomly assigned to argan oilgroup while 49 patients were randomly assigned to control group with no treatment. Mean age of our patients was 58.24 ± 7.2 years, with a majority of women (93%). Following 8 weeks of argan oil consumption, argan oil group had a very significant decrease of VAS for pain (p< 0.0001), with a significant decrease in WOMAC pain index (p < 0.0001), and improvement of WOMAC function index (p < 0.0001). Lequesne index (p < 0.0001) as well as walking distance (p =0,002) significantly improved. When data of argan oil group were compared to those of control group, we found statistically significant differences in all the above measured parameters: VAS of pain (P=0,02), WOMAC pain (p<0,0001), WOMAC function (p<0,0001), walking distance (p=0,001) and lequesne index (p<0,0001).

CONCLUSION
Patient's consumption of argan oil seems to be safe and efficacious in improving clinical symptoms of KOA.

Essouiri|Jamila|J|
Harzy|Taoufik|T|
Benaicha|Nadia|N|
Errasfa|Mourad|M|
Abourazzak|Fatima Ezzahra|FE|

Argan oil
knee osteoarthritis
pain
function
visual analogue scale
Knee OA symptoms


Autonomy and Enhancement.

Abstract: Some have objected to human enhancement on the grounds that it violates the autonomy of the enhanced. These objections, however, overlook the interesting possibility that autonomy itself could be enhanced. How, exactly, to enhance autonomy is a difficult problem due to the numerous and diverse accounts of autonomy in the literature. Existing accounts of autonomy enhancement rely on narrow and controversial conceptions of autonomy. However, we identify one feature of autonomy common to many mainstream accounts: reasoning ability. Autonomy can then be enhanced by improving people's reasoning ability, in particular through cognitive enhancement; given how valuable autonomy is usually taken to be, this gives us extra reason to pursue such cognitive enhancements. Moreover, autonomy-based objections will be especially weak against such enhancements. As we will argue, those who are worried that enhancements will inhibit people's autonomy should actually embrace those enhancements that will improve autonomy.

Schaefer|G Owen|GO|
Kahane|Guy|G|
Savulescu|Julian|J|

Autonomy Enhancement Reasoning Cognition


Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb Ischemia.

Abstract:
BACKGROUND/AIMS
In clinical settings, the pulsatility index (PI) has become a widely used tool for monitoring obstetrics or other vascular diseases. It is based on the maximum Doppler shift waveform derived from ultrasonography. However, it remains unclear whether the PI levels are correctly predicted from the perfusion in mouse model of hindlimb ischemia.

METHODS
To explore the relationship between PI and perfusion, we generated a unilateral hindlimb ischemia model in 8-week-old C57BL/6 male mice by ligation of the right common iliac artery and femoral artery. These mice were monitored with laser Doppler perfusion imaging (LDPI) and an ultrasound system (Vevo2100). Vessel densities in ischemic skeletal muscles were measured with vWF staining, which functions as a marker for endothelial cells. In order to further verify PI evaluation in other conditions, we performed therapeutic experiments using hindlimb ischemic mouse with PBS or FGF2 treatment.

RESULTS
In the mouse model of hindlimb ischemia, the PI levels were continuously elevated and were accompanied by an increased ratio of perfusion to blood flow. 1 and 4 weeks after ischemia, the densities of vWF staining were correlated with PI values. Moreover, the PI index exactly reflected the perfusion in hindlimb ischemic mice after FGF2 treatment, while it indicated the condition of angiogenesis after therapeutic treatment based on the association between PI values and the number of vWF-positive stained cells in muscles.

CONCLUSION
This study confirms the utility of a noninvasive and reproducible ultrasound index for a rapid evaluation of perfusion and blood recovery after hindlimb ischemia in vivo. PI, as one stable and comparable parameter, is correlated with angiogenesis in hindlimb ischemic mouse. Moreover, PI can exactly reflect perfusion and angiogenesis in therapeutic hindlimb ischemic mouse models. This study suggested that PI can serve as a novel index for relatively reproducible and repeatable blood flow recovery in the evaluation of emerging ischemic therapies and disease development in mouse models of hindlimb ischemia.

Xu|Hairong|H| Lu|Shan|S| Ding|Lexi|L| Lyu|Liangkun|L| Ma|Zejun|Z| Lu|Qiulun|Q|

Pulsatility index
Perfusion
Hindlimb ischemia
Blood flow


Ridge Preservation After Tooth Extraction With Buccal Bone Plate Deficiency Using Tunnel Structured β-Tricalcium Phosphate Blocks: A 2-Month Histologic Pilot Study in Beagle Dogs.

Abstract:
BACKGROUND
Reduction in alveolar ridge volume is a direct consequence of tooth extraction. Tunnel β-tricalcium phosphate (β-TCP) blocks were manufactured from randomly organized tunnel-shaped β-TCP ceramic. Efficacy of these blocks compared to extraction alone for alveolar ridge preservation after tooth extraction with buccal bone deficiency was evaluated.

METHODS
Maxillary first premolars of six beagle dogs were extracted after removing the buccal bone, and bone defects of 4 × 4 × 5 mm (mesio-distal width × bucco-palatal width × depth) were created. Fresh extraction sockets with buccal bone defects were filled with tunnel β-TCP blocks at test sites. Two months after the operation, histologic and histometric evaluations were performed.

RESULTS
Regarding histologic sections, coronal and middle horizontal widths of the alveolar ridge were significantly greater at test sites (3.2 ± 0.5 and 3.6 ± 0.4 mm, respectively) than at control sites (1.2 ± 0.3 and 2.0 ± 0.6 mm, respectively). The amount of woven bone was significantly greater at test sites (62.4% ± 7.9%) than at control sites (26.8% ± 5.3%), although that of connective tissue and bone marrow was significantly greater at control sites (38.1% ± 6.2% and 16.0% ± 6.9%, respectively) than at test sites (10.7% ± 5.7% and 4.1% ± 2.2%, respectively). Regarding basic multicellular units, no statistically significant difference was found between the test and control sites (0.5% ± 0.1% and 0.6% ± 0.1%, respectively).

CONCLUSION
Tunnel β-TCP blocks represent an effective bone-graft material for alveolar ridge preservation in fresh extraction sockets with buccal bone defects.

Ikawa|Takahiro|T|
Akizuki|Tatsuya|T|
Matsuura|Takanori|T|
Hoshi|Shu|S|
Ammar|Shujaa Addin|SA|
Kinoshita|Atsuhiro|A|
Oda|Shigeru|S|
Izumi|Yuichi|Y|

D000539:Alveolar Process
D000818:Animals
D001860:Bone Plates
D004285:Dogs
D010865:Pilot Projects
D014081:Tooth Extraction
D020390:Tooth Socket

tooth extraction
dogs
Alveolar ridge augmentation
beta-tricalcium phosphate
biocompatible materials
osteogenesis


Crocin Promotes Apoptosis in Human EBV-Transformed B-Lymphocyte via Intrinsic Pathway.

Abstract:
Background
As a major carotenoid in saffron, crocin demonstrates potent anti-cancer impacts. However, its anti-lymphoma effects remain vague, especially in the human EBV-associated B-cell lymphoproliferative disorders. This study examined crocin's apoptogenic potential and its underlying mechanism in CO 88BV59-1 cell line vs. normal human peripheral blood B cells.

Methods
CO 88BV59-1 cells were treated with crocin alone or in combination with vincristine for up to 72 h. The cell viability was examined using a resazurin assay. Flow cytometry using annexin V and propidium iodide labeling was performed to detect apoptotic cells. Also, the expression levels of genes and proteins involved in apoptosis (CASP3, CASP8, CASP9, P53, Bax, and Bcl-2) were respectively determined via real-time PCR and Western blot analysis.

Results
Crocin concentration-dependently reduced cell viability in CO 88BV59-1 cells with no significant toxicity toward normal B cells. Similar to vincristine, crocin significantly increased apoptosis in these cells during 72 h of incubation. Furthermore, the combination of crocin (80 μM) and vincristine (1 μM) enhanced apoptosis in CO 88BV59-1 cells. Therefore, this synergistic effect was detected in human EBV-transformed B-lymphocyte. CASP3, CASP9, P53, and Bax/Bcl-2 ratio expressions were significantly raised in CO 88BV59-1 cells, whereas CASP8 was unaltered. It was proposed that crocin promoted apoptosis in CO 88BV59-1 cells in a time- and concentration-dependent manner via the induction of the intrinsic pathway.

Conclusion
The results suggest that crocin may serve as a good alternative/coadjuvant to vincristine in EBV-associated B-cell lymphoproliferative disorders.

Jahromi|Abdolreza Sotoodeh|AS|
Kargar|Mohammad|M|
Kafilzadeh|Farshid|F|
Jamalidoust|Marzieh|M|
Moradzadeh|Maliheh|M|


Audiovisual infotainment in European news: A comparative content analysis of Dutch, Spanish, and Irish television news programs.

Abstract: This study investigates to what extent audiovisual infotainment features can be found in the narrative structure of television news in three European countries. Content analysis included a sample of 639 news reports aired in the first 3 weeks of September 2013, in six prime-time TV news broadcasts of Ireland, Spain, and the Netherlands. It was found that Spain and Ireland included more technical features of infotainment in television news compared to the Netherlands. Also, the use of infotainment techniques is more often present in commercial, than in public broadcasting. Finally, the findings indicate no clear pattern of the use of infotainment techniques across news topics as coded in this study.

Audiovisual infotainment
content analysis
television news
Europe


A membrane protein display platform for receptor interactome discovery.

Abstract: Cell surface receptors are critical for cell signaling and constitute a quarter of all human genes. Despite their importance and abundance, receptor interaction networks remain understudied because of difficulties associated with maintaining membrane proteins in their native conformation and their typically weak interactions. To overcome these challenges, we developed an extracellular vesicle-based method for membrane protein display that enables purification-free and high-throughput detection of receptor-ligand interactions in membranes. We demonstrate that this platform is broadly applicable to a variety of membrane proteins, enabling enhanced detection of extracellular interactions over a wide range of binding affinities. We were able to recapitulate and expand the interactome for prominent members of the B7 family of immunoregulatory proteins such as PD-L1/CD274 and B7-H3/CD276. Moreover, when applied to the orphan cancer-associated fibroblast protein, LRRC15, we identified a membrane-dependent interaction with the tumor stroma marker TEM1/CD248. Furthermore, this platform enabled profiling of cellular receptors for target-expressing as well as endogenous extracellular vesicles. Overall, this study presents a sensitive and easy to use screening platform that bypasses membrane protein purification and enables characterization of interactomes for any cell surface-expressed target of interest in its native state.

Cao|Shengya|S|0000-0002-4717-4927
Peterson|Sean M|SM|
Müller|Sören|S|
Reichelt|Mike|M|
McRoberts Amador|Christian|C|
Martinez-Martin|Nadia|N|

D054730:Protein Interaction Domains and Motifs

membrane protein
extracellular vesicle
high-throughput screening
receptor–ligand interaction


Intake patterns and dietary associations of soya protein consumption in adults and children in the Canadian Community Health Survey, Cycle 2.2.

Abstract: Soya foods are one of the recommended alternatives to meat in many dietary guidelines. While this is expected to increase the intake of some nutrients, potential concerns regarding others have been raised. The purpose of the present study was to examine the prevalence and the association of soya food consumption with nutrient intakes and dietary patterns of Canadians (age ≥ 2 years). Cross-sectional data from the 2004 Canadian Community Health Survey (Cycle 2.2; n 33,218) were used to classify soya consumers and non-consumers. Soya consumers were further divided into two groups based on their soya protein intake. Sample weights were applied and logistic regression analysis was used to explore the association between nutrient intakes and soya consumption, with cultural background, sex, age and economic status being included as covariates. On any given day, 3.3% (n 1085) of Canadians consume soya foods, with females, Asian Canadians and adults with post-secondary education being more likely to be soya consumers. As a whole, adolescent and adult respondents who had consumed at least one soya food during their 24 h dietary recall had higher energy intakes, as well as increased intakes of nutrients such as protein, fibre, vitamin C, vitamin B6, naturally occurring folate, thiamin, Ca, P, Mg, PUFA, Fe and K and lowered intakes of saturated fat. These data indicate that soya food consumption is associated with improved diet quality of Canadians. However, future research is necessary to investigate the association between increased energy intake and soya consumption.

Mudryj|Adriana N|AN|
Aukema|Harold M|HM|
Yu|Nancy|N|

Soya protein
Canadian Community Health Survey
Health surveys
Dietary intakes


Multivariate representation of food preferences in the human brain.

Abstract: One major goal in decision neuroscience is to investigate the neuronal mechanisms being responsible for the computation of product preferences. The aim of the present fMRI study was to investigate whether similar patterns of brain activity, reflecting category dependent and category independent preference signals, can be observed in case of different food product categories (i.e. chocolate bars and salty snacks). To that end we used a multivariate searchlight approach in which a linear support vector machine (l-SVM) was trained to distinguish preferred from non-preferred chocolate bars and subsequently tested its predictive power in case of chocolate bars (within category prediction) and salty snacks (across category prediction). Preferences were measured by a binary forced choice decision paradigm before the fMRI task. In the scanner, subjects saw only one product per trial which they had to rate after presentation. Consistent with previous multi voxel pattern analysis (MVPA) studies, we found category dependent preference signals in the ventral parts of medial prefrontal cortex (mPFC), but also in dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC). Category independent preference signals were observed in the dorsal parts of mPFC, dACC, and dlPFC. While the first two results have also been reported in a closely related study, the activation in dlPFC is new in this context. We propose that the dlPFC activity does not reflect the products' value computation per se, but rather a modulatory signal which is computed in anticipation of the forthcoming product rating after stimulus presentation. Furthermore we postulate that this kind of dlPFC activation emerges only if the anticipated choices fall into the domain of primary rewards, such as foods. Thus, in contrast to previous studies which investigated preference decoding for stimuli from utterly different categories, the present study revealed some food domain specific aspects of preference processing in the human brain.

Pogoda|Luca|L| Holzer|Matthias|M| Mormann|Florian|F| Weber|Bernd|B|

Food preferences
Multi voxel pattern analysis
Medial prefrontal cortex
Dorsolateral prefrontal cortex
Decision making


Neonatal short-term outcomes of gestational diabetes mellitus in saudi mothers: a retrospective cohort study.

Abstract:
BACKGROUND
Gestational diabetes mellitus (GDM) affects up to 10% of all pregnancies and results in significant maternal and neonatal morbidities.

OBJECTIVES
Our main objective was to investigate retrospectively the rate of neonatal intensive care unit (NICU) admissions and significant neonatal complications in pregnant mothers with gestational diabetes.

MATERIALS AND METHODS
A retrospective cohort study was conducted. The medical records of King Khalid University Hospital (KKUH) were reviewed from January till December 2007. All pregnant women with GDM along with their offsprings were included and matched with healthy pregnant women. The primary outcome was the rate of NICU admission, hypoglycemia, birth weight and length of hospital stay.

RESULTS
A total of 766 mothers (419 GDM mothers and 347 controls) with their term babies were included. Infants born to GDM mothers had significantly higher risk of NICU admissions [OR 2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and macrosomia; however, the difference did not reach statistical significance.

CONCLUSION
GDM remains a significant morbidity to newborns resulting in increased intensive care admission, prolongation of hospital stay and higher rates of neonatal hypoglycemia. More efforts to assure early recognition and strict sugar control during pregnancy are still needed.

Al-Khalifah|R|R|
Al-Subaihin|A|A|
Al-Kharfi|T|T|
Al-Alaiyan|S|S|
Alfaleh|Khalid M|KM|

Gestational diabetes mellitus
neonatal intensive care unit
hypoglycemia
macrosomia
large for gestational age


Kallikrein augments the anticoagulant function of the protein C system in thrombin generation.

Abstract:
BACKGROUND
Genetics play a significant role in coagulation phenotype and venous thromboembolism risk. Resistance to the anticoagulant activated protein C (APC) is an established risk for thrombosis. Herein, we explored the genetic determinants of thrombin generation (TG) and thrombomodulin (TM)-modulated TG using plasma from the Human Functional Genomics Project.

METHODS
Calibrated TG was measured both in absence and presence of TM using tissue factor as trigger. Genetic determinants of TG parameters and protein C pathway function were assessed using genome-wide single-nucleotide polymorphism (SNP) genotyping. Plasma samples were supplemented with purified apolipoprotein A-IV, prekallikrein, or kallikrein to test their influence on the anticoagulant function of TM and APC in TG.

RESULTS
Thrombin generation data from 392 individuals were analyzed. Genotyping showed that the KLKB1 gene (top SNP: rs4241819) on chromosome 4 was associated with the normalized sensitivity ratio of endogenous thrombin potential to TM at genome-wide level (nETP-TMsr, P = 4.27 × 10-8 ). In vitro supplementation of kallikrein, but not prekallikrein or apolipoprotein A-IV, into plasma dose-dependently augmented the anticoagulant effect of TM and APC in TG. Variations of rs4241819 was not associated with the plasma concentration of prekallikrein. Association between rs4241819 and nETP-TMsr was absent when TG was measured in presence of a contact pathway inhibitor corn trypsin inhibitor.

CONCLUSIONS
Our results suggest that kallikrein plays a role in the regulation of the anticoagulant protein C pathway in TG, which may provide a novel mechanism for the previously observed association between the KLKB1 gene and venous thrombosis.

kallikrein
protein C
thrombin
thrombosis
genetic association


Acanthamoeba Infection in a Drowning Child.

Abstract:
BACKGROUND
Acanthamoeba infection is a potential life-threatening complication of drowning. The management of drowning-associated Acanthamoeba infection remains controversial. Survival reports on Acanthamoeba infection have been on case reports only.

CASE DETAILS
A 2-year-old, previously healthy Indonesian boy presented with decreased consciousness and inadequate breathing, followingdrowning. The event was unsupervised with unknown estimated time of submersion. Resuscitation was commenced and mechanical ventilated was applied. Sputum specimen revealed alive Acanthamoeba with pseudopods and cysts. Sputum culture resulted in Pseudomonas aeruginosa and cerebrospinal fluid was supportive for Acanthamoeba with 1-3 trophozoites and cyst. Imaging of the head showed cerebral edema and encephalitis. The patient received intravenous ceftazidime, metronidazole, fluconazole and rifampicin. The patient's consciousness was unsatisfactory regained resulting in an altered mental status.

CONCLUSION
No treatment so far has given a succesful outcome for Acanthamoeba. In this case, management with metronidazole, rifampicin and fluconazole showed regain of consciousness resulting in altered mental status.

Gunawan|Prastiya Indra|PI|
Idarto|Areta|A|
Saharso|Darto|D|


Spherically Restricted Random Hyperbolic Diffusion.

Abstract: This paper investigates solutions of hyperbolic diffusion equations in R 3 with random initial conditions. The solutions are given as spatial-temporal random fields. Their restrictions to the unit sphere S 2 are studied. All assumptions are formulated in terms of the angular power spectrum or the spectral measure of the random initial conditions. Approximations to the exact solutions are given. Upper bounds for the mean-square convergence rates of the approximation fields are obtained. The smoothness properties of the exact solution and its approximation are also investigated. It is demonstrated that the Hölder-type continuity of the solution depends on the decay of the angular power spectrum. Conditions on the spectral measure of initial conditions that guarantee short- or long-range dependence of the solutions are given. Numerical studies are presented to verify the theoretical findings.

stochastic partial differential equations


Scope definition and resection significance of No. 12a group lymph nodes in gastric cancer.

Abstract: A discrepancy exists between the 7th edition guidelines of the American Joint Committee on Cancer (AJCC) and the 3rd edition Japanese treatment guidelines in terms of the classification of No. 12a lymph nodes as regional or distant lymph nodes in D2 lymphadenectomy for gastric cancer. The scope definition of No. 12a lymph nodes has yet to be fully elucidated. The present study aimed to assess the appropriateness of reclassifying No. 12a lymph node metastasis as distant metastasis according to the survival rate outcome, and to provide a clear and practical definition of the No. 12a group lymph nodes of gastric cancer. A retrospective analysis was performed on patients with gastric cancer who underwent standard or greater lymphadenectomy between January 2000 and December 2009 to find an association between No. 12a node metastasis and survival outcome. The present study first presented a clear and practical scope definition of the No. 12a group lymph nodes of gastric cancer, according to our clinical experiences and practices (Table I and Fig. 1). The survival outcome of patients with gastric cancer and No. 12a lymph node metastasis was poorer compared with that of patients with no No. 12a lymph node metastasis (P=0.0003). The results were similar in stage III patients with gastric cancer (P<0.0001). However, the survival outcome of patients was similar with or without No. 12a lymph node metastasis in stage IV gastric cancer (P=0.1968). Cox regression analysis revealed that the AJCC stage was independently associated with an unfavorable cumulative survival rate. Logistic regression analysis revealed that tumor location, AJCC stage, intravascular cancer emboli and nerve invasion were associated with No. 12a lymph node metastasis. In conclusion, the data in the present study suggested that No. 12a lymph node metastasis is associated with distant metastasis, and therefore they concur with the 7th edition AJCC gastric cancer guidelines, which appear to be correct in terms of considering No. 12a lymph node metastasis as distant metastasis.

Huang|Yongjian|Y| Zhu|Guangwei|G| Zheng|Wei|W| Hua|Jin|J| Yang|Shugang|S| Zhuang|Jinfu|J| Wang|Jinzhou|J| Ye|Jianxin|J|

gastric cancer
No. 12a lymph nodes
lymphadenectomy
metastasis


Factors associated with attitudes toward the elderly in a sample of elderly caregivers.

Abstract:
BACKGROUND
The number of elderly caregivers is increasing in the world. It is important to know the attitudes toward the elderly, because they can influence a range of behaviors. Our aim was to determine factors associated with attitudes toward the elderly in a sample of older carers.

METHODS
Three hundred and thirteen elderly caregivers (75.4% women, mean age 69.7 ± 7.1) who cared for a dependent older person at home completed a cross-sectional household interview. In addition to the four domains of the Neri Scale to Assess Attitudes Toward the Elderly, participants were evaluated regarding the demographics, care recipient (CR) characteristics, functional and cognitive status, general health, life satisfaction, perceived stress, and depressive symptoms.

RESULTS
Overall, attitudes toward the elderly were neutral in this sample. More negative attitudes in some Neri Scale domains were associated with being older, living in an urban setting, taking more medications per day, caring for an elderly dependent in basic Activities of Daily Living (ADLs), being "more or less" satisfied with life, and having higher levels of perceived stress. There was a negative association between positive attitudes and educational level.

CONCLUSIONS
The results highlight the need for public policies to promote more positive attitudes toward aging and change negative stereotypes usually used to designate older people. These public policies can try to modify some predictors of negative attitudes, such as perceived stress, which was associated with all four domains of Neri Scale.

Luchesi|Bruna Moretti|BM|
Alexandre|Tiago da Silva|TD|
de Oliveira|Nathalia Alves|NA|
Brigola|Allan Gustavo|AG|
Kusumota|Luciana|L|
Pavarini|Sofia Cristina Iost|SC|
Marques|Sueli|S|

carers
aged care
attitudes to aging
psychological well-being


Impact of the 2003 to 2018 Population Salt Intake Reduction Program in England: A Modeling Study.

Abstract: [Figure: see text].

Alonso|Sergi|S|
Tan|Monique|M|
Wang|Changqiong|C|
Kent|Seamus|S|
Cobiac|Linda|L|
MacGregor|Graham A|GA|
He|Feng J|FJ|
Mihaylova|Borislava|B|

United Kingdom
cardiovascular disease
diet
health care cost
incidence
ischemic heart disease
salt reduction
stroke


Unconsciously elicited perceptual prior.

Abstract: Increasing evidence over the past decade suggests that vision is not simply a passive, feed-forward process in which cortical areas relay progressively more abstract information to those higher up in the visual hierarchy, but rather an inferential process with top-down processes actively guiding and shaping perception. However, one major question that persists is whether such processes can be influenced by unconsciously perceived stimuli. Recent psychophysics and neuroimaging studies have revealed that while consciously perceived stimuli elicit stronger responses in higher visual and frontoparietal areas than those that fail to reach conscious awareness, the latter can still drive high-level brain and behavioral responses. We investigated whether unconscious processing of a masked natural image could facilitate subsequent conscious recognition of its degraded counterpart (a black-and-white "Mooney" image) presented many seconds later. We found that this is indeed the case, suggesting that conscious vision may be influenced by priors established by unconscious processing of a fleeting image.

Chang|Raymond|R|
Baria|Alexis T|AT|
Flounders|Matthew W|MW|
He|Biyu J|BJ|

perceptual prior
unconscious processing
Mooney images
perceptual insight
visual masking


Division rate, cell size and proteome allocation: impact on gene expression noise and implications for the dynamics of genetic circuits.

Abstract: The cell division rate, size and gene expression programmes change in response to external conditions. These global changes impact on average concentrations of biomolecule and their variability or noise. Gene expression is inherently stochastic, and noise levels of individual proteins depend on synthesis and degradation rates as well as on cell-cycle dynamics. We have modelled stochastic gene expression inside growing and dividing cells to study the effect of division rates on noise in mRNA and protein expression. We use assumptions and parameters relevant to Escherichia coli, for which abundant quantitative data are available. We find that coupling of transcription, but not translation rates to the rate of cell division can result in protein concentration and noise homeostasis across conditions. Interestingly, we find that the increased cell size at fast division rates, observed in E. coli and other unicellular organisms, buffers noise levels even for proteins with decreased expression at faster growth. We then investigate the functional importance of these regulations using gene regulatory networks that exhibit bi-stability and oscillations. We find that network topology affects robustness to changes in division rate in complex and unexpected ways. In particular, a simple model of persistence, based on global physiological feedback, predicts increased proportion of persister cells at slow division rates. Altogether, our study reveals how cell size regulation in response to cell division rate could help controlling gene expression noise. It also highlights that understanding circuits' robustness across growth conditions is key for the effective design of synthetic biological systems.

stochastic gene expression
E. coli
agent-based modelling
bistable switches
genetic oscillators
growth rate


Probing phosphoethanolamine-containing lipids in membranes with duramycin/cinnamycin and aegerolysin proteins.

Abstract: In this mini-review, we summarize current knowledge about the lipid-binding characteristics of two types of toxins used to visualize the membrane distribution of phosphoethanolamine-containing lipid species: the glycerophospholipid, phosphatidylethanolamine (PE) and the sphingolipid, ceramide phosphoethanolamine (CPE). The lantibiotic cinnamycin and the structurally-related peptide duramycin produced by some Gram-positive bacteria were among the first toxins characterized by their specificity for PE which is widely present in animal kingdoms from bacteria to mammals. These toxins promoted their binding to PE-containing membranes by changing membrane curvature and by inducing transbilayer lipid movement. The recognition of the conical shape and negative curvature adopted by the PE species within the membrane, is important to understand how lipid-peptide interaction can occur. Three mushroom-derived proteins belonging to the aegerolysin family, pleurotolysin A2, ostreolysin and erylysin A were recently described as efficient tools to visualize the membrane distribution of CPE which is found in trace amounts in mammalian cells but in higher amounts in some developmental stages of lower eukaryotes like Trypanosoma and in invertebrates such as Drosophila. The recent development of lantibiotic-based PE-specific and aegerolysin-based CPE-specific probes is useful to visualize and specify the role of these lipids in various pathophysiological events such as cell division, apoptosis, tumor vasculature and parasite developmental stages.

Hullin-Matsuda|Françoise|F| Makino|Asami|A| Murate|Motohide|M| Kobayashi|Toshihide|T|

Phosphatidylethanolamine
Ceramide phosphoethanolamine
Lantibiotics
Pleurotolysin A2
Ostreolysin
Erylysin


Rapidly identifying bioactive compounds from Zhisou oral liquid by immobilized receptor-based high-performance affinity chromatography.

Abstract: The identification of bioactive compounds in complex matrices remains a major challenge due to the lack of highly efficient and specific methods. This work developed an approach based on high-performance affinity chromatography to identify the potential antitussive compounds from Zhisou oral liquid . The main methods include the synthesis of immobilized beta2-adrenoceptor by a one-step method, the screening and identification of the potential bioactive compounds by the receptor column coupled with mass spectrometry, and the binding mechanism analysis of the compounds to the receptor by the in vivo experiment, injection amount dependent method and molecular simulation. We identified the potential bioactive compounds of Zhisou oral liquid as glycyrrhizic acid, platycodin D, tuberostemonine, and hesperidin. In vivo experiment showed that the combinational utilization of the four compounds was possible to present an equivalent antitussive effect to the formula. The docking results demonstrated that hydrogen bonds and Van der Waals forces were the main forces to drive the binding of the four compounds to beta2-adrenoceptor. We concluded that the four compounds are the effective components in Zhisou oral liquid. The proposed strategy is possible to provide an alternative for the development of highly efficient methods to pursue the bioactive compounds of complex matrices.

bioactive compounds
Zhisou oral liquid
immobilized beta2-adrenoceptor
rapid identification
traditional Chinese medicine


Molecular Correlates of Long Survival in IDH-Wildtype Glioblastoma Cohorts.

Abstract: IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or undersampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a "molecular grade IV" astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.

Galbraith|Kristyn|K|
Kumar|Ashwani|A|
Abdullah|Kalil G|KG|
Walker|Jamie M|JM|
Adams|Steven H|SH|
Prior|Timothy|T|
Dimentberg|Ryan|R|
Henderson|Fraser C|FC|
Mirchia|Kanish|K|
Sathe|Adwait Amod|AA|
Viapiano|Mariano S|MS|
Chin|Lawrence S|LS|
Corona|Robert J|RJ|
Hatanpaa|Kimmo J|KJ|
Snuderl|Matija|M|
Xing|Chao|C|
Brem|Steven|S|
Richardson|Timothy E|TE|

Long survival
Glioblastoma
Astrocytoma
GBM
IDH1/2
Prognosis
TCGA


A local safety standard for invasive procedures for out-patient endonasal procedures performed under local anaesthetic: a template from Newcastle upon Tyne hospitals.

Abstract:
BACKGROUND
In November 2017, a working feasibility analysis commenced of a local anaesthetic endonasal procedures out-patient clinic service at Freeman Hospital, Newcastle upon Tyne. Fundamental to introducing an innovative ambulatory out-patient practice is the development of a novel local safety standard for invasive procedures to support this service.

OBJECTIVE
This paper presents the new safety standard developed for this purpose and implemented in our institution.

CONCLUSION
Increasingly, there is a shift toward ambulatory services, directed by patient choice, technological advances and the opportunity for cost savings. It is hoped that this local safety standard for invasive procedures will provide a useful template for those considering implementing ambulatory endonasal services, or other novel procedures, within the specialty of ENT.

Local
Ambulatory Surgical Procedures
Anesthetics
Checklist
Clinical Governance
Endoscopy
Nasal Polyps
Nose


How has urinary proteomics contributed to the discovery of early biomarkers of acute kidney injury?

Abstract: In the past decade, analysis of the urinary proteome (urinary proteomics) has intensified in response to the need for novel biomarkers that support early diagnosis of kidney diseases. In particular, this also applies to acute kidney injury, which is a heterogeneous complex syndrome with a still-increasing incidence at the intensive care unit. Unfortunately, this major need remains largely unmet to date. The current report aims to explain why attempts to implement urinary proteomic-discovered acute kidney injury diagnostic candidates in the intensive care unit setting have not yet led to success. Subsequently, some key notes are provided that should enhance the chance of translating selected urinary proteomic candidates to valuable tools for the nephrologist and intensivist in the near future.

De Loor|Jorien|J|
Gevaert|Kris|K|
Hoste|Eric|E|
Meyer|Evelyne|E|

urinary proteomics
acute kidney injury
intensive care unit
animal model
diagnostic biomarker
early detection


Basics of cytology.

Abstract: This overview is intended to give a general outline about the basics of Cytopathology. This is a field that is gaining tremendous momentum all over the world due to its speed, accuracy and cost effectiveness. This review will include a brief description about the history of cytology from its inception followed by recent developments. Discussion about the different types of specimens, whether exfoliative or aspiration will be presented with explanation of its rule as a screening and diagnostic test. A brief description of the indications, utilization, sensitivity, specificity, cost effectiveness, speed and accuracy will be carried out. The role that cytopathology plays in early detection of cancer will be emphasized. The ability to provide all types of ancillary studies necessary to make specific diagnosis that will dictate treatment protocols will be demonstrated. A brief description of the general rules of cytomorphology differentiating benign from malignant will be presented. Emphasis on communication between clinicians and pathologist will be underscored. The limitations and potential problems in the form of false positive and false negative will be briefly discussed. Few representative examples will be shown. A brief description of the different techniques in performing fine needle aspirations will be presented. General recommendation for the safest methods and hints to enhance the sensitivity of different sample procurement will be given. It is hoped that this review will benefit all practicing clinicians that may face certain diagnostic challenges requiring the use of cytological material.


Acidaminococcus provencensis sp. nov., a new bacterium isolated from a fresh human stool specimen.

Abstract: Acidaminococcus provencensis strain Marseille-P4266T (= CSURP4266T) is a new species isolated from a fresh human stool specimen.

Takakura|T|T|
Anani|H|H|
Fadlane|A|A|
Fontanini|A|A|
Raoult|D|D|
Bou Khalil|J Y|JY|

Acidaminococcus provencensis
Stool
New species
Culturomics
Microbiota
TM4000
Taxonogenomics


First description of HTLV-1/2 seroprevalence in HIV-infected inmates in Mozambique.

Abstract: No study has yet been conducted to estimate the burden of co-infection of HIV and HTLV-1/2 in inmates in sub-Saharan Africa. To investigate prevalence of co-infection in inmates in Mozambique, a total of 2140 inmates were screened for HIV, of which 515 were HIV seropositive. All HIV seropositive inmates were further screened for HTLV infection, and eight (1.55%) were co-infected. Co-infection was higher in females (3.45% [2/58; CI: 0.42-11.91]) as compared to males (1.35% [6/445; CI: 0.55-3.06]). Early screening of HTLV in prisons is urgently needed in Mozambique in order to improve the care provided to incarcerated individuals, including initiation of ART.

Augusto|Ângelo|Â|0000-0001-9017-2065
Augusto|Orvalho|O|
Taquimo|Atija|A|
Nhachigule|Carina|C|
Siyawadya|Narcisa|N|
Tembe|Nelson|N|
Bhatt|Nilesh|N|
Mbofana|Francisco|F|
Gudo|Eduardo Samo|ES|

HTLV-1/2
inmates
mozambique
HIV
Sub Saharan Africa


Submandibular gland preservation during concurrent neck dissection and transoral surgery for oropharyngeal squamous cell carcinoma.

Abstract:
OBJECTIVES
Analyze the effect of ipsilateral submandibular gland preservation on patients undergoing concurrent neck dissection and transoral surgery for oropharyngeal squamous cell carcinoma. Evaluate for (1) intraoperative and postoperative communications between the oropharynx and neck and (2) oncologic outcomes.

STUDY DESIGN
Retrospective chart review of prospectively collected data.

SETTING
Tertiary academic referral center.

METHODS AND SUBJECTS
Retrospective chart review of patients undergoing transoral laser resection of oropharyngeal squamous cell carcinoma with simultaneous neck dissection(s) for primary, persistent, recurrent, and second primary disease between January 1999 and February 2013. Data analyzed for operative technique, pathologic diagnosis, postoperative course, complications, and oncologic outcomes.

RESULTS
Overall 253 patients were identified. Of these, 96 patients underwent ipsilateral submandibular gland preservation and 157 underwent ipsilateral submandibular gland removal at the time of neck dissection. The prevalence of intraoperative communication between the neck and oropharynx was significantly lower in cases with submandibular gland preservation (2/96, 2.08%) compared to those with submandibular gland removal (22/157, 14.13%). No postoperative leaks occurred in the gland preservation group (0/96, 0%) compared to a leak prevalence of 8.92% (14/157) when the gland was removed (P = .0041). There was no difference in local, regional, or distant disease recurrence between submandibular gland preservation and gland removal. Similarly, Kaplan-Meier analysis showed no difference in disease free survival, disease specific survival, or overall survival.

CONCLUSIONS
Submandibular gland preservation during neck dissection in patients undergoing transoral surgery for oropharyngeal squamous cell carcinoma significantly reduces the risk of intraoperative and postoperative salivary leaks without compromising oncologic outcomes.

Howard|Brittany E|BE|
Hinni|Michael L|ML|
Nagel|Thomas H|TH|
Chang|Yu-Hui|YH|
Cheng|Meng-Ru|MR|
Hayden|Richard E|RE|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D002294:Carcinoma, Squamous Cell
D015331:Cohort Studies
D018572:Disease-Free Survival
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D008297:Male
D008875:Middle Aged
D009055:Mouth
D037981:Neck Dissection
D009926:Organ Preservation
D059351:Organ Sparing Treatments
D009959:Oropharyngeal Neoplasms
D061214:Patient Safety
D012189:Retrospective Studies
D018570:Risk Assessment
D013363:Submandibular Gland
D016019:Survival Analysis
D016896:Treatment Outcome

submandibular gland
transoral surgery
squamous cell carcinoma
laser
disease free survival
disease specific survival
overall survival
head and neck cancer
oropharyngeal neoplasms
robotics
squamous cell neoplasms
transoral laser microsurgery
transoral robotic surgery


Single-Pill Triple Fixed Dose Combination Therapy with Single Component Drug Monitoring in Treatment-Resistant Hypertension: A Pilot Study.

Abstract:
BACKGROUND
Single-pill fixed dose combination (FDC) therapies are widely used in the treatment of arterial hypertension.

OBJECTIVE
This pilot study aimed to evaluate the effects of a FDC therapy combined with therapeutic drug monitoring (TDM) on blood pressure (BP) in patients with treatment resistant hypertension.

METHOD
The study population included patients with suspected treatment-resistant hypertension during treatment with at least 3 antihypertensive drugs. We evaluated the effect of switching all patients to a regime including a single-pill triple FDC containing olmesartan, amlodipine and hydrochlorothiazide. Adherence was evaluated by measuring serum concentrations of amlodipine in a single-blinded fashion.

RESULTS
We enrolled 13 patients (mean age 57.2±9.1 years, 8 males) with resistant hypertension (office systolic and diastolic BP 158.3±17.3 and 94.8±11.1 mmHg); mean use of antihypertensive drugs was 3.8±1.1. Medication intake of FDC was confirmed in all patients at 18 weeks. Systolic and diastolic office BP were significantly lower (-22.8 and -13.6 mmHg) after 18 weeks of treatment with triple FDC (135.5±20.1 and 81.2±6.3 mmHg, p<0.01, respectively); mean use of antihypertensive drugs was 3.8±0.9. In 9 patients with 24-h ambulatory BP monitoring (ABPM) both at baseline and after 18 weeks, 24-h mean arterial pressure decreased (-9.3 mmHg, p=0.055). Overall, 9 (69%) patients achieved BP control in office BP and 4 (31%) in 24-h ABPM.

CONCLUSION
Our results support the use of single-pill triple FDC therapy in combination with TDM for the management of patients with suspected treatment-resistant hypertension and further testing in clinical studies.

D018660:Blood Pressure Monitoring, Ambulatory

single-pill fixed dose combination
therapeutic drug monitoring
blood pressure
resistant hypertension
Antihypertensive drugs
adherence


Single centre clinical experience with fidaxomicin in the treatment of Clostridium difficile infection in Slovakia.

Abstract:
OBJECTIVE
Clostridium difficile infection (CDI) has become one of the most common causes of hospital-acquired infections. Fidaxomicin is one of the latest antibiotics used in the treatment of CDI, however, treatment cost affects recommendations for its use in several countries. We have analysed the treatment of our patients with CDI, treated by fidaxomicin since it was introduced to the market in 2018 and became available in the second biggest Slovak hospital, University Hospital of L. Pasteur. Our aim was to determine efficacy and safety of fidaxomicin in the treatment of CDI in Slovak patients.

METHODS
We reviewed all courses of fidaxomicin use in our hospital (n = 60). Fidaxomicin was used for first recurrence (12 times), second recurrence (4 times), third recurrence (2 times), and fifth recurrence (1 patient). 41 patients received fidaxomicin first-line.

RESULTS
Success of fidaxomicin treatment was recorded at 86.7% within the whole cohort. In the recurrent Clostridium difficile infection (rCDI) subgroup, fidaxomicin was 63% effective with three patients dying (15.7%) and two patients developing subsequent rCDI. During the duration of the study, 6 patients in total died. Only one of three patients, with three or more recurrences of CDI, had no further presentations after eight weeks of completion of treatment.

CONCLUSIONS
The biggest benefit from fidaxomicin treatment was shown in a cohort of patients with primary CDI infection demonstrating a low recurrence rate and significant reduction of fidaxomicin effectiveness in preventing a recurrence when treating patients with multiple rCDI.

Novotný|Martin|M| Jarčuška|Pavol|P| Gombošová|Laura|L| Hockicko|Ján|J| Hockicková|Ivana|I| Rovňáková|Alena|A| Zahornacký|Ondrej|O| Schréter|Ivan|I| Dorko|Erik|E| Rimárová|Kvetoslava|K|

Clostridium difficile infection
recurrence
fidaxomicin treatment


Aging Prisoners' Views on Healthcare Services in Swiss Prisons.

Abstract:
OBJECTIVE
Due to the higher morbidity prevalent in the increasing older population, prisons are facing new challenges on a structural, ethical, and financial level. This study's goal was to explore older prisoners' views and experiences regarding the quality of medical services.

METHOD
In this qualitative study, 35 semi-structured interviews were conducted with older inmates aged 50 years and above in 12 different prisons in the German-speaking (23 interviews) and the French-speaking parts (12 interviews) of Switzerland.

RESULTS
The majority of older prisoners in this sample expressed concerns about quality of treatment throughout incarceration. Topics addressed reached from quality of the entrance to routine examinations, quality of the treatment received, and delays in care and services provided.

CONCLUSION
This study's findings suggest that healthcare in prison is often perceived as insufficient and inadequate by older inmates.

Galli|Serena|S|
Bretschneider|Wiebke|W|
Elger|Bernice Simone|BS|
Handtke|Violet|V|
Shaw|David|D|

aging detainees
inmates rights
principle of equivalence of care
prison healthcare


Enhanced Recovery After Surgery-Based Perioperative Protocol for Head and Neck Free Flap Reconstruction.

Abstract:
Objectives
Evaluate an enhanced recovery after surgery (ERAS)-based free flap management protocol implemented at our center.

Study Design
Prospective cohort study of patients after implementation of an ERAS-based perioperative care protocol for patients undergoing free flap reconstruction of the head and neck as compared with a historical control group.

Setting
Tertiary care academic medical center.

Participants and Methods
All patients undergoing free flap reconstruction were prospectively enrolled in the ERAS protocol group. A retrospective control group was identified by randomly selecting an equivalent number of patients from a records search of those undergoing free flap surgery between 2009 and 2015. Blood transfusion, complications, 30-day readmission rates, intensive care unit (ICU) and hospital length of stay, and costs of hospitalization were compared.

Results
Sixty-one patients were included in each group. Patients in the ERAS group underwent less frequent flap monitoring by physicians and had lower rates of intraoperative (70.5% vs 86.8%, P = .04) and postoperative (49.2% vs 27.2%, P = .026) blood transfusion, were more likely to be off vasopressors (98.3% vs 50.8%, P < .01) and ventilator support (63.9% vs 9.8%, P < .01) at the conclusion of surgery, and had shorter ICU stays (2.11 vs 3.39 days, P = .017). Length of stay, readmissions, and complication rates did not significantly differ between groups.

Conclusion
ERAS-based perioperative practices for head and neck free flap reconstruction can reduce time on the ventilator and in the ICU and the need for vasopressors, blood transfusions, and labor-intensive flap monitoring, without adverse effects on outcomes.

Bertelsen|Caitlin|C|
Hur|Kevin|K|
Nurimba|Margaret|M|
Choi|Janet|J|
Acevedo|Joseph R|JR|
Jackanich|Anna|A|
Sinha|Uttam K|UK|
Kochhar|Amit|A|
Kokot|Niels|N|
Swanson|Mark|M|

free flap
enhanced recovery after surgery
perioperative care
early awakening


Virus-host interactome: Putting the accent on how it changes.

Abstract: Viral infections are extremely complex processes that could only be well understood by precisely characterizing the interaction networks between the virus and the host components. In recent years, much effort has gone in this direction with the aim of unveiling the molecular basis of viral pathology. These networks are mostly formed by viral and host proteins, and are expected to be dynamic both with time and space (i.e., with the progression of infection, as well as with the virus and host genotypes; what we call plastodynamic). This largely overlooked spatio-temporal evolution urgently calls for a change both in the conceptual paradigms and experimental techniques used so far to characterize virus-host interactions. More generally, molecular plasticity and temporal dynamics are unavoidable components of the mechanisms that underlie any complex disease; components whose understanding will eventually enhance our ability to modulate those networks with the aim of improving disease treatments.

Rodrigo|Guillermo|G|
Daròs|José-Antonio|JA|
Elena|Santiago F|SF|

D000818:Animals
D054884:Host-Pathogen Interactions
D006801:Humans
D060066:Protein Interaction Maps
D062211:Spatio-Temporal Analysis
D014764:Viral Proteins
D014777:Virus Diseases

Evolution
Protein network
Systems biology
Virology


Yields and Utility of Endoscopic Ultrasonography-Guided 19-Gauge Trucut Biopsy versus 22-Gauge Fine Needle Aspiration for Diagnosing Gastric Subepithelial Tumors.

Abstract:
BACKGROUND/AIMS
To evaluate the yields and utility of 19-gauge (G) Trucut biopsy (TCB) versus 22 G fine needle aspiration (FNA) for diagnosing gastric subepithelial tumors (SETs).

METHODS
We retrieved data for 152 patients with a gastric SET larger than 2 cm who had undergone endoscopic ultrasonography (EUS)-guided 19 G TCB (n=90) or 22 G FNA (n=62). Relevant clinical, tumor-specific, and EUS procedural information was reviewed retrospectively.

RESULTS
A specific diagnosis was made for 76 gastrointestinal stromal tumors (GISTs) and 51 non-GIST SETs. The diagnostic yield of TCB was greater than that of FNA (77.8% vs. 38.7%, p<0.001). The percentage of non-diagnostic specimens (suspicious and insufficient) was significantly lower in the TCB group (6.7% and 15.5%, respectively) than in the FNA group (22.6% and 38.7%, respectively; both p<0.001). TCB accurately diagnosed 90.9% of GISTs and 81.1% of non-GIST SETs, whereas FNA accurately diagnosed 68.8% of GISTs and 14.3% of non-GIST SETs. There were nine technical failures with TCB, and the rate of adverse events did not differ between the groups (TCB vs. FNA, 3.3% vs. 8.1%; p=0.27).

CONCLUSIONS
Nineteen-gauge TCB is safe and highly valuable for diagnosing gastric SETs larger than 2 cm if technical failure can be avoided.

Na|Hee Kyong|HK|
Lee|Jeong Hoon|JH|
Park|Young Soo|YS|
Ahn|Ji Yong|JY|
Choi|Kwi-Sook|KS|
Kim|Do Hoon|DH|
Choi|Kee Don|KD|
Song|Ho June|HJ|
Lee|Gin Hyug|GH|
Jung|Hwoon-Yong|HY|
Kim|Jin-Ho|JH|

Endoscopic ultrasound-guided fine needle aspiration


De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials.

Abstract: Iatrogenic complications associated with current treatment protocols for oropharyngeal squamous cell carcinoma are noted to cause high rates of acute and chronic morbidity. The aims of this study are to provide an overview of the current de-escalation trials for human papillomavirus positive (HPV+) oropharyngeal carcinoma and to evaluate the evidence supporting improved response to treatment of patients within this viral cohort. This study reviewed all completed or in progress randomised controlled trials (RCTs) assessing clinical interventions for human papillomavirus-associated locally advanced oropharyngeal squamous cell carcinoma. We utilised a validated 'risk of bias' tool to assess study quality. We identified nine RCTs that met the full inclusion criteria for this review (all of which are currently on-going and will report from 2015 onwards). Five RCTs performed a post hoc analysis by HPV status, which allowed meta-analysis of 1130 patients. The data reveal a significant difference in overall survival (hazard ratio (HR) 0.49 [95% confidence interval (CI) 0.35-0.69]), loco-regional failure (HR 0.43 [95% CI 0.17-1.11]) and disease specific survival (0.41 [95% 0.3-0.56]) in favour of the HPV+ category. In considering de-escalation treatment protocols, nine studies are currently ongoing. Our meta-analysis provides strong evidence for an improved prognosis in the viral associated cohort when treated by platinum based chemotherapy in combination with radiotherapy or primary radiotherapy. So far, one trial (with moderate to high risk of bias) suggests a reduced survival outcome for the HPV+ population when using the epidermal growth factor receptor (EGFR) inhibitor cetuximab.

Masterson|Liam|L|
Moualed|Daniel|D|
Liu|Zi Wei|ZW|
Howard|James E F|JE|
Dwivedi|Raghav C|RC|
Tysome|James R|JR|
Benson|Richard|R|
Sterling|Jane C|JC|
Sudhoff|Holger|H|
Jani|Piyush|P|
Goon|Peter K C|PK|

D016032:Randomized Controlled Trials as Topic

Human papillomavirus
Oropharyngeal carcinoma
De-escalation of treatments


Decay of internal reference information in duration discrimination: Intertrial interval modulates the Type B effect.

Abstract: Psychophysical evidence suggests that human perception of a stimulus is assimilated towards previous stimuli. The internal reference model (IRM) explains such assimilation through an internal reference (IR), which integrates past and present stimulus representations and thus might be conceived as a form of perceptual memory. In this study, we investigated whether the IR decays with time, as previously shown for perceptual memory representations in general. One specific prediction of IRM is higher discrimination sensitivity when a constant standard precedes rather than follows a variable comparison in a two-alternative forced-choice (2AFC) discrimination task. Furthermore, the magnitude of this so-called negative Type B effect should decrease with decreasing weighting of past stimulus information in the integration process. Therefore, decay of the IR should result in a reduced Type B effect. To examine this prediction, we carried out a 2AFC duration discrimination experiment with a short (1,600 ms) and a long (3,200 ms) intertrial interval (ITI). As expected, a reduced negative Type B effect was observed at the long compared with the short ITI, consistent with the idea that humans rely on the immediate past when evaluating current sensory input, however, less so when the IR incorporating the perceptual short-term memory representation of these past stimuli has already decayed.

Ellinghaus|Ruben|R|
Gick|Mareike|M|
Ulrich|Rolf|R|
Bausenhart|Karin M|KM|

D000328:Adult
D002755:Choice Behavior
D004192:Discrimination, Psychological
D006801:Humans
D008570:Memory, Short-Term
D011597:Psychomotor Performance
D011601:Psychophysics
D013998:Time Perception
D055815:Young Adult

Type B effect
assimilation
internal reference model
perceptual memory
Stimulus discrimination


The ensemble of genetic factors and angiogenic signals via VEGF receptors in lung cancer progression.

Abstract: Lung cancer is the major cause of cancer-related mortality worldwide owing to its late-stage detection and aggressive behavior. Epidemiologically, several genetic and epigenetic factors contribute to the development of lung cancer. Angiogenesis, a critical process in tumor progression has become an important target for anti-cancer therapy particularly in lung cancer. Besides commercially available angiogenic inhibitors, numerous anti-angiogenic therapies have been developed to limit tumor growth, although, most of them have not proved beneficial in terms of long-term survival. Despite, logical advances in treatment strategies, NSCLC still remains a major health concern due to poor prognosis of the diseases state. This calls for a comprehensive analysis of signaling processes governing tumor angiogenesis and treatment options available thereof for development of a sustainable strategy to control cancer. In this review, several aspects of lung cancer have been discussed starting from its pathological characterization to the development of modern therapeutics.

Danish|Qazi|Q|
Mokhdomi|Taseem A|TA|
Bukhari|Shoiab|S|
Ahmad|Raies|R|

D040262:Receptors, Vascular Endothelial Growth Factor


New glucosyloxybenzyl 2R-benzylmalate derivatives from the undergrounds parts of Arundina graminifolia (Orchidaceae).

Abstract: Phytochemical investigation of the underground part of the blossoming tropical orchid Arundina graminifolia led to the isolation of six new glucosyloxybenzyl 2R-benzylmalate derivatives named arundinosides L-Q (1-6) together with 5 known compounds arundinosides D-F, J and K (7-11). The structures of the isolated compounds were determined by extensive spectroscopic data analysis. The anti-α-glucosidase and antioxidant activities of the isolated compounds were determined. The result indicated that compounds 4-6 and 9 showed moderate to weak α-glucosidase inhibitory effects as well as moderate antioxidant effect.

Auberon|Florence|F|
Olatunji|Opeyemi Joshua|OJ|
Waffo-Teguo|Pierre|P|
Adekoya|Ademola Ezekiel|AE|
Bonté|Frédéric|F|
Mérillon|Jean-Michel|JM|
Lobstein|Annelise|A|


Vibration transmittance measures sternotomy stability - a preliminary study in human cadavers.

Abstract:
BACKGROUND
Stability is essential for the normal healing of a sternotomy. Mechanical vibration transmittance may provide a new means of early detection of diastasis in the sternotomy and thus enable the prevention of further complications. We sought to confirm that vibration transmittance detects sternal diastasis in human tissue.

METHODS
Ten adult human cadavers (8 males and 2 females) were used for sternal assessments with a device constructed in-house to measure the transmittance of a vibration stimulus across the median sternotomy at the second, third, and fourth costal cartilage. Intact bone was compared to two fixed bone junctions, namely a stable wire fixation and an unstable wire fixation with a 10 mm wide diastasis mimicking a widely rupturing sternotomy. A generalized Linear Mixed Model with the lme function was used to determine the ability of the vibration transmittance device to differentiate mechanical settings in the sternotomy.

RESULTS
The transmitted vibration power was statistically significantly different between the intact chest and stable sternotomy closure, stable and unstable closure, as well as intact and unstable closure (t-values and p-values respectively: t = 6.87, p < 0.001; t = 7.41, p < 0.001; t = 14.3, p < 0.001). The decrease of vibration transmittance from intact to stable at all tested costal levels was 78%, from stable to unstable 58%, and from intact to unstable 91%. The vibration transmittance power was not statistically significantly different between the three tested costal levels (level 3 vs. level 2; level 4 vs. level 2; level 4 vs. level 3; t-values and p-values respectively t = - 0.36, p = 0.723; t = 0.35, p = 0.728; t = 0.71, p = 0.484).

CONCLUSIONS
Vibration transmittance analysis differentiates the intact sternum, wire fixation with exact apposition, and wire fixation with a gap. The gap detection capability is not dependent on the tested costal level. The method may prove useful in the early detection of sternal instability and warrants further exploration.

Vibration transmittance
Sternotomy
Sternum
Electronics
Integrity
Postoperative complications
Wound healing


Self-Powered and Green Ionic-Type Thermoelectric Paper Chips for Early Fire Alarming.

Abstract: Early fire alarming is of vital importance to lower the damages led by forest fires. Thus far, methods to monitor the forest fires at their early stage are mainly focused on artificial ground patrol, unmanned aerial vehicle cruise monitoring, observation by watchtower, or satellite inspection, whereas these methods are practically encountered with the problems of untimely feedback before the forest fires are out of control. This work proposes a particular kind of self-powered, low-cost, and green thermoelectric paper chips based on the principle of self-assembly and disassembly of ionic liquids on the surface of gold electrodes. By adjustment of the species of ionic liquids, both "n- and p-type" thermoelectric behaviors have been exploited that correspond to the opposite open-circuit voltages. Owing to the fluidic nature of ionic liquids, those "n- and p-type" thermoelectric units can be readily connected in series on one paper chip, leading to remarkable voltage signals in the presence of the temperature difference of 35 K. Followed by signal acquisition and transmission, such a thermoelectric paper chip successfully affords immediate electrical alarming at the early stage of an afire circumstance.

paper chip
early fire alarming
ionic liquid
signal amplification
temperature−voltage response


The Effect of the Health Insurance Mandate on Labor Market Activity and Time Allocation: Evidence from the Federal Dependent Coverage Provision.

Abstract: The primary goal of the federal dependent coverage mandate was to increase health insurance coverage among young adults, the group with the lowest prevalence of health insurance coverage. To understand the full impacts of the federal dependent coverage mandate, it is important to evaluate how the mandate affects labor market activities and time spent away from work among young adults. Using data from the Consumer Population Survey (CPS) and the American Time Use Survey (ATUS) and implementing a difference-in-differences framework, we find: (1) Young adults substitute employer sponsored insurance for dependent coverage, (2) Affected individuals reduce their work time and switch from full- to part-time employment, and (3) The additional time from reduced labor market activity is reallocated towards more time spent on leisure activities, mainly watching television. The effects of the mandate on labor market activities are stronger in later years. Furthermore, we show that young adults do not increase the time they spend on activities that could enhance their human capital such as education and health, which reemphasizes potential unintended consequences of the mandate. These findings suggest that future work is necessary to fully understand the overall welfare effects of the policy.


The changing relationship between unemployment and total fertility.

Abstract: The aim of this paper is to investigate whether there has been a fundamental change in the relationship between economic conditions and fertility. We use panel data methods to study the short-term changes in total fertility and the unemployment rate in a range of Organisation for Economic Co-operation and Development (OECD) countries from 1957 to 2014. We find that although fertility was counter-cyclical before 1970, with good economic times being associated with lower fertility, since then it has become pro-cyclical, with good economic times being associated with higher fertility.

Karaman Örsal|Deniz D|DD|
Goldstein|Joshua R|JR|

total fertility
unemployment rate
counter-cyclical
pro-cyclical


Pediatric foreign body aspiration: A nidus for Aspergillus colonization.

Abstract: We describe an immunocompetent child with bronchial fungus following foreign body aspiration. A two-year-old male presented with cough. Workup revealed air trapping and bronchoscopy showed aspirated foreign material in the right mainstem bronchus. Histopathology revealed fungal organisms suggestive of Aspergillus within an ulcer of the adjacent bronchial mucosa. Foreign body aspiration has been posited as a nidus for aspergilloma formation but is not yet described in the available English-language pediatric literature. Here, the foreign body provided a site for fungal growth in the bronchus of an otherwise healthy child. This case suggests that bronchial foreign body may pose risk of fungal colonization even in immunocompetent children.

Mitchell|Candace A|CA|
Kreiger|Portia|P|
Goff|Christopher|C|
Shah|Udayan K|UK|

Pediatric
Foreign body aspiration
Aspergillus
Fungus


The situation of low vision services in Papua New Guinea: an exploratory study.

Abstract:
BACKGROUND
The aim of this study was to investigate the current situation of low vision services and barriers to low vision service delivery in Papua New Guinea (PNG).

METHODS
An exploratory study was undertaken to assess the situation of available services, human resources, training, equipment and assistive devices, supportive policies, needs of people with low vision and community attitudes toward people with low vision. In-depth interviews with 50 key informants were conducted in-country. Key informants included eye-care practitioners (n = 13), special education teachers (n = 10), community-based rehabilitation workers (n = 3), other stakeholders providing disability-related services (n = 8), and people with low vision (n = 14) and their family members (n = 2). Interview transcripts were analysed inductively and deductively using thematic analysis.

RESULTS
Barriers were identified at systems and community levels. The barriers at the systems level were: low vision not a priority area for eye care and rehabilitation programs, limited availability of low vision services, trained personnel and low vision devices; low vision not included in training programs of eye-care practitioners and lack of awareness of available referral services among service providers. The barriers identified at the community level were lack of awareness of services, distance, costs and limited transport to access services and negative community attitudes.

CONCLUSION
This study has identified barriers from the perspectives of different stakeholders, including service providers and people with low vision and their families. Knowledge of these barriers can now guide the development of future low vision services in PNG.

Marella|Manjula|M| Yu|Mitasha|M| Paudel|Prakash|P| Michael|Alois|A| Ryan|Kevin|K| Yasmin|Sumrana|S| Minto|Hasan|H|

low vision
Papua New Guinea
barriers
situation analysis


Anesthesia Preoperative Clinic Evaluation of Obstructive Sleep Apnea Using Nasal Fiberoptic Videoendoscopy: A Pilot Study Comparison with Polysomnography.

Abstract:
Background
Nasal fiberoptic videoendoscopy is an established technique to assess upper airway pathology in conscious and sedated patients.

Objectives
The authors conducted a prospective proof-of-concept pilot study to evaluate whether airway narrowing detected using nasal fiberoptic videoendoscopy in the anesthesia preoperative clinic was capable of defining the severity of obstructive sleep apnea (OSA) in patients scheduled for elective surgery.

Methods
After application of topical local anesthesia (4% lidocaine with phenylephrine), sixteen patients (ASA physical status 2 or 3) underwent nasal fiberoptic videoendoscopy in sitting position. The magnitudes of retropalatal and retrolingual luminal narrowing were assessed as predictors of OSA. Patients also underwent polysomnography and completed STOP-Bang questionnaires. The endoscopist's clinical impression of OSA severity based on the history and airway examination was quantified.

Results
Retropalatal luminal narrowing and STOP-Bang score ≥ 4 predicted OSA severity as either "none or mild" or "moderate to severe" in 13 (81%) and 9 (56%) of 16 patients who underwent polysomnography, respectively. OSA severity was significantly (Spearman's rank correlation coefficient) associated with retropalatal airway narrowing (P = 0.0048), STOP-BANG score (P = 0.0072), and body mass index (P = 0.0091), whereas clinical impression and retrolingual pharyngeal narrowing were not (P=0.093 and P = 0.11, respectively).

Conclusions
The current results suggest that nasal fiberoptic videoendoscopy quantification of retropalatal airway narrowing may be a useful tool for assessing the severity of OSA in the anesthesia preoperative clinic. The current findings document a proof-of-concept feasibility of nasal fiberoptic videoendoscopy as a screening tool for OSA in conscious patients during preoperative evaluation that may justify further prospective clinical trials of this technique.

Jain|Sandeep|S|
Kallio|Peter J|PJ|
Less|Kenneth|K|
Novalija|Jutta|J|
Pagel|Paul S|PS|
Ebert|Thomas J|TJ|

Anesthesia Preoperative Clinic
Obstructive Sleep Apnea
fiberoptic Videoendoscopy
Polysomnography
STOP-Bang


The controlled drug release by pH-sensitive molecularly imprinted nanospheres for enhanced antibacterial activity.

Abstract: In this study, we prepared pH-sensitive hybrid nanospheres through the implementation of a facile molecularly imprinted polymer (MIP) technique combined with a UV-initiated precipitation polymerization method using vancomycin (VA) for the templates. During the course of this investigation, both 2-hydroxyethyl methacrylate (HEMA) and 2-(diethylamino) ethyl methacrylate (DEAEMA) were utilized as the functional monomers, while ethylene glycol dimethacrylate (EGDMA) was used as a cross-linker. The obtained MIP nanospheres exhibited well-controlled particle size, with a drug loading capacity of about 17%, much higher than that of the non-imprinted polymer (NIP) nanospheres (5%). In addition, the VA loading quantity was closely correlated with the dosage of the cross-linking agent, and the MIP nanospheres exhibited a slower and more controlled VA release rate than the NIP nanospheres. Moreover, these MIP nanospheres were sensitive to pH values, and consequently showed an increasing release rate of VA as the pH level was decreased. The VA-loaded MIP nanospheres showed the higher antibacterial ratio of over 92% against Staphylococcus aureus (S. aureus) while the NIP nanospheres were friendly to S. aureus. These MIP nanospheres can be promising for targeting drug delivery system to achieve specific therapies such as preventing bacterial infections and killing cancer cells without damaging health cells and tissues.

Mao|Congyang|C|
Xie|Xianzhou|X|
Liu|Xiangmei|X|
Cui|Zhenduo|Z|
Yang|Xianjin|X|
Yeung|K W K|KWK|
Pan|Haobo|H|
Chu|Paul K|PK|
Wu|Shuilin|S|

D000900:Anti-Bacterial Agents
D065546:Drug Liberation
D006863:Hydrogen-Ion Concentration
D054802:Molecular Imprinting
D054118:Nanospheres
D011108:Polymers
D013211:Staphylococcus aureus

pH-sensitive
Molecularly imprinted nanospheres
Antibacterial
Polymerization
Drug delivery


Meeting report: IUPS and ADInstruments 2017 Teaching Workshop.

Abstract: Every 4 yr, the International Union of Physiological Sciences (IUPS) Teaching Workshop is held as a traditional satellite event of the IUPS Congress. The 2017 satellite workshop was held August 5-8, 2017 in Búzios, Rio de Janeiro, Brazil. The workshop provided an opportunity for discussion and experiences in physiology teaching for educators at various levels, graduate students, and undergraduate students. This report describes the workshop activities and reports the participants' perceptions of this event. For evaluation of perception, an anonymous questionnaire was sent by e-mail to all participants, addressing nine items: appropriate topics, time of activities, poster session, congress venue, registration fee, attention of the organizing committee before and during the event, social event, and food. Responses were ranked according to a five-point Likert scale. Of the 145 participants, 77 answered the questionnaire. The participants' perception was positive, noting in particular opportunities to share knowledge, space for reflection of teaching practice, contact networks for future, exchanges of experience, and collaborations in research in physiological education.

Marcondes|Fernanda Klein|FK|
Cardozo|Lais Tono|LT|
Luchi|Kelly Cristina Gaviao|KCG|
Irfannuddin|Muhammad|M|
Karatzaferi|Christina|C|
Rocha|Maria José|MJ|
Carroll|Robert G|RG|

teaching
physiology education
active teaching-learning methodologies
teacher education