Person-to-Person Transmission of Andes Virus in Hantavirus Pulmonary Syndrome, Argentina, 2014.

Abstract: Andes virus is unique among hantaviruses because it can be transmitted from person to person. This mechanism was previously supported by epidemiologic data and genetic evidence based only on partial sequences. We used full-length virus sequencing to confirm person-to-person transmission of this virus in a cluster of 3 cases in Argentina in 2014.

Alonso|Daniel O|DO|
Pérez-Sautu|Unai|U|
Bellomo|Carla M|CM|
Prieto|Karla|K|
Iglesias|Ayelén|A|
Coelho|Rocío|R|
Periolo|Natalia|N|
Domenech|Isabel|I|
Talmon|Gabriel|G|
Hansen|Romina|R|
Palacios|Gustavo|G|
Martinez|Valeria P|VP|

person-to-person transmission
Andes virus
hantavirus
hantavirus pulmonary syndrome
Argentina
next-generation sequencing
viruses


Problem behaviors in adult laying hens - identifying risk factors during rearing and egg production.

Abstract: Feather pecking, toe pecking, cannibalism, smothering, social clumping, hens laying eggs outside the nest boxes, and reduced feather quality are examples of problem behaviors and consequences reported by egg producers. The aim of this study was to identify rearing- and production-related risk factors associated with producer-reported problem behaviors in Norwegian layer flocks. Questionnaires were distributed to 410 egg producers nationwide, and 120 producers responded to the survey (response rate 29%). After exclusion of data that did not comply with the instructions, the final dataset included 78 flocks (19%). The survey covered questions about the farm, the flock's production results, the housing environment, climate and management routines, and the behavior of the birds from 16 wk of age until the flock was euthanized at 70-80 wk of age. The individual problem behaviors were combined to generate a continuous index variable called "problem behavior", ranging from 0 (none) to 8 (all the listed problem behaviors) reported. Multilevel linear regression models were applied to evaluate associations between the index and selected risk factors during rearing and production. The primary predictor was housing system during egg production: producers with aviary flocks on average (± standard deviation) reported 1.6 (± 0.60) more problem behaviors compared to producers with furnished cages (P < 0.001). Within aviaries (n = 40), producers, on average reported 1.7 (± 0.50) more problem behaviors in flocks that experienced problems with climatic conditions, compared to flocks without climatic problems (P = 0.001). For respondents with furnished cages (n = 30), on average 1.1 (± 0.50) fewer problem behaviors were reported in farms with ≥ 7,500 birds compared to farms with < 7,500 birds (P = 0.027). In conclusion, this is the first study assessing management and housing factors during the rearing and laying phase associated with problem behaviors as reported by Norwegian egg producers. As this study relied on producer reported observations, future studies are needed to investigate whether objective measurements can verify these results.

Brantsæter|Margrethe|M|
Nordgreen|Janicke|J|
Hansen|Tone B|TB|
Muri|Karianne|K|
Nødtvedt|Ane|A|
Moe|Randi O|RO|
Janczak|Andrew M|AM|

problem behavior
laying hen
rearing
production
welfare


Factors affecting population dynamics of leaf beetles in a subarctic region: The interplay between climate warming and pollution decline.

Abstract: Understanding the mechanisms by which abiotic drivers, such as climate and pollution, influence population dynamics of animals is important for our ability to predict the population trajectories of individual species under different global change scenarios. We monitored four leaf beetle species (Coleoptera: Chrysomelidae) feeding on willows (Salix spp.) in 13 sites along a pollution gradient in subarctic forests of north-western Russia from 1993 to 2014. During a subset of years, we also measured the impacts of natural enemies and host plant quality on the performance of one of these species, Chrysomela lapponica. Spring and fall temperatures increased by 2.5-3°C during the 21-year observation period, while emissions of sulfur dioxide and heavy metals from the nickel-copper smelter at Monchegorsk decreased fivefold. However, contrary to predictions of increasing herbivory with climate warming, and in spite of discovered increase in host plant quality with increase in temperatures, none of the beetle species became more abundant during the past 20years. No directional trends were observed in densities of either Phratora vitellinae or Plagiodera versicolora, whereas densities of both C. lapponica and Gonioctena pallida showed a simultaneous rapid 20-fold decline in the early 2000s, remaining at very low levels thereafter. Time series analysis and model selection indicated that these abrupt population declines were associated with decreases in aerial emissions from the smelter. Observed declines in the population densities of C. lapponica can be explained by increases in mortality from natural enemies due to the combined action of climate warming and declining pollution. This pattern suggests that at least in some tri-trophic systems, top-down factors override bottom-up effects and govern the impacts of environmental changes on insect herbivores.

Zvereva|Elena L|EL|
Hunter|Mark D|MD|
Zverev|Vitali|V|
Kozlov|Mikhail V|MV|

Host plant quality
Insect herbivores
Air pollution
Climate change
Kola Peninsula
Predation


Inferring natural selection signals in Plasmodium vivax-encoded proteins having a potential role in merozoite invasion.

Abstract: Detecting natural selection signals in Plasmodium parasites antigens might be used for identifying potential new vaccine candidates. Fifty-nine Plasmodium vivax-Sal-I genes encoding proteins having a potential role in invasion were used as query for identifying them in recent P. vivax strain genome sequences and two closely-related Plasmodium species. Several measures of DNA sequence variation were then calculated and selection signatures were detected by using different approaches. Our results may be used for determining which genes expressed during P. vivax merozoite stage could be prioritised for further population genetics or functional studies for designing a P. vivax vaccine which would avoid allele-specific immune responses.

Garzón-Ospina|Diego|D|
Forero-Rodríguez|Johanna|J|
Patarroyo|Manuel A|MA|

D019295:Computational Biology
D014644:Genetic Variation
D006790:Host-Parasite Interactions
D010802:Phylogeny
D010966:Plasmodium vivax
D011110:Polymorphism, Genetic
D015800:Protozoan Proteins
D012641:Selection, Genetic
D017422:Sequence Analysis, DNA

Natural selection signal
Allele-specific response
Anti-malarial vaccine
Plasmodium vivax


Ultrasonic accelerates asparagine-glucose non-enzymatic browning reaction without acrylamide formation.

Abstract: Ultrasonic accelerated the asparagine-glucose non-enzymatic browning reaction with significant decrease of glucose and asparagine concentrations, and marked increase of intermediate products (UV-absorbance value at 294nm, Abs294), melanoidins (UV-absorbance value at 420nm, Abs420) and in vitro antioxidant activity (DPPH free radical scavenging activity). As the ultrasonic intensity was 17.83W/cm2, the asparagine-glucose solution's Abs294, Abs420 and antioxidant activity increased from 0 to 1.26, 0.88 and 21.56%, respectively, and the glucose and asparagine concentrations of the asparagine-glucose solution reduced 58.97 and 12.57%, respectively. The high performance liquid chromatography (HPLC)-Diode Array Detector (DAD) analyses showed that no acrylamide was detected after 50-min ultrasonic reaction. This study suggested that ultrasonic at higher intensity was a potential method to accelerate the non-enzymatic browning reaction in the asparagine-glucose solution without acrylamide production.

Ultrasonic
Non-enzymatic browning reaction
Acrylamide
Antioxidant activity


Fluidization of elongated particles-Effect of multi-particle correlations for drag, lift, and torque in CFD-DEM.

Abstract: Having proper correlations for hydrodynamic forces is essential for successful CFD-DEM simulations of a fluidized bed. For spherical particles in a fluidized bed, efficient correlations for predicting the drag force, including the crowding effect caused by surrounding particles, are already available and well tested. However, for elongated particles, next to the drag force, the lift force, and hydrodynamic torque also gain importance. In this work, we apply recently developed multi-particle correlations for drag, lift and torque in CFD-DEM simulations of a fluidized bed with spherocylindrical particles of aspect ratio 4 and compare them to simulations with widely used single-particle correlations for elongated particles. Simulation results are compared with previous magnetic particle tracking experimental results. We show that multi-particle correlations improve the prediction of particle orientation and vertical velocity. We also show the importance of including hydrodynamic torque.

fluidized bed
lift force
hydrodynamic torque
CFD‐DEM
multi‐particle correlations
nonspherical particles


A bluetooth low energy dataset for the analysis of social interactions with commercial devices.

Abstract: This paper describes a data collection campaign and a dataset of BLE beacons for detecting and analysing human social interactions. The dataset has been collected by involving 15 volunteers that interacted in indoor environments for a total of 11 hours of activity. The dataset is released as a collection of CSV files with a timestamp, RSSI (Received Signal Strength Indicator) and a unique identifier of the emitting and of the receiving devices. Volunteers wear a wristband equipped with BLE tags emitting beacons at a fixed rate, and a mobile application able to collect and to store beacons. We organized 6 interaction sessions, designed to reproduce the three common stages of an interaction (Non Interaction, Approaching and Interaction). Moreover, we reproduced interactions by varying the volunteer's posture as well as the position of the receiving device. The dataset is released with a ground truth annotation reporting the exact time intervals during which volunteers actually interacted. The combination of such factors, provides a rich dataset useful to experiment algorithms for detecting interactions and for analyzing dynamics of interactions in a real-world setting. We present in detail the dataset and its evaluation in "Sensing Social Interactions through BLE Beacons and Commercial Mobile Devices", in which we focus on two orthogonal analysis: quality of the dataset and RSSI symmetry of the channel during the interaction stage between pairs of users.

Bluetooth low energy
Social interactions
Co-location
Social sensing


Evaluation and Management of Stage 2 Hypertension in Pediatric Patients.

Abstract:
PURPOSE OF REVIEW
To update the definition and clinical practice of stage 2 hypertension (HTN) in pediatrics.

RECENT FINDINGS
The 2017 American Academy of Pediatrics Clinical Practice Guideline (AAP CPG) for Screening and Management of High Blood Pressure in Children and Adolescent includes new normative blood pressure tables for children and adolescents ages 1 to 17 years and new definitions for stage 2 HTN. This review will highlight these aspects as well as new recommendations in the guideline specific to stage 2 HTN. It will outline how the new guideline differs from the previous 2004 guideline, the implications of these differences, and suggested changes in evaluation and management of stage 2 HTN. Lastly, the review will address topics relevant to daily clinical practice including competitive athletic participation, investigation for secondary HTN and HTN comorbidities, and blood pressure-lowering therapy. With the publication of the new AAP CPG introducing revised normative tables, the prevalence of stage 2 HTN in pediatrics is expected to rise. Based on the new guidelines, there is less emphasis on investigation for secondary HTN and more attention to lifestyle modifications for primary HTN. Future research should address whether there is BP level within the stage 2 HTN range above which the approach to evaluation and management should be altered in this heterogeneous patient population.

2017 AAP Clinical Practice Guideline for High Blood Pressure in Children and Adolescents


Fetal and Placental DNA Stimulation of TLR9: A Mechanism Possibly Contributing to the Pro-inflammatory Events During Parturition.

Abstract:
INTRODUCTION
While there is evidence for a relationship between cell-free fetal DNA (cffDNA) and parturition, questions remain regarding whether cffDNA could trigger a pro-inflammatory response on the pathway to parturition. We hypothesized that placental and/or fetal DNA stimulates toll-like receptor 9 (TLR9) leading to secretion of pro-inflammatory cytokines by macrophage cells.

METHODS
Four in vitro DNA stimulation studies were performed using RAW 264.7 mouse peritoneal macrophage cells incubated in media containing the following DNA particles: an oligodeoxynucleotide (ODN2395), intact genomic DNA (from mouse placentas, fetuses and adult liver), mouse DNA complexed with DOTAP (a cationic liposome forming compound), and telomere-depleted mouse DNA. Interleukin 6 (IL6) secretion was measured in the media by enzyme-linked immunosorbent assay; and the cell pellet was homogenized for protein content (picograms IL6/mg protein).

RESULTS
Robust IL6 secretion was observed in response to ODN2395 (a CpG-rich TLR9 agonist), mouse DNA-DOTAP complexes, and telomere-depleted mouse DNA in concentrations of 5 to 15 μg/mL. In contrast, ODN A151 (containing telomere sequence motifs), intact genomic mouse DNA, and restriction enzyme-digested DNA had no effect on IL6 secretion. The IL6 response was significantly inhibited by chloroquine (10 μg/mL), thereby confirming the important role for TLR9 in the response by macrophage cells.

CONCLUSIONS
DNA derived from mouse placentas and fetuses, and depleted of telomeric sequences, stimulates a robust pro-inflammatory response by macrophage cells, thereby supporting the hypothesis that cffDNA is able to stimulate an innate immune response that could trigger the onset of parturition. These findings are of clinical importance, as we search for effective treatment/prevention of preterm parturition.

Goldfarb|Ilona Telefus|IT|
Adeli|Sharareh|S|
Berk|Tucker|T|
Phillippe|Mark|M|

placental DNA
toll-like receptor 9
telomeres
fetal cell-free DNA
mouse macrophage cells


3'-Hydroxypterostilbene Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis.

Abstract:
BACKGROUND
A natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3'-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear.

PURPOSE
The aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism.

STUDY DESIGN AND METHODS
This study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated.

RESULTS
The results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes.

CONCLUSION
This is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.

Lee|Pei-Sheng|PS| Chiou|Yi-Shiou|YS| Chou|Pin-Yu|PY| Nagabhushanam|Kalyanam|K| Ho|Chi-Tang|CT| Pan|Min-Hsiung|MH|


Neurocircuitry associated with symptom dimensions at baseline and with change in borderline personality disorder.

Abstract: Borderline personality disorder (BPD) is a serious illness associated with chronic suffering and self-injurious behavior. Parsing the relationships between specific symptom domains and their underlying biological mechanisms may help us further understand the neural circuits implicated in these symptoms and how they might be amenable to change with treatment. This study examines the association between symptom dimensions (Affective Disturbance, Cognitive Disturbance, Disturbed Relationships, and Impulsivity) and amygdala resting-state functional connectivity (RSFC) in a sample of adults with BPD (n = 18). We also explored the relationships between change in symptom dimensions and change in amygdala RSFC in a subset of this sample (n = 13) following 8 weeks of quetiapine or placebo. At baseline, higher impulsivity was associated with increased positive RSFC between right amygdala and left hippocampus. There were no significant differences in neural change between treatment groups. Improvement in cognitive disturbance was associated with increased positive RSFC between left amygdala and temporal fusiform and parahippocampal gyri. Improvement in disturbed relationships was associated with increased negative RSFC between right amygdala and frontal pole. These results support that specific dimensions of BPD are associated with specific neural connectivity patterns at baseline and with change, which may represent neural treatment targets.

Westlund Schreiner|Melinda|M|
Klimes-Dougan|Bonnie|B|
Mueller|Bryon A|BA|
Nelson|Katharine J|KJ|
Lim|Kelvin O|KO|
Cullen|Kathryn R|KR|

Symptom dimension
Borderline personality disorder
Resting-state functional connectivity
Neuroimaging


Responses of fresh-cut products of four mango cultivars under two different storage conditions.

Abstract: Due to availability of minimally processed products, the consumption of fresh produce has increased over recent years. The present study has been undertaken with the objective of screening of four mango cultivars ('Kesar', 'Rajapuri', 'Totapuri' and 'Ladvo') for evaluating the consequences of minimal processing on their quality attributes under storage at two different temperatures (5 ± 1 °C, 95% RH and 10 ± 1 °C, 87% RH) up to 12 days. The result of the study revealed significant impacts of low temperature storage on the quality parameters of fresh-cut mango cultivars. The evaluated bioactive compounds such as total phenolics, vitamin C and carotenoids were better retained in the samples stored at 5 °C as compared with that of 10 °C. Moreover, the storage of fresh-cut mango cultivars at 5 °C showed lower water loss and microbial contamination. Sensory analyses revealed that the storage of fresh-cut mango cultivars at 10 °C influenced overall acceptability due to changes in their visual perception, though taste, odor and firmness were less affected. This study revealed a significant variation in the storability of fresh-cut mango cultivars with respect to the storage temperature. Among currently studied four cultivars of mango, slices of 'Totapuri' showed comparatively the least change in color, firmness and sensory properties during storage at 5 and 10 °C and it can be a potential cultivar for fresh-cut processing.

Sharma|Sonu|S|
Rao|Tadapaneni Venkata Ramana|TVR|

Fresh-cut Mango Storage Temperature Bioactive Shelf-life


Gluten-Free Labeling Is Misused Frequently in Foods Marketed in Northwestern Mexico.

Abstract: Background: Patients with celiac disease (CD) require a gluten-free (GF) diet, including industrialized products containing ≤ 20 mg gluten/kg. The market status of GF food products is almost unknown in Mexico. Therefore, we studied the GF-labeled products on the northwestern Mexican market and analyzed their gluten content. Methods: We searched for GF type of foods in three different supermarkets of each chain in Mexicali Baja California and Hermosillo Sonora and corroborated the price, origin, and GF certification of each item using internet sites. We quantified the gluten in the foods using the sandwich R5-enzyme-linked immunosorbent assay (ELISA) and detected their immune-reactivity for IgA from patients with CD. Results: The study included >263 different GF-labeled foodstuffs, and 55% of them were made in Mexico. The Mexican items were principally flours, sausages, bread and bakery, milk-type products, and tortillas, while pasta, snacks, and breakfast cereals were mainly imported. The cost ratio of GF products to the conventional mean was 3.5, ranging principally from 1 to 13. The most common GF-labeled foods were flours and pasta (34), cookies and snacks (32), breakfast cereals, sausages, and milk-type products (18-20). Although 36% of the products were certified, 17.4% of the analyzed samples contained >20 mg gluten/kg, mainly the non-certified ones and those made in Mexico. IgA from patients with CD reacted in vitro against gluten proteins from the contaminated GF-labeled products. Conclusion: The accessibility of GF products in the northwestern Mexican market is wide; however, such products are expensive, and some could be risky for patients with CD because they contain gluten, which is recognized by the immune systems of these patients.

Calderón de la Barca|Ana M|AM|
Luna-Alcocer|Valeria|V|
Valenzuela-Miranda|José R|JR|
Mejía-León|Maria E|ME|

gluten-free labeling
foods
celiac disease
mexican market
analysis


Matching Task Difficulty to Patient Ability During Task Practice Improves Upper Extremity Motor Skill After Stroke: A Proof-of-Concept Study.

Abstract:
OBJECTIVE
To test the feasibility of the Fugl-Meyer Assessment of the Upper Extremity "keyform," derived from Rasch analysis, as a method for systematically planning and progressing rehabilitation.

DESIGN
Feasibility study, single group design.

SETTING
University rehabilitation research laboratory.

PARTICIPANTS
Participants (N=10; mean age, 59.70±9.96y; 24.1±30.54mo poststroke) with ischemic or hemorrhagic stroke >3 months prior, voluntarily shoulder flexion ≥30°, and simultaneous elbow extension ≥20°.

INTERVENTIONS
The keyform method defined initial rehabilitation targets (goals) and progressed the rehabilitation program after every third session. Targets were repetitively practiced within the context of client-selected functional tasks not in isolation.

MAIN OUTCOME MEASURES
Feasibility was defined by subject's pain or fatigue, upper extremity motor function (Wolf Motor Function Test), and movement patterns (kinematics). Assessments were administered pre- and posttreatment and compared using paired t tests. Task-difficulty and patient-ability measures were calculated using Rasch analysis and compared using paired t tests (P<.05).

RESULTS
Ten participants completed 9 sessions, 200 movement repetitions per session in <2 hours without pain or fatigue. Participants gained upper extremity motor function (Wolf Motor Function Test: pretreatment, 22.23±24.26s; posttreatment, 15.46±22.12s; P=.01), improved shoulder-elbow coordination (index of curvature: pretreatment, 1.30±0.15; posttreatment, 1.21±0.11; P=.01), and exhibited reduced trunk compensatory movement (trunk displacement: pretreatment, 133.97±74.15mm; posttreatment, 108.08±64.73mm; P=.02). Task-difficulty and patient-ability measures were not statistically different throughout the program (person-ability measures of 1.01±0.05, 1.64±0.45, and 2.22±0.65 logits and item-difficulty measures of 0.93±0.37, 1.70±0.20, and 2.06±0.24 logits at the 3 testing time points, respectively; P>.05).

CONCLUSIONS
The Fugl-Meyer Assessment of the Upper Extremity keyform is a feasible method to ensure that the difficulty of tasks practiced were well matched to initial and evolving levels of upper extremity motor ability.

Woodbury|Michelle L|ML|
Anderson|Kelly|K|
Finetto|Christian|C|
Fortune|Andrew|A|
Dellenbach|Blair|B|
Grattan|Emily|E|
Hutchison|Scott|S|

Stroke
Rehabilitation
Occupational therapy


Analysis and Experimental Investigation of the Light Dimming Effect on Automotive Visible Light Communications Performances.

Abstract: The use of Visible Light Communications (VLC) in vehicular applications has become a major research area due to its simplicity, high performance to cost ratio, and great deployment potential. In this context, this article provides one of the very few analyses and experimental evaluations concerning the integration of a light dimming function in vehicular VLC systems. For this purpose, a vehicle-to-vehicle VLC prototype has been implemented and used to evaluate the systems' communication performances in light dimming conditions, while decreasing the duty cycle from 40% to 1%, and increasing the communication range from 1 to 40-50 m. The experimental results showed that in normal lighting conditions, the VLC technology can easily support low duty cycle light dimming for ranges up to 40 m, while maintaining a 10-6 BER. Nevertheless, in strong optical noise conditions, when the system reaches its SNR limit, the communication range can decrease by half, whereas the BER can increase by 2-4 orders of magnitude. This article provides consistent evidence concerning the high potential of the VLC technology to support inter-vehicle communication links, even in light dimming conditions.

“lights-off” visible light communications


Molecular Mechanisms Underlying Pituitary Pathogenesis.

Abstract: During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

Sapochnik|Melanie|M|
Nieto|Leandro Eduardo|LE|
Fuertes|Mariana|M|
Arzt|Eduardo|E|

Pituitary tumors
Senescence
PTTG
IL-6
OIS


What is the effectiveness of radiofrequency ablation in the management of patients with spinal metastases? A systematic review and meta-analysis.

Abstract:
PURPOSE
Spinal metastases are indicative of progressive cancer which can lead to vertebral body fractures and spinal cord compression. Radiofrequency ablation (RFA) treatment is infrequently used in patients with refractory pain. The aim of this systematic review is to determine the clinical efficacy of RFA, with the scope of using it as front-line management of spinal metastases.

METHODS
Electronic databases were searched (to July 2020) for studies evaluating RFA treatment for spinal metastases in adults. Measured outcomes were pain (primary), disability, health-related quality of life (HRQOL), complications, tumour control and mortality. Study inclusion, data extraction and risk of bias using the ROBIN-I tool were assessed. Meta-analysis was conducted for pooled results with homogeneity, and narrative synthesis was conducted otherwise.

RESULTS
15 studies were included. RFA reduces pain scores at 3-5 weeks [standardised mean difference (SMD 2.24, 95% confidence intervals (CI) 1.55-2.93], 3-4 months (SMD 3.00, 95% CI 1.11-4.90) and 5-6 months (SMD 3.54, 95% CI 1.96-5.11). RFA is effective in reducing disability/improving HRQOL in the short-term but longer-term efficacy remains unclear. 13.2% cases reported local tumour control failure (2.5 months-5 year follow-up) whereas mortality was 23.6% (follow-up of up to 1 year).

CONCLUSION
Low quality evidence has proven RFA to be safe and effective in reducing pain and disability, especially in the short-term. RFA may be routinely implemented in all cases involving refractory pain or radiotherapy-resistant tumours but controlled trials are required to compare the efficacy of RFA to current frontline treatments. PROSPERO protocol registration number: CRD42020202377.

Radiofrequency ablation
Spinal metastases
Spinal cord compression
Back pain
Radiotherapy


Multiple Midfrontal Thetas Revealed by Source Separation of Simultaneous MEG and EEG.

Abstract: Theta-band (∼6 Hz) rhythmic activity within and over the medial PFC ("midfrontal theta") has been identified as a distinctive signature of "response conflict," the competition between multiple actions when only one action is goal-relevant. Midfrontal theta is traditionally conceptualized and analyzed under the assumption that it is a unitary signature of conflict that can be uniquely identified at one electrode (typically FCz). Here we recorded simultaneous MEG and EEG (total of 328 sensors) in 9 human subjects (7 female) and applied a feature-guided multivariate source-separation decomposition to determine whether conflict-related midfrontal theta is a unitary or multidimensional feature of the data. For each subject, a generalized eigendecomposition yielded spatial filters (components) that maximized the ratio between theta and broadband activity. Components were retained based on significance thresholding and midfrontal EEG topography. All of the subjects individually exhibited multiple (mean 5.89, SD 2.47) midfrontal components that contributed to sensor-level midfrontal theta power during the task. Component signals were temporally uncorrelated and asynchronous, suggesting that each midfrontal theta component was unique. Our findings call into question the dominant notion that midfrontal theta represents a unitary process. Instead, we suggest that midfrontal theta spans a multidimensional space, indicating multiple origins, but can manifest as a single feature at the sensor level because of signal mixing.SIGNIFICANCE STATEMENT "Midfrontal theta" is a rhythmic electrophysiological signature of the competition between multiple response options. Midfrontal theta is traditionally considered to reflect a single process. However, this assumption could be erroneous because of "mixing" (multiple sources contributing to the activity recorded at a single electrode). We investigated the dimensionality of midfrontal theta by applying advanced multivariate analysis methods to a multimodal MEG/EEG dataset. We identified multiple topographically overlapping neural sources that drove response conflict-related midfrontal theta. Midfrontal theta thus reflects multiple uncorrelated signals that manifest with similar EEG scalp projections. In addition to contributing to the cognitive control literature, we demonstrate both the feasibility and the necessity of signal demixing to understand the narrowband neural dynamics underlying cognitive processes.

Zuure|Marrit B|MB|
Hinkley|Leighton B|LB|
Tiesinga|Paul H E|PHE|
Nagarajan|Srikantan S|SS|
Cohen|Michael X|MX|0000-0002-1879-3593

theta
source separation
response conflict
multivariate analysis
conflict processing
midfrontal cortex


MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53.

Abstract:
OBJECTIVES
Radiotherapy is the primary option for bladder cancer patients, but it does not have obvious curative effects. This study was to investigate how to increase radiosensitivity in bladder cancer.

MATERIALS AND METHODS
The curcumin and irradiation treated T24 cells were used for analysis of microRNA expression (miRNA microarray), cell viability (Cell Proliferation Assay Kit), colony formation, apoptosis (Annexin V-FITC/7-AAD flow cytometry), miR-1246 and p53 mRNA (real-time PCR) and protein (Western blot) expression.

RESULTS
Microarray assay identified 17 differentially expressed miRNAs (twofold change) in curcumin treated cells compared to control cells. Among them, miR-1246 was the miRNA with the largest change in expression after curcumin treatment. Curcumin significantly decreased T24 cell viability and colony formation in a concentration-dependent manner compared to control cells. miR-1246 expression was significantly higher in T24 cells than in SV-HUC-1 cells and the higher concentrations (10 or 20 μM) of curcumin significantly down-regulated miR-1246 expression in T24 and HT-1376 cells. The combination of 10 µM curcumin and irradiation was more effective in decreasing miR-1246 expression, cell viability and colony formation than curcumin or irradiation alone. Inhibition of miR-1246 significantly decreased cell viability and colony formation in T24 and HT-1376 cells. Transfection with antagomiR-1246 significantly increased the G0/G1-phase of T24 cells and induced apoptosis compared to cells transfected with antagomiR-NC. Luciferase reporter assay showed that the overexpression of miR-1246 suppressed the luciferase activity of the P53 3'-UTR reporter genes.

CONCLUSION
miR-1246 is involved in the anti-cancer effects of curcumin and irradiation through targeting the inhibition of p53 gene translation in bladder cancer cells.

Xu|Ran|R| Li|Huabing|H| Wu|Shuiqing|S| Qu|Jian|J| Yuan|Haiyan|H| Zhou|Yangang|Y| Lu|Qiong|Q|

Curcumin
Bladder cancer
p53
MicroRNA
Radiation


Application of Bacillus coagulans in Animal Husbandry and Its Underlying Mechanisms.

Abstract: In recent decades, probiotics have attracted widespread attention and their application in healthcare and animal husbandry has been promising. Among many probiotics, Bacillus coagulans (B. coagulans) has become a key player in the field of probiotics in recent years. It has been demonstrated to be involved in regulating the balance of the intestinal microbiota, promoting metabolism and utilization of nutrients, improving immunity, and more importantly, it also has good industrial properties such as high temperature resistance, acid resistance, bile resistance, and the like. This review highlights the effects of B. coagulans in animal husbandry and its underlying mechanisms.

Zhou|Yuanhao|Y| Zeng|Zihan|Z| Xu|Yibin|Y| Ying|Jiafu|J| Wang|Baikui|B| Majeed|Muhammed|M| Majeed|Shaheen|S|0000-0001-6400-8245 Pande|Anurag|A| Li|Weifen|W|

Bacillus coagulans
probiotics
antioxidant
immunomodulation
nutrient metabolism


Intense pulsed light and laser treatment regimen improves scar evolution after cleft lip repair surgery.

Abstract:
OBJECTIVE
To observe the effects of intense pulsed light (IPL) and lattice CO2 laser treatment on scar evolution following cleft lip repair.

METHODS
Fifty cleft lip repair patients were enrolled in this study. Twenty-five patients used conventional approach with scar cream massage combined with silica gel products after operation. While other 25 patients which received IPL and lattice CO2 laser treatments. The treatments commenced 1 week after removal of stitches and observation of scar hyperplasia. Scar evolution was evaluated with the Vancouver scar scale (VSS) by postoperative photographs.

RESULTS
Relative to the conventional approach, the laser treatments showed improved scar softening and flattening. These differences were reflected in the groups' significantly different VSS scores.

CONCLUSION
Intense pulsed light combined with lattice CO2 laser treatment can improve cleft lip surgery scar pliability and appearance, while alleviating children from having to endure the pain of scar massage.

IPL
lattice CO2 laser
collagen
remodeling
scar contracture


Safety of Intra-arterial Catheter Directed Thrombolysis: Does Level of Care Matter?

Abstract:
OBJECTIVES
The aim was to assess whether the level of care influenced the safety related outcomes of catheter directed thrombolysis (CDT) for patients presenting with limb ischaemia and dialysis access thrombosis.

METHODS
This was a retrospective cohort study. All consecutive patients at two tertiary referral centres for vascular surgery undergoing CDT for limb ischaemia and dialysis access thrombosis (N = 252) between 2012 and 2014 were included. Patients at Centre 1 were cared for on a general vascular ward and patients at Centre 2 were kept on a post-operative recovery unit with an increased level of care including invasive haemodynamic monitoring. Patient medical records were retrospectively scrutinised and data collected on comorbidities, anti-thrombotic medication, indications for CDT, technical success of CDT, bleeding and non-bleeding related complications, and transfer to a higher level of care.

RESULTS
There were no differences in the frequency of non-bleeding related complications between Centre 1 and Centre 2. Patients on the vascular ward had a higher frequency of minor bleeding (p = .002) but there was no difference in major bleeding (p = .12). Eleven patients on the ward required an increased level of care for medical reasons and six were moved for a lack of resources. The presence of cardiac disease was an independent risk factor for patient transfer (OR 3.2; 95% CI 1.04-9.8, p = .04).

CONCLUSIONS
CDT may be undertaken outside of a high dependency setting without a significantly increased risk of complications. Pre-existing cardiac disease was an independent risk factor for transfer to a higher level of care. These findings could have an implication for the clinical cost-effectiveness of CDT.

Koraen-Smith|L|L| Wängberg|M|M| Montán|C|C| Gillgren|P|P| Wahlgren|C-M|CM|

D002406:Catheterization, Peripheral
D006801:Humans
D007511:Ischemia
D012189:Retrospective Studies
D015912:Thrombolytic Therapy
D016896:Treatment Outcome
D020246:Venous Thrombosis

Haemorrhage
Patient selection
Thrombolytic therapy


Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis.

Abstract:
BACKGROUND
KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting the immunopathogenic pathways.

OBJECTIVE
Assess the safety and tolerability of repeated doses of KHK4083 in patients with moderate to severe AD, and investigate the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the clinical efficacy and pharmacodynamics as exploratory objectives.

METHODS
In this phase 1, single-center, open-label, repeated-dose study, a total of 22 patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were followed until Day 155.

RESULTS
There were no deaths, serious adverse events (SAEs), or discontinuations due to adverse events (AEs). Common treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory values, vital signs, and electrocardiogram recordings were observed. The Cmax was 267 ± 53 μg/mL and the t1/2 was 303 ± 88 h at Day 29. The overall assessment of antibodies against KHK4083 (immunogenicity) showed low positive responses. Continued improvement in the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA) scores were observed throughout the study. The mean and median percent changes in thymus and activation-regulated chemokine (TARC) continued to decrease over time to -70.4 and -78.8 % until Day 155.

CONCLUSION
Repeated intravenous infusion of KHK4083 had an acceptable safety profile in patients with moderate to severe AD. Sustained improvement in the symptoms of AD was observed after completion of KHK4083 treatment.

Nakagawa|Hidemi|H| Iizuka|Hajime|H| Nemoto|Osamu|O| Shimabe|Munetake|M| Furukawa|Yasunobu|Y| Kikuta|Natsuko|N| Ootaki|Kenji|K|


Gene Therapy for Hemophilia.

Abstract: The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions.

Nienhuis|Arthur W|AW|
Nathwani|Amit C|AC|
Davidoff|Andrew M|AM|

D001803:Blood Transfusion
D000229:Dependovirus
D005164:Factor IX
D005169:Factor VIII
D015870:Gene Expression
D015316:Genetic Therapy
D005822:Genetic Vectors
D006467:Hemophilia A
D002836:Hemophilia B
D006801:Humans
D016086:Lentivirus
D009154:Mutation


Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.

Abstract: Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis.

Lv|Jiaoyan|J| Zou|Linlin|L| Zhao|Lina|L| Yang|Wei|W| Xiong|Yingluo|Y| Li|Bingji|B| He|Rui|R|

skin homing
neutrophils
CD8 T cells
elicitation phase of contact dermatitis
leukotriene B4-BLT1 axis


The experience of fatigue in people with inflammatory bowel disease: an exploratory study.

Abstract:
AIMS
To explore fatigue, the impact it has on daily life and the strategies used to ameliorate the symptom, as described by people with inflammatory bowel disease.

BACKGROUND
Fatigue is the most troublesome symptom during remission of inflammatory bowel disease. Fatigue affects people's daily functioning, impacting on quality of life. There is limited understanding of the nature of and the ways fatigue in inflammatory bowel disease is experienced and managed in everyday adult life.

DESIGN
An epistemological interpretive approach to understand participants' self-reported experiences of disease-related fatigue.

METHODS
A convenience sample of 46 participants was recruited from the Crohn's and Colitis UK member database. Five focus group interviews (November 2008-February 2009) were conducted, audio-recorded, transcribed, and analysed using an inductive thematic framework.

FINDINGS
Five themes were identified: the experience of fatigue, causes of fatigue, managing fatigue, consequences of fatigue, and seeking support. Fatigue had a debilitating effect on the social and emotional well-being of participants and limited their employment opportunities. People used a range of strategies to cope and reported that fatigue-related issues seemed to be poorly understood by clinicians and were not addressed in medical consultations.

CONCLUSION
Fatigue was an inextricable part of daily life for some people with inflammatory bowel disease. Specialist nurses and medical colleagues need to address the personal, social, and economic consequences of fatigue, whilst further nursing research would improve understanding of the impact of fatigue and help develop appropriate intervention strategies for people with inflammatory bowel disease.

Czuber-Dochan|Wladyslawa|W|
Dibley|Lesley B|LB|
Terry|Helen|H|
Ream|Emma|E|
Norton|Christine|C|

fatigue
inflammatory bowel disease
specialist nurses
nursing


Use of environmental scans in health services delivery research: a scoping review.

Abstract:
OBJECTIVE
To examine the extent and nature of evidence on the use of the environmental scan (ES) in the health services delivery literature.

DESIGN
Scoping review.

METHODS
This scoping review followed the five-stage scoping review methodology outlined by Khalil et al. A Peer Review of Electronic Search Strategies was completed. Seven electronic databases and the grey literature were searched. Pairs of researchers independently performed two levels of screening and data extraction. Data were analysed using qualitative content and thematic analysis.

RESULTS
Ninety-six studies were included in the scoping review. Researchers conducted ESs for many purposes, the most common being to examine the current state of programmes, services or policies. Recommendations were informed by ESs in 20% of studies. Most common data collection methods were literature review (71%), key informant or semistructured interviews (46%) and surveys (35%). Over half (53%) of the studies used a combination of passive (looking at information eg, literature, policies, guidelines) and active (looking for information eg, surveys, interviews) approaches to data collection. Person sources of data (eg, healthcare stakeholders, community representatives) and non-person sources of data (eg, documents, electronic databases, the web) were drawn on to a similar extent. The thematic analysis of the definitions/descriptions yielded several themes including instrument of discovery, knowledge synthesis, forward-looking and decision making. Research gaps identified included absence of a standard definition, inconsistencies in terminology and lack of guiding frameworks in the health services delivery context.

CONCLUSION
ESs were conducted to gather evidence and to help inform decision making on a range of policy and health services delivery issues across the continuum of care. Consistency in terminology, a consensus definition and more guidance on ES design may help provide structure for researchers and other stakeholders, and ultimately advance ES as a methodological approach. A working definition of ES in a health services delivery context is presented.

health policy
public health
statistics & research methods


Breakthroughs and Bottlenecks in Microbiome Research.

Abstract: Over the past 15 years, the research community has witnessed unprecedented progress in microbiome research. We review this increasing knowledge and first attempts of its clinical application, and also limitations and challenges faced by the research community, in mechanistically understanding host-microbiome interactions and integrating these insights into clinical practice.

microbiome
microbiota
precision medicine


Regulatory control of Sgs1 and Dna2 during eukaryotic DNA end resection.

Abstract: In the repair of DNA double-strand breaks by homologous recombination, the DNA break ends must first be processed into 3' single-strand DNA overhangs. In budding yeast, end processing requires the helicase Sgs1 (BLM in humans), the nuclease/helicase Dna2, Top3-Rmi1, and replication protein A (RPA). Here, we use single-molecule imaging to visualize Sgs1-dependent end processing in real-time. We show that Sgs1 is recruited to DNA ends through Top3-Rmi1-dependent or -independent means, and in both cases Sgs1 is maintained in an immoble state at the DNA ends. Importantly, the addition of Dna2 triggers processive Sgs1 translocation, but DNA resection only occurs when RPA is also present. We also demonstrate that the Sgs1-Dna2-Top3-Rmi1-RPA ensemble can efficiently disrupt nucleosomes, and that Sgs1 itself possesses nucleosome remodeling activity. Together, these results shed light on the regulatory interplay among conserved protein factors that mediate the nucleolytic processing of DNA ends in preparation for homologous recombination-mediated chromosome damage repair.

Xue|Chaoyou|C|
Wang|Weibin|W|
Crickard|J Brooks|JB|
Moevus|Corentin J|CJ|
Kwon|Youngho|Y|
Sung|Patrick|P|
Greene|Eric C|EC|

DNA end resection
homologous recombination
helicase
DNA repair
single molecule


Drivers of daily movement patterns affecting an endangered vulture flight activity.

Abstract:
BACKGROUND
The development of satellite tracking technology enables the gathering of huge amounts of accurate data on animal movements over measured time intervals, to reveal essential information about species' patterns of spatial use. This information is especially important in optimizing the design of conservation and management strategies for endangered species. In this study, we analysed the main drivers of daily patterns in the flight activity of the threatened Bearded Vulture Gypaetus barbatus. We studied 19 Bearded Vultures tagged with solar-powered GPS transmitters from 2006 to 2016 in the Pyrenees (Spain). We assessed the relative influence of external factors (season and daylight time) and internal factors (sex, breeding season and territorial status) on their daily activity behaviour by computing mean hourly distance travelled, maximum displacement and cumulative distance travelled per hour.

RESULTS
Our findings showed a clear difference in all the estimators between territorial and non-territorial (floating) members of the population, showing that non-territorial individuals spent much longer in flight and travelled larger distances per day. We detected an important influence of daylight time and season on the daily rhythms of Bearded Vultures; flight activity increased during the last three quarters of daylight and was greatest in the spring. Breeding period and sex had also an effect on the maximum displacement and cumulative distance travelled. Individuals flew more during the breeding period and females tended to exhibit greater cumulative and maximum distances per hour than males regardless of breeding season.

CONCLUSIONS
Pyrenean Bearded Vultures flight daily activity was strongly influenced by daylight time, season, and territorial status, while individual sex and breeding season showed a milder effect on the birds' movement behaviour. This study gives a novel insight into how external factors act as main drivers of the daily flight activity pattern of a long-lived avian scavenger.

D003247:Conservation of Natural Resources

Daily movements
Gypaetus barbatus
GPS
Spain
Season
Daylight time
Territorial status


Caloric compensation in infants: developmental changes around the age of 1 year and associations with anthropometric measurements up to 2 years.

Abstract:
BACKGROUND
Previous results based on dietary recall suggest that the ability to adjust eaten quantities to food energy density (ED) may deteriorate around the age of 1 y. However, this hypothesis has not been investigated experimentally.

OBJECTIVES
The first aim of the study was to describe changes in the short-term caloric compensation ability of infants around the age of 1 y. We expected a decrease in this ability with age. The second aim was to identify individual factors [e.g., breastfeeding duration, body mass index (BMI) z-score, and change in BMI z-score] related to interindividual variations in caloric compensation ability.

METHODS
We adapted the preload paradigm to calculate a COMPX score. The measure was performed in the laboratory at 11 and 15 mo. The parent offered a food preload that was either low or high in ED (LED = 33 kcal/100 g or HED = 97.9 kcal/100 g, respectively), followed by an ad libitum meal after 25 min. The infants were measured and weighed. Information about the infants' milk-feeding history was collected.

RESULTS
We obtained COMPX scores at 11 and 15 mo for 31 infants (12 females). As hypothesized, the caloric compensation ability significantly decreased with age (COMPX11 = 52% ± 133%; COMPX15 = -14% ± 151%; P = 0.03). The more the COMPX score decreased, the more the BMI z-score between 11 and 15 mo increased (P = 0.03) and the higher the BMI z-score was at 2 y (P = 0.03). No associations were found between COMPX scores and breastfeeding duration (all P > 0.60).

CONCLUSIONS
Caloric compensation ability decreases between 11 and 15 mo. This decrease is associated with a larger increase in weight status from 11 to 15 mo and a higher weight status at 2 y. This study calls for further research to better understand the early determinants of caloric compensation ability. This trial was registered at www.clinicaltrials.gov as NCT03409042 (https://clinicaltrials.gov/ct2/show/NCT03409042).

Brugaillères|Pauline|P| Issanchou|Sylvie|S| Nicklaus|Sophie|S| Chabanet|Claire|C| Schwartz|Camille|C|

D007227:Infant Nutritional Physiological Phenomena

BMI z-score
appetite control
eating behavior
energy compensation
food intake
longitudinal study


Transmission of areca palm velarivirus 1 (APV1) by mealybugs causes yellow leaf disease (YLD) in betel palm (Areca catechu).

Abstract: Yellow leaf disease (YLD) is the most destructive disease of betel palm (Areca catechu). A strong association between YLD and areca palm velarivirus 1 (APV1) has been observed. However, the causal relationship between APV1 and disease, and the transmission mode, require further investigation. This work showed that APV1 was transmitted by both Ferrisia virgata and Pseudococcus cryptus mealybugs, and caused YLD symptoms in betel palm seedlings; therefore, we demonstrate that APV1 is a causal agent of YLD. APV1 was detected in the stylets, foreguts, midguts, and hindguts of the vectors via both immunocapture RT-PCR and immunofluorescence assays. APV1 was not transmitted transovarially from viruliferous female F. virgata to their progeny. In summary, the transmission of APV1 by F. virgata may occur in a non-circulative, semi-persistent manner. This study fills important gaps in our knowledge of velarivirus transmission, which is critical for developing YLD management practices.

Zhang|Huaiwen|H|
Zhao|Xue|X|
Cao|Xianmei|X|
Khan|Latif Ullah|LU|
Zhao|Ruibai|R|
Wang|Hongxing|H|
Huang|Xi|X|


Molecular profiling analysis for colorectal cancer patients with Pi-Xu or Shi-Re syndrome.

Abstract:
Background
Traditional Chinese medicine (TCM) syndromes (ZHENG in Chinese) constitute the basis of understanding the disorders of patients and guiding the use of the Chinese herbs. Colorectal cancer is divided into various subtypes mainly according to the ZHENG identification.

Objective
We aimed to determine the molecular basis underlying Pi-Xu (spleen deficiency) and Shi-Re (dampness-heat) ZHENG that are commonly found in colorectal cancer patients.

Methods
About 80 colorectal cancer patients, including 47 Pi-Xu ZHENG and 33 Shi-Re ZHENG were enrolled. Blood and tissue samples of these patients were available for protein and mRNA expression. The protein expression was determined by Immunohistochemistry (IHC) staining and mRNA profiling was detected by expression microarray. Furthermore, mRNA fold change was evaluated by qRT-PCR.

Results
The colorectal cancer patients with Shi-Re ZHENG had a poor prognosis, compared with Pi-Xu ZHENG (95% CI: 0.05-0.33; p < 0.0001). Moreover, there was a significant difference in protein expression levels (especially for mutant TP53, PCNA, PD-L1 and Ki-67) among Pi-Xu and Shi-Re ZHENG (p < 0.01). Meanwhile, mRNA expression (especially for wild type TP53, KDM6A, PCNA, PD-L1, Ki-67, CCL-2, IL-1a and COX-2) was also remarkably different between Pi-Xu and Shi-Re groups (p < 0.01).

Conclusion
Our results suggest that Shi-Re ZHENG conditions may contribute to poor overall survival in patients with colorectal cancer. Compared with Pi-Xu ZHENG, high expression of mutant TP53, PCNA, PD-L1, Ki-67, CCL-2, IL-1a and COX-2 may serve as potential biomarkers for diagnosis and prognosis of colorectal cancer patients displayed Shi-Re ZHENG.

Sui|Xinbing|X| Guo|Yong|Y| Ni|Wei|W| Jin|Haiyan|H| Lin|Haoming|H| Xie|Tian|T|

Molecular profiling
Colorectal cancer
Traditional Chinese medicine
ZHENG


Multiscale entropy analysis to quantify the dynamics of motor movement signals with fist or feet movement using topographic maps.

Abstract:
BACKGROUND
Brain neural activity is measured using electroencephalography (EEG) recording from the scalp. The EEG motor/imagery tasks help disabled people to communicate with the external environment.

OBJECTIVE
In this paper, robust multiscale sample entropy (MSE) and wavelet entropy measures are employed using topographic maps' analysis and tabulated form to quantify the dynamics of EEG motor movements tasks with actual and imagery opening and closing of fist or feet movements.

METHODS
To distinguish these conditions, we used the topographic maps which visually show the significance level of the brain regions and probes for dominant activities. The paired t-test and Posthoc Tukey test are used to find the significance levels.

RESULTS
The topographic maps results obtained using MSE reveal that maximum electrodes show the significance in frontpolar, frontal, and few frontal and parietal brain regions at temporal scales 3, 4, 6 and 7. Moreover, it was also observed that the distribution of significance is from frontoparietal brain regions. Using wavelet entropy, the significant results are obtained at frontpolar, frontal, and few electrodes in right hemisphere. The highest significance is obtained at frontpolar electrodes followed by frontal and few central and parietal electrodes.

Hussain|Lal|L|
Aziz|Wajid|W|
Alshdadi|Abdulrahman A|AA|
Abbasi|Adeel Ahmed|AA|
Majid|Abdul|A|
Marchal|Ali Raza|AR|

Electroencephalography (EEG)
multiscale sample entropy (MSE)
multiscale wavelet entropy (MWE)


The intervertebral disc, the endplates and the vertebral bone marrow as a unit in the process of degeneration.

Abstract:
OBJECTIVES
The association of disc degeneration (DD) and vertebral endplate degeneration (EPD) is still not well understood. This study aimed to find segmental predictive risk factors for DD and EPD and to illuminate associations of the disc, endplate and bone marrow changes in the process of degeneration.

METHODS
After institutional review board approval, 450 lumbar levels, followed up with MRI for at least 4 years, were retrospectively graded for DD according to Pfirrmann (PFG), for EPD according to the endplate score (EPS) and according to the presence, extension and type of Modic changes (MC). Clustered logistic regression and multivariate analysis was applied in nested, matched case-control subgroups to evaluate potential local risk factors for progression.

RESULTS
An EPS score of  ≥4 was identified as an independent risk factor for progression of DD (OR = 2.32, 95%CI:1.07-5.01,p = 0.03) and MC (OR = 5.49,95%CI:2.30-13.10,p < 0.001). Progression of DD was significantly accompanied by progression or evolution of MC (OR = 12.25,95%CI:1.49-100.6,p = 0.02) and with progression of EPS (OR = 1.71, 95%CI:1.00-1.05, p = 0.01). Once advanced DD has occurred, it becomes a risk factor for progression in EPS (OR = 2.24,95%CI:1.23-4.12,p < 0.01).

CONCLUSIONS
The degenerative processes in the disc, endplate and bone marrow are highly associated. An EPS ≥ 4 is an independent risk factor for DD and MC progression in a population with low back pain.

KEY POINTS
• The degenerative processes in the disc, endplate and bone marrow are associated. • An endplate score ≥4 is a risk factor for DD and MC progression. • Modic changes are last to occur in the development of segmental intervertebral degeneration. • A new segmental grading system is suggested.

Farshad-Amacker|Nadja A|NA|
Hughes|Alexander|A|
Herzog|Richard J|RJ|
Seifert|Burkhardt|B|
Farshad|Mazda|M|

Intervertebral disc
Vertebral bone marrow
Endplate changes
Segmental degeneration
Spine degeneration


Randomized Phase II Study with Cetuximab in Combination with 5-FU and Cisplatin or Carboplatin vs. Cetuximab in Combination with Paclitaxel and Carboplatin for Treatment of Patients with Relapsed or Metastatic Squamous Cell Carcinoma of the Head and Neck (CETMET Trial).

Abstract:
BACKGROUND
Platinum-based chemotherapy with cetuximab is the standard of care for relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). The aim of this trial was to investigate whether cetuximab and paclitaxel/carboplatin can achieve similar progression-free survival (PFS) with standard cetuximab and 5-FU/platinum-based chemotherapy. Standard chemotherapy treatment for SCCHN is related to severe toxicity and new, less toxic regimens are needed.

METHODS
In this multicentre, randomized, controlled, phase 2 trial, 85 patients with relapsed or metastatic SCCHN were randomized in a 1:1 ratio to cetuximab and 5-FU/cisplatin or carboplatin (arm A) vs. cetuximab and paclitaxel/carboplatin (arm B). Eligibility criteria included age ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, and adequate organ functions. The primary endpoint was to investigate whether PFS in arm B is significantly worse than PFS in arm A.

RESULTS
Median PFS in arm A was 4.37 months (95% CI: 2.9-5.9 m) and 6.5 months (95% CI: 4.8-8.2 m) in arm B, (p = 0.064). Median overall survival (OS) was 8.4 months (95% CI: 5.3-11.5 m) in arm A and 10.2 months (95% CI: 5.4-15 m) in arm B, (HR = 0.71; 95% CI: 0.43-1.16). PFS HR for arm B was not significantly worse than arm A (HR = 0.65; 95% CI: 0.41-1.03). Adverse events ≥ grade 3 were more frequent in arm A than arm B (60% vs. 40%; p = 0.034).

CONCLUSION
Cetuximab and paclitaxel/carboplatin was found to have similar efficacy and less toxicity compared to cetuximab and 5-FU/cisplatin or carboplatin. The experimental arm is easier to administer rendering it a favorable alternative to standard therapy.

Tsakonas|Georgios|G|
Specht|Lena|L|
Kristensen|Claus Andrup|CA|
Moreno|Maria Herlestam Calero|MHC|
Cange|Hedda Haugen|HH|
Soderstrom|Karin|K|0000-0002-3683-3763
Friesland|Signe|S|

cetuximab
carboplatin/paclitaxel
cisplatin/5-FU
first-line therapy
relapsed/metastatic SCCHN


Prevalence of silent breast cancer in autopsy specimens, as studied by the disease being held by image-guided biopsies: The pilot study and literature review.

Abstract: Breast cancer epidemiological patterns vary in European countries, which present different incidence rates. Data have suggested that the reduction in breast cancer mortality is not only due to the early detection of the disease, but is, in almost equal part, due to screening and to the advances that have been made in molecular medicine and the development of novel therapies. The aim of the present study is to quantify the actual number of cases of breast cancer present in both of the sexes by calculating the prevalence of silent breast cancer in corpses. To achieve this quantification, bilateral subcutaneous radical mastectomies are performed in corpses of either sex above 40 years of age that lacked any clinical manifestation of the disease, and where the breast cancer or its complications was not the cause of death. Only five publications exist in the international literature based on medico-legal autopsies that were designed to define the 'natural reservoir' of the disease. To the best of our knowledge, the present study is the first one to appraise breast tissue via imaging by means of orienting the biopsy incision. In conclusion, to the best of our knowledge, the design of the present study is the first of its type, where image-guided biopsies are used to define the prevalence of silent breast cancer. The study aims to demonstrate that the 'disease reservoir' is, in reality, higher than was originally considered to be so. Furthermore, the study aims to contribute towards an improved definition of the disease by determining which tumour profiles potentially do not benefit from aggressive treatments (for example, in case where a high prevalence of low-grade ductal carcinoma in situ is to be detected). According to our pilot study, this analysis represents a feasible protocol.

Sidiropoulou|Zacharoula|Z|
Vasconcelos|Ana Paula|AP|
Couceiro|Cristiana|C|
Dos Santos|Carlos|C|
Araújo|Ana Virginia|AV|
Alegre|Inês|I|
Santos|Claudia|C|
Costa|Filipa|F|
Henriques|Vanessa|V|
Neves|Carlos|C|
Cardoso|Fátima|F|
Gascon|Pere|P|

silent breast cancer
breast cancer epidemiology
breast cancer overtreatment
breast cancer prevalence
cancer and forensic autopsies


Natural products, the continuous source of therapeutic molecules for various diseases: literature landscape analysis.

Abstract:
BACKGROUND
Substances present in nature have been a continuous source for the development of drugs for cardiovascular and infectious diseases, cancer, and many other diseases. As the literature concerning these natural products grows, it becomes more difficult for a reader to quickly grasp the essential facts and develop a well-informed impression of this field of research. Until now, it has also been difficult to determine which natural products and research objectives were receiving the most attention as measured by number of citations.

OBJECTIVE
The current study of all published articles concerned with natural products sought to identify which natural products and which research objectives are connected with the major contributors to scientific journals based on the number of relevant publications and the number of times each publication was cited elsewhere.

METHODS
Bibliometric data, including citation data, were extracted from the Web of Science database using the search string TS=("natural product*)" and analyzed by the VOSviewer software.

RESULTS
The search yielded 63,194 articles, with more than half of the manuscripts published since 2012. The ratio of original articles to reviews was 5.8:1. The major contributing countries were the United States, China, Germany, Japan, and India. Articles were published mainly in journals focused on chemistry, pharmacology or biochemistry. Curcumin, resveratrol, and terpenoids were the most frequently cited natural products.

CONCLUSION
The results of the current study provide researchers from different backgrounds and healthcare professionals with a brief overview of the major trends in natural-product research in the form of a citation-based summary of the relevant literature.

Yeung|Andy Wai Kan|AWK|
Mocan|Andrei|A|
Tzvetkov|Nikolay T|NT|
Šmejkal|Karel|K|
Heiss|Elke H|EH|
Atanasov|Atanas G|AG|

natural products
bibliometrics
Bioactive molecules
alkaloids
citation analysis
pharmacology.
polyketides


Fermentation properties of isomaltooligosaccharides are affected by human fecal enterotypes.

Abstract: Isomaltooligosaccharides (IMOs) are enzymatically synthesized oligosaccharides that have potential prebiotic effects. Five IMO substrates with 2-16° of polymerization (DP) were studied for their fermentation capacities using human microbiomes in an in vitro batch fermentation model. Eleven fecal slurries belonging to three enterotypes, including the Bacteroides-, Prevotella- and Mixed-type, exhibited different degradation rates for long chain IMOs (DP 7 to 16). In contrast, the degradation rates for short chain IMOs (DP 2 to 6) were not affected by enterotypes. Both 16S rRNA gene sequencing and quantitative PCR demonstrated that, after fermentation, the Bifidobacterium growth with IMOs was primarily detected in the Bacteroides- and Mixed-type (non-Prevotella-type), and to a lesser degree in the Prevotella-type. Interestingly, the Prevotella-type microbiome had higher levels of propionic acid and butyric acid production than non-Prevotella-type microbiome after IMOs fermentation. Moreover, principal coordinate analysis (PCoA) of both denaturing gradient gel electrophoresis (DGGE) profiling and 16S rRNA sequencing data demonstrated that the microbiome community compositions were separately clustered based on IMO chain length, suggesting significant impact of DP on the bacterial community structure. The current results clearly demonstrated that the IMO chain length could modulate the structure and composition of the human colonic microbiome. Different responses to short and long chain IMOs were observed from three human enterotypes, indicating that IMOs may be used as therapeutic substrates for directly altering human colonic bacteria.

Wu|Qinqin|Q|
Pi|Xiong'e|X|
Liu|Wei|W|
Chen|Huahai|H|
Yin|Yeshi|Y|
Yu|Hongwei D|HD|
Wang|Xin|X|
Zhu|Liying|L|

Enterotype
IMO
Degree of polymerization
Human gut microbiota
SCFAs


Prevalence and factors associated with alcohol consumption among persons with diabetes in Kampala, Uganda: a cross sectional study.

Abstract:
BACKGROUND
The prevalence of diabetes has been rising increasing rapidly in middle- and low-income countries. In Africa, the World Health Organization projections anticipate diabetes mellitus to be the seventh leading cause of death in by 2030. Alcohol consumption influences diabetes evolution, in such a way that it can interfere with self-care behaviours which are important determinants of diabetes prognosis. In this study, we evaluated factors associated with alcohol consumption among persons with diabetes in Kampala to inform management policies and improve comprehensive diabetes care.

METHODOLOGY
A cross-sectional study was conducted systematically among 290 adults with diabetes, attending diabetic clinics at Mulago National Referral Hospital and St Francis Hospital Nsambya. Data were entered and analysed in Epi-Info version 7 and STATA 13 software. Modified Poisson regression was used to identify factors associated with alcohol consumption among persons with diabetes. All tests were two-sided and the significance level for all analyses was set to p < 0.05.

RESULTS
The prevalence of alcohol consumption among persons with diabetes was 23.45% [95% CI: 18.9-28.7%]. Divorced, separated and widowed patients (Adj PR: 0.42, 95% CI: 0.21-0.83); and Protestant (Adj PR: 0.44, 95% CI: 0.24-0.82); Muslim (Adj PR: 0.30, 95% CI: 0.14-0.62); and Pentecostal (Adj PR: 0.32, 95% CI: 0.15-0.65) patients were less likely to consume alcohol. Diabetic patients who had a diabetes duration greater than 5 years were more likely to consume alcohol (Adj PR: 1.90, 95% CI: 1.25-2.88).

CONCLUSION
Approximately one-quarter of participants consumed alcohol. However being catholic, never being married and having diabetes for more than 5 years predisposed persons with diabetes to alcohol consumption. Sensitization messages regarding alcohol consumption among persons with diabetes should be target patients who have never been married and those who have spent more than 5 years with diabetes; religion should also be considered as an important venue for health education in the community.

Salama|Maki Sifa|MS|
Isunju|Jonh Bosco|JB|
David|Salama Kaishusha|SK|
Muneza|Fiston|F|
Ssemanda|Sylvester|S|
Tumwesigye|Nazarius Mbona|NM|

Alcohol consumption
Persons with diabetes
Self-care behaviours


A 15-year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom.

Abstract:
PURPOSE
This study aimed to develop hypotheses to explain the increasing tramadol utilisation, evaluate the impact of tramadol classification, and explore the trend between tramadol utilisation and related deaths in the United Kingdom.

METHODS
This cross-sectional study used individual patient data, the Clinical Practice Research Datalink from 1993 to 2015, to calculate monthly defined daily dose (DDD)/1000 registrants, monthly prevalence and incidence of tramadol users, annual supply days, and mean daily dose of tramadol. Aggregated-level national statistics and reimbursement data from 2004 to 2015 were also used to quantify annual and monthly tramadol DDD/1000 inhabitants and rate of tramadol-related deaths in England and Wales. Interrupted time-series analysis was used to evaluate the impact of tramadol classification in June 2014.

RESULTS
Prevalence of tramadol users increased from 23 to 97.6/10 000 registrants from 2000 to 2015. Both annual dose and annual supply days of existing tramadol users were higher than new users. Level and trend of monthly utilisation (β2 : -12.9, β3 : -1.6) and prevalence of tramadol users (β2 : -6.4, β3 : -0.37) significantly reduced after classification. Both annual tramadol utilisation and rate of tramadol-related deaths increased before tramadol classification and decreased thereafter.

CONCLUSIONS
Increasing tramadol utilisation was influenced by the increase in prevalence and incidence of tramadol users, mean daily dose, and day of supply. Prevalence of tramadol users, tramadol utilisation, and reported deaths declined after tramadol classification. Future studies need to evaluate the influencing factors to ensure the safety of long-term tramadol use.

tramadol classification
drug utilisation
interrupted time series analysis
pharmacoepidemiology
tramadol-related mortality


Flecainide toxicity late after liver transplantation.

Abstract: Flecainide is an antiarrhythmic agent indicated for patients with supraventricular arrhythmias without ischemic or structural heart disease. Flecainide toxicity is a rare condition in which patients may present with bradycardia, widening of QRS, PR prolongation, ventricular tachycardia, syncope, malaise, dizziness, visual disturbance, nausea, vomiting, and/or lethargy. It carries an associated mortality rate of approximately 10%. Herein, we describe the course of a patient who experienced flecainide toxicity in the setting of renal and liver failure.

flecainide
Antiarrhythmic
supraventricular tachycardia


Simultaneous targeted analysis of trimethylamine-N-oxide, choline, betaine, and carnitine by high performance liquid chromatography tandem mass spectrometry.

Abstract: Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization. Separation of analytes was achieved on an amide column with acetonitrile-water as the mobile phase. This method has been fully validated in this study in terms of selectivity, linearity, sensitivity, precision, accuracy, and carryover effect, and the stability of the analyte under various conditions has been confirmed. This developed method has successfully been applied to plasma samples of our mouse model.

Liu|Jia|J| Zhao|Mingming|M| Zhou|Juntuo|J| Liu|Changjie|C| Zheng|Lemin|L| Yin|Yuxin|Y|

D002851:Chromatography, High Pressure Liquid

Choline Betaine Carnitine TMAO HPLC-ESI-MS/MS


Profiling of the known-unknown Passiflora variant complement by liquid chromatography - Ion mobility - Mass spectrometry.

Abstract: Liquid Chromatography - Ion Mobility - Mass Spectrometry (LC-IM-MS) was utilized for non-targeted screening analysis to understand the variance in the composition of Passiflora species. Multivariate analysis was employed to explore a chemometric processing strategy for IM based Passiflora variant differentation. This approach was applied to the comparative analyses of extracts of the medicinal plants Passiflora alata, Passiflora edulis, Passiflora incarnata and Passiflora caerulea. In total, 255 occurrences of IM-MS resolved coeluting marker isomers and isobaric species were detected, providing increased coverage and specificity of species component markers compared to conventional LC-MS. A large proportion of medical plant phytochemical analysis information often remains redundant in that it is not phenotypic specific. Here, generation of Passiflora variant 'known-unknown' libraries has been used to compare Passiflora species to investigate unique variant features. Investigations of predicted collision cross section have enabled comparison of an element of the 'known-unknown' IM isomeric complement to be performed, facilitating a reduction in the number of possible variant unique isomeric identifications. In combination with spectral interpretation, it has been possible to resassign isomeric 'known-unknowns' as 'knowns'. The strategies employed illustrates the potential to facilitate identification of medicinal plant phytochemical components.

McCullagh|Michael|M|
Goshawk|Jeff|J|
Eatough|David|D|
Mortishire-Smith|Russell J|RJ|
Pereira|Cintia Am|CA|
Yariwake|Janete H|JH|
Vissers|Johannes Pc|JP|

Measured and predicted collision cross sections

Medicinal plant isomeric and isobaric flavonoids


Interprofessional collaboration associated with frequency of life-saving links to HIV continuum of care services in the urban environment of Newark, New Jersey.

Abstract:
BACKGROUND
HIV continuum of care has been used as a strategy to reduce HIV transmission rates, with timely engagement in HIV testing being the first and most critical step. This study examines interprofessional-collaboration (IPC) after controlling for agency/ provider demographics, provider training and self-efficacy as a significant predictor of how frequently HIV service providers link their clients to HIV testing.

METHODS
Multilevel binary logistic regression analysis was conducted to examine the effects of IPC on links to HIV testing while controlling for demographic and agency information, provider training, and standardized measures of providers' feelings, attitudes, and opinions about IPC. Cross-sectional data from 142 providers in 13 agencies offering treatment and prevention services for HIV and substance-use disorders were collected via a survey.

RESULTS
Those who scored higher on the IPC scale reported significantly higher rates of linkages to HIV testing. Compared to the null model (i.e., no predictor model), the final multilevel binary logistic regression model showed a significantly improved likelihood of linkage to HIV testing by 11.4%, p. < .05. The final model correctly classified 90.2% of links to HIV testing. Providers in agencies with smaller budgets and in agencies offering substance use disorder services were more likely to link clients to HIV testing. Younger providers who received HIV training were also more likely to link clients to HIV testing.

CONCLUSIONS
Findings suggest IPC training as a potential strategy to improve linkages to HIV testing for clients at risk for HIV infection. Future research is recommended to identify specific areas of IPC that might have differential effects on links to HIV testing.

D000328:Adult
D003266:Continuity of Patient Care
D003299:Cooperative Behavior
D003430:Cross-Sectional Studies
D005260:Female
D015658:HIV Infections
D000082922:HIV Testing
D006282:Health Personnel
D006801:Humans
D007318:Inservice Training
D008297:Male
D008875:Middle Aged
D009515:New Jersey
D019966:Substance-Related Disorders
D011795:Surveys and Questionnaires
D019037:Urban Health Services

Interprofessional collaboration
HIV continuum of care
HIV testing
Substance-use disorder (SUD) treatment


Congenital heart surgery outcome analysis: Indian experience.

Abstract:
BACKGROUND
The study aimed to analyze the outcome of congenital heart surgery in a subset of Indian patients, using the Aristotle Basic Complexity score, the Risk Adjustment for Congenital Heart Surgery categories, and the Society of Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality categories.

PATIENTS AND METHODS
1312 patients <18 years of age undergoing congenital heart surgery were assigned the 3 scores and studied for outcome indices of difficulty (cardiopulmonary bypass time or duration of surgery >120 min), morbidity (intensive care unit stay >7 days), and mortality.

RESULTS
The overall mortality was 6.85%, with mean a Aristotle Basic Complexity score, Risk Adjustment for Congenital Heart Surgery category, and Society of Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality category of 7.17 ± 2.04, 2.28 ± 0.78, and 2.24 ± 1.06, respectively. The mortality predictive capacity of the Risk Adjustment for Congenital Heart Surgery category (c = 0.76) was similar to that of the Society of Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality category (c = 0.75); both were better compared to the Aristotle Basic Complexity score (c = 0.66). The Risk Adjustment for Congenital Heart Surgery category and Aristotle Basic Complexity score correlated with morbidity and difficulty outcomes.

CONCLUSION
The study shows that the Aristotle Basic Complexity score, the Risk Adjustment for Congenital Heart Surgery category, and the Society of Thoracic Surgeons and European Association for Cardiothoracic Surgery mortality category are tools of case mix stratification to analyze congenital heart surgery outcomes in a subset of the Indian population.

Vasdev|Sumit|S| Chauhan|Sandeep|S| Malik|Madhur|M| Talwar|Sachin|S| Velayoudham|Devagourou|D| Kiran|Usha|U|

D010043:Outcome and Process Assessment, Health Care

congenital
risk adjustment
Aristotle score
heart defects


Electrochemical in Situ Tracking of Volumetric Changes in Two-Dimensional Metal Carbides (MXenes) in Ionic Liquids.

Abstract: We report the volumetric changes of MXenes in contact with different ionic liquids and the swelling/contraction during electrochemical voltage cycling by complementing electrochemical dilatometry with in situ X-ray diffraction measurements. A drastic, initial, and irreversible volume expansion of MXenes occurs during first contact to ionic liquids (wetting). Voltage cycling evidenced a highly reversible expansion and contraction of electrodes at a very large amplitude of strain (corresponding with max. 12 vol %), which may allow the use of MXene as a high-performance electrochemical actuator.

Jäckel|Nicolas|N|
Krüner|Benjamin|B|
Van Aken|Katherine L|KL|
Alhabeb|Mohamed|M|
Anasori|Babak|B|
Kaasik|Friedrich|F|
Gogotsi|Yury|Y|
Presser|Volker|V|

MXene
ionic liquid
electrochemical dilatometry
in situ XRD
pseudocapacitance


Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition.

Abstract: Cellular transitions require dramatic changes in gene expression that are supported by regulated mRNA decay and new transcription. The maternal-to-zygotic transition is a conserved developmental progression during which thousands of maternal mRNAs are cleared by post-transcriptional mechanisms. Although some maternal mRNAs are targeted for degradation by microRNAs, this pathway does not fully explain mRNA clearance. We investigated how codon identity and translation affect mRNA stability during development and homeostasis. We show that the codon triplet contains translation-dependent regulatory information that influences transcript decay. Codon composition shapes maternal mRNA clearance during the maternal-to-zygotic transition in zebrafish, Xenopus, mouse, and Drosophila, and gene expression during homeostasis across human tissues. Some synonymous codons show consistent stabilizing or destabilizing effects, suggesting that amino acid composition influences mRNA stability. Codon composition affects both polyadenylation status and translation efficiency. Thus, the ribosome interprets two codes within the mRNA: the genetic code which specifies the amino acid sequence and a conserved "codon optimality code" that shapes mRNA stability and translation efficiency across vertebrates.

translation
decay
zebrafish
codon optimality
maternal‐to‐zygotic transition


The lateral "backdoor" approach to open thyroid surgery: A comparative study.

Abstract:
INTRODUCTION
The traditionally taught technique for conventional open thyroidectomy is via a midline splitting of the strap muscles following a skin crease neck incision - midline approach (MA). The lateral "backdoor" approach (LA) uses the same central neck incision but approaches the thyroid gland between the anterior border of sternocleidomastoid (SCM) and strap muscles. This technique is usually reserved for re-do thyroid surgery. We compared the results of the two approaches in patients undergoing conventional thyroidectomy for the first time.

METHODS
A case-control study was performed on 90 patients undergoing conventional open thyroidectomy from 2012 to 2014. The first 45 patients underwent MA and subsequent 45 patients underwent LA. All patients were given 10 ml of 1% Marcaine infiltration into the neck incision before closure. Basic demographic data, operative time, incision length, weight of gland, need for transection of strap muscles and complications were recorded. Revision thyroid surgery and minimally invasive thyroid operations were excluded.

RESULTS
The demographics, operative timing, gland weight and incisional length showed no significant difference. Post-operative pain was significantly lower in the LA group. 5 patients (11%) in MA group needed horizontal transection of strap muscles to extract large goitres compared to 1 patient (2.2%) in the LA group. No major complications occurred in either group.

CONCLUSION
The LA method is as safe as the midline technique with comparable operative time and significantly lower pain scores. It avoids midline separation and suturing of strap muscles and reduces the need for strap muscle transection to removal large goitres.

Singaporewalla|R M|RM|
Tan|B C|BC|
Rao|A D|AD|

Backdoor
Lateral approach
Open throidectomy
Sternomastoid


Ion mobility-mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy.

Abstract: Peripheral myelin protein (PMP22) is an integral membrane protein that traffics inefficiently even in wild-type (WT) form, with only 20% of the WT protein reaching its final plasma membrane destination in myelinating Schwann cells. Misfolding of PMP22 has been identified as a key factor in multiple peripheral neuropathies, including Charcot-Marie-Tooth disease and Dejerine-Sottas syndrome. While biophysical analyses of disease-associated PMP22 mutants show altered protein stabilities, leading to reduced surface trafficking and loss of PMP22 function, it remains unclear how destabilization of PMP22 mutations causes mistrafficking. Here, native ion mobility-mass spectrometry (IM-MS) is used to compare the gas phase stabilities and abundances for an array of mutant PM22 complexes. We find key differences in the PMP22 mutant stabilities and propensities to form homodimeric complexes. Of particular note, we observe that severely destabilized forms of PMP22 exhibit a higher propensity to dimerize than WT PMP22. Furthermore, we employ lipid raft-mimicking SCOR bicelles to study PMP22 mutants, and find that the differences in dimer abundances are amplified in this medium when compared to micelle-based data, with disease mutants exhibiting up to 4 times more dimer than WT when liberated from SCOR bicelles. We combine our findings with previous cellular data to propose that the formation of PMP22 dimers from destabilized monomers is a key element of PMP22 mistrafficking.

membrane protein
mass spectrometry
protein misfolding


A Small RNA Isolation and Sequencing Protocol and Its Application to Assay CRISPR RNA Biogenesis in Bacteria.

Abstract: Next generation high-throughput sequencing has enabled sensitive and unambiguous analysis of RNA populations in cells. Here, we describe a method for isolation and strand-specific sequencing of small RNA pools from bacteria that can be multiplexed to accommodate multiple biological samples in a single experiment. Small RNAs are isolated by polyacrylamide gel electrophoresis and treated with T4 polynucleotide kinase. This allows for 3' adapter ligation to CRISPR RNAs, which don't have pre-existing 3'-OH ends. Pre-adenylated adapters are then ligated using T4 RNA ligase 1 in the absence of ATP and with a high concentration of polyethylene glycol (PEG). The 3' capture step enables precise determination of the 3' ends of diverse RNA molecules. Additionally, a random hexamer in the ligated adapter helps control for potential downstream amplification bias. Following reverse-transcription, the cDNA product is circularized and libraries are prepared by PCR. We show that the amplified library need not be visible by gel electrophoresis for efficient sequencing of the desired product. Using this method, we routinely prepare RNA sequencing libraries from minute amounts of purified small RNA. This protocol is tailored to assay for CRISPR RNA biogenesis in bacteria through sequencing of mature CRISPR RNAs, but can be used to sequence diverse classes of small RNAs. We also provide a fully worked example of our data processing pipeline, with instructions for running the provided scripts.

Silas|Sukrit|S|
Jain|Nimit|N|
Stadler|Michael|M|
Fu|Becky Xu Hua|BXH|
Sánchez-Amat|Antonio|A|
Fire|Andrew Z|AZ|
Arribere|Joshua|J|

Small RNA
CRISPR
CRISPR RNA
Guide RNA
High throughput sequencing
crRNA biogenesis
crRNA maturation
crRNA processing


Temperature Effects on Optical Trapping Stability.

Abstract: In recent years, optically trapped luminescent particles have emerged as a reliable probe for contactless thermal sensing because of the dependence of their luminescence on environmental conditions. Although the temperature effect in the optical trapping stability has not always been the object of study, the optical trapping of micro/nanoparticles above room temperature is hindered by disturbances caused by temperature increments of even a few degrees in the Brownian motion that may lead to the release of the particle from the trap. In this report, we summarize recent experimental results on thermal sensing experiments in which micro/nanoparticles are used as probes with the aim of providing the contemporary state of the art about temperature effects in the stability of potential trapping processes.

temperature
optical trapping
Brownian motions
optical forces


Retene, pyrene and phenanthrene cause distinct molecular-level changes in the cardiac tissue of rainbow trout (Oncorhynchus mykiss) larvae, part 2 - Proteomics and metabolomics.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are global contaminants of concern. Despite several decades of research, their mechanisms of toxicity are not very well understood. Early life stages of fish are particularly sensitive with the developing cardiac tissue being a main target of PAHs toxicity. The mechanisms of cardiotoxicity of the three widespread model polycyclic aromatic hydrocarbons (PAHs) retene, pyrene and phenanthrene were explored in rainbow trout (Oncorhynchus mykiss) early life stages. Newly hatched larvae were exposed to sublethal doses of each individual PAH causing no detectable morphometric alterations. Changes in the cardiac proteome and metabolome were assessed after 7 or 14 days of exposure to each PAH. Phase I and II enzymes regulated by the aryl hydrocarbon receptor were significantly induced by all PAHs, with retene being the most potent compound. Retene significantly altered the level of several proteins involved in key cardiac functions such as muscle contraction, cellular tight junctions or calcium homeostasis. Those findings were quite consistent with previous reports regarding the effects of retene on the cardiac transcriptome. Significant changes in proteins linked to iron and heme metabolism were observed following exposure to pyrene. While phenanthrene also altered the levels of several proteins in the cardiac tissue, no clear mechanisms or pathways could be highlighted. Due to high variability between samples, very few significant changes were detected in the cardiac metabolome overall. Slight but significant changes were still observed for pyrene and phenanthrene, suggesting possible effects on several energetic or signaling pathways. This study shows that early exposure to different PAHs can alter the expression of key proteins involved in the cardiac function, which could potentially affect negatively the fitness of the larvae and later of the juvenile fish.

Rigaud|Cyril|C| Eriksson|Andreas|A| Rokka|Anne|A| Skaugen|Morten|M| Lihavainen|Jenna|J| Keinänen|Markku|M| Lehtivuori|Heli|H| Vehniäinen|Eeva-Riikka|ER|

Proteomics
Metabolomics
Polycyclic aromatic hydrocarbons (PAHs)
Cardiotoxicity
Aquatic toxicology
Developmental toxicity


Discrete state space modeling and control of nonlinear unknown systems.

Abstract: A novel procedure for integrating neural networks (NNs) with conventional techniques is proposed to design industrial modeling and control systems for nonlinear unknown systems. In the proposed approach, a new recurrent NN with a special architecture is constructed to obtain discrete-time state-space representations of nonlinear dynamical systems. It is referred as the discrete state-space neural network (DSSNN). In the DSSNN, the outputs of the hidden layer neurons of the DSSNN represent the system's (pseudo) state. The inputs are fed to output neurons and the delayed outputs of the hidden layer neurons are fed to their inputs via adjustable weights. The discrete state space model of the actual system is directly obtained by training the DSSNN with the input-output data. A training procedure based on the back-propagation through time (BPTT) algorithm is developed. The Levenberg-Marquardt (LM) method with a trust region approach is used to update the DSSNN weights. Linear state space models enable to use well developed conventional analysis and design techniques. Thus, building a linear model of a system has primary importance in industrial applications. Thus, a suitable linearization procedure is proposed to derive the linear state space model from the nonlinear DSSNN representation. The controllability, observability and stability properties are examined. The state feedback controllers are designed with both the linear quadratic regulator (LQR) and the pole placement techniques. The regulator and servo control problems are both addressed. A full order observer is also designed to estimate the state variables. The performance of the proposed procedure is demonstrated by applying for both single-input single-output (SISO) and multiple-input multiple-output (MIMO) nonlinear control problems.

Neural network
State-space
BPTT
LM
Linearization
State feedback
Pole placement
MIMO
LQ


Impact of acetylsalicylic Acid on the clinicopathological characteristics and prognosis of patients with invasive breast cancer.

Abstract:
BACKGROUND
The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer.

PATIENTS AND METHODS
Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890).

RESULTS
The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50).

CONCLUSION
Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.

Sendur|Mehmet A N|MA|
Aksoy|Sercan|S|
Ozdemir|Nuriye Y|NY|
Zengin|Nurullah|N|
Altundag|Kadri|K|

Acetylsalicylic acid
Breast cancer
Aspirin
NSAIDs