Agreement between rebound (Icare ic200) and applanation tonometry (Perkins) in patients with primary congenital glaucoma.

Abstract:
PURPOSE
To examine agreement between intraocular pressure (IOP) measurements made using the rebound tonometer Icare ic200 (RT200) and the Perkins handheld applanation tonometer (PAT) in patients with primary congenital glaucoma (PCG). The impacts of several covariables on measurements using the two devices were also assessed.

MATERIALS AND METHODS
Intraocular pressure measurements were made in a single session in 86 eyes of 86 patients with PCG (46 under anaesthesia, 40 in the office). The order was RT200 then PAT. The variables age, central corneal thickness (CCT), corneal state and anaesthesia were recorded in each patient. Data were compared by determining interclass correlation coefficients (ICC) for each tonometer and representing the differences detected as Bland-Altman plots. Effects of covariables were assessed through univariate and multivariate regression.

RESULTS
Mean IOP difference between tonometers (RT200 minus PAT) was 1.26 mmHg (95%: 0.22-2.31). Absolute agreement (ICC) was 0.73 (95% CI: 0.62-0.82). Lower and upper limits of agreement (95%) were -8.06 mmHg (95% CI: -9.87 to -6.25) and 10.59 mmHg (95% CI: 8.77-12.40), respectively. The tonometers showed systematic differences (a = -4.63 mmHg; 95% CI: -9.11 to -1.44) and proportional differences; for each mmHg increase in PAT-IOP, the RT200 reading increased by 1.28 mmHg (b = 1.28; 95% CI: 1.12-1.53). None of the variables tested as predictors were able to explain differences between the tonometers.

CONCLUSIONS
Despite the good overall agreement between both tonometers, caution should be taken in high values of IOP, considering the interchangeability of its readings as systematic and proportional differences appear to exist between both methods.

Icare ic200
primary congenital glaucoma
rebound tonometer
RT200


Investigating the genetic and environmental architecture of interpack aggression in North American grey wolves.

Abstract: Aggression confers several fitness benefits including increased breeding opportunities and resource acquisition. Determining the relative contributions of genetic and environmental components to shaping aggression is essential for advancing our understanding of how selection affects the distribution of aggressive phenotypes in a population. In a From the Cover article in this issue of Molecular Ecology, vonHoldt et al. (2020) used RAD-seq methods to obtain genome-wide single nucleotide polymorphism (SNP) data to estimate heritability of interpack aggression of 141 North American grey wolves (Canis lupus) surveyed from 1995-2018. The authors inferred heritability using both a SNP-based genetic relationship matrix (GRM) and a consensus pedigree informed by: (a) previously obtained microsatellite data; (b) past observations of parentage; and (c) statistical reconstruction of parent-offspring pairs. SNP-based (i.e., GRM) and pedigree-based (i.e., consensus pedigree) heritability estimates were 37% and 14%, respectively, with an additional 14%-16% explained by natal pack effects. The study confirmed the previously discovered strong effects of relative pack size and breeding status on interpack aggression, illustrating how social dynamics and density-dependent factors induce variance in aggressive behaviours. Finally, the authors found associations between average individual aggression scores (IAS) and specific candidate genes (MY09A and TRAK1). In sum, vonHoldt et al. (2020) provides an unprecedented and nuanced synthesis that not only suggests gene-aggression associations, but also emphasizes how additive genetic variance and density-dependent factors interact to maintain phenotypic variance in aggression over time.

aggression
grey wolves
RAD-seq
heritability
density-dependent
stabilizing selection


Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.

Abstract:
PURPOSE
To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study.

METHODS
Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study.

RESULTS
The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF.

CONCLUSION
IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not.

TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02305238.

Ohji|Masahito|M|
Okada|Annabelle A|AA|
Sasaki|Koji|K|
Moon|SungChul Charles|SC|
Machewitz|Tobias|T|
Takahashi|Kanji|K|
|||

D040262:Receptors, Vascular Endothelial Growth Factor

D042461:Vascular Endothelial Growth Factor A

Exudative age-related macular degeneration


The Event Detection System in the NEXT-White Detector.

Abstract: This article describes the event detection system of the NEXT-White detector, a 5 kg high pressure xenon TPC with electroluminescent amplification, located in the Laboratorio Subterráneo de Canfranc (LSC), Spain. The detector is based on a plane of photomultipliers (PMTs) for energy measurements and a silicon photomultiplier (SiPM) tracking plane for offline topological event filtering. The event detection system, based on the SRS-ATCA data acquisition system developed in the framework of the CERN RD51 collaboration, has been designed to detect multiple events based on online PMT signal energy measurements and a coincidence-detection algorithm. Implemented on FPGA, the system has been successfully running and evolving during NEXT-White operation. The event detection system brings some relevant and new functionalities in the field. A distributed double event processor has been implemented to detect simultaneously two different types of events thus allowing simultaneous calibration and physics runs. This special feature provides constant monitoring of the detector conditions, being especially relevant to the lifetime and geometrical map computations which are needed to correct high-energy physics events. Other features, like primary scintillation event rejection, or a double buffer associated with the type of event being searched, help reduce the unnecessary data throughput thus minimizing dead time and improving trigger efficiency.

xenon TPC
FPGA
data acquisition circuits
trigger concepts


Dopamine D1/D5 receptors mediate informational saliency that promotes persistent hippocampal long-term plasticity.

Abstract: Dopamine (DA) plays an essential role in the enablement of cognition. It adds color to experience-dependent information storage, conferring salience to the memories that result. At the synaptic level, experience-dependent information storage is enabled by synaptic plasticity, and given its importance for memory formation, it is not surprising that DA comprises a key neuromodulator in the enablement of synaptic plasticity, and particularly of plasticity that persists for longer periods of time: Analogous to long-term memory. The hippocampus, that is a critical structure for the synaptic processing of semantic, episodic, spatial, and declarative memories, is specifically affected by DA, with the D1/D5 receptor proving crucial for hippocampus-dependent memory. Furthermore, D1/D5 receptors are pivotal in conferring the properties of novelty and reward to information being processed by the hippocampus. They also facilitate the expression of persistent forms of synaptic plasticity, and given reports that both long-term potentiation and long-term depression encode different aspects of spatial representations, this suggests that D1/D5 receptors can drive the nature and qualitative content of stored information in the hippocampus. In light of these observations, we propose that D1/D5 receptors gate hippocampal long-term plasticity and memory and are pivotal in conferring the properties of novelty and reward to information being processed by the hippocampus.

cognition
synaptic plasticity
hippocampus
learning and memory
review


Two Zn(II)-based Coordination Polymers: Fe3+ Ion and Prevention Activity Detection On Postpartum Hemorrhage By Regulating Anticoagulant Factor Activity.

Abstract: Two new Zn(II)-based coordination polymers {[Zn3(L1)6(H2O)]∙(H2O)4}n (1, HL1 = 4-(tetrazol-5-yl)phenyl-4,2':6',4″-terpyridine) and [Zn2Cl2(L2)2H2O]n (2, HL2 = 4-([2,2':6',2″'-terpyridin]-4'-yl)benzoic acid) have been successfully prepared using two similar organic ligands with distinct donor groups under similar reaction conditions. The distinct structural features and donor atoms make the two complexes show different water stability, and the complex 1 with good water stability, which can be utilized as the sensor for Fe3+ ion detection in water. The value of Stern-Volmer quenching constant of 1 to the Fe3+ is 5.77 × 104 M- 1, which lies in the top region of the reported CP-based sensors. The mechanism investigation reveals that the energy transfer of resonance from the complex 1 to the Fe3+ ion can account for its fluorescent quenching behavior. The treatment activity of compounds 1 and 2 on the postpartum hemorrhage (PPH) was assessed. First, the cytotoxicity of compounds 1 and 2 on human umbilical vein endothelial cells was assessed with Cell Counting Kit-8 detection kit. Then, to evaluate the prevention of compounds 1 and 2 on the PPH, we conducted the Lowry method and detected the clotting factor IX and anticoagulant factor III contents after the indicated treatment. Finally, the inflammatory response in mice was determined by ELISA method, and the IL-6 and IL-8 levels were determined.

Wu|Xia|X| Wen|Yu|Y| Tan|Xiao-Qing|XQ| Liang|Miao|M| Qin|Yan|Y| Gan|Xiao-Ling|XL|

D061307:Human Umbilical Vein Endothelial Cells

Coordination polymer
postpartum hemorrhage
ELISA assay
Fe3+ sensor


Two Bacterial Small Heat Shock Proteins, IbpA and IbpB, Form a Functional Heterodimer.

Abstract: Small heat shock proteins (sHsps) are a conserved class of ATP-independent chaperones which in stress conditions bind to unfolded protein substrates and prevent their irreversible aggregation. Substrates trapped in sHsps-containing aggregates are efficiently refolded into native structures by ATP-dependent Hsp70 and Hsp100 chaperones. Most γ-proteobacteria possess a single sHsp (IbpA), while in a subset of Enterobacterales, as a consequence of ibpA gene duplication event, a two-protein sHsp (IbpA and IbpB) system has evolved. IbpA and IbpB are functionally divergent. Purified IbpA, but not IbpB, stably interacts with aggregated substrates, yet both sHsps are required to be present at the substrate denaturation step for subsequent efficient Hsp70-Hsp100-dependent substrate refolding. IbpA and IbpB interact with each other, influence each other's expression levels and degradation rates. However, the crucial information on how these two sHsps interact and what is the basic building block required for proper sHsps functioning was missing. Here, based on NMR, mass spectrometry and crosslinking studies, we show that IbpA-IbpB heterodimer is a dominating functional unit of the two sHsp system in Enterobacterales. The principle of heterodimer formation is similar to one described for homodimers of single bacterial sHsps. β-hairpins formed by strands β5 and β7 of IbpA or IbpB crystallin domains associate with the other one's β-sandwich in the heterodimer structure. Relying on crosslinking and molecular dynamics studies, we also propose the orientation of two IbpA-IbpB heterodimers in a higher order tetrameric structure.

Piróg|Artur|A| Cantini|Francesca|F| Nierzwicki|Łukasz|Ł| Obuchowski|Igor|I| Tomiczek|Bartłomiej|B| Czub|Jacek|J| Liberek|Krzysztof|K|

bacterial small heat shock proteins
chaperones
heterodimer of sHsps
modification of protein aggregation
protein refolding


Intermittent Exotropia Treatment with Dichoptic Visual Training Using a Unique Virtual Reality Platform.

Abstract: We evaluated the effect of dichoptic visual training based on a unique virtual reality (VR) platform mounted display in patients with intermittent exotropia (IXT). A total of 25 IXT patients (8 men, 17 women) with a mean age of 12.3 years (range, 5-39 year) were recruited. The Hirschberg test, prism and alternate cover testing (with accommodative targets for fixation at 33 cm in all patients), perceptual eye position (PEP), and stereopsis were evaluated after 1, 3, and 6 months of dichoptic visual neuroplasticity training with a computer-controlled perceptual examination evaluation system. Data collected before and after training were evaluated using SPSS software. After 6 months of perceptual training, a new order stereopsis was established, and eye positions were improved in all 25 patients. After training for 1 and 6 months, the horizontal PEP pixels were much lower than those pretraining, respectively (Δ1-0 = -0.53, p = 0.028; Δ6-0 = -0.80, p = 0.018). There was no statistically significant difference between pretraining and 3 months after training in horizontal PEP (Δ3-0 = -0.29, p = 0.370). There was no significant difference between pretraining and post-training in vertical PEP (p > 0.05). There were significant differences between pretraining and post-training in the cornea's optical reflection and prism diopters (p < 0.01). Dichoptic visual neuroplasticity training based on a VR platform is an effective nonsurgical treatment in patients with IXT. With the VR treatment, the degree of strabismus and stereopsis was improved in IXT patients. Perceptual training with VR can remove obstacles in the visual processing channel and repair defects in visual function. The clinical manifestations of improvement were the decrease in the degree of strabismus and the re-establishment of stereopsis.

Li|Xue|X|
Yang|Cheng|C|
Zhang|Guanrong|G|
Zhang|Yan|Y|
Lan|Jianqing|J|
Chu|Hang|H|
Li|Juan|J|
Xie|Wenjuan|W|
Wang|Shujun|S|
Wiederhold|Brenda K|BK|
Wiederhold|Mark D|MD|
Yan|Li|L|
Zeng|Jin|J|

intermittent exotropia
virtual reality
stereopsis
perceptual training


Cross sectional analysis of depression amongst Australian rural business owners following cyclone-related flooding.

Abstract:
Background
Flooding is an increasingly prevalent natural hazard worldwide and can have a profound impact on the mental health of those directly and indirectly affected. Little is known about the impact on business owners, who may be particularly vulnerable to the mental health complications of flooding given the additional economic stressors.

Methods
A large cross-sectional survey was conducted six months after severe flooding in the rural Northern Rivers region of New South Wales, Australia in 2017. The survey assessed demographics, probable depression (using the Patient Health Questionnaire-2), flood exposure, flood-related financial factors, prior flood exposure and support from various organisations. Logistic regression was used to identify predictors of probable depression in 653 of the 745 participants who identified as business owners.

Results
The prevalence of probable depression in our sample was 17.0%. A quarter (25.1%) of business owners whose business was flooded suffered from probable depression, compared to 12.4% of non-flooded business owners. The multivariable model for probable depression demonstrated elevated adjusted odds ratios (AOR) for business owners who had to evacuate their business (AOR = 2.11, 95% Confidence Interval (CI) 1.25-3.57) compared to those who did not evacuate. Insurance disputes/rejections were a strong predictor for probable depression (AOR = 3.76, CI 1.86-7.60). Those whose income was reduced due to the flood and had not returned to normal six months post-flood demonstrated an increased AOR for probable depression (AOR 2.53, CI 1.26-5.07) compared to those whose income had returned to normal. The univariable analysis found elevated crude odds ratios (OR) for the cumulative effect of multiple flood exposures and unmet support needs by the state government (OR = 2.74, CI 1.12-6.68). The majority of business owners felt their needs were not met by most organisations providing flood-related support.

Conclusion
The impact of flood exposure and flood-related financial factors on probable depression was highly significant for the business owner population. Furthermore, business owners felt under-supported by flood-related services. These findings highlight the vulnerability of exposed business owners and the need for increased support. Disaster planning programs in conjunction with system level changes such as infrastructure and education are vital for disaster preparedness.

Depression
Business
Floods
Mental health
Insurance
Natural disasters


The brain during free movement - What can we learn from the animal model.

Abstract: Animals, just like humans, can freely move. They do so for various important reasons, such as finding food and escaping predators. Observing these behaviors can inform us about the underlying cognitive processes. In addition, while humans can convey complicated information easily through speaking, animals need to move their bodies to communicate. This has prompted many creative solutions by animal neuroscientists to enable studying the brain during movement. In this review, we first summarize how animal researchers record from the brain while an animal is moving, by describing the most common neural recording techniques in animals and how they were adapted to record during movement. We further discuss the challenge of controlling or monitoring sensory input during free movement. However, not only is free movement a necessity to reflect the outcome of certain internal cognitive processes in animals, it is also a fascinating field of research since certain crucial behavioral patterns can only be observed and studied during free movement. Therefore, in a second part of the review, we focus on some key findings in animal research that specifically address the interaction between free movement and brain activity. First, focusing on walking as a fundamental form of free movement, we discuss how important such intentional movements are for understanding processes as diverse as spatial navigation, active sensing, and complex motor planning. Second, we propose the idea of regarding free movement as the expression of a behavioral state. This view can help to understand the general influence of movement on brain function. Together, the technological advancements towards recording from the brain during movement, and the scientific questions asked about the brain engaged in movement, make animal research highly valuable to research into the human "moving brain".

Free movement
Animal research
Brain activity
Recording methods
Virtual reality


Intra-articular and Peri-articular Tumours and Tumour Mimics- What a Clinician and Onco-imaging Radiologist Should Know.

Abstract: Definitive determination of the cause of articular swelling may be difficult based on just the clinical symptoms, physical examinations and laboratory tests. Joint disorders fall under the realms of rheumatology and general orthopaedics; however, patients with joint conditions manifesting primarily as intra-articular and peri-articular soft tissue swelling may at times be referred to an orthopaedic oncology department with suspicion of a tumour. In such a situation, an onco-radiologist needs to think beyond the usual neoplastic lesions and consider the diagnoses of various non-neoplastic arthritic conditions that may be clinically masquerading as masses. Differential diagnoses of articular lesions include infectious and non-infectious synovial proliferative processes, degenerative lesions, deposition diseases, vascular malformations, benign and malignant neoplasms and additional miscellaneous conditions. Many of these diseases have specific imaging findings. Knowledge of these radiological characteristics in an appropriate clinical context will allow for a more confident diagnosis.

Dhanda|Sunita|S|
Quek|Swee Tian|ST|
Bathla|Girish|G|
Jagmohan|Pooja|P|

intra-articular peri-articular tumours synovial


Molecular Evaluation of Genetic Diversity in Wild-Type Mastic Tree (Pistacia lentiscus L.).

Abstract: In this study, the patterns of genetic variation and phylogenetic relationships of mastic tree (Pistacia lentiscus L.) genotypes including 12 males and 12 females were evaluated using SSR, RAPD, ISSR, and ITS markers yielding 40, 703, 929 alleles, and 260-292 base pairs for ITS1 region, respectively. The average number of alleles produced from SSR, RAPD, and ISSR primers were 5.7, 14, and 18, respectively. The grouping pattern obtained from Bayesian clustering method based on each marker dataset was produced. Principal component analyses (PCA) of molecular data was investigated and neighbor joining dendrograms were subsequently created. Overall, the results indicated that ISSR and RAPD markers were the most powerful to differentiate the genotypes in comparison with other types of molecular markers used in this study. The ISSR results indicated that male and female genotypes were distinctly separated from each other. In this frame, M9 (Alaçatı) and M10 (Mesta Sakız Adası-Chios) were the closest genotypes and while F11 (Seferihisar) and F12 (Bornova/Gökdere) genotypes fall into same cluster and showing closer genetic relation. The RAPD pattern indicated that M8 (Urla) and M10 (Mesta Sakız Adası-Chios), and F10 (Mesta Sakız Adası-Chios) and F11 (Seferihisar) genotypes were the closest male and female genotypes, respectively.

Abuduli|Alimu|A|
Aydin|Yıldız|Y|
Sakiroglu|Muhammet|M|
Onay|Ahmet|A|
Ercisli|Sezai|S|
Uncuoglu|Ahu Altinkut|AA|

D054458:Amplified Fragment Length Polymorphism Analysis

Genetic diversity
Phylogenetic relationship
DNA markers
Population structure
Principle component analysis


Circulating CXCR3-CCR6-CXCR5+CD4+ T cells are associated with acute allograft rejection in liver transplantation.

Abstract: Circulating T follicular helper (cTFH) cells have been demonstrated to be involved in B-cell-mediated alloreactive responses in kidney and liver transplantation; however, whether these cells are involved in acute liver allograft rejection after liver transplantation, and which subsets are involved, remains to be clarified. The present study aimed to investigate the profiles of cTFH cells in acute liver allograft rejection, including the CXC motif receptor 3 (CXCR3)+ chemokine receptor 6 (CCR6)- subset, the CXCR3-CCR6- subset, and the CXCR3-CCR6+ subset. Twelve liver transplant patients with acute rejection (AR) and 20 with no acute rejection (NAR) were enrolled in the study. The results showed that the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was significantly increased and the proportion of CXCR3-CCR6+CXCR5+CD4+ T cells was significantly decreased in patients with AR compared with patients with NAR. In addition, the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was positively correlated with the proportion of B cells in patients with AR. The level of serum interleukin (IL)-21 was higher in the AR group than in the NAR groups. Furthermore, the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was positively correlated with alanine amino transferase (ALT), whereas the proportion of CXCR3-CCR6+ CXCR5+CD4+ T cells was negatively correlated with ALT. B cells and TFH cells were detected in follicular-like structures in liver allograft tissues from patients with AR. These results suggest that CXCR3-CCR6-CXCR5+CD4+ T cells may be involved in acute allograft rejection after liver transplantation.

Zhang|Ke|K| Sun|Yan-Ling|YL| Zhou|Shuang-Nan|SN| Xu|Ruo-Nan|RN| Liu|Zhen-Wen|ZW| Wang|Fu-Sheng|FS| Shi|Ming|M|

Liver transplantation
Acute rejection
T follicular helper cells


Dehydrogenation Mechanism of Three Stereoisomers of Butane-2,3-Diol in Pseudomonas putida KT2440.

Abstract: Pseudomonas putida KT2440 is a promising chassis of industrial biotechnology due to its metabolic versatility. Butane-2,3-diol (2,3-BDO) is a precursor of numerous value-added chemicals. It is also a microbial metabolite which widely exists in various habiting environments of P. putida KT2440. It was reported that P. putida KT2440 is able to use 2,3-BDO as a sole carbon source for growth. There are three stereoisomeric forms of 2,3-BDO: (2R,3R)-2,3-BDO, meso-2,3-BDO and (2S,3S)-2,3-BDO. However, whether P. putida KT2440 can utilize three stereoisomeric forms of 2,3-BDO has not been elucidated. Here, we revealed the genomic and enzymic basis of P. putida KT2440 for dehydrogenation of different stereoisomers of 2,3-BDO into acetoin, which will be channeled to central mechanism via acetoin dehydrogenase enzyme system. (2R,3R)-2,3-BDO dehydrogenase (PP0552) was detailedly characterized and identified to participate in (2R,3R)-2,3-BDO and meso-2,3-BDO dehydrogenation. Two quinoprotein alcohol dehydrogenases, PedE (PP2674) and PedH (PP2679), were confirmed to be responsible for (2S,3S)-2,3-BDO dehydrogenation. The function redundancy and inverse regulation of PedH and PedE by lanthanide availability provides a mechanism for the adaption of P. putida KT2440 to variable environmental conditions. Elucidation of the mechanism of 2,3-BDO catabolism in P. putida KT2440 would provide new insights for bioproduction of 2,3-BDO-derived chemicals based on this robust chassis.

Liu|Yidong|Y| Wang|Xiuqing|X| Ma|Liting|L| Lü|Min|M| Zhang|Wen|W| Lü|Chuanjuan|C| Gao|Chao|C| Xu|Ping|P| Ma|Cuiqing|C|

butane-2,3-diol
Pseudomonas putida KT2440
quinoprotein alcohol dehydrogenase
lanthanide
(2R,3R)-butane-2,3-diol dehydrogenase


Effect of microstructure on the mechanical properties of lithium disilicate glass-ceramics.

Abstract: The mechanical properties of lithium disilicate glass-ceramics depend on various factors, a prominent one being their microstructure. The aim of this review article is to elucidate the effect of processing parameters such as annealing temperature, holding time, number of heating stages and chemical composition and additives on the microstructure and physical properties of these glass-ceramics.

D002516:Ceramics
D003776:Dental Porcelain
D008422:Materials Testing
D055595:Mechanical Phenomena
D013314:Stress, Mechanical

Microstructure
Mechanical properties
Lithium disilicate glass-ceramics


Sex differences in obesity and cognitive function in a cognitively normal aging Chinese Han population.

Abstract:
BACKGROUND
Sex differences in Alzheimer's disease and mild cognitive impairment have been well recognized. However, sex differences in cognitive function and obesity in cognitively normal aging Chinese Han population have not attracted much attention.

OBJECTIVE
The aim of this study was to investigate the relationship between sex, obesity, and cognitive function in an elderly Chinese population with normal cognitive function.

SUBJECTS AND METHODS
A total of 228 cognitively normal aging participants (males/females =93/135) entered this study. Their general demographic information (sex, age, and education) was collected by standardized questionnaire. Apolipoprotein E (APOE) genotype and serum lipid levels were measured. The Montreal Cognitive Assessment (MoCA) was used to assess participants' cognitive function.

RESULTS
The prevalence of obesity in elderly women (18/133, 13.5%) was significantly higher than that in men (5/92, 5.4%, P=0.009). Regression analyses showed that obesity was associated with drinking alcohol (OR =13.695, P=0.045) and triglyceride (OR =1.436, P=0.048) in women and limited to low-density lipoprotein (OR =11.829, P=0.023) in men. Women performed worse on the naming score for MoCA than men (P<0.01). Stepwise linear regression analysis showed that education (t=3.689, P<0.001) and smoking (t=2.031, P=0.045) were related to the score of naming in female, while high-density lipoprotein (t=-2.077, P=0.041) was related to the score of naming in male; however, no correlation was found between body mass index and cognitive function in both male and female (P>0.05).

CONCLUSION
Our finding suggests that there are significant sex differences in obesity and specific cognitive domains in aging Chinese Han population with normal cognitive function.

Li|Wei|W| Qiu|Qi|Q| Sun|Lin|L| Yue|Ling|L| Wang|Tao|T| Li|Xia|X| Xiao|Shifu|S|

sex difference
obesity
cognitive function
elderly Chinese
lipids


Biomechanical evaluation of different suture techniques for arthroscopic transtibial pull-out repair of posterior medial meniscus root tears.

Abstract:
BACKGROUND
A tear of the posterior medial meniscus root (PMMR) is increasingly recognized as a serious knee joint injury. Several suture techniques for arthroscopic transtibial pull-out repair have been described; however, only limited data about the biomechanical properties of these techniques are currently available.

HYPOTHESIS
There are significant differences between the tested suture techniques, with more complex suture configurations providing superior biomechanical properties.

STUDY DESIGN
Controlled laboratory study.

METHODS
A total of 40 porcine medial menisci were randomly assigned to 1 of 4 groups (10 specimens each) according to suture technique: two simple stitches (TSS), horizontal mattress suture (HMS), modified Mason-Allen suture (MMA), and two modified loop stitches (TLS). Meniscus-suture constructs were subjected to cyclic loading followed by load-to-failure testing in a servohydraulic material testing machine.

RESULTS
During cyclic loading, the HMS and TLS groups showed a significantly higher displacement after 100, 500, and 1000 cycles compared with the TSS and MMA groups. After 1000 cycles, the highest displacement was found for the TLS group, with significant differences compared with all other groups. During load-to-failure testing, the highest maximum load and yield load were observed for the MMA group, with statistically significant differences compared with the TSS and TLS groups. With regard to stiffness, the TSS and MMA groups showed significantly higher values compared with the HMS and TLS groups.

CONCLUSION
The MMA technique provided the best biomechanical properties with regard to cyclic loading and load-to-failure testing. The TSS technique seems to be a valuable alternative. Both the HMS and TLS techniques have the disadvantage of lower stiffness and higher displacement during cyclic loading.

CLINICAL RELEVANCE
Using a MMA technique may improve healing rates and avoid progressive extrusion of the medial meniscus after transtibial pull-out repair of PMMR tears. The TSS technique may be used as an alternative that is easier to perform, but a more careful rehabilitation program is possibly necessary to avoid early failure.

Feucht|Matthias J|MJ|
Grande|Eduardo|E|
Brunhuber|Johannes|J|
Burgkart|Rainer|R|
Imhoff|Andreas B|AB|
Braun|Sepp|S|

D000818:Animals
D001696:Biomechanical Phenomena
D050724:Fractures, Cartilage
D007718:Knee Injuries
D008422:Materials Testing
D008592:Menisci, Tibial
D012421:Rupture
D013536:Suture Techniques
D013537:Sutures
D013552:Swine
D013718:Tensile Strength
D000070600:Tibial Meniscus Injuries
D014945:Wound Healing

biomechanics
pull-out repair
meniscus
meniscus root
root tear
knee
Mason-Allen
biomechanical testing


Hepatic demethylation of methoxy-bromodiphenyl ethers and conjugation of the resulting hydroxy-bromodiphenyl ethers in a marine fish, the red snapper, Lutjanus campechanus, and a freshwater fish, the channel catfish, Ictalurus punctatus.

Abstract: Methoxylated bromodiphenyl ethers (MeO-BDEs), marine natural products, can be demethylated by cytochrome P450 to produce hydroxylated bromodiphenyl ethers (OH-BDEs), potentially toxic metabolites that are also formed by hydroxylation of BDE flame retardants. The OH-BDEs may be detoxified by glucuronidation and sulfonation. This study examined the demethylation of 6-MeO-BDE47, 2'-MeO-BDE68 and 4'-MeO-BDE68, in hepatic microsomes from the red snapper, Lutjanus campechanus, a marine fish likely to be exposed naturally to MeO-BDEs, and the channel catfish, Ictalurus punctatus, a freshwater fish in which pathways of xenobiotic biotransformation have been studied. We further studied the glucuronidation and sulfonation of the resulting OH-BDEs as well as of 6-OH-2'-MeO-BDE68 in hepatic microsomes and cytosol fractions of these fish. The three studied biotransformation pathways were active in both species, with high individual variability. The range of activities overlapped in the two species. Demethylation of MeO-BDEs, studied in the concentration range 10-500 μM, followed Michaelis-Menten kinetics in both fish species, however enzyme efficiencies were low, ranging from 0.024 to 0.334 μL min.mg protein. Conjugation of the studied OH-BDEs followed Michaelis-Menten kinetics in the concentration ranges 1-50 μM (glucuronidation) or 2.5-100 μM (sulfonation). These OH-BDEs were readily glucuronidated and sulfonated in the fish livers of both species, with enzyme efficiencies one to three orders of magnitude higher than for demethylation of the precursor MeO-BDEs. The relatively low efficiencies of demethylation of the MeO-BDEs, compared with higher efficiencies for OH-BDE conjugation, suggests that MeO-BDEs are more likely than OH-BDEs to bioaccumulate in tissues of exposed fish.

Sultan|Amany|A|
Hindrichs|Christiane|C|
Cisneros|Katherine V|KV|
Weaver|Claire J|CJ|
Faux|Laura R|LR|
Agarwal|Vinayak|V|
James|Margaret O|MO|

Demethylation
Methoxy-bromodiphenyl ethers
Hydroxy-bromodiphenyl ethers
Marine fish
Freshwater fish
Glucuronidation
Sulfonation


Both Intracranial and Intravenous Administration of Functionalized Carbon Nanotubes Protect Dopaminergic Neuronal Death from 6-Hydroxydopamine.

Abstract:
Purpose
Although single-walled nanotubes (SWNTs) with functional groups have been suggested as a potential nanomedicine to treat neuronal disorders, effective routes to administer SWNTs have not been compared thus far. The blood-brain barrier is a considerable challenge for the development of brain-targeting drugs, and therefore functionalized SWNT routes of administration have been needed for testing Parkinson's disease (PD) treatment. Here, effective administration routes of functionalized SWNTs were evaluated in PD mouse model.

Methods
Three different administration routes were tested in PD mouse model. Functionalized SWNTs were injected directly into the lateral ventricle three days before (Method 1) or after (Method 2) 6-hydroxydopamine (6-OHDA) injection to compare the protective effects of SWNTs against dopaminergic neuronal death or functionalized SWNTs were injected intravenously at three and four days after 6-OHDA injection (Method 3). Asymmetric behaviors and histological assessment from all animals were performed at two weeks after 6-OHDA injection.

Results
Ventricular injections of SWNTs both before or after 6-OHDA exposure protected dopaminergic neurons both in the substantia nigra and striatum and alleviated rotational asymmetry behavior in PD mice. Moreover, intravenous administration of SWNTs three and four days after 6-OHDA injection also prevented neuronal death and PD mice behavioral impairment without apparent cytotoxicity after six months post-treatment.

Conclusion
Our study demonstrates that functionalized SWNTs could effectively protect dopaminergic neurons through all administration routes examined herein. Therefore, SWNTs are promising nanomedicine agents by themselves or as therapeutic carriers to treat neuronal disorders such as PD.

Kim|Ok-Hyeon|OH|0000-0001-6496-1669
Park|Jun Hyung|JH|
Son|Jong In|JI|
Kim|Kyung-Yong|KY|
Lee|Hyun Jung|HJ|

D061605:Administration, Intravenous
D000818:Animals
D000975:Antioxidants
D001522:Behavior, Animal
D016923:Cell Death
D002454:Cell Differentiation
D045744:Cell Line, Tumor
D004195:Disease Models, Animal
D059290:Dopaminergic Neurons
D006801:Humans
D008297:Male
D008813:Mice, Inbred ICR
D037742:Nanotubes, Carbon
D000071446:Neuronal Outgrowth
D018696:Neuroprotective Agents
D018384:Oxidative Stress
D016627:Oxidopamine
D010300:Parkinson Disease
D011092:Polyethylene Glycols
D014446:Tyrosine 3-Monooxygenase

intracranial
intravenous
single-walled nanotubes
nanomedicine
Parkinson’s disease


Homing Ants Get Confused When Nest Cues Are Also Route Cues.

Abstract: The desert ant Cataglyphis fortis inhabits the salt pans of Tunisia. Individual ants leave the nest for foraging trips that can cover distances of more than 1,500 m [1]. Homing ants use path integration [2, 3], but they also rely on visual [4] and olfactory [5] nest-defining cues to locate the nest entrance. However, nest cues can become ambiguous when they are ubiquitous in the environment. Here we show how ants behave during the nest search when the same cues occur at the nest and along the route. Homing ants focused their search narrowly around a visual or olfactory cue that in training they had experienced only at the nest. However, when ants were trained to the same cue not only at the nest but also repeatedly along the foraging route, they later exhibited a less focused search around the cue. This uncertainty was eliminated when ants had a composite cue at the nest that consisted of two components, one unique to the nest and another that also occurred along the route. Here, the ants focused their search on that part of the binary blend that was presented only at the nest and ignored the other, ubiquitous component. Ants thus not only seem to be able to pinpoint their nest by following learned visual and olfactory cues, but also take into account which cues uniquely specify the nest and which, due to their ubiquity, are less informative and so less reliable. VIDEO ABSTRACT.

Cataglyphis
composite cues
confusing cues
cue ambiguity
navigation
olfaction
vision


Associations of mRNA:microRNA for the Shared Downstream Molecules of EGFR and Alternative Tyrosine Kinase Receptors in Non-small Cell Lung Cancer.

Abstract: Lung cancer is the top cancer killer worldwide with high mortality rate. Majority belong to non-small cell lung cancers (NSCLCs). The epidermal growth factor receptor (EGFR) has been broadly explored as a drug target for therapy. However, the drug responses are not durable due to the acquired resistance. MicroRNAs (miRNAs) are small non-coding and endogenous molecules that can inhibit mRNA translation initiation and degrade mRNAs. We wonder if some downstream molecules shared by EGFR and the other tyrosine kinase receptors (TKRs) further transduce the signals alternatively, and some miRNAs play the key roles in affecting the expression of these downstream molecules. In this study, we investigated the mRNA:miRNA associations for the direct EGFR downstream molecules in the EGFR signaling pathway shared with the other TKRs, including c-MET (hepatocyte growth factor receptor), Ron (a protein tyrosine kinase related to c-MET), PDGFR (platelet-derived growth factor receptor), and IGF-1R (insulin-like growth factor receptor-1). The multiple linear regression and support vector regression (SVR) models were used to discover the statistically significant and the best weighted miRNAs regulating the mRNAs of these downstream molecules. These two models revealed the similar mRNA:miRNA associations. It was found that the miRNAs significantly affecting the mRNA expressions in the multiple regression model were also those with the largest weights in the SVR model. To conclude, we effectively identified a list of meaningful mRNA:miRNA associations: phospholipase C, gamma 1 (PLCG1) with miR-34a, phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2) with miR-30a-5p, growth factor receptor-bound protein 2 (GRB2) with miR-27a, and Janus kinase 1 (JAK1) with miR-302b and miR-520e. These associations could make great contributions to explore new mechanism in NSCLCs. These candidate miRNAs may be regarded as the potential drug targets for treating NSCLCs with acquired drug resistance.

Wang|Fengfeng|F|
Meng|Fei|F|
Wang|Lili|L|
Wong|S C Cesar|SC|
Cho|William C S|WC|
Chan|Lawrence W C|LW|

microRNA
EGFR
alternative tyrosine kinase receptors
non-small cell lung cancer
multiple linear regression
support vector regression model


Mechanical and Corrosion Properties of Laser Surface-Treated Ti13Nb13Zr Alloy with MWCNTs Coatings.

Abstract: Titanium and its alloys is the main group of materials used in prosthetics and implantology. Despite their popularity and many advantages associated with their biocompatibility, these materials have a few significant disadvantages. These include low biologic activity-which reduces the growth of fibrous tissue and allows loosening of the prosthesis-the possibility of metallosis and related inflammation or other allergic reactions, as well as abrasion of the material during operation. Searching for the best combinations of material properties for implants in today's world is not only associated with research on new alloys, but primarily with the modification of their surface layers. The proposed laser modification of the Ti13Nb13Zr alloy with a carbon nanotube coating is aimed at eliminating most of the problems mentioned above. The carbon coating was carried out by electrophoretic deposition (EPD) onto ground and etched substrates. This form of carbon was used due to the confirmed biocompatibility with the human body and the ability to create titanium carbides after laser treatment. The EPD-deposited carbon nanotube coating was subjected to laser treatment. Due to high power densities applied to the material during laser treatment, non-equilibrium structures were observed while improving mechanical and anti-corrosive properties. An electrophoretically deposited coating of carbon nanotubes further improved the effects of laser processing through greater strengthening, hardness or Young's modulus similar to that required, as well as led to an increase in corrosion resistance. The advantage of the presented laser modification of the Ti13Nb13Zr alloy with a carbon coating is the lack of surface cracks, which are difficult to eliminate with traditional laser treatment of Ti alloys. All samples tested showed contact angles between 46° and 82° and thus, based on the literature reports, they have hydrophilic surfaces suitable for cell adhesion.

Ti13Nb13Zr alloy
carbon nanotubes
electrophoretic deposition
laser treatment nanoindentation
potentiodynamic polarization


Long-Term Antibiotic Treatment Prior to Laparoscopic Nephrectomy for Xanthogranulomatous Pyelonephritis Improves Postoperative Outcomes: Results from a Multicenter Study.

Abstract:
PURPOSE
Xanthogranulomatous pyelonephritis is a destructive bacterial infection typically necessitating nephrectomy. We hypothesized that long-term preoperative antibiotics would facilitate laparoscopic nephrectomy by reducing the renal inflammation.

MATERIALS AND METHODS
We reviewed the records of all patients with histologically confirmed xanthogranulomatous pyelonephritis at 3 University of California institutions between 2005 and 2018. Patients were stratified by antibiotic treatment duration and surgical approach. Patients treated with long-term preoperative antibiotics (28 days or more of continuous treatment until surgery) were compared to patients treated with short-term antibiotics (less than 28 days) and those who only received single-dose prophylactic antibiotics before surgery. Patient demographics and operative outcomes were analyzed. Complications were assigned by Clavien-Dindo classification.

RESULTS
Among the 61 patients, 51 (84%) were female and mean age was 50 years. There were 21 (34%) open procedures and 40 (66%) laparoscopic procedures. Median duration of antibiotic treatment was 5 days in those who received a short-term treatment and 87 days in those who received long-term treatment. Eleven patients received only prophylactic single-dose antibiotics. Using multivariate analysis among patients undergoing laparoscopic nephrectomy, controlling for preoperative drainage, long-term antibiotics resulted in a 6.5-day shorter length of stay (p=0.023) and less overall as well as milder postoperative complications (p <0.001).

CONCLUSIONS
Greater than or equal to 4 weeks of preoperative antibiotics before laparoscopic nephrectomy for xanthogranulomatous pyelonephritis was associated with shorter length of stay and fewer, less severe postoperative complications.

Xie|Lillian|L|
Tapiero|Shlomi|S|
Flores|Alec R|AR|
Armas-Phan|Manuel|M|
Limfueco|Luke|L|
Karani|Rajiv|R|
Jiang|Pengbo|P|
Cobb|Kaitlan D|KD|
Sur|Roger L|RL|
Chi|Thomas|T|
Landman|Jaime|J|
Kaler|Kamaljot S|KS|
Clayman|Ralph V|RV|

anti-bacterial agents
laparoscopy
pyelonephritis, xanthogranulomatous


The pre-exponential voltage-exponent as a sensitive test parameter for field emission theories.

Abstract: For field electron emission (FE), an empirical equation for measured current I m as a function of measured voltage V m has the form I m = CV m  exp[-B/V m], where B is a constant and C and k are constants or vary weakly with V m. Values for k can be extracted (i) from simulations based on some specific FE theory, and in principle (ii) from current-voltage measurements of sufficiently high quality. This paper shows that a comparison of theoretically derived and experimentally derived k-values could provide a sensitive and useful tool for comparing FE theory and experiment, and for choosing between alternative theories. Existing methods of extracting k-values from experimental or simulated current-voltage data are discussed, including a modernized 'least residual' method, and existing knowledge concerning k-values is summarized. Exploratory simulations are reported. Where an analytical result for k is independently known, this value is reliably extracted. More generally, extracted k-values are sensitive to details of the emission theory used, but also depend on assumed emitter shape; these two influences will need to be disentangled by future research, and a range of emitter shapes will need examination. Other procedural conclusions are reported. Some scientific issues that this new tool may eventually be able to help investigate are indicated.

Forbes|R G|RG|0000-0002-8621-3298
Popov|E O|EO|
Kolosko|A G|AG|
Filippov|S V|SV|

field electron emission theory–experiment comparisons


Prospective Evaluation of an R2* Method for Assessing Liver Iron Concentration (LIC) Against FerriScan: Derivation of the Calibration Curve and Characterization of the Nature and Source of Uncertainty in the Relationship.

Abstract:
BACKGROUND
FerriScan is the method-of-choice for noninvasive liver iron concentration (LIC) quantification. However, it has a number of drawbacks including cost and expediency.

PURPOSE/HYPOTHESIS
To characterize an R2*-based MRI technique that may potentially be used as an alternative to FerriScan. This was accomplished through the derivation of a calibration curve that characterized the relationship between FerriScan-derived LIC and R2*. The nature and source of uncertainty in this curve were investigated. It was hypothesized that the source of uncertainty is heterogeneity of LIC across the liver.

STUDY TYPE
Prospective.

SUBJECTS
In all, 125 patients (69 women, 56 men) undergoing chelation treatment for iron overload prospectively underwent FerriScan and R2* MRI during the same exam.

FIELD STRENGTH/SEQUENCE
Pulse sequences included 2D multislice spin-echo pulse for FerriScan, and a prototype 3D 6-echo gradient echo acquisition for R2* mapping at 1.5T.

ASSESSMENT
A linear calibration curve was derived from the relationship between FerriScan-derived LIC estimates and R2* through least-squares fitting.

STATISTICAL TESTS
The nature of the uncertainty in the curve was characterized through tests of normality and homoscedasticity. The source of uncertainty was tested by comparing the magnitude of LIC variation over the FerriScan ROI to the observed uncertainty in the R2*-derived LIC estimates.

RESULTS
A linear relationship between logarithmically transformed FerriScan-derived LIC and R2* (log{FerriScan-derived LIC} = 1.029 log{R2*} - 3.822) was confirmed. Uncertainty was random, with a behaviour that was normal and homoscedastic. The source of uncertainty was confirmed as iron heterogeneity across the liver. The nontransformed calibration curve was: FerriScan-derived LIC = 0.0266⋅R2*, with a constant coefficient-of-variation of 0.32.

DATA CONCLUSION
FerriScan and R2* techniques were found to provide equivalent quantification of LIC in this study. Any difference in accuracy or precision was at a level lower than the uncertainty caused by variation in LIC over the liver.

LEVEL OF EVIDENCE
1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1467-1474.

FerriScan
MRI
R2* mapping
iron heterogeneity
liver iron quantification


Diagnostic performance of conventional and advanced imaging modalities for assessing newly diagnosed cervical cancer: systematic review and meta-analysis.

Abstract:
OBJECTIVES
To review the diagnostic performance of contemporary imaging modalities for determining local disease extent and nodal metastasis in patients with newly diagnosed cervical cancer.

METHODS
Pubmed and Embase databases were searched for studies published from 2000 to 2019 that used ultrasound (US), CT, MRI, and/or PET for evaluating various aspects of local extent and nodal metastasis in patients with newly diagnosed cervical cancer. Sensitivities and specificities from the studies were meta-analytically pooled using bivariate and hierarchical modeling.

RESULTS
Of 1311 studies identified in the search, 115 studies with 13,999 patients were included. MRI was the most extensively studied modality (MRI, CT, US, and PET were evaluated in 78, 12, 9, and 43 studies, respectively). Pooled sensitivities and specificities of MRI for assessing all aspects of local extent ranged between 0.71-0.88 and 0.86-0.95, respectively. In assessing parametrial invasion (PMI), US demonstrated pooled sensitivity and specificity of 0.67 and 0.94, respectively-performance levels comparable with those found for MRI. MRI, CT, and PET performed comparably for assessing nodal metastasis, with low sensitivity (0.29-0.69) but high specificity (0.88-0.98), even when stratified to anatomical location (pelvic or paraaortic) and level of analysis (per patient vs. per site).

CONCLUSIONS
MRI is the method of choice for assessing any aspect of local extent, but where not available, US could be of value, particularly for assessing PMI. CT, MRI, and PET all have high specificity but poor sensitivity for the detection of lymph node metastases.

KEY POINTS
• Magnetic resonance imaging is the method of choice for assessing local extent. • Ultrasound may be helpful in determining parametrial invasion, especially in lower-resourced countries. • Computed tomography, magnetic resonance imaging, and positron emission tomography perform similarly for assessing lymph node metastasis, with high specificity but low sensitivity.

D005260:Female
D019788:Fluorodeoxyglucose F18
D006801:Humans
D008207:Lymphatic Metastasis
D008279:Magnetic Resonance Imaging
D009361:Neoplasm Invasiveness
D049268:Positron-Emission Tomography
D012680:Sensitivity and Specificity
D014057:Tomography, X-Ray Computed
D014463:Ultrasonography
D002583:Uterine Cervical Neoplasms

Magnetic resonance imaging
Neoplasm staging
Positron-emission tomography
Ultrasonography
Uterine cervical neoplasms


Role of endothelium in vasomotor responses to endothelin system and protein kinase C activation in porcine retinal arterioles.

Abstract:
PURPOSE
Endothelial cells synthesize vasodilator nitric oxide (NO) and vasoconstrictor endothelin-1 (ET-1) from NO synthase (eNOS) and endothelin-converting enzyme-1 (ECE-1), respectively. Protein kinase C (PKC) and Rho kinase (ROCK) are major signaling molecules mediating vasoconstriction. Although endothelial cells express eNOS, ECE-1, endothelin B (ET(B)) receptors, PKC, and ROCK, their influences on ET-1-induced vasoconstriction remain elusive. We studied whether these endothelial signaling molecules modulate retinal arteriolar constriction to ET-1.

METHODS
Porcine retinal arterioles were isolated and pressurized for vasomotor study, under conditions with intact or denuded endothelium, using videomicroscopic techniques.

RESULTS
Retinal arterioles developed similar resting tone (≈45% of maximum diameter) with or without endothelium. Endothelial denudation attenuated vasoconstriction to ET-1 precursor, big ET-1, by almost equal to 50%, but did not affect vasoconstrictions to ET-1, ET(B) agonist sarafotoxin S6c, or PKC activator phorbol-12, 13-dibutyrate (PDBu). The ROCK inhibitor H-1152 caused vasodilation, and abolished vasoconstrictions to ET-1 and PDBu independent of endothelium. With L-type voltage-operated calcium channel (L-VOCC) blocker nifedipine, PDBu-induced vasoconstriction was abolished and converted to NO-mediated vasodilation in the presence of endothelium. The ET-1-induced vasoconstriction was unaffected by NO released from endothelium during flow elevation.

CONCLUSIONS
Endothelial and smooth muscle ECE-1 contribute equally to synthesis of vasoactive ET-1 in retinal arterioles, with nominal role of endothelial ETB receptors in vasoconstriction to ET-1. The PKC activation leads to endothelium-dependent NO-mediated vasodilation when smooth muscle contraction is ablated by L-VOCC blockade. Endothelial cells and NO appear to have modest roles in modulating ROCK-dependent vasoconstriction, and are insufficient to counteract smooth muscle contractions to ET-1 and PKC activation.

Potts|Luke B|LB|
Bradley|Patrick D|PD|
Xu|Wenjuan|W|
Kuo|Lih|L|
Hein|Travis W|TW|

endothelium
endothelins
arterioles
PKC
retinal blood flow


Wind of Change in the Treatment of Childhood-Onset Takayasu Arteritis: a Systematic Review.

Abstract:
PURPOSE OF REVIEW
We lack evidence-based data for the treatment of childhood-onset Takayasu arteritis (c-TA) since it is a rare disease in children. In this systematic literature review, we aimed to evaluate the treatment choices in c-TA patients and integrate our experience for the treatment of our patients in the recent years/in the biologic era.

RECENT FINDINGS
We reviewed 24 articles addressing treatments of 413 c-TA patients. Steroids were given to 352 patients (85.2%) as the main immunosuppressive therapy. Other immunosuppressive agents included methotrexate (37.3%), cyclophosphamide (24.5%), azathioprine (16.9%), and mycophenolate mofetil (7.9%). Besides, various biological agents were used, including tumor necrosis factor-alpha inhibitors in 70 of 107 c-TA patients (65.4%) and interleukin-6 inhibitors in 33 of them (30.8%). Biologics are increasingly used in our center as well. Even in severe patients, CYC is switched to either anti-TNF or antiIL6 once disease control is achieved. Recently, in addition to conventional immunosuppressants, biologics are increasingly used in c-TA. We have revised our treatment protocol to start with 1-3 doses of high-dose steroids and CYC, in a child with TA with types III-V involvement and high acute phase reactants; once clinical features subside and CRP normalizes, biologics should be started to replace CYC while decreasing the steroid dose.

D000079424:Tumor Necrosis Factor Inhibitors

Treatment
Childhood-onset Takayasu arteritis
Tumor necrosis factor-alpha inhibitors
Interleukin-6 inhibitors
Pediatric Takayasu


Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation.

Abstract:
BACKGROUND
Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited.

OBJECTIVE
We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output.

STUDY DESIGN
A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued.

RESULTS
Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P<.007), and left ventricular global longitudinal strain showed less deformation than at baseline (P=.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<.05). Nifedipine did not alter fetal left ventricular functional parameters or cardiac output. When normoxemia was restored, fetal right ventricular functional parameters and cardiac output returned to baseline level.

CONCLUSION
In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.

Alanne|Leena|L| Bhide|Amarnath|A| Lantto|Juulia|J| Huhta|Heikki|H| Kokki|Merja|M| Haapsamo|Mervi|M| Acharya|Ganesh|G| Räsänen|Juha|J|

pregnancy
hypertension
antihypertensive medication
blood flow
heart
hemodynamics
physiology
ultrasound


Effect of IL-15-Mediating IFN-γ on HTR-8/SVneo Cells and a Preeclampsia Mouse Model Induced by Lipopolysaccharides.

Abstract:
OBJECTIVE
Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS.

METHODS
Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best's carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression.

RESULTS
LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and NKp46 were found in placentas of PE mice treated with IL-15 siRNA.

CONCLUSION
IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.


Oxidative Stress and Trace Elements in Pulmonary Tuberculosis Patients During 6 Months Anti-tuberculosis Treatment.

Abstract: Pulmonary tuberculosis (TB) is a well-known cause of imbalance in oxidative stress (OS) status and trace element levels. However, little information is available for targeting the correlation between OS and trace elements in pulmonary TB patients. The aim of our study was to analyze the OS status and its correlation with trace elements in patients initially and during 6 months anti-TB treatment. Eighty-six newly diagnosed pulmonary TB patients were consecutively recruited, and 112 age- and sex-matched healthy controls participated in the study. Serum markers of OS and trace elements levels were tested and analyzed in all subjects during 6 months anti-TB treatment. Compared with healthy controls, significantly increased level of malondialdehyde (MDA), decreased glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities were found in TB patients. The activities of SOD and CAT and GSH level recovered till normal range at treatment final. Zinc (Zn), selenium (Se), and copper (Cu) concentrations were significantly lower in TB patients in comparison with healthy controls, whereas Zn, Cu, and Se concentrations rise during 6 months anti-TB treatment. Zn was positively correlated with Cu, Se, and GSH, while MDA was negatively correlated with Zn, Se, SOD, and CAT, and SOD was positively correlated with Cu, Zn, and CAT. Our findings indicate that anti-TB treatment could reduce the status of OS and increase the levels of trace elements. The routine assessment of OS markers and element traces may guarantee improved monitoring the anti-TB treatment.

Oxidative stress
Trace elements
Pulmonary tuberculosis
Correlation


RSF1 in cancer: interactions and functions.

Abstract: RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.


The Role and Mechanism of S1PR5 in Colon Cancer.

Abstract:
Purpose
To investigate the role and mechanism of S1PR5 in colon cancer.

Materials and Methods
Lentiviral infection and drug screening helped to establish colon cancer cell lines with stable overexpression and knockdown of S1PR5. Effects of S1PR5 expression on cell growth, proliferation, migration, and invasion were analyzed using a subcutaneous xenograft model in nude mice. Western blot (WB) was used to detect the effects of S1PR5 expression on p-AKT, STAT3, NF-κB, and p-JNK. The distribution of p65 was evaluated in nuclear and cytoplasmic fractions using WB. CCK-8, Transwell migration, and Transwell invasion assays analyzed cell growth, proliferation, migration, and invasion. qRT-PCR analysis revealed that S1PR5 expression was associated with altered expression levels of NF-κB downstream target genes, such as IL-6, TNF-α, and indoleamine 2, 3-dioxygenase 1 (IDO1).

Results
qRT-PCR and WB analysis showed that the S1PR5 level in colon cancer cell lines-SW480, SW620, HCT116, and LoVo-was significantly higher than in NCM460, a healthy colonic epithelial cell line. SW620 and SW480, with high and low expression of S1PR5, respectively, were selected as model cell lines. S1PR5 knockdown in SW620 caused the growth rate, proliferation, migration, invasion, and subcutaneous tumor formation rate to decrease in mice, whereas S1PR5 overexpression in SW480 caused all of these parameters to increase. WB analysis showed an increase in phospho-p65 and its nuclear translocation. S1PR5 knockdown caused a decrease in phospho-p65 levels and its nuclear import, thereby inhibiting its activity. In S1PR5 knockdown and overexpressing cells, p65 was overexpressed and knocked down, respectively. qRT-PCR and WB showed that S1PR5 over-expression up-regulates IDO1, and S1PR5 knockdown inhibits IDO1. CCK-8 and Transwell assays showed that p65 and IDO1 overexpression antagonizes the antitumor effect of S1PR5 knockdown, and that p65 and IDO1 knockdown antagonizes the tumorigenic effect of S1PR5 overexpression.

Conclusion
S1PR5 overexpression promotes the growth, migration, and invasion of cancer by activating the NF-κB/IDO1 signaling pathway.

Zhou|Huijun|H| Yin|Xianli|X| Bai|Fei|F| Liu|Wu|W| Jiang|Shaofeng|S| Zhao|Jinfeng|J|


Feasibility of a Texting Intervention to Improve Medication Adherence Among Older HIV+ African Americans: A Mixed-Method Pilot Study.

Abstract: Antiretroviral therapy (ART) is the primary treatment for HIV, and adherence to it is crucial to addressing health disparities. Approximately half of individuals in the United States living with HIV are African Americans, and those over 45 years of age are more likely to die early from HIV/AIDS than their White counterparts. This mixed-method pilot study evaluated the feasibility of a text-based mobile phone intervention designed to improve ART adherence among older African Americans with HIV. Feasibility was assessed via implementation, participant adherence, acceptability, and satisfaction, as well as short-term impact on medication adherence, adherence-related self-efficacy, and positive affect. The intervention utilized pill reminder, motivational, and health educational texts. Participants (N = 21) ranged in age from 50 to 68 years. Outcomes were evaluated via quantitative results from self-report measures and qualitative data from four focus groups. Attrition to the study was 100%. After 8 weeks, participants reported statistically significant improvements in medication adherence, but not in self-efficacy or affect scores. Qualitative findings highlight the psychologically supportive potential of the intervention, challenges to adherence, as well as suggestions for improvement. The study demonstrates that a text messaging intervention may be feasible for older African Americans with HIV, and helpful in supporting ART adherence.

Pagan-Ortiz|Marta E|ME|
Goulet|Paul|P|
Kogelman|Laura|L|
Levkoff|Sue E|SE|
Weitzman|Patricia Flynn|PF|

adherence
African Americans
aging
HIV/AIDS
older adults
technology


Effect of supra-nutritional selenium-enriched probiotics on hematobiochemical, hormonal, and Doppler hemodynamic changes in male goats.

Abstract: In this study, the influence of supra-nutritional organic selenium (Se) supplement on hematology and plasma biochemicals, including antioxidant parameters and plasma reproductive hormones, as well as blood flow characteristics in the supratesticular and common carotid arteries (STA and CCA, respectively) were investigated. For this purpose, 15 male goats were used and classified into three equal groups according to the supplementation of the basal diet (BD): negative control (NC), probiotic (Pro), and Se-probiotic (Se-Pro) groups. Blood perfusion in the STA and CCA was assessed by Doppler ultrasonography at three different time intervals: at the experimental onset (T0), 3 weeks of dietary supplement (T3), and after 6 weeks of observation (T6). Concomitantly, blood samples were withdrawn for hematobiochemical and hormonal changes. Results revealed no evidence of clinical abnormality, with some enhanced hematological parameters and antioxidant (SOD and GPX) levels in goats of the Se-Pro and Pro groups. High concentrations of FSH were found in the Se-Pro at T6 compared to its values in other groups. Similarly, testosterone levels were elevated in the Pro and Se-Pro groups at T3 compared to other time points. There were significant increases in levels of IGF-1 in the Pro and Se-Pro groups compared to the NC group. Significant (P < 0.05) increases in the values of the blood volume within the CCA and the STA were noted in the Se-Pro group, and the highest values were observed at T6 (CCA, 427.4 ± 33 ml/min; STA, 49.9 ± 5.0 ml/min). In conclusion, supra-nutritional organic selenium improves some hematobiochemical parameters, reproductive hormones, and the blood perfusion within the CCA and STA in goats.

Mandour|Ahmed S|AS|
Samir|Haney|H|
El-Beltagy|Marwa A|MA|
Abdel-Daim|Mohamed M|MM|
Izumi|Watanabe|W|
Ma|Danfu|D|
Matsuura|Katsuhiro|K|
Tanaka|Ryou|R|
Watanabe|Gen|G|

Selenium-enriched probiotic
Goats
Hematology
Antioxidants
Reproductive hormones
Blood flow
Common carotid artery
Doppler ultrasonography


Seaweeds-derived compounds modulating effects on signal transduction pathways: A systematic review.

Abstract:
BACKGROUND
Recently, the study of marine natural products has gained interest due to their relevant biological activities. Specially, seaweeds produce bioactive compounds that could act as modulators of cell signaling pathways involved in a plethora of diseases. Thereby, the description of the molecular mechanisms by which seaweeds elicit its biological functions will certainly pave the way to the pharmacological development of drugs.

AIM
This review describes the molecular mechanisms by which seaweeds act and its possible utilization in the design of new drugs.

METHODS
This review was conducted according to the PRISMA-P guidelines for systematic reviews. Two independent authors searched into four different databases using combinations of keywords. Two more authors selected the articles following the eligibility criteria. Information extraction was conducted by two separated authors and entered into spreadsheets. Methodological quality and risk of bias were determined applying a 12-question Risk of Bias criteria tool.

RESULTS AND DISCUSSION
We found 2360 articles (SCOPUS: 998; PubMed: 678; Wiley: 645 and EBSCO: 39) using the established keywords, of which 113 articles fit the inclusion criteria and were included in the review. This work comprises studies in cell lines, and animal models, any clinical trial was excluded. The articles were published from 2005 up to March 31st 2018. The biggest amount of articles was published in 2017. Furthermore, the seaweeds tested in the studies were collected in 15 countries, mainly in Eastern countries. We found that the main modulated signaling pathways by seaweeds-derivate extracts and compounds were: L-Arginine/NO, TNF-α, MAPKs, PI3K/AKT/GSK, mTOR, NF-κB, extrinsic and intrinsic apoptosis, cell cycle, MMPs and Nrf2. Finally, the articles we analyzed showed moderate risk of bias in almost all the parameters evaluated. However, the studies fail to describe the place and characteristics of sample collection, the sample size, and the blindness of the experimental design.

CONCLUSION
In this review we identified and summarized relevant information related to seaweed-isolated compounds and extracts having biological activity; their role in different signal pathways to better understand their potential to further development of cures for cancer, diabetes, and inflammation-related diseases.

Juárez-Portilla|Claudia|C|
Olivares-Bañuelos|Tatiana|T|
Molina-Jiménez|Tania|T|
Sánchez-Salcedo|José Armando|JA|
Moral|Diana I Del|DID|
Meza-Menchaca|Thuluz|T|
Flores-Muñoz|Mónica|M|
López-Franco|Óscar|Ó|
Roldán-Roldán|Gabriel|G|
Ortega|Arturo|A|
Zepeda|Rossana C|RC|

Molecular mechanisms
Cancer
Diabetes
Algae
Anti-inflammatory
Anti-oxidant


Validating the use of brain volume cutoffs to identify clinically relevant atrophy in RRMS.

Abstract:
BACKGROUND
Baseline brain volume (BV) is predictive at a group level but is difficult to interpret at the single patient level.

OBJECTIVE
To validate BV cutoffs able to identify clinically relevant atrophy in relapsing-remitting multiple sclerosis (RRMS) patients.

METHODS
The expected normalized brain volume (NBV) for each patient was calculated using RRMS patients from two phase III clinical trials, applying a linear formula developed on the baseline variable of an independent data set. The difference between these expected NBV values and those actually observed was calculated and used to categorize the patients in the low-NBV, medium-NBV, and high-NBV groups.

RESULTS
The 2-year probability of 3-month confirmed disability worsening was significantly associated with the NBV categorization ( p = 0.006), after adjusting for treatment effect. Taking the high-NBV group as a reference, the hazard ratios for the medium-NBV and low-NBV groups were 1.22 (95% confidence interval (CI): 0.85-1.76, p = 0.27) and 1.69 (95% CI: 1.11-2.57, p = 0.01), respectively.

CONCLUSION
This study validates the use of BV cutoffs to identify clinically relevant atrophy in RRMS study by showing that the three groups classified according to the baseline NBV adjusted for the other prognostic variables have a significant prognostic impact on the risk of disability progression.

Bovis|Francesca|F|
De Stefano|Nicola|N|
Steinerman|Joshua R|JR|
Knappertz|Volker|V|
Sormani|Maria Pia|MP|

D016032:Randomized Controlled Trials as Topic

Multiple sclerosis
normalized brain volume
disability progression
laquinimod


Endurance of erythrocyte series in chemotherapy.

Abstract: Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Increasing the intensity of chemotherapy doses (higher doses or more frequent administration) would improve antitumor effects, but the hematological toxicity does not allow these dose increases. This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. We selected 855 evaluations performed before the administration of chemotherapy belonging to the treatments initiated during the period December 2018-February 2020, containing 5-fluorouracil, cisplatin, docetaxel, epirubicin or pemetrexed. The data of the 644 evaluations related to the cycles 1-4 of chemotherapy were subject to this processing. The average relative loss of hemoglobin is -11% after the first three cycles of treatment, with statistically significant differences in hemoglobin levels in favor of men. There are risk factors associated with higher average losses, such as age <50 years or >65 years (statistically significant), body mass index (BMI) >25, cisplatin treatment (insufficient number of cases to reach statistical significance).

Săftescu|Sorin|S| Popovici|Dorel|D| Oprean|Cristina|C| Negru|Alina|A| Croitoru|Adina|A| Zemba|Mihail|M| Yasar|Ionela|I| Preda|Maria|M| Negru|Șerban|Ș|

erythrocytes
chemotherapy
bone marrow
cancer
haemoglobin


Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

Abstract:
BACKGROUND
The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features.

METHODS
Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts.

RESULTS
Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age <65 years, male sex, nonwhite race, use of a community treatment facility, non-Medicare insurance, and diagnosis before 2004. Improved and clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, <12 lymph nodes evaluated, positive resection margins, or T4 histology), age, or chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; P<.001). There was no difference in survival noted between single and multiagent adjuvant chemotherapy regimens.

CONCLUSIONS
In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society.

Casadaban|Leigh|L|
Rauscher|Garth|G|
Aklilu|Mebea|M|
Villenes|Dana|D|
Freels|Sally|S|
Maker|Ajay V|AV|

D000971:Antineoplastic Combined Chemotherapy Protocols

chemotherapy
survival
stage II colon cancer
National Cancer Data Base
adjuvant treatment


Doppler Radar Vital Signs Detection Method Based on Higher Order Cyclostationary.

Abstract: Due to the non-contact nature, using Doppler radar sensors to detect vital signs such as heart and respiration rates of a human subject is getting more and more attention. However, the related detection-method research meets lots of challenges due to electromagnetic interferences, clutter and random motion interferences. In this paper, a novel third-order cyclic cummulant (TOCC) detection method, which is insensitive to Gaussian interference and non-cyclic signals, is proposed to investigate the heart and respiration rate based on continuous wave Doppler radars. The k-th order cyclostationary properties of the radar signal with hidden periodicities and random motions are analyzed. The third-order cyclostationary detection theory of the heart and respiration rate is studied. Experimental results show that the third-order cyclostationary approach has better estimation accuracy for detecting the vital signs from the received radar signal under low SNR, strong clutter noise and random motion interferences.

Doppler radar
vital signs
higher order cyclostationary
heart and respiration rate
signal processing


Simultaneous X-ray diffraction and phase-contrast imaging for investigating material deformation mechanisms during high-rate loading.

Abstract: Using a high-speed camera and an intensified charge-coupled device (ICCD), a simultaneous X-ray imaging and diffraction technique has been developed for studying dynamic material behaviors during high-rate tensile loading. A Kolsky tension bar has been used to pull samples at 1000 s(-1) and 5000 s(-1) strain-rates for super-elastic equiatomic NiTi and 1100-O series aluminium, respectively. By altering the ICCD gating time, temporal resolutions of 100 ps and 3.37 µs have been achieved in capturing the diffraction patterns of interest, thus equating to single-pulse and 22-pulse X-ray exposure. Furthermore, the sample through-thickness deformation process has been simultaneously imaged via phase-contrast imaging. It is also shown that adequate signal-to-noise ratios are achieved for the detected white-beam diffraction patterns, thereby allowing sufficient information to perform quantitative data analysis diffraction via in-house software (WBXRD_GUI). Of current interest is the ability to evaluate crystal d-spacing, texture evolution and material phase transitions, all of which will be established from experiments performed at the aforementioned elevated strain-rates.

Hudspeth|M|M| Sun|T|T| Parab|N|N| Guo|Z|Z| Fezzaa|K|K| Luo|S|S| Chen|W|W|


Tobacco retail availability and risk of relapse among smokers who make a quit attempt: a population-based cohort study.

Abstract:
INTRODUCTION
The availability of tobacco is thought to influence smoking behaviour, but there are few longitudinal studies examining if the location and number of tobacco outlets has a prospective impact on smoking cessation.

METHODS
The Ontario Tobacco Survey, a population-representative sample of Ontario adult smokers who were followed every 6 months for up to 3 years, was linked with tobacco outlet location data from the Ontario Ministry of Health. Proximity (distance), threshold (at least one outlet within 500 m) and density (number of outlets within 500 m) with respect to a smokers' home were calculated among urban and suburban current smokers (n=2414). Quit attempts and risk of relapse were assessed using logistic regression and survival analysis, adjusted for neighbourhood effects and individual characteristics.

RESULTS
Increased density of tobacco outlets was associated with decreased odds of making a quit attempt (OR: 0.54; 95% CI 0.35 to 0.85) in high-income neighbourhoods, but not in lower income ones. There was an increased risk of relapse among those who had at least one store within 500 m (HR: 1.41 (95% CI 1.06 to 1.88). Otherwise, there was no association of proximity with quit attempts or relapse.

CONCLUSIONS
The existence of a tobacco retail outlet within walking distance from home was associated with difficulty in succeeding in a quit attempt, while the increased density of stores was associated with decreased attempts in higher income neighbourhoods. The availability of tobacco may influence tobacco use through multiple mechanisms.

Cessation
Public policy
Tobacco industry


Liver Tumors in Pediatric Patients.

Abstract: The most recent advance in the care of children diagnosed with hepatoblastoma and hepatocellular carcinoma is the Pediatric Hepatic International Tumor Trial, which opened to international enrollment in 2018. It is being conducted as a collaborative effort by the pediatric multicenter trial groups in North America, Europe, and the Far East. This international effort was catalyzed by a new unified global risk stratification system for hepatoblastoma, an international histopathologic consensus classification for pediatric liver tumors, and a revised 2017 collaborative update of the PRE-Treatment EXTent of disease radiographic based staging system.

Meyers|Rebecka|R|
Hiyama|Eiso|E|
Czauderna|Piotr|P|
Tiao|Greg M|GM|

Undifferentiated embryonal sarcoma of the liver


Unexplored regulatory sequences of divergently paired GLA and HNRNPH2 loci pertinent to Fabry disease in human kidney and skin cells: Presence of an active bidirectional promoter.

Abstract: Fabry disease (FD) is a rare hereditary disorder characterized by a wide range of symptoms caused by a variety of mutations in the galactosidase α (GLA) gene. The heterogeneous nuclear ribonucleoprotein (HNRNPH2) gene is divergently paired with GLA on chromosome X and is thought to be implicated in FD. However, insufficient information is available on the regulatory mechanisms associated with the expression of HNRNPH2 and the GLA loci. Therefore, the current study performed bioinformatics analyses to assess the GLA and HNRNPH2 loci and investigate the regulatory mechanisms involved in the expression of each gene. The regulatory mechanisms underlying GLA and HNRNPH2 were revealed. The expression of each gene was associated with a bidirectional promoter (BDP) characterized by the absence of TATA box motifs and the presence of specific transcription factor binding sites (TFBSs) and a CpG Island (CGI). The nuclear run-on transcription assay confirmed the activity of BDP GLA and HNRNPH2 transcription in 293T. Methylation-specific PCR analysis demonstrated a statistically significant variation in the DNA methylation pattern of BDP in several cell lines, including human adult epidermal keratinocytes (AEKs), human renal glomerular endothelial cells, human renal epithelial cells and 293T cells. The highest observed significance was demonstrated in AEKs (P<0.05). The results of the chromatin-immunoprecipitation assay using 293T cells identified specific TFBS motifs for Yin Yang 1 and nuclear respiratory factor 1 transcription factors in BDPs. The National Center for Biotechnology Information-single nucleotide polymorphism database revealed pathogenic variants in the BDP sequence. Additionally, a previously reported variant associated with a severe heterozygous female case of GLA FD was mapped in BDP. The results of the present study suggested that the expression of the divergent paired loci, GLA and HNRNPH2, were controlled by BDP. Mutations in BDP may also serve a role in FD and may explain clinical disease diversity.

Al-Obaide|Mohammed A Ibrahim|MAI|
Al-Obaidi|Ibtisam I|II|
Vasylyeva|Tetyana L|TL|

GLA
HNRNPH2
Fabry disease
bidirectional promoter
gene expression


Association of chronic kidney disease with outcomes in acute stroke.

Abstract: Previous studies have found an association between chronic kidney disease and poor outcomes in stroke patients. However, there is a paucity of literature evaluating this association by stroke type. We therefore aimed to explore the association between CKD and stroke outcomes according to type of stroke. The data consisting of 594,681 stroke patients were acquired from Universal Coverage Health Security Insurance Scheme Database in Thailand. Binary logistic regression was used to assess the relationship of CKD and outcomes, which were as follows; in-hospital mortality, long length of stay (>3 days), pneumonia, sepsis, respiratory failure and myocardial infarction. Results: after fully adjusting for covariates, CKD was associated with increased odds of in-hospital mortality in patients with ischemic (OR 1.32; 95% CI = 1.27-1.38), haemorrhagic (OR 1.31; 95% CI = 1.24-1.39), and other undetermined stroke type (OR 1.44; 95% CI = 1.21-1.73). CKD was found to be associated with increased odds of pneumonia, sepsis, respiratory failure and myocardial infarction in ischaemic stroke. While CKD was found to be associated with increase odds of sepsis, respiratory failure, and myocardial infarction, decrease odds of pneumonia was observed in patients with haemorrhagic stroke. In other undetermined stroke type, CKD was found to only be associated with increase odds of sepsis and respiratory failure, while there is no significant association of CKD and increase or decrease odds with pneumonia and myocardial infarction. CKD was associated with poor outcomes in all stroke types. CKD should be considered as part of stroke prognosis as well as identifying at risk patient population for in-hospital complications.

Chronic kidney disease
Outcome
Stroke
Stroke type
Haemorrhagic
Ischaemic
Complications


OELs derivation in Poland and in the former Eastern Bloc with reference to approaches and practices applied in the EU.

Abstract: Based on the literature, current legislation and the European Union (EU) directives, the rules to protect the health of workers in Poland and the countries of the former Eastern Bloc were analyzed. Since 2002, the activities in the field of hygiene standards in the countries of the former Eastern Bloc have been correlated with the EU policy. The functioning of the system of maximum admissible concentrations (MAC) having been implemented in Poland for many years before the accession to the EU, has provided for a relatively quick adjustment of Polish regulations on chemicals to the relevant European law. The Polish list includes 543 substances. In the former Eastern Bloc countries, intensification of work after joining the EU has caused the lists in those countries to contain from 285 substances in Slovakia to 780 in Lithuania. Currently, all substances included in the EU lists (up to and including the 3rd list of occupational exposure limit values of the Directive 2009/161/EC) have been governed by the Polish, Lithuanian, Czech, Latvian and Hungarian law. In Estonia and Slovakia the provisions of the Directive 2006/15/EC establishing the second list of occupational exposure limits have been implemented. Individual national lists contain much more chemicals than the EU list containing currently 122 substances. The legislative process in the EU is slow, and that is why the national law is important and necessary due to the local needs in selected areas. It is necessary to correlate the activities in the field of determining regional occupational exposure limit (OEL) values in the countries of the Eastern Bloc and the EU.

D000395:Air Pollutants, Occupational
D005060:Europe
D005062:European Union
D006077:Government Agencies
D006801:Humans
D019570:Inhalation Exposure
D008452:Maximum Allowable Concentration
D016273:Occupational Exposure
D016272:Occupational Health
D011044:Poland

Poland
occupational exposure
Eastern Europe
MAC-STEL
MAC-TWA
UE


A large dataset of synthetic SEM images of powder materials and their ground truth 3D structures.

Abstract: This data article presents a data set comprised of 2048 synthetic scanning electron microscope (SEM) images of powder materials and descriptions of the corresponding 3D structures that they represent. These images were created using open source rendering software, and the generating scripts are included with the data set. Eight particle size distributions are represented with 256 independent images from each. The particle size distributions are relatively similar to each other, so that the dataset offers a useful benchmark to assess the fidelity of image analysis techniques. The characteristics of the PSDs and the resulting images are described and analyzed in more detail in the research article "Characterizing powder materials using keypoint-based computer vision methods" (B.L. DeCost, E.A. Holm, 2016) [1]. These data are freely available in a Mendeley Data archive "A large dataset of synthetic SEM images of powder materials and their ground truth 3D structures" (B.L. DeCost, E.A. Holm, 2016) located at http://dx.doi.org/10.17632/tj4syyj9mr.1[2] for any academic, educational, or research purposes.

Computer vision
Computational materials science
Image databases
Metal powder
Microstructural analysis


Rational Enzyme Design without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases.

Abstract: Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering is useful to remedy this, but it usually requires prior structural knowledge of the target enzyme, and/or relies on extensive, time-consuming screening and analysis. Here, a straightforward strategy that involves rational rapid in silico analysis of protein sequences is described. The method pinpoints 6-12 single-mutant candidates to improve transglycosylation yields. Requiring very little prior knowledge of the target enzyme other than its sequence, the method is generic and procures catalysts for the formation of glycosidic bonds involving various d/l-, α/β-pyranosides or furanosides, and exo or endo action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.

hydrolases
protein engineering
transglycosylation
enzyme catalysis
multiple sequences alignment
oligosaccharide synthesis


Evidence for Multiple Applications of Monoclonal Antibody 5G10.

Abstract: We had earlier obtained a murine monoclonal antibody (mAb), termed 5G10, that bound to Salmonella flagellin (SF) and subsequently impaired the latter property of Toll-like receptor 5 (TLR5) signaling activation. Besides interrupting SF-mediated TLR5 activation, mAb 5G10 probably had other potential applications. In this study, we explored multiple functions of 5G10. A short peptide QRVRELAV (designated T5) derived from SF in either terminal of proteins was specifically recognized by 5G10. T5 tag expressed in eukaryotic cell was also detected by 5G10 when analyzed by Western blot, immunofluorescence assay (IFA), and fluorescent-activated cell sorting (FACS). The result of the co-immunoprecipitation assay showed that 5G10 as a bait antibody dragged out the complex of enterovirus 71 (EV71) 2A and mitochondrial antiviral signaling (MAVS) protein. More importantly, 5G10 helped to purify fusion proteins T5-tagged (EV71) 2A and T5-Japanese encephalitis virus NS5 methyltransferase (MTase). Thus, it has been suggested that mAb 5G10 could be useful in several biological applications, including protein identification, location, and affinity purification.

Xie|Lilan|L| Chen|Wangsheng|W| Li|Jianjun|J| Li|Yi|Y| Li|Yaoming|Y|

D048868:Adaptor Proteins, Signal Transducing

monoclonal antibody
flagellin
protein purification


Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial.

Abstract:
BACKGROUND & AIMS
Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome.

METHODS & RESULTS
In total 112 participants (men [50%] and women [50%]) aged 21-70 years with BMI 30-45 kg/m2 (mean 35.2 [SD 3.7]) were randomized to intermittent or continuous energy restriction. A 6-month weight-loss phase including 10 visits with dieticians was followed by a 6-month maintenance phase without additional face-to-face counselling. The intermittent energy restriction group was advised to consume 400/600 kcal (female/male) on two non-consecutive days. Based on dietary records both groups reduced energy intake by ∼26-28%. Weight loss was similar among participants in the intermittent and continuous energy restriction groups (8.0 kg [SD 6.5] versus 9.0 kg [SD 7.1]; p = 0.6). There were favorable improvements in waist circumference, blood pressure, triglycerides and HDL-cholesterol with no difference between groups. Weight regain was minimal and similar between the intermittent and continuous energy restriction groups (1.1 kg [SD 3.8] versus 0.4 kg [SD 4.0]; p = 0.6). Intermittent restriction participants reported higher hunger scores than continuous restriction participants on a subjective numeric rating scale (4.7 [SD 2.2] vs 3.6 [SD 2.2]; p = 0.002).

CONCLUSIONS
Both intermittent and continuous energy restriction resulted in similar weight loss, maintenance and improvements in cardiovascular risk factors after one year. However, feelings of hunger may be more pronounced during intermittent energy restriction.

TRIAL REGISTRATION
www.clinicaltrials.govNCT02480504.

Sundfør|T M|TM|
Svendsen|M|M|
Tonstad|S|S|

Weight loss
Cardiometabolic risk factors
Metabolic syndrome
Intermittent energy restriction


Modeling and testing maternal and newborn care mHealth interventions: a pilot impact evaluation and follow-up qualitative study in Guatemala.

Abstract:
Objective
To develop a descriptive model of structural characteristics of mHealth in the context of newborn nutrition, and to assess the effects of illustrative interventions through a mixed-methods study consisting of an impact evaluation and a qualitative assessment.

Materials and Methods
We conducted a 23-week intervention with 100 mothers in rural Guatemala in 2013 and 2014. In group 1 ( n  = 24), participants received health-promoting text messages. In group 2 ( n  = 32), peer-to-peer groups were formed. In group 3 ( n  = 30), peer-to-peer groups were formed, a health professional participated in the discussions, and participants received health-promoting messages. In the control group ( n  = 14), participants were simply given a mobile phone. We measured changes in knowledge and self-reported behavior. Four focus groups in 2015 showed the perceptions of 44 additional women and the potential of the previously tested interventions in other marginalized areas.

Results
Significant relationships were found between group membership and changes in knowledge ( P  < .001), and between changes in knowledge and self-reported behavior ( P  = .010). Within peer-to-peer groups, 3665 text messages were shared; discussions covered topics such as breastfeeding practices, health concerns, and emotional issues. Focus groups revealed a deficit of support for mothers, a precariousness of public services, different cultural barriers affecting access to care, and the potential for scaling up.

Discussion
The complementarity of structural arrangements of mHealth interventions can play an important role in helping to encourage recommended breastfeeding attitudes along with providing rich information about challenges in rural areas.

Conclusion
A mixed-methods study was appropriate to compare the effects and assess the potential of mHealth strategies in a complex rural setting.

Prieto|José Tomás|JT|
Zuleta|Clara|C|
Rodríguez|Jorge Tulio|JT|

D007722:Health Knowledge, Attitudes, Practice

D007227:Infant Nutritional Physiological Phenomena

mobile
knowledge
self-reported behavior
breastfeeding
comparison
mixed methods