Acute Caffeine and Coconut Oil Intake, Isolated or Combined, Does Not Improve Running Times of Recreational Runners: A Randomized, Placebo-Controlled and Crossover Study.

Abstract: The aim was to evaluate the effect of caffeine (CAF) and extra virgin coconut oil (CO), isolated or combined, on running performance in runners. Methods: A randomized, placebo-controlled, and crossover study was conducted with thirteen recreational runners aged 18-40. All volunteers performed a 1600 m time trial at a 400 m track, each ingesting four different substances: (1) placebo (water), (2) decaffeinated coffee plus isolated CAF (DECAF + CAF), (3) decaffeinated coffee plus isolated CAF plus soy oil (DECAF + CAF + SO), and (4) decaffeinated coffee plus isolated CAF plus extra virgin coconut oil (DECAF + CAF + CO). The substances were ingested 60 min before the trials, the order of the situations was randomized, and there were one-week intervals between them. At the end of the trials, the Borg scale was applied to evaluate the rating of perceived exertion (RPE) and the time was measured. Results: Our data did not show differences in running time among the trials (placebo: 7.64 ± 0.80, DECAF + CAF: 7.61 ± 1.02, DECAF + CAF + SO: 7.66 ± 0.89, and DECAF + CAF + CO: 7.58 ± 0.74 min; p = 0.93), nor RPE (placebo: 6.15 ± 2.03, DECAF + CAF: 6.00 ± 2.27, DECAF + CAF + SO: 6.54 ± 2.73, and DECAF + CAF + CO: 6.00 ± 2.45 score; p = 0.99). Lactate concentrations (placebo: 6.23 ± 2.72, DECAF + CAF: 4.43 ± 3.77, DECAF + CAF + SO: 5.29 ± 3.77, and DECAF + CAF + CO: 6.17 ± 4.18 mmol/L; p = 0.55) also was not modified. Conclusion: Our study shows that ingestion of decaffeinated coffee with the addition of isolated CAF and extra virgin CO, either isolated or combined, does not improve 1600 m running times, nor influence RPE and lactate concentrations in recreational runners. Thus, combination of coffee with CO as a pre-workout supplement seems to be unsubstantiated for a short-distance race.

caffeine
coconut oil
running
performance
coffee
nutrients


Biothreat & One Health: Current scenario & way forward.

Abstract: There is an increased connectedness among humans, animals, and the environment and the current pandemic has taught the interlinking of the health of humans, animals and the planet. This inter-connectedness and factors like population growth, migration, urbanization, and climate change contribute significantly to the enhanced probability of emergence of previously unknown wildlife source pathogens at any place, any time, and without warning. Lurking in the background is the massive potential for the deliberate use of biological agents as weapons by State or non-State entities. Biological weapons have been used in wars since antiquity, however, newer research and techniques have led to these being real threats with a vast potential of harm to humans, animals, and crops. Over a period, it has become increasingly difficult to differentiate between deliberate and natural biothreat incidents. The response to both types is alike to safeguard lives, livestock, crops and the environment and reduce the consequent socio-economic ramifications. Biothreat may be targeted towards humans, animals, or crops, or all these concurrently. Every country including India is at risk of biothreat. The concept of one health is thus essential for responding to emerging infectious diseases or biothreats. Comprehensive surveillance for early detection, reporting and early concerted action is needed for prevention and blunting the effect of biothreats, which require close coordination and collaboration among various stakeholders within each country as well as globally.


A DNA methylation profile of long non-coding RNAs can predict OS in prostate cancer.

Abstract: Prostate cancer (PCa) is the most common male reproductive tract malignant tumor, accurate evaluation of PCa characterization and prognostic prediction at diagnosis are vital for the effective administration of the disease, especially at the molecular level. In this study, 48 CpG sites with differential methylation associated with overall survival (OS) were screened out between PCa and normal adjacent tissues. 16 CpG sites were selected by the least absolute shrinkage and selection operator (LASSO) and the risk score formula for methylated-based classifier was established. For 16-lncRNAs-CpG-classifier, the area under the curve (AUC) were 0.890, 0.917, and 0.932 at 3 years, 5 years and 7 years, respectively. Kaplan-Meier curves indicated that patients with high-risk scores had worse OS than those with low-risk scores. Prognostic methylation model of lncRNAs was identified from the whole genome in patients with PCa. This novel finding provides a novel insight for screening biomarkers of a prognosis for PCa.

Cheng|Wei|W| Cao|Jie|J|0000-0002-9293-6513 Xia|Yong|Y| Lei|Xin|X| Wu|Lili|L| Shi|Liang|L|

methylation
Prostate cancer
prognostic
lncRNAs


Biological Characterization and Inhibition of Streptococcus pyogenes ZUH1 Causing Chronic Cystitis by Crocus sativus Methanol Extract, Bee Honey Alone or in Combination with Antibiotics: An In Vitro Study.

Abstract: Streptococcus pyogenes (S. pyogenes) ZUH1 was isolated and characterized using morphological, cultural and biochemical methods. The results showed that the marker genes (namely spyCEP, ssa, sic, sdaB and speG) indicating group A streptococci (GAS) were detected in the S. pyogenes genome. The results showed that the S. pyogenes strain was inhibited by Crocus sativus methanol extract (CSME), bee honey (BH) and catfish glycoprotein (CFG). The inhibitory activity of these natural agents were compared with standard antibiotics such as Ceftazidime (30 μg/mL), Cefoperazone (75 μg/mL), Cefoxitin (30 μg/mL) and Imipenem (10 μg/mL). There was a synergistic effect between certain antibiotics and CSME. GC-MS and IR analysis of CSME showed different cyclic ketones, aldehydes, esters, alcohols and acids. The main compounds were tetradecanoic acid, safranal and isophorone. Transmission electron microscopy (TEM) images of S. pyogenes cells treated with CSME showed signs of an irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged bacterial cells or cellular debris. The marker genes (spyCEP, ssa, sic, sdaB and speG) could be used as a rapid diagnostic tool for GAS. CSME, BH and CFG showed distinctive anti-streptococcal activity either alone or in combinations with antibiotics; their action on S. pyogenes cells was studied by TEM. There was a synergistic effect between antibiotics and Crocus sativus, bee honey, and glycoprotein against S. pyogenes ZUH1. The action of natural agents on the pathogenic cells was shown using TEM.

Abdel-Shafi|Seham|S|
Al-Mohammadi|Abdul-Raouf|AR|
Hamdi|Sara|S|
Moustafa|Ahmed H|AH|
Enan|Gamal|G|

Group A streptococci (GAS), S. pyogenes ZUH1


Opposing effects of shear-mediated dilation and myogenic constriction on artery diameter in response to handgrip exercise in humans.

Abstract: While the impact of changes in blood flow and shear stress on artery function are well documented, the acute effects of increases in arterial pressure are less well described in humans. The aim of this study was to assess the effect of 30 min of elevated blood pressure, in the absence of changes in shear stress or sympathetic nervous system (SNS) activation, on conduit artery diameter. Ten healthy male subjects undertook three sessions of 30 min unilateral handgrip exercise at 5, 10, and 15% of maximal voluntary contractile (MVC) strength. Brachial artery shear rate and blood flow profiles were measured simultaneously during exercise in the active and contralateral resting arms. Bilateral brachial artery diameter was simultaneously assessed before and immediately postexercise. In a second experiment, six subjects repeated the 15% MVC condition while continuous vascular measurements were collected during muscle sympathetic nerve activity (MSNA) assessment using peroneal microneurography. We found that unilateral handgrip exercise at 5, 10, and 15% MVC strength induced stepwise elevations in blood pressure (P < 0.01, Δmean arterial pressure: 7.06 ± 2.44, 8.50 ± 2.80, and 18.35 ± 3.52 mmHg, P < 0.01). Whereas stepwise increases were evident in shear rate in the exercising arm (P < 0.001), no changes were apparent in the nonexercising limb (P = 0.42). Brachial artery diameter increased in the exercising arm (P = 0.02), but significantly decreased in the nonexercising arm (P = 0.03). At 15% MVC, changes in diameter were significantly different between arms (interaction effect: P = 0.01), whereas this level of exertion produced no significant changes in MSNA. We conclude that acute increases in transmural pressure, independent of shear rate and changes in SNS activation, reduce arterial caliber in normotensive humans in vivo. These changes in diameter were mitigated by exercise-induced elevations in shear rate in the active limb.

Atkinson|Ceri L|CL|
Carter|Howard H|HH|
Naylor|Louise H|LH|
Dawson|Ellen A|EA|
Marusic|Petra|P|
Hering|Dagmara|D|
Schlaich|Markus P|MP|
Thijssen|Dick H J|DH|
Green|Daniel J|DJ|

myogenic
exercise
shear stress
blood pressure


Development of zirconia nanoparticles-decorated calcium alginate hydrogel fibers for extraction of organophosphorous pesticides from water and juice samples: Facile synthesis and application with elimination of matrix effects.

Abstract: In this research, novel zirconia nanoparticles-decorated calcium alginate hydrogel fibers (ZNCAHF) were synthesized through a simple, green procedure. ZNCAHF were used as an adsorbent in the micro-solid-phase extraction (MSPE) of methyl parathion (MP), fenitrothion (FT) and malathion (MT) as model pesticides prior to gas chromatography-mass spectroscopic detection (GC-MS). The composition and morphology of the prepared fiber were characterized by Fourier transform-infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), energy dispersive X-ray diffraction (EDX), and differential scanning calorimetry (DSC). Various parameters affecting fabrication of the fiber (weight ratio of components) and relative extraction recovery (pH, amount of adsorbent, extraction time, salt addition, and desorption conditions) were investigated and optimized. Under optimized conditions, the calibration curves were obtained in the concentration range of 0.01-500ngmL-1 with regression coefficients between 0.9997 and 0.9999. The limits of detection (LOD) (S/N=3) and limits of quantification (LOQ) (S/N=10) of the method ranged from 0.001 to 0.004ngmL-1 and 0.003 to 0.012ngmL-1, respectively. The intra-day and inter-day relative standard deviations (RSDs) were 2.2-5.9% and 3.2-7.8%, respectively. The applicability of the fabricated adsorbent was investigated by extraction of selected organophosphorous pesticides (OPPs) from real samples of juice and water. The obtained relative recoveries were in the range of 90.6-105.4%, demonstrating elimination of matrix effects which can be attributed to the remarkable affinity of OPPs toward ZNCAHF.

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

D017550:Spectroscopy, Fourier Transform Infrared

Alginate
Organophosphorous pesticides
Gas chromatography
Micro solid phase extraction
Zirconia nanoparticles


The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: A systematic review of clinical trials of preventative pharmacological migraine treatments.

Abstract:
OBJECTIVE
To evaluate the association between the degree of response to placebo in migraine studies and the observed difference between drug and placebo across studies of preventative treatments for migraine.

METHODS
A systematic review was performed using MEDLINE and the Cochrane Central Register of Controlled Clinical Trials from January 1988 to June 2019. Randomized, double-blind, parallel-group, placebo-controlled trials on oral or injection preventative treatments for migraine were included. Single- and multi-variable linear regression analyses were performed on the placebo-subtracted response rate (i.e. placebo responders subtracted from active responders), and the proportion of placebo responders. Fisher's exact tests were performed on the level of placebo response and the success in meeting the study's primary endpoint.

RESULTS
After adjusting for route of administration and number of randomized subjects, there was a statistically significant association between the proportion of patients who were placebo responders and the placebo-subtracted response rate (b = -0.27, p = 0.02). There was a statistically significant difference in trial success rate (60%) between studies with ≤20% placebo responders and studies with > 30% placebo responders (p = 0.03).

CONCLUSION
Considering the detrimental impact that high placebo response can have on clinical trials, it is imperative to find effective solutions to decrease the placebo response and increase assay sensitivity.

Evans|Kathryn|K|0000-0001-7675-6750
Romero|Heather|H|
Spierings|Egilius Lh|EL|
Katz|Nathaniel|N|

Placebo response
migraine
preventative treatment
assay sensitivity
trial failure


Mycobiome of Cysts of the Soybean Cyst Nematode Under Long Term Crop Rotation.

Abstract: The soybean cyst nematode (SCN), Heterodera glycines Ichinohe (Phylum Nematoda), is a major pathogen of soybean. It causes substantial yield losses worldwide and is difficult to control because the cyst protects the eggs which can remain viable for nearly a decade. Crop rotation with non-host crops and use of biocontrol organisms such as fungi and bacteria offer promising approaches, but remain hampered by lack of knowledge of the biology of nematode parasitic organisms. We used a high-throughput metabarcoding approach to characterize fungal communities associated with the SCN cyst, a microenvironment in soil that may harbor both nematode parasites and plant pathogens. SCN cysts were collected from a long-term crop rotation experiment in Southeastern Minnesota at three time points over two growing seasons to characterize diversity of fungi inhabiting cysts and to examine how crop rotation and seasonal variation affects fungal communities. A majority of fungi in cysts belonged to Ascomycota and Basidiomycota, but the presence of several early diverging fungal subphyla thought to be primarily plant and litter associated, including Mortierellomycotina and Glomeromycotina (e.g., arbuscular mycorrhizal fungi), suggests a possible role as nematode egg parasites. Species richness varied by both crop rotation and season and was higher in early years of crop rotation and in fall at the end of the growing season. Crop rotation and season also impacted fungal community composition and identified several classes of fungi, including Eurotiomycetes, Sordariomycetes, and Orbiliomycetes (e.g., nematode trapping fungi), with higher relative abundance in early soybean rotations. The relative abundance of several genera was correlated with increasing years of soybean. Fungal communities also varied by season and were most divergent at midseason. The percentage of OTUs assigned to Mortierellomycotina_cls_Incertae_sedis and Sordariomycetes increased at midseason, while Orbiliomycetes decreased at midseason, and Glomeromycetes increased in fall. Ecological guilds of fungi containing an animal-pathogen lifestyle, as well as potential egg-parasitic taxa previously isolated from parasitized SCN eggs, increased at midseason. The animal pathogen guilds included known (e.g., Pochonia chlamydosporia) and new candidate biocontrol organisms. This research advances knowledge of the ecology of nematophagous fungi in agroecosystems and their use as biocontrol agents of the SCN.

Hu|Weiming|W|
Strom|Noah|N|
Haarith|Deepak|D|
Chen|Senyu|S|
Bushley|Kathryn E|KE|

soybean cyst nematode
crop rotation
Heterodera glycines
Mortierellomycotina
arbuscular mycorrhizal fungi
nematophagous fungi
next generation sequencing


Interactions of multiple rhythms in a biophysical network of neurons.

Abstract: Neural oscillations, including rhythms in the beta1 band (12-20 Hz), are important in various cognitive functions. Often neural networks receive rhythmic input at frequencies different from their natural frequency, but very little is known about how such input affects the network's behavior. We use a simplified, yet biophysical, model of a beta1 rhythm that occurs in the parietal cortex, in order to study its response to oscillatory inputs. We demonstrate that a cell has the ability to respond at the same time to two periodic stimuli of unrelated frequencies, firing in phase with one, but with a mean firing rate equal to that of the other. We show that this is a very general phenomenon, independent of the model used. We next show numerically that the behavior of a different cell, which is modeled as a high-dimensional dynamical system, can be described in a surprisingly simple way, owing to a reset that occurs in the state space when the cell fires. The interaction of the two cells leads to novel combinations of properties for neural dynamics, such as mode-locking to an input without phase-locking to it.

Neural oscillations
Phase-locking
Phase-response curve
State reset
Time-division multiplexing


Prediction of Primary Slow-Pathway Ablation Success Rate according to the Characteristics of Junctional Rhythm Developed during the Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia.

Abstract:
BACKGROUND
Nowadays, developed junctional rhythm (JR) that occurs during slow-pathway radiofrequency (RF) catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) has been focused upon as a highly sensitive surrogate end point for successful radiofrequency ablation. This study was conducted to assess the relationship between the presence and pattern of developed JR during the RF ablation of AVNRT and a successful outcome.

METHODS
Seventy-five patients aged between 14 and 88 who underwent slow-pathway RF ablation due to symptomatic AVNRT were enrolled into the study and received a total of 162 RF energy applications. Combined anatomic and electrogram mapping approach was used for slow-pathway RF ablation. The ablation procedure consisted of 60-second, 60 °C temperature-controlled energy delivery. After each ablation pulse, successful ablation was assessed according to the loss of AVNRT inducibility via isoproterenol infusion. Four different patterns were considered for the developed JR, namely sparse, intermittent, continuous, and transient block. Success ablation rate was assessed with respect to the position, pattern, and number of junctional beats.

RESULTS
Successful RF ablation with a loss of AVNRT inducibility was achieved in 43 (57.3%) patients using 119 RF energy applications (73.5%). JR developed in 133 of the 162 (82.1%) applications with a given sensitivity of 90.8% and low specificity of 41.9% as an end point of successful RF ablation, with a negative predictive value of 62.1%. The mean number of the developed junctional beats was significantly higher in the successful ablations (p value < 0.001), and the ROC analysis revealed that the best cut-off point of the cumulative junctional beats for identifying accurate AVNRT ablation therapy is 14 beats with 90.76 % sensitivity and 90.70% specificity. There were no significant differences in terms of successful ablation rates according to the four different patterns of JR and its positions (p value=0.338, p value=0.105, respectively) in the univariate analyses.

CONCLUSION
JR is a sensitive but non-specific predictor of the successful RF ablation of AVNRT. Nevertheless, according to the results, its specificity could increase with the presence of more than 14 cumulative junctional beats. Although the development of JR during slow-pathway RF ablation seems not to be reliable as a success end point, its absences could be a marker of requiring more energy application to ablate the slow pathway.

Bagherzadeh|Ataallah|A|
Rezaee|Mohammad Esmaeel|ME|
Farahani|Maryam Moshkani|MM|

Junctional rhythm
Catheter ablation
atrioventricular nodal reentrant
Tachycardia
supraventricular


Lennox-Gastaut syndrome in adulthood: Long-term clinical follow-up of 38 patients and analysis of their recorded seizures.

Abstract: Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox-Gastaut syndrome. We identified 38 (22 females, 16 males) patients with LGS older than age 18years at their last evaluation, with mean age of 43.3±10.6years. Median follow-up was 14.4years (range: 2-40). All of our patients had 3 or more seizure types during their clinical history. The most prevalent seizure types at follow-up were atypical absences (28/38), tonic (28/38), generalized tonic-clonic (17/38), focal (11/38), and myoclonic seizures (9/38). All patients had drug-resistant seizures. Besides epilepsy, intellectual disability and behavioral problems were prominent features. Surprisingly, paroxysmal nonepileptic seizures were reported in 3 patients. Our observations confirm the poor outcome of Lennox-Gastaut syndrome through adulthood, regardless of age at seizure onset, etiology, and history of previous West syndrome.

Vignoli|Aglaia|A|
Oggioni|Gaia|G|
De Maria|Giovanni|G|
Peron|Angela|A|
Savini|Miriam Nella|MN|
Zambrelli|Elena|E|
Chiesa|Valentina|V|
La Briola|Francesca|F|
Turner|Katherine|K|
Canevini|Maria Paola|MP|

Seizures
Drug-resistance
Lennox–Gastaut syndrome
Long-term evolution
Video-EEG recordings


The lens growth process.

Abstract: The factors that regulate the size of organs to ensure that they fit within an organism are not well understood. A simple organ, the ocular lens serves as a useful model with which to tackle this problem. In many systems, considerable variance in the organ growth process is tolerable. This is almost certainly not the case in the lens, which in addition to fitting comfortably within the eyeball, must also be of the correct size and shape to focus light sharply onto the retina. Furthermore, the lens does not perform its optical function in isolation. Its growth, which continues throughout life, must therefore be coordinated with that of other tissues in the optical train. Here, we review the lens growth process in detail, from pioneering clinical investigations in the late nineteenth century to insights gleaned more recently in the course of cell and molecular studies. During embryonic development, the lens forms from an invagination of surface ectoderm. Consequently, the progenitor cell population is located at its surface and differentiated cells are confined to the interior. The interactions that regulate cell fate thus occur within the obligate ellipsoidal geometry of the lens. In this context, mathematical models are particularly appropriate tools with which to examine the growth process. In addition to identifying key growth determinants, such models constitute a framework for integrating cell biological and optical data, helping clarify the relationship between gene expression in the lens and image quality at the retinal plane.

D036341:Intercellular Signaling Peptides and Proteins

Lens
Growth
Mathematical model
Branching process
FGF
Notch
Stochastic
Wnt


Different limb lengths in gastric bypass surgery: study protocol for a Swiss multicenter randomized controlled trial (SLIM).

Abstract:
BACKGROUND
Obesity and type 2 diabetes mellitus are reaching epidemic proportions. In morbidly obese patients, bariatric operations lead to sustained weight loss and relief of comorbidities in the majority of patients. Laparoscopic Roux-Y-gastric bypass (RYGB) is one of the most frequently performed operations, but it is still unknown why some patients respond better than others. Therefore, a number of variations of this operation have been introduced. Recent evidence suggests that a longer bypassed biliopancreatic limb (BPL) has the potential to be more effective compared to the standard RYGB with a shorter BPL length. This article describes the design and protocol of a randomized controlled trial comparing the outcome of a RYGB operation with a long versus short BPL.

METHODS/DESIGN
The trial is designed as a multicenter, randomized, patient- and observer-blinded trial. The relevant ethics committee has approved the trial protocol. To demonstrate that long BPL RYGB is superior compared to short BPL RYGB in terms of weight loss and resolution of T2DM, the study is conducted as a superiority trial. Postoperative percent total weight loss and nutritional deficiency rate are the primary endpoints, whereas morbidity, mortality, remission of obesity-related comorbidities and quality of life are secondary endpoints. Eight hundred patients, between 18 and 65 years and with a body mass index (BMI) from 35 to 60 kg/m2 who meet the regulatory rules for bariatric surgery in Switzerland, will be randomized. The endpoints and baseline measurements will be assessed pre-, intra-, and postoperatively.

DISCUSSION
With its high number of patients and a 5-year follow-up, this study will answer questions about effectiveness and safety of long BPL RYGB and provide level I evidence for improvement of the standard RYGB. These findings might therefore potentially influence global bariatric surgery guidelines.

TRIAL REGISTRATION
ClinicalTrials.gov NCT04219787 . Registered on 7 January 2020.

D016032:Randomized Controlled Trials as Topic

Different limb lengths
Randomized controlled trial
Weight loss
Roux-en-Y gastric bypass


In Vivo Murine-Matured Human CD3+ Cells as a Preclinical Model for T Cell-Based Immunotherapies.

Abstract: Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors. The use of matured human T cells in mice usually leads to graft-versus-host disease (GvHD), which severely limits the effectiveness of such studies. Alternatively, adult apheresis CD34+ cells engraft in neonatal non-obese diabetic (NOD)-severe combined immunodeficiency (SCID)-common γ chain-/- (NSG) mice and lead to the development of CD3+ T cells in peripheral circulation. We demonstrate that these in vivo murine-matured autologous CD3+ T cells from humans (MATCH) can be collected from the mice, engineered with lentiviral vectors, reinfused into the mice, and detected in multiple lymphoid compartments at stable levels over 50 days after injection. Unlike autologous CD3+ cells collected from human donors, these MATCH mice did not exhibit GvHD after T cell administration. This novel mouse model offers the opportunity to screen different immunotherapy-based treatments in a preclinical setting.

Haworth|Kevin G|KG|
Ironside|Christina|C|
Norgaard|Zachary K|ZK|
Obenza|Willimark M|WM|
Adair|Jennifer E|JE|
Kiem|Hans-Peter|HP|

Immunotherapy
adoptive cellular immunotherapy
NSG
MATCH mice
mouse model
ACI
CAR
HIV
T cell therapy
chimeric antigen receptor


The response of soil respiration to precipitation change is asymmetric and differs between grasslands and forests.

Abstract: Intensification of the Earth's hydrological cycle amplifies the interannual variability of precipitation, which will significantly impact the terrestrial carbon (C) cycle. However, it is still unknown whether previously observed relationship between soil respiration (Rs ) and precipitation remains applicable under extreme precipitation change. By analyzing the observations from a much larger dataset of field experiments (248 published papers including 151 grassland studies and 97 forest studies) across a wider range of precipitation manipulation than previous studies, we found that the relationship of Rs response with precipitation change was highly nonlinear or asymmetric, and differed significantly between grasslands and forests, between moderate and extreme precipitation changes. Response of Rs to precipitation change was negatively asymmetric (concave-down) in grasslands, and double-asymmetric in forests with a positive asymmetry (concave-up) under moderate precipitation changes and a negative asymmetry (concave-down) under extreme precipitation changes. In grasslands, the negative asymmetry in Rs response was attributed to the higher sensitivities of soil moisture, microbial and root activities to decreased precipitation (DPPT) than to increased precipitation (IPPT). In forests, the positive asymmetry was predominantly driven by the significant increase in microbial respiration under moderate IPPT, while the negative asymmetry was caused by the reductions in root biomass and respiration under extreme DPPT. The different asymmetric responses of Rs between grasslands and forests will greatly improve our ability to forecast the C cycle consequences of increased precipitation variability. Specifically, the negative asymmetry of Rs response under extreme precipitation change suggests that the soil C efflux will decrease across grasslands and forests under future precipitation regime with more wet and dry extremes.

extreme precipitation
nonlinear
autotrophic respiration
carbon cycle
double asymmetry model
drought
heterotrophic respiration


Are males and females of Populus cathayana differentially sensitive to Cd stress?

Abstract: This study clarifies the mechanisms of Cd uptake, translocation and detoxification in Populus cathayana Rehder females and males, and reveals a novel strategy for dioecious plants to cope with Cd contamination. Females exhibited a high degree of Cd uptake and root-to-shoot translocation, while males showed extensive Cd accumulation in roots, elevated antioxidative capacity, and effective cellular and bark Cd sequestration. Our study also found that Cd is largely located in epidermal and cortical tissues of male roots and leaves, while in females, more Cd was present in vascular tissues of roots and leaves, as well as in leaf mesophyll. In addition, the distributions of sulphur (S) and phosphorus (P) were very similar as that of Cd in males, but the associations were weak in females. Scanning electron microscopy and energy spectroscopy analyses suggested that the amounts of tissue Cd were positively correlated with P and S amounts in males, but not in females (a weak correlation between S and Cd). Transcriptional data suggested that Cd stress promoted the upregulation of genes related to Cd uptake and translocation in females, and that of genes related to cell wall biosynthesis, metal tolerance and secondary metabolism in males. Our results indicated that coordinated physiological, microstructural and transcriptional responses to Cd stress endowed superior Cd tolerance in males compared with females, and provided new insights into mechanisms underlying sexually differential responses to Cd stress.

Liu|Miao|M| Liu|Xingxing|X| Kang|Jieyu|J| Korpelainen|Helena|H| Li|Chunyang|C|

D018506:Gene Expression Regulation, Plant

Cd stress
Cd uptake
Cd sequestration
Transcripts
Dioecy
Sexual differences


Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells.

Abstract: We have previously demonstrated that the circadian clock protein period (Per)1 coordinately regulates multiple genes involved in Na(+) reabsorption in renal collecting duct cells. Consistent with these results, Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice. The proximal tubule is responsible for a majority of Na(+) reabsorption. Previous work has demonstrated that expression of Na(+)/H(+) exchanger 3 (NHE3) oscillates with a circadian pattern and Na(+)-glucose cotransporter (SGLT)1 has been demonstrated to be a circadian target in the colon, but whether these target genes are regulated by Per1 has not been investigated in the kidney. The goal of the present study was to determine if Per1 regulates the expression of NHE3, SGLT1, and SGLT2 in the kidney. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of SGLT1 and NHE3 but not SGLT2 in the renal cortex of mice. Per1 small interfering RNA and pharmacological blockade of Per1 nuclear entry in human proximal tubule HK-2 cells yielded the same results. Examination of heterogeneous nuclear RNA suggested that the effects of Per1 on NHE3 and SGLT1 expression occurred at the level of transcription. Per1 and the circadian protein CLOCK were detected at promoters of NHE3 and SGLT1. Importantly, both membrane and intracellular protein levels of NHE3 and SGLT1 were decreased after blockade of nuclear Per1 entry. This effect was associated with reduced activity of Na(+)-K(+)-ATPase. These data demonstrate a role for Per1 in the transcriptional regulation of NHE3 and SGLT1 in the kidney.

Solocinski|Kristen|K|
Richards|Jacob|J|
All|Sean|S|
Cheng|Kit-Yan|KY|
Khundmiri|Syed J|SJ|
Gumz|Michelle L|ML|

transcription
kidney
Na+-glucose cotransporter 1
Na+/H+ exchanger
gene regulation
period 1
renal sodium reabsorption


PTHrP in differentiating human mesenchymal stem cells: transcript isoform expression, promoter methylation, and protein accumulation.

Abstract: Human PTHrP gene displays a complex organization with nine exons producing diverse mRNA variants due to alternative splicing at 5' and 3' ends and the existence of three different transcriptional promoters (P1, P2 and P3), two of which (P2 and P3) contain CpG islands. It is known that the expression of PTHrP isoforms may be differentially regulated in a developmental stage- and tissue-specific manner. To search for novel molecular markers of stemness/differentiation, here we have examined isoform expression in fat-derived mesenchymal stem cells both maintained in stem conditions and induced toward adipo- and osteogenesis. In addition, the expression of the splicing isoforms derived from P2 and P3 promoters was correlated to the state of methylation of the latter. Moreover, we also performed a quantitative evaluation of intracellular and secreted PTHrP protein product in undifferentiated stem cells and in parallel cultures at various differentiation stages. The data obtained indicate that from the stemness condition to that of osteo- and adipo-genic differentiated cells, the expression of isoforms becomes increasingly selective, thereby being a potential gene signature for the monitoring of cell stem or committed/differentiating state and that the switching-off of PTHrP isoform expression is mostly promoter methylation-dependent. Moreover, PTHrP intracellular retention is down-regulated in osteo-differentiating cells whereas the secretion of the protein in the extracellular medium is up-regulated with respect to stem cells, thereby suggesting that these variations of the intracellular and extracellular levels of PTHrP could potentially be enclosed in the list of the available protein signature of osteogenic differentiation.

Longo|Alessandra|A| Librizzi|Mariangela|M| Naselli|Flores|F| Caradonna|Fabio|F| Tobiasch|Edda|E| Luparello|Claudio|C|

microtiter immunocytochemical ELISA assay

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


Use of a Yeast tRNase Killer Toxin to Diagnose Kti12 Motifs Required for tRNA Modification by Elongator.

Abstract: Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin's action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g., nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them.

Mehlgarten|Constance|C|
Prochaska|Heike|H|
Hammermeister|Alexander|A|
Abdel-Fattah|Wael|W|
Wagner|Melanie|M|
Krutyhołowa|Rościsław|R|
Jun|Sang Eun|SE|
Kim|Gyung-Tae|GT|
Glatt|Sebastian|S|
Breunig|Karin D|KD|
Stark|Michael J R|MJR|
Schaffrath|Raffael|R|

D048868:Adaptor Proteins, Signal Transducing

tRNase
Kti12
zymocin
ribotoxin
Elongator complex
tRNA anticodon modification


Cytotoxic Activity of Piperazin-2-One-Based Structures: Cyclic Imines, Lactams, Aminophosphonates, and Their Derivatives.

Abstract: N-Heterocycles are considered as desirable scaffolds for the development of novel lead compounds for anticancer drug research. Among them, phosphorus-containing amino-derivatives play a crucial role. A series of imines and products of their further reactions with P-nucleophiles were obtained starting from vicinal bisamines. Reaction of ethylenediamine and α-carbonyl esters yielded in novel unexpected products, which structures were confirmed by crystallographic measurements. The cytotoxic activity evaluation was done on a variety of cell lines including HUH7, AKH12, DAOY, UW228-2, D283, D425, and U251. Human umbilical vein endothelial cells (HUVECs) were used as control. Two of the tested compounds, bearing TADDOL-derived, and trifluoromethyl substituents showed a significant effect on cell viability, though comparable to nonmalignant cells.

cytotoxic activity
cyclic imines
aminophosphonates
Mannich bases
Pudovik reaction
viability assay


The future role of metal-on-metal hip resurfacing.

Abstract:
PURPOSE
The purpose of this review was to assess the ten to 15-year outcomes of metal-on-metal hip resurfacing (MoM HR) when performed at designing and independent centres, and make recommendations for the future use of MoM HR.

METHODS
Studies reporting ten to 15-year outcomes for modern MoM HR devices from both designing and independent centres were reviewed. Outcomes from these studies were assessed to allow the formulation of recommendations for the future use of MoM HR.

RESULTS
Two MoM HR designs, the Birmingham Hip Resurfacing (BHR) and Conserve Plus, have outcomes reported at a minimum of ten years. The BHR was the only device with outcomes reported at a minimum of ten years by both designing (overall survival of up to 95.8 % at 15 years) and independent surgeons (overall survival of 87.1-94.5 % at ten years). Implant survival in these seven BHR studies was influenced by the pre-operative diagnosis (primary osteoarthritis had better outcomes), gender (male patients had better outcomes), and femoral component head size (larger sizes had better outcomes). In contrast to independent centres, designing surgeons reported acceptable outcomes in female patients undergoing BHR.

CONCLUSIONS
There remains a role for MoM HR in young active male patients with primary osteoarthritis, provided the surgeon has sufficient experience in the procedure, the implant has an established record, and the patient is aware of the potential risks associated with MoM bearings and HR. Very experienced HR surgeons may also consider this procedure in females provided they meet the refined inclusion criteria described (including femoral head sizes of 46 mm and above).

Matharu|Gulraj S|GS|
Pandit|Hemant G|HG|
Murray|David W|DW|
Treacy|Ronan B C|RB|

D019644:Arthroplasty, Replacement, Hip
D005544:Forecasting
D006622:Hip Prosthesis
D006801:Humans
D061825:Metal-on-Metal Joint Prostheses
D016896:Treatment Outcome

Metal-on-metal
Hip resurfacing
Outcomes
Survival
Indications


ENPP1 in the Regulation of Mineralization and Beyond.

Abstract: ENPP1 is well known for its role in regulating skeletal and soft tissue mineralization. It primarily exerts its function through the generation of pyrophosphate, a key inhibitor of hydroxyapatite formation. Several previous studies have suggested that ENPP1 also contributes to a range of human diseases including diabetes, cancer, cardiovascular disease, and osteoarthritis. In this review, we summarize the pathological roles of ENPP1 in mineralization and these soft tissue disorders. We also discuss the underlying mechanisms through which ENPP1 exerts its pathological effects. A fuller understanding of the pathways through which ENPP1 acts may help to develop novel therapeutic strategies for these commonly diagnosed morbidities.

Roberts|Fiona|F|
Zhu|Dongxing|D|
Farquharson|Colin|C|
Macrae|Vicky E|VE|

ENPP1
mineralization
diabetes
cardiovascular disease
pathological effects


Plasmodium falciparum Clag9-Associated PfRhopH Complex Is Involved in Merozoite Binding to Human Erythrocytes.

Abstract: Cytoadherence-linked asexual gene 9 (Clag9), a conserved Plasmodium protein expressed during the asexual blood stages, is involved in the cytoadherence of infected red blood cells (RBCs) to the endothelial lining of blood vessels. Here, we show that Plasmodium falciparum Clag9 (PfClag9) is a component of the PfClag9-RhopH complex that is involved in merozoite binding to human erythrocytes. To characterize PfClag9, we expressed four fragments of PfClag9, encompassing the entire protein. Immunostaining analysis using anti-PfClag9 antibodies showed expression and localization of PfClag9 at the apical end of the merozoites. Mass spectrometric analysis of merozoite extracts after immunoprecipitation using anti-PfClag9 antibody identified P. falciparum rhoptry-associated protein 1 (PfRAP1), PfRAP2, PfRAP3, PfRhopH2, and PfRhopH3 as associated proteins. The identified rhoptry proteins were expressed, and their association with PfClag9 domains was assessed by using protein-protein interaction tools. We further showed that PfClag9 binds human RBCs by interacting with the glycophorin A-band 3 receptor-coreceptor complex. In agreement with its cellular localization, PfClag9 was strongly recognized by antibodies generated during natural infection. Mice immunized with the C-terminal domain of PfClag9 were partially protected against a subsequent challenge infection with Plasmodium berghei, further supporting a biological role of PfClag9 during natural infection. Taken together, these results provide direct evidence for the existence of a PfRhopH-Clag9 complex on the Plasmodium merozoite surface that binds to human RBCs.

Chourasia|Bishwanath Kumar|BK|
Deshmukh|Arunaditya|A|
Kaur|Inderjeet|I|
Paul|Gourab|G|
Panda|Ashutosh|A|
Rathore|Sumit|S|
Singh|Susheel K|SK|
Theisen|Michael|M|
Mohmmed|Asif|A|
Malhotra|Pawan|P|


Dual drug loaded liposome bearing apigenin and 5-Fluorouracil for synergistic therapeutic efficacy in colorectal cancer.

Abstract: Multidrug-based combinatorial therapeutic regiments which target multiple pathways simultaneously are being utilized as a therapeutic strategy of choice due to reduction in toxicity profile and enhancement of therapeutic index of the individual drugs. 5-Fluorouracil is a clinically approved drug which has limited response rate in the realm of colorectal cancer amelioration, hence our study aims to improve its efficacy by aiming the simultaneous delivery of 5-Flurouracil and apigenin which is naturally occurring flavone abundantly present in fruit and vegetables through a single liposome to combat and control colorectal cancer effectively in-vitro and in-vivo. The liposomal nanocarrier bearing the anti-tumorigenic agent apigenin was designed in this study in order to improve the bioavailability of the flavone while at the same time achieve combinatorial drug regime with 5- Fluorouracil. This study reports the synthesis and production of a relatively robust dual drug-loaded liposomal formulation by modified thin film hydration method which substantially entraps both the drugs. Even though there have been reports of the combinatorial regimen involving apigenin and 5-Flurouracil our study reports the optimal molar ratio for effective synergistic therapeutic application of this drug combination to alleviate colorectal cancer. The cytotoxicity and cellular effects of individual, combinatorial free drugs and their liposomal counterparts tested against two human colon cancer cell lines revealed significantly higher cytotoxicity of the dual-drug liposomes. The dual-drug liposomes demonstrated enhanced inhibition of angiogenesis, better reduction in cell proliferation and increased apoptotic potential. Cell signaling studies indicating a significant upregulation of pAMPK and activity against downstream targets by dual drug liposomes suggested its role in the reversal of Warburg effect. The formulation was tested in a preclinical setting in nude mice tumor xenograft model and was found to have greater anti-neoplastic and anti-tumorigenic effect. The study indicated that the increased chemotherapeutic potential in vivo was due to the passive targeting achieved by the liposomal drug loaded nano-carrier and the synergistic effect of apigenin in 5-Fluorouracil treatment offers a new attractive alternative to enhance the therapeutic potency of drugs and paves way for potential clinical applications.

D000971:Antineoplastic Combined Chemotherapy Protocols

D015972:Gene Expression Regulation, Neoplastic

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D023041:Xenograft Model Antitumor Assays

Dual drug loaded liposomes
Apigenin
5-Fluorouracil
Colorectal cancer
Drug delivery


Cytotoxicity and transcriptome changes triggered by CuInS2/ZnS quantum dots in human glial cells.

Abstract: As a newly developed cadmium-free quantum dot (QD), CuInS2/ZnS has great application potential in many fields, but its biological safety has not been fully understood. In this study, the in vitro toxicity of CuInS2/ZnS QDs on U87 human glioma cell line was explored. The cells were treated with different concentrations of QDs (12.5, 25, 50 and 100 μg/mL), and the uptake of QDs by the U87 cells was detected by fluorescence imaging and flow cytometry. The cell viability was observed by MTT assay, and the gene expression profile was analyzed by transcriptome sequencing. These results showed that QDs could enter the cells and mainly located in the cytoplasm. The uptake rate was over 90 % when the concentration of QDs reached 25 μg/mL. The cell viability (50 and 100 μg/mL) increased at 24 h (P < 0.05), but no significant difference after 48 h and 72 h treatment. The results of differential transcription showed that coding RNA accounted for the largest proportion (62.15 %), followed by long non-coding RNA (18.65 %). Total 220 genes were up-regulated and 1515 genes were down-regulated, and significantly altered gene functions included nucleosome, chromosome-DNA binding, and chromosome assembly. In conclusion, CuInS2/ZnS QDs could enter U87 cells, did not reduce the cell viability, but would obviously alter the gene expression profile. These findings provide valuable information for a proper understanding of the toxicity risk of CuInS2/ZnS QD and promote the rational utilization of QDs in the future.

Xue|Dahui|D| Zou|Wenyi|W| Liu|Dongmeng|D| Li|Li|L| Chen|Tingting|T| Yang|Zhiwen|Z| Chen|Yajing|Y| Wang|Xiaomei|X| Lu|Wencan|W| Lin|Guimiao|G|

Cytotoxicity
Transcriptome
Quantum dots
Neurotoxicity


The Positive Role of Nanometric Molybdenum-Vanadium Carbides in Mitigating Hydrogen Embrittlement in Structural Steels.

Abstract: The influence of hydrogen on the fracture toughness and fatigue crack propagation rate of two structural steel grades, with and without vanadium, was evaluated by means of tests performed on thermally precharged samples in a hydrogen reactor at 195 bar and 450 °C for 21 h. The degradation of the mechanical properties was directly correlated with the interaction between hydrogen atoms and the steel microstructure. A LECO DH603 hydrogen analyzer was used to study the activation energies of the different microstructural trapping sites, and also to study the hydrogen eggresion kinetics at room temperature. The electrochemical hydrogen permeation technique was employed to estimate the apparent hydrogen diffusion coefficient. Under the mentioned hydrogen precharging conditions, a very high hydrogen concentration was introduced within the V-added steel (4.3 ppm). The V-added grade had stronger trapping sites and much lower apparent diffusion coefficient. Hydrogen embrittlement susceptibility increased significantly due to the presence of internal hydrogen in the V-free steel in comparison with tests carried out in the uncharged condition. However, the V-added steel grade (+0.31%V) was less sensitive to hydrogen embrittlement. This fact was ascribed to the positive effect of the precipitated nanometric (Mo,V)C to alleviate hydrogen embrittlement. Mixed nanometric (Mo,V)C might be considered to be nondiffusible hydrogen-trapping sites, in view of their strong hydrogen-trapping capability (~35 kJ/mol). Hence, mechanical behavior of the V-added grade in the presence of internal hydrogen was notably improved.

fracture toughness
electrochemical hydrogen permeation
nanometric (Mo,V)C
TDA analysis
fatigue crack growth rate


Crumpling and Unfolding of Montmorillonite Hybrid Nanocoatings as Stretchable Flame-Retardant Skin.

Abstract: Flame-retardant coatings are widely used in a variety of personnel or product protection, and many applications would benefit from film stretchability if suitable materials are available. It is challenging to develop flame-retardant coatings that are stretchable, eco-friendly, and capable of being integrated on mechanically dynamic devices. Here, a concept is reported that uses pretextured montmorillonite (MMT) hybrid nanocoatings that can undergo programed unfolding to mimic the stretchability of elastomeric materials. These textured MMT coatings can be transferred onto an elastomeric substrate to achieve an MMT/elastomer bilayer device with high stretchability (225% areal strain) and effective flame retardancy. The bilayer composite is utilized as flame-retardant skin for a soft robotic gripper, and it is demonstrated that the actuated response can manipulate and rescue irregularly shaped objects from a fire scene. Furthermore, by depositing the conformal MMT nanocoatings on nitrile gloves, the firefree gloves can endure direct flame contact without ignition.

Chang|Ting-Hsiang|TH|
Tian|Yuan|Y|
Wee|Daniel L Y|DLY|
Ren|Hongliang|H|
Chen|Po-Yen|PY|

flame retardancy
soft robotics
crumpled and wrinkled textures
mechanical stretchability
montmorillonite nanostructures


High endemicity in aquatic dance flies of Corsica, France (Diptera, Empididae, Clinocerinae and Hemerodromiinae), with the description of a new species of Chelipoda.

Abstract: All known records of aquatic dance flies (Empididae, Clinocerinae: 21 species; Hemerodromiinae: eight species) from the island of Corsica (France) are summarized, including previously unpublished data and data on the newly described species Chelipoda puschae Ivković, Perović & Grootaert, sp. nov. This species was collected during the "La Planète Revisitée Corsica 2019" survey and represents the first description of a new species in the genus Chelipoda from the European-Mediterranean region in more than 180 years. A key to European species of Chelipoda is provided. Including the new species, five species are recorded from Corsica for the first time: Dolichocephala malickyi Wagner, 1995, Dolichocephala oblongoguttata (Dale, 1878), Dolichocephala ocellata (Costa, 1854), Chelifera subangusta Collin, 1961, and Hemerodromia unilineata Zetterstedt, 1842. The new species is described and illustrated, and new records of aquatic dance flies from Corsica are given, with new data on 17 species in eight different genera. At present, 29 species of aquatic dance flies are known from Corsica, with 10 species endemic to the island.

endemicity
Empididae
new species
Distribution
Our Planet Reviewed expedition


The effect of pain on presence and severity of depressive disorders in older persons: The role of perceived control as mediator.

Abstract:
BACKGROUND
The relation between pain and depression is reported repeatedly. It is suggested that pain by itself is not sufficient for the development of depression. We aim to study the role of perceived control as mediating factor in the relation between pain and depressive disorders at old age.

METHODS
Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used, including 345 persons with DSM-IV depressive disorders (CIDI) and 125 control persons without depressive disorders, aged 60 years and over. Measures included severity of depression (Inventory of Depressive Symptomatology), presence and intensity of pain and pain-related disability (Chronic Graded Pain scale), and a general measure of perceived control over life (Pearlin Mastery Scale). In mediation analyses direct and indirect effects were estimated.

RESULTS
Older persons with depressive disorders reported pain more frequently with higher intensity than controls. After controlling for confounding, the direct effect of pain intensity and the indirect effect through perceived control on depression were OR=1.10 (CI 95% .98;1.25) and OR=1.24 (1.15;1.35). For pain-related disability these were OR=1.14 (1.02;1.29) and OR=1.21 (1.13;1.29). In depressed persons there was a strong direct effect of pain intensity and disability and a smaller indirect effect through perceived control on severity of depressive symptoms.

LIMITATIONS
This cross-sectional study cannot give evidence on causal direction.

CONCLUSIONS
Perceived control plays an important role as mediator in the association between pain and presence of depression. In depressed persons however, the direct role of pain seems more important in the association with depression severity.

de Waal|M W M|MW|
Hegeman|J M|JM|
Gussekloo|J|J|
Verhaak|P F M|PF|
van der Mast|R C|RC|
Comijs|H C|HC|

D039721:Diagnostic and Statistical Manual of Mental Disorders

Pain
Depressive disorder
Perceived control
Mediator
Aged


Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation.

Abstract:
AIMS
A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess cost-effectiveness of this nurse-led care programme vs. usual care.

METHODS AND RESULTS
A cost-effectiveness analysis was undertaken alongside the randomized controlled trial in which 712 patients were included at the Maastricht University Medical Centre, The Netherlands, and allocated to nurse-led care or usual care. Nurse-led care implied guideline-adherent management, steered by dedicated software, supervised by cardiologists. Usual care was regular outpatient care performed by cardiologists. A cost per life-year and a cost per quality-adjusted life-year (QALY) analysis was performed, both from a hospital perspective. The nurse-led care programme was associated with slightly more life-years and QALYs at a lower cost. Specifically, the nurse-led programme contributed to 0.009 QALY gains with a reduced cost of €1109 per patient and a gain of 0.02 life-years with a reduced cost of €735 per patient. Therefore, the nurse-led programme would be considered dominant. In fact, for all the possible values of willingness to pay for a QALY the nurse-led programme is considered to be more likely cost-effective than the care as usual.

CONCLUSION
The cost-effectiveness analysis in the present study demonstrated that a nurse-led integrated care approach will save costs and improve survival and quality of life, and is therefore a cost-effective management strategy for patients with AF.

Hendriks|Jeroen|J|
Tomini|Florian|F|
van Asselt|Thea|T|
Crijns|Harry|H|
Vrijhoef|Hubertus|H|

D019033:Delivery of Health Care, Integrated

Cardiovascular hospitalization and death


Expression and function of microRNA-9 in the mid-hindbrain area of embryonic chick.

Abstract:
BACKGROUND
MiR-9 is a small non-coding RNA that is highly conserved between species and primarily expressed in the central nervous system (CNS). It is known to influence proliferation and neuronal differentiation in the brain and spinal cord of different vertebrates. Different studies have pointed to regional and species-specific differences in the response of neural progenitors to miR-9.

METHODS
In ovo and ex ovo electroporation was used to overexpress or reduce miR-9 followed by mRNA in situ hybridisation and immunofluorescent stainings to evaluate miR- expression and the effect of changed miR-9 expression.

RESULTS
We have investigated the expression and function of miR-9 during early development of the mid-hindbrain region (MH) in chick. Our analysis reveals a closer relationship of chick miR-9 to mammalian miR-9 than to fish and a dynamic expression pattern in the chick neural tube. Early in development, miR-9 is diffusely expressed in the entire brain, bar the forebrain, and it becomes more restricted to specific areas of the CNS at later stages. MiR-9 overexpression at HH9-10 results in a reduction of FGF8 expression and premature neuronal differentiation in the mid-hindbrain boundary (MHB). Within the midbrain miR-9 does not cause premature neuronal differentiation it rather reduces proliferation in the midbrain.

CONCLUSION
Our findings indicate that miR-9 has regional specific effects in the developing mid-hindbrain region with a divergence of response of regional progenitors.

Alwin Prem Anand|A|A|
Huber|Carola|C|
Asnet Mary|John|J|
Gallus|Nancy|N|
Leucht|Christoph|C|
Klafke|Ruth|R|
Hirt|Bernhard|B|
Wizenmann|Andrea|A|0000-0001-9766-2315

D018507:Gene Expression Regulation, Developmental

Mid-hindbrain area
Chick
miR-9
Brain development
microRNA


The Exploration of Health-Related Quality of Life.

Abstract: The purpose of this study was to explore quality of life (QoL) and the factors influencing QoL in gynecological cancer patients. One hundred sixty-seven patients with gynecologic cancers were recruited from a district hospital in Southern Taiwan. The instruments used included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Version 3.0 in Chinese (EORTC QLQ-C30), the Symptom Distress Scale, and demographic characteristics and disease-related variables. The results showed that the mean score for the QLQ-C30 was 61.13 ( SD = 22.71). In the stepwise regression model, two factors predicted overall global QoL: symptom distress (33.8%) and current occupation (2.2%). These predictors accounted for 36.0% of the total variance. These results showed that symptom distress was a predictor of QoL. This study provides a reference for use when designing improved educational care programs that reduce patient symptom distress and enhance gynecologic cancer patients' QoL.

Wu|Shu-Fen|SF| Tong|Hong-Yi|HY| Kan|Yuen-Yee|YY| Su|Sheng-Hui|SH| Lee|Meng-Chi|MC| Kao|Chia-Chan|CC| Lin|Yu-Hua|YH|

D003430:Cross-Sectional Studies
D005260:Female
D005833:Genital Neoplasms, Female
D006801:Humans
D008875:Middle Aged
D010353:Patient Education as Topic
D011788:Quality of Life
D011795:Surveys and Questionnaires
D013624:Taiwan

quality of life
gynecologic cancer
symptom distress


Rapid and effective photodynamic treatment of biofilm infections using low doses of amoxicillin-coated gold nanoparticles.

Abstract: Bacterial biofilm are complex microbial communities covered by a matrix of extracellular polymeric substances, which develops when a community of microorganisms irreversibly adheres to a living or inert surface. This structure is considered an important virulence factor because it is difficult to eradicate and often responsible for treatment failures. This adherent community represents one of the greatest problems in public health due to the continued emergence of conventional antibiotic-therapy resistance. Photodynamic Antimicrobial Therapy (PACT) is a therapeutic alternative and promises to be an effective treatment against multiresistant bacteria biofilm, demonstrating a broad spectrum of action. This work demonstrates the reduction in biofilms of relevant clinical isolates (as Pseudomonas aeruginosa and Staphylococcus aureus) treated with PACT using low concentrations of amoxicillin-coated gold nanoparticles (amoxi@AuNP) as a photosensitizer. Moreover, the viability reduction of 60% in S. aureus biofilms and 70% in P. aeruginosa biofilms were obtained after three hours of irradiation with white light and amoxi@AuNP. Scanning electron microscopy analysis revealed that amoxi@AuNP could penetrate and cause damage to the biofilm matrix, and interact with bacteria cells. A strong biofilm production in P. aeruginosa was observed by confocal laser scanning microscopy using acridine orange as a probe, and a markedly decrease in live bacteria was appreciated when PACT was applied. The use of amoxi@AuNP for PACT allows the viability reduction of clinical Gram positive and Gram negative biofilms. This novel strategy needs shorter irradiation times and lower concentrations of nanoparticles than other reports described. This could be attributed to two major innovations: the selectivity for the bacterial wall given by the amoxicillin and the polydispersity of size and shapes with seems to contribute to the photo-antibacterial capacity.

Rocca|Diamela M|DM|
Silvero C|M Jazmin|MJ|
Aiassa|Virginia|V|
Cecilia Becerra|M|M|

Biofilms
PACT
Pseudomonas aeruginosa
Staphylococcus aureus
Amoxi@AuNP


Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation.

Abstract: Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.

Lu|Tian-Fei|TF| Yang|Tai-Hua|TH| Zhong|Cheng-Peng|CP| Shen|Chuan|C| Lin|Wei-Wei|WW| Gu|Guang-Xiang|GX| Xia|Qiang|Q| Xu|Ning|N|

Hepatic macrophages
Liver transplantation
Ischemia-reperfusion injury
Kupffer cells
Pattern recognition receptors
Tumor necrosis factor-α


Diabetes mellitus and functional sperm characteristics: A meta-analysis of observational studies.

Abstract:
OBJECTIVE
Insulin resistance and diabetes mellitus (DM) are well defined causes of female infertility. Animal studies present evidence for decreased sperm quality, but conflicting results have been presented in clinically-orientated studies. We sought to evaluate whether DM affects functional sperm characteristics.

STUDY DESIGN
We searched the Medline, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials databases.

RESULTS
DM seems to decrease the seminal volume (MD -0.66ml, 95% CI -1.10, -0.22) and the percentage of motile cells (MD -14.29%, 95% CI -22.76, -5.82) and increase the FSH values (MD 0.47mIU/ml, 95% CI 0.01, 0.93) of men who were screened for infertility. It does not, however, influence the total sperm count (MD 13.16 106 cells, 95% CI -22.75, 49.07), the percentage of normal sperm morphology (-3.06%, 95% CI -6.25, 0.14), or LH (MD 0.65mIU/ml, 95% CI -0.84, 2.13 Supp. Fig. 2) and testosterone values (MD -0.18ng/ml, 95% CI -0.60, 0.24).

CONCLUSION
Current evidence suggests that the presence of DM seems to influence functional sperm characteristics. Firm results are, however, precluded due to the significant heterogeneity of the included studies. Future prospective studies will clarify whether the DM affects semen quality and IVF outcome.

Pergialiotis|Vasilios|V|
Prodromidou|Anastasia|A|
Frountzas|Maximos|M|
Korou|Laskarina Maria|LM|
Vlachos|Georgios D|GD|
Perrea|Despina|D|

Diabetes Sperm FSH LH Testosterone Semen


Parents' observed responses to children's emotional distress: Relations with social competence in preschool.

Abstract: Although affective interactions in the family are important for development, home observational data are sparse. We replicated and extended one such study, Roberts & Strayer (1987, Developmental Psychology, 23, 415). Interactions in 33 two-parent families (mean child age = 4.8 years; 48% girls) were observed for four evenings, from suppertime until the child settled for the night. Parents completed the Child Rearing Practices Q-sort. Peer interactions and friendship networks in preschool were observed over four days. Teachers and observers completed the Preschool Behavior Q-Sort. Based on Q-rated peer competence and aggression, three expected groups of children were identified, one of them high on both aggression and peer competence. Although socially active and accepted by peers, they were, compared with other children, less cooperative with adults, less prosocial with peers, more impulsive, less achievement oriented, less purposive, and less happy (mean η2  = .52). Parenting, especially observed impatience, threats, and use of force when children were emotionally distressed, showed important differences across groups.

social competence
friendships
aggression
bullying
prosocial behaviours
socialization of emotion


Primary health care reform in Saudi Arabia: progress, challenges and prospects.

Abstract:
Background
Saudi Arabia embarked on transforming its primary health care system in 2016 to meet international standards, gain the people's trust and respond to the growing burden of noncommunicable diseases, as proposed in the Saudi Vision 2030.

Aims
This review aims to highlight the progress, identify challenges and prospects for Saudi Arabia's PHC reform process in order to make recommendations to facilitate strengthening of the PHC system.

Methods
A review of previous studies and governmental reports was undertaken to extract, analyse, synthesize and report the findings.

Results
The review has indicated that by mid-2019, the reform has contributed to an increase of 37.5% in the rate of PHC visits and 4.7% increase in patient satisfaction, enhanced coverage of rural communities (from 78% to 83%), and contributed to increasing the screening rate for prevalent chronic diseases. However, the country still faces gaps and challenges pertaining to human resources issues, cultural and lifestyle behaviour, geography, intersectoral collaboration and PHC infrastructure.

Conclusion
PHC reform process in Saudi Arabia has demonstrated that positive change is achievable. This has been aided by building on previous accomplishments and the wealth of experience gained throughout the PHC journey in Saudi Arabia. However, despite improvement in the quality of services, continuous improvement is required to meet the rising expectations of the population.

Al Khashan|Hesham|H|
Abogazalah|Fouad|F|
Alomary|Shaker|S|
Nahhas|Mahmoud|M|
Alwadey|Ali|A|
Al-Khudhair|Basema|B|
Alamri|Fahad|F|
Aleisa|Nouf|N|
Mahmoud|Nagla|N|
Hassanein|Mustafa|M|

D018166:Health Care Reform
D006801:Humans
D017060:Patient Satisfaction
D011320:Primary Health Care
D012529:Saudi Arabia
D000078329:Workforce

primary health care
reform
Saudi Arabia
transformation


Differential transcriptional regulation of hypoxia-inducible factor-1α by arsenite under normoxia and hypoxia: involvement of Nrf2.

Abstract:
Arsenite (As(III)) is widely distributed in nature and can be found in water, food, and air. There is significant evidence that exposure to As(III) is associated with human cancers originated from liver, lung, skin, bladder, kidney, and prostate. Hypoxia plays a role in tumor growth and aggressiveness; adaptation to it is, at least to a large extent, mediated by hypoxia-inducible factor-1α (HIF-1α). In the current study, we investigated As(III) effects on HIF-1α under normoxia and hypoxia in the hepatoma cell line HepG2. We found that As(III) increased HIF-1α protein levels under normoxia while the hypoxia-mediated induction of HIF1α was reduced. Thereby, the As(III) effects on HIF-1α were dependent on both, transcriptional regulation via the transcription factor Nrf2 mediated by NOX4, PI3K/Akt, and ERK1/2 as well as by modulation of HIF-1α protein stability. In line, the different effects of As(III) via participation of HIF-1α and Nrf2 were also seen in tube formation assays with endothelial cells where knockdown of Nrf2 and HIF-1α abolished As(III) effects. Overall, the present study shows that As(III) is a potent inducer of HIF-1α under normoxia but not under hypoxia which may explain, in part, its carcinogenic as well as anti-carcinogenic actions.

KEY MESSAGE
As(III) increased HIF-1α under normoxia but reduced its hypoxia-dependent induction. The As(III) effects on HIF-1α were dependent on ROS, NOX4, PI3K/Akt, and ERK1/2. The As(III) effects under normoxia involved transcriptional regulation via Nrf2. Knockdown of Nrf2 and HIF-1α abolished As(III) effects in tube formation assays. The data may partially explain As(III)'s carcinogenic and anti-carcinogenic actions.

Al Taleb|Zukaa|Z|
Petry|Andreas|A|
Chi|Tabughang Franklin|TF|
Mennerich|Daniela|D|
Görlach|Agnes|A|
Dimova|Elitsa Y|EY|
Kietzmann|Thomas|T|0000-0003-0242-8636

D048049:Extracellular Signal-Regulated MAP Kinases

D017395:Plasminogen Activator Inhibitor 1

Arsenite As(III)
Hypoxia-inducible factor 1 (HIF-1α)
Mitogen-activated protein kinase (MAPK)
NADPH enzyme oxidase 4 (NOX4)
Reactive oxygen species (ROS)


Decline of Orientation and Direction Sensitivity in the Aging Population.

Abstract: While the aging population is growing, our knowledge regarding age-related deterioration of visual perception remains limited. In the present study, we investigated the effects of aging on orientation and direction sensitivity in a healthy population using a weighted up-down adaptive method to improve the efficiency and reliability of the task. A total of 57 healthy participants aged 22-72 years were included and divided into old and young groups. Raw experimental data were processed using a psychometric method to determine the differences between the two groups. In the orientation task, the threshold of the discrimination angle and bias (i.e., the difference between the perceived midpoint from the logistic function and the reference point) was increased, while the lapsing rate (i.e., 1-the maximum logistic function) did not significantly change in the old group compared with the young group. In the motion direction task, the threshold, bias, and lapsing rate were significantly increased in the old group compared with the young group. These results suggest that the decreased ability of old participants in discrimination of stimulus orientation and motion direction could be related to the impaired function of visual cortex.

Xia|Lin|L| Chen|He|H| Dong|Jiong|J| Luo|Sha|S| Feng|Lixia|L|

orientation
aging
motion direction
perception deficits
psychometric function
vision


MicroRNA-664 functions as an oncogene in cutaneous squamous cell carcinomas (cSCC) via suppressing interferon regulatory factor 2.

Abstract:
BACKGROUND
Aberrant expression of microRNA-664 was involved in tumor growth and metastasis of various cancers. The specific role of miR-664 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated.

OBJECTIVE
The present study aimed to investigate the molecular mechanisms underpinning of cSCC development and provide translational insights for future therapeutics.

METHODS
Human cSCC specimens were used to determine the miR-664 by in situhybridization and IRF2 by immunohistochemistry. To study the potential mechanisms in tumorigenesis, three cSCC cell lines including HSC-5, HSC-1 and A431 as well as BALB/C mouse tumor model was utilized.

RESULTS
We found that miR-664 was remarkably high in cSCC patient specimens and cSCC cell lines. Overexpression of miR-664 promotes tumorigenic behaviors such as increased cell proliferation, migration and invasion capacities in vitro and enhanced tumorigenicity in xenograft mouse model. Our data further identified IRF2 as a direct downstream target of miR-664. Knockdown of IRF2 reverses pro-tumorigenesis phenotype of miR-664; whereas IRF2 over-expression inhibits miR-664 tumorigenesis in cSCC. Together, it revealed miR-664 functions as an oncogene in cSCC via suppression of IRF2.

CONCLUSION
Our data demonstrates that aberrant expression of miR-664 plays a critical role in carcinogenesis of cSCC. The discovery of novel targets such as miR-664 and IRF2 will facilitate future development of therapeutic interventions.

Li|Xiangzhi|X| Zhou|Cheng|C| Zhang|Chen|C| Xie|Xiongxiong|X| Zhou|Zhaoming|Z| Zhou|Meijuan|M| Chen|Longhua|L| Ding|Zhenhua|Z|

MicroRNA-664
Cutaneous squamous cell carcinomas
Interferon regulatory factor 2
Metastasis
Proliferation
Carcinogenesis


Phase diagram of spiking neural networks.

Abstract: In computer simulations of spiking neural networks, often it is assumed that every two neurons of the network are connected by a probability of 2%, 20% of neurons are inhibitory and 80% are excitatory. These common values are based on experiments, observations, and trials and errors, but here, I take a different perspective, inspired by evolution, I systematically simulate many networks, each with a different set of parameters, and then I try to figure out what makes the common values desirable. I stimulate networks with pulses and then measure their: dynamic range, dominant frequency of population activities, total duration of activities, maximum rate of population and the occurrence time of maximum rate. The results are organized in phase diagram. This phase diagram gives an insight into the space of parameters - excitatory to inhibitory ratio, sparseness of connections and synaptic weights. This phase diagram can be used to decide the parameters of a model. The phase diagrams show that networks which are configured according to the common values, have a good dynamic range in response to an impulse and their dynamic range is robust in respect to synaptic weights, and for some synaptic weights they oscillates in α or β frequencies, independent of external stimuli.

phase diagram
dynamic range
evolutionary neuroscience
impulse response
izhikevich spiking neuronal network
parameter estimation
recurrent neural network


The gingival health status of 8-12 year-old children in Damascus city in Syria during the Syrian Crisis: a cross-sectional epidemiological oral health survey.

Abstract:
OBJECTIVE
The aim of this study was to assess the current gingival health status in children aged 8-12 years in Damascus city. No contemporary data was available with an immense need for studies evaluating the gingival health status in Syrian children, especially under the current circumstances of the Syrian crisis.

RESULTS
The study followed the school-based health survey model using stratified random cluster sampling. A total of 1500 children were clinically examined. The mean PI was at (1.39 ± 0.57) and the mean GI was at (1.12 ± 0.46). Of the total sample, (97.93%) had gingivitis. There is a statistically significant relationship between the used indices means and the children's distribution as to the city's localities. Also, there is a statistically significant relationship between the used indices means and the children's gender. Gingival health was seen to be better and plaque accumulations were less in females. The gingival health status is moderate and is within the acceptable ranges while the plaque accumulations are right above moderate. Still, gingivitis prevalence is high and special care as well as developing and implementing advanced preventive programmes are highly needed.

Gingivitis
Children
Syria
Oral health
Prevalence
Gingival Index
Plaque Index


Cadmium stress suppresses lateral root formation by interfering with the root clock.

Abstract: A biological clock activated by oscillating signals, known as root clock, has been linked to lateral root (LR) formation and is essential for regular LR spacing along the primary root. However, it remains unclear how this internal mechanism is influenced by environmental factors known to affect the LR pattern. Here, we report that excessive cadmium (Cd) inhibits LR formation by disrupting the lateral root cap (LRC)-programmed cell death (PCD)-regulated root clock. Cd restricts the frequency of the oscillating signal rather than its amplitude. This could be attributed to the inhibition on meristematic activity by Cd, which resulted in decreased LRC cell number and LRC-PCD frequency. Genetic evidence further showed that LRC cell number is positively correlated with root resistance to Cd. Our study reveals root cap dynamics as a novel mechanism mediating root responses to Cd, providing insight into the signalling pathways of the root clock responding to environmental cues.

Xie|Yuanming|Y| Wang|Jiahui|J| Zheng|Lulu|L| Wang|Yu|Y| Luo|Long|L| Ma|Mingyue|M| Zhang|Chi|C| Han|Yi|Y|0000-0002-4424-1485 Beeckman|Tom|T| Xu|Guohua|G| Cai|Qingsheng|Q| Xuan|Wei|W|0000-0002-4859-2637

cadmium
lateral root
root clock
primary root
root cap
programmed cell death


Early-childhood BMI trajectories in relation to preclinical cardiovascular measurements in adolescence.

Abstract: Cardiovascular diseases are the leading causes of morbidity and mortality. Overweight, obesity, and accelerated growth during early childhood have been associated with adverse cardiovascular outcomes in later life. Few studies have assessed whether trajectories of accelerated growth in early childhood are associated with preclinical cardiovascular measurements. We aimed to evaluate the associations between childhood body mass index (BMI) growth trajectories and measures of macro- and microvascular function in early adolescence. Measurements of macrovascular function (systolic and diastolic blood pressure (SBP and DBP), pulse wave velocity (PWV), and microvascular function (central retinal arteriolar/veinular equivalent) were assessed at 11 years old in a Spanish birth cohort study (n = 489). BMI trajectories from birth to 9 years were identified using latent class growth analysis. Multiple linear regression assessed the associations between the BMI trajectories and macro- and microvascular function. Compared to children with average birth size and slower BMI gain (reference), children with a lower birth size and accelerated BMI gain had increased SBP [β = 6.57; (95% CI 4.00, 9.15)], DBP [β = 3.65; (95% CI 1.45, 5.86)], and PWV [β = 0.14; (95% CI 0.01, 0.27)]. Children with higher birth size and accelerated BMI gain had increased SBP [β = 4.75; (95% CI 1.79, 7.71) compared to the reference. No significant associations between BMI trajectories and the microvascular measurements were observed. In conclusion, we found that childhood BMI trajectories characterized by accelerated growth are associated with preclinical macrovascular measurements in young adolescents.

Growth
body mass index (BMI)
growth trajectories
blood pressure
cardiovascular health


Heart sound classification based on improved MFCC features and convolutional recurrent neural networks.

Abstract: Heart sound classification plays a vital role in the early detection of cardiovascular disorders, especially for small primary health care clinics. Despite that much progress has been made for heart sound classification in recent years, most of them are based on conventional segmented features and shallow structure based classifiers. These conventional acoustic representation and classification methods may be insufficient in characterizing heart sound, and generally suffer from a degraded performance due to the complicated and changeable cardiac acoustic environment. In this paper, we propose a new heart sound classification method based on improved Mel-frequency cepstrum coefficient (MFCC) features and convolutional recurrent neural networks. The Mel-frequency cepstrums are firstly calculated without dividing the heart sound signal. A new improved feature extraction scheme based on MFCC is proposed to elaborate the dynamic characteristics among consecutive heart sound signals. Finally, the MFCC-based features are fed to a deep convolutional and recurrent neural network (CRNN) for feature learning and later classification task. The proposed deep learning framework can take advantage of the encoded local characteristics extracted from the convolutional neural network (CNN) and the long-term dependencies captured by the recurrent neural network (RNN). Comprehensive studies on the performance of different network parameters and different network connection strategies are presented in this paper. Performance comparisons with state-of-the-art algorithms are given for discussions. Experiments show that, for the two-class classification problem (pathological or non-pathological), a classification accuracy of 98% has been achieved on the 2016 PhysioNet/CinC Challenge database.

Deng|Muqing|M| Meng|Tingting|T| Cao|Jiuwen|J| Wang|Shimin|S| Zhang|Jing|J| Fan|Huijie|H|

D006347:Heart Sounds
D006801:Humans
D016571:Neural Networks, Computer
D059629:Signal-To-Noise Ratio

Heart sound classification
Improved MFCC features
Recurrent neural network
Convolutional neural network


Describing pediatric fractures in the era of ICD-10.

Abstract: Childhood fractures are extremely common. The recent trend is to direct certain fracture care from orthopedic specialists to primary care clinicians. However, to confirm an appropriate level of treatment, the initial diagnosis must be accurate, the description precise, and the communication between those caring for the child consistent. This review illustrates descriptors used at one institution that are based on terminology consensually created between radiologists and orthopedic surgeons for common pediatric fracture types and their displacement, and that satisfy the expanded and detailed International Statistical Classification of Diseases and Related Health Problems (ICD)-10 requirements for successful coding.

D038801:International Classification of Diseases

Fracture Extremity Description Classification Bones Children Radiography Trauma


Inequality in mortality in pre-industrial southern Europe during an epidemic episode: socio-economic determinants (eighteenth - nineteenth centuries Spain).

Abstract: The objective of this study is to gain more comprehensive knowledge about social inequality in mortality in pre-industrial periods. With this aim, we have reconstructed the life courses of the inhabitants of the town of Vera in south-east Spain for the period 1797-1812 in order to estimate the influence of socio-economic status on ordinary and extraordinary mortality, given that, during this period, the town suffered from several epidemic outbreaks of yellow fever. As a result of these outbreaks, around a quarter of the town's population died. The results obtained indicate social inequality in mortality at least from the end of the eighteenth century. Although the differences are higher in mortality caused by non-infectious diseases or ill-defined causes, the coefficients also show a certain social gradient in mortality derived from infectious diseases. However, with respect to this latter type of mortality, the place of residence - seems to have a greater influence on the chances of survival than socio-economic status.

Luque de Haro|Víctor A|VA|
Pujadas-Mora|Joana M|JM|
García-Gómez|José J|JJ|

Inequality
Mortality
Nineteenth century
Mediterranean economies
Socioeconomic status


A geometric morphometric approach to the study of variation of shovel-shaped incisors.

Abstract:
OBJECTIVES
The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three-dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1).

MATERIALS AND METHODS
We analyzed 87 modern human UI1s by means of virtual imaging and the ASU-UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method.

RESULTS
Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra- and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling.

DISCUSSION
In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method.

Carayon|Delphine|D|0000-0002-0274-3065
Adhikari|Kaustubh|K|
Monsarrat|Paul|P|
Dumoncel|Jean|J|
Braga|José|J|
Duployer|Benjamin|B|
Delgado|Miguel|M|
Fuentes-Guajardo|Macarena|M|
de Beer|Frikkie|F|
Hoffman|Jakobus W|JW|
Oettlé|Anna C|AC|
Donat|Richard|R|
Pan|Lei|L|0000-0003-1164-0364
Ruiz-Linares|Andres|A|
Tenailleau|Christophe|C|
Vaysse|Frédéric|F|
Esclassan|Rémi|R|
Zanolli|Clément|C|

Procrustes and non-Procrustes superimpositions


Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

Abstract:
BACKGROUND/AIMS
A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms.

METHODS
Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis.

RESULTS
Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver.

CONCLUSION
These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.

Jia|Yingli|Y| He|Jinzhao|J| Wang|Liang|L| Su|Limin|L| Lei|Lei|L| Huang|Wei|W| Geng|Xiaoqiang|X| Zhang|Shun|S| Meng|Xiaolu|X| Zhou|Hong|H| Yang|Baoxue|B|

Type 2 diabetes mellitus
Diabetic nephropathy
Glucose homeostasis
Gluconeogenic key enzymes
SGLT2 inhibitor


COVID-19 Lockdown Restrictions and Online Media Consumption in Germany.

Abstract: The lockdown restrictions due to the COVID-19 pandemic have led to increased stress levels and feelings of anxiety in the general population. Problematic usage of certain online applications is one frequent way to compensate for negative feelings and stress. The current study investigated changes of online media consumption during the lockdown in Germany. Gender and age specific differences in specific online activities were assessed. n = 3245 subjects participated in an online survey conducted between the 8th April and the 11th May 2020. Participants' age ranged between 18 and >55 years. A considerably high percentage (71.4%) of participants reported increased online media consumption during the lockdown. Male participants were more likely to increase their consumption of gaming and erotic platforms, while female participants reported a higher increase in the engagement in social networks, information research, and video streaming than males. The findings revealed an increased usage of all online applications during the lockdown. For the clarification whether the increase might present a risk for elevated Internet-use disorders or can be regarded as a functional and time-limited phenomenon, further studies, assessing changes in these online activities after the end of the pandemic, are needed.

Lemenager|Tagrid|T|0000-0001-5175-0168 Neissner|Miriam|M| Koopmann|Anne|A| Reinhard|Iris|I| Georgiadou|Ekaterini|E| Müller|Astrid|A|0000-0001-6176-2947 Kiefer|Falk|F| Hillemacher|Thomas|T|

online media consumption
COVID-19 pandemic
age and gender specific differences


Protein⁻Protein Interactions with Connexin 43: Regulation and Function.

Abstract: Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating rhythm. A number of connexin interacting proteins have been described and are known gap junction regulators either through direct effects (e.g., kinases) or the formation of larger multifunctional complexes (e.g., cytoskeleton scaffold proteins). Most connexin partners can be categorized as either proteins promoting coupling by stimulating forward trafficking and channel opening or inhibiting coupling by inducing channel closure, internalization, and degradation. While some interactions have only been implied through co-localization using immunohistochemistry, others have been confirmed by biophysical methods that allow detection of a direct interaction. Our understanding of these interactions is, by far, most well developed for connexin 43 (Cx43) and the scope of this review is to summarize our current knowledge of their functional and regulatory roles. The significance of these interactions is further exemplified by demonstrating their importance at the intercalated disc, a major hub for Cx43 regulation and Cx43 mediated effects.

Sorgen|Paul L|PL|
Trease|Andrew J|AJ|
Spagnol|Gaelle|G|
Delmar|Mario|M|
Nielsen|Morten S|MS|

connexin
gap junction
intercalated disc
intrinsically disordered protein
post-translational modification
protein–protein interaction


In vitro digestibility and Caco-2 cell bioavailability of sea lettuce (Ulva fenestrata) proteins extracted using pH-shift processing.

Abstract: Seaweed is a promising sustainable source of vegan protein as its farming does not require arable land, pesticides/insecticides, nor freshwater supply. However, to be explored as a novel protein source the content and nutritional quality of protein in seaweed need to be improved. We assessed the influence of pH-shift processing on protein degree of hydrolysis (%DH), protein/peptide size distribution, accessibility, and cell bioavailability of Ulva fenestrata proteins after in vitro gastrointestinal digestion. pH-shift processing of Ulva, which concentrated its proteins 3.5-times, significantly improved the %DH from 27.7±2.6% to 35.7±2.1% and the amino acid accessibility from 56.9±4.1% to 72.7±0.6%. Due to the higher amino acid accessibility, the amount of most amino acids transported across the cell monolayers was higher in the protein extracts. Regarding bioavailability, both Ulva and protein extracts were as bioavailable as casein. The protein/peptide molecular size distribution after digestion did not disclose a clear association with bioavailability.

Trigo|João P|JP|
Engström|Niklas|N|
Steinhagen|Sophie|S|
Juul|Louise|L|
Harrysson|Hanna|H|
Toth|Gunilla B|GB|
Pavia|Henrik|H|
Scheers|Nathalie|N|
Undeland|Ingrid|I|

Caco-2 cells
Seaweed
Phenolic content
Protein isolation
Protein size distribution
Simulated gastrointestinal digestion


Disease related knowledge and quality of life: a descriptive study focusing on hypertensive population in Pakistan.

Abstract:
OBJECTIVE
This study aims to evaluate association between Health related quality of lifeand disease state knowledge among hypertensive population of Pakistan.

METHODS
A cross sectional descriptive study was undertaken with a representative cohort of hypertension patients. Using prevalence based sampling technique, a total of 385 hypertensive patients were selected from two public hospitals of Quetta city, Pakistan. Hypertension Fact Questionnaire (HFQ) and European Quality of Life scale (EQ-5D) were used for data collection. Statistical Package for the Social Sciences 16.0 was used to compute descriptive analysis of patients' demographic and disease related information. Categorical variables were described as percentages while continuous variables were expressed as mean ± standard deviation (SD). Spearman's rho correlation was used to identify the association between study variables.

RESULTS
The mean (SD) age of the patients was 39.02 (6.59), with 68.8% males (n=265). The mean (SD) duration of hypertension was 3.01 (0.93) years. Forty percent (n=154) had bachelor degree with 34.8% (n=134) working in private sector. Almost forty one percent (n=140) had monthly income of more than 15000 Pakistan rupees per month with 75.1% (n=289) having urban residency. The mean EQ-5D descriptive score (0.46±0.28) and EQ-VAS score (63.97±6.62) indicated lower HRQoL in our study participants. Mean knowledge score was 8.03 ± 0.42. Correlation coefficient between HRQoL and knowledge was 0.208 (p< 0.001), indicating a week positive association.

CONCLUSION
Results of this study highlight hypertension knowledge to be weakly associated with HRQoL suggesting that imparting knowledge to patients do not necessarily improve HRQoL. More attention should be given to identify individualized factors affecting HRQoL.

Saleem|Fahad|F|
Hassali|Mohamed Azmi|MA|
Shafie|Asrul Akmal|AA|
Atif|Muhammad|M|
Ul Haq|Noman|N|
Aljadhey|Hisham|H|

Knowledge
Hypertension
Correlation.
Health Related Quality of Life


A Rare High-Grade Glioma with a Histone H3 K27M Mutation in the Hypothalamus of an Adult Patient.

Abstract:
BACKGROUND
Diffuse midline glioma H3 K27M mutant is a new tumor entity described in the revised 2016 World Health Organization classification. It is most frequently observed in children and develops in midline structures, including the brainstem, thalamus, and spine. We describe a rare diffuse midline glioma with an H3 K27M mutation arising in the hypothalamus of an adult.

CASE DESCRIPTION
A 27-year-old woman was admitted to our department complaining of amenorrhea, polydipsia, and diuresis for the previous 3 months, and headache and lethargy for approximately 10 days. Computed tomography scan showed an oval isodense solid mass extending from the pituitary toward the suprasellar cistern. A gadolinium-enhanced magnetic resonance imaging (MRI) showed a strongly heterogeneous enhanced solid lesion and nonenhanced cystic lesion. The patient underwent surgery and chemoradiotherapy with temozolomide. Histologic and immunohistochemical analyses revealed H3 K27M-mutant diffuse midline glioma. The patient underwent another resection for a recurrent tumor 5 months after the first surgery. Three months after the second operation, the patient relapsed, with MRI revealing spinal cord and meningeal metastases; she died shortly afterward.

CONCLUSIONS
Diffuse midline glioma with an H3 K27M mutation occurring in the hypothalamus of an adult is rare but should be considered in differential diagnoses. Because histone H3 K27M mutations are associated with aggressive clinical behavior and poor prognosis, molecular analyses should be used to determine the clinical and histopathologic features of such tumors. This will contribute to developing targeted drugs and gene therapy going forward.

He|Pin|P|
Chen|Wei|W|
Qiu|Xi Xiong|XX|
Xi|Yi Bin|YB|
Guan|Hong|H|
Xia|Jun|J|

Glioma
H3 K27M mutation
Hypothalamus
Adult patient