bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes
Authors: Nieman David C. , Valacchi Giuseppe , Wentz Laurel M. , Ferrara Francesca , Pecorelli Alessandra , Woodby Brittany , Sakaguchi Camila A. , Simonson Andrew
Published: November 2019

This double-blinded, placebo controlled, randomized crossover trial investigated the influence of 2-week mixed flavonoid versus placebo supplementation on oxinflammation markers after a 75-km cycling time trial in 22 cyclists (42.3 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr post 75-km cycling (176 ± 5.4 min, 73.4 ±2.0% maximal oxygen consumption). The supplement provided 678-mg flavonoids with quercetin (200 mg), green tea catechins (368 mg, 180-mg epigallocatechin gallate), and anthocyanins (128 mg) from bilberry extract, with caffeine, vitamin C, and omega-3 fatty acids added as adjuvants. Blood samples were analyzed for blood leukocyte counts, oxinflammation biomarkers, including 4-hydroxynonenal, protein carbonyls, and peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and glutathione peroxidase. Each of the blood biomarkers was elevated postexercise (time effects, all ps < .01), with lower plasma levels for 4-hydroxynonenal (at 21-hr postexercise) in flavonoid versus placebo (interaction effect, p = .008). Although elevated postexercise, no trial differences for the neutrophil/lymphocyte ratio (p = .539) or peripheral blood mononuclear mRNA expression for cyclooxygenease-2 (p = .322) or glutathione peroxidase (p = .839) were shown. Flavonoid supplementation prior to intensive exercise decreased plasma peroxidation and oxidative damage, as determined by 4-hydroxynonenal. Postexercise increases were similar between the flavonoid and placebo trials for peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and the nuclear factor erythroid 2-related factor 2 related gene glutathione peroxidase (NFE2L2). The data support the strategy of flavonoid supplementation to mitigate postexercise oxidative stress in endurance athletes.
A sperm peptide enhances long-term memory in female
Drosophila
Authors: Scheunemann L. , Lampin-Saint-Amaux A. , Schor J. , Preat T.
Published: November 2019

A sperm peptide transferred during mating controls a long-term memory checkpoint in the brain of female
Drosophila
.
Discovery of fossil asteroidal ice in primitive meteorite Acfer 094
Authors: Matsumoto Megumi , Tsuchiyama Akira , Nakato Aiko , Matsuno Junya , Miyake Akira , Kataoka Akimasa , Ito Motoo , Tomioka Naotaka , Kodama Yu , Uesugi Kentaro , Takeuchi Akihisa , Nakano Tsukasa , Vaccaro Epifanio
Published: November 2019

Discovery of fossil asteroidal ice in a meteorite provides new insight into asteroid formation in the early Solar System.
New skulls and skeletons of the Cretaceous legged snake
Najash
, and the evolution of the modern snake body plan
Authors: Garberoglio Fernando F. , Apesteguía Sebastián , Simões Tiago R. , Palci Alessandro , Gómez Raúl O. , Nydam Randall L. , Larsson Hans C. E. , Lee Michael S. Y. , Caldwell Michael W.
Published: November 2019

New fossils from the legged snake
Najash
reveal the evolutionary origins of key features of the modern snake skull and body.
Agreement between reconstructed and modeled boreal precipitation of the Last Interglacial
Authors: Scussolini Paolo , Bakker Pepijn , Guo Chuncheng , Stepanek Christian , Zhang Qiong , Braconnot Pascale , Cao Jian , Guarino Maria-Vittoria , Coumou Dim , Prange Matthias , Ward Philip J. , Renssen Hans , Kageyama Masa , Otto-Bliesner Bette , Aerts Jeroen C. J. H.
Published: November 2019

Models used to project climate change agree with geological evidence of precipitation in most boreal land in a past warm climate.
Brain-targeted enzyme-loaded nanoparticles: A breach through the blood-brain barrier for enzyme replacement therapy in Krabbe disease
Authors: Del Grosso Ambra , Galliani Marianna , Angella Lucia , Santi Melissa , Tonazzini Ilaria , Parlanti Gabriele , Signore Giovanni , Cecchini Marco
Published: November 2019

GALC-loaded nanoparticles can reinstate enzymatic activity in the brain of the mouse model of Krabbe disease.
When T cells lap up lactate
Authors: El-Kenawi Asmaa
Published: November 2019

Lactate drives rheumatoid arthritis progression by altering CD4
+
T cell metabolism.
Bound to get to the heart of a sticky problem
Authors: O’Cearbhaill Eoin
Published: November 2019

A cleverly designed biodegradable double-side sticky tape can adhere soft tissues together or to implantable medical devices.
Rifabutin Is Active against Mycobacterium abscessus in Mice
Authors: Dick Thomas , Shin Sung Jae , Koh Won-Jung , Dartois Véronique , Gengenbacher Martin
Published: November 2019

There is no reliable cure for
Mycobacterium abscessus
lung disease. Rifampin is not used clinically due to poor
in vitro
potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent
in vitro
against
M. abscessus
. Here, we report that rifabutin is as active as clarithromycin against
M. abscessus
K21 in NOD.CB17-Prkdc
scid
/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with
M. abscessus
disease.
Hepatitis Delta Virus Alters the Autophagy Process To Promote Its Genome Replication
Authors: Khabir Marwa , Aliche Asma Zahra , Sureau Camille , Blanchet Matthieu , Labonté Patrick
Published: November 2019

Hepatitis delta virus is a defective RNA virus that requires hepatitis B virus envelope proteins (HBsAg) to fulfill its life cycle. Thus, HDV can only infect individuals at the same time as HBV (coinfection) or superinfect individuals who are already chronic carriers of HBV. The presence of HDV in the liver accelerates the progression of infection to fibrosis and to hepatic cancer. Since current treatments against HBV are ineffective against HDV, it is of paramount importance to study the interaction between HBV, HDV, and host factors. This will help unravel new targets whereby a therapy that is capable of simultaneously impeding both viruses could be developed. In this research paper, we evidence that the autophagy machinery promotes the replication of HBV and HDV at different steps of their life cycle. Notwithstanding their contribution to HBV release, autophagy proteins seem to assist HDV intracellular replication but not its secretion.
Living at the edge of an active volcano: Risk from lava flows on Mt. Etna
Authors: Del Negro Ciro , Cappello Annalisa , Bilotta Giuseppe , Ganci Gaetana , Hérault Alexis , Zago Vito
Published: November 2019

Lava flows represent the greatest threat by far to exposed population and infrastructure on Mt. Etna, Italy. The increasing exposure of a larger population, which has almost tripled in the area around Mt. Etna during the past 150 years, has resulted from poor assessment of the volcanic hazard and inappropriate land use in vulnerable areas. Here we quantify the lava flow risk on the flanks of Mt. Etna volcano using a Geographic Information System (GIS)-based approach that integrates the hazard with the exposure of elements at stake. The hazard, which shows the long-term probability related to lava flow inundation, is obtained by combining three different kinds of information: the spatiotemporal probability of new flank eruptive vents opening in the future, the event probability associated with classes of expected eruptions, and the overlapping of lava flow paths simulated by the MAGFLOW model. Data including all exposed elements were gathered from institutional web portals and high-resolution satellite imagery and organized in four thematic layers: population, buildings, service networks, and land use. The total exposure is given by a weighted linear combination of the four thematic layers, where weights are calculated using the Analytic Hierarchy Process (AHP). The resulting risk map shows the likely damage caused by a lava flow eruption and allows rapid visualization of the areas subject to the greatest losses if a flank eruption were to occur on Mt. Etna. The highest risk is found in the southeastern flank due to the combination of high hazard and population density.
Holocene earthquake history and slip rate of the southern Teton fault, Wyoming, USA
Authors: DuRoss Christopher B. , Gold Ryan D. , Briggs Richard W. , Delano Jaime E. , Ostenaa Dean A. , Zellman Mark S. , Cholewinski Nicole , Wittke Seth J. , Mahan Shannon A.
Published: November 2019

The 72-km-long Teton normal fault bounds the eastern base of the Teton Range in northwestern Wyoming, USA. Although geomorphic surfaces along the fault record latest Pleistocene to Holocene fault movement, the postglacial earthquake history of the fault has remained enigmatic. We excavated a paleoseismic trench at the Buffalo Bowl site along the southernmost part of the fault to determine its Holocene rupture history and slip rate. At the site, ∼6.3 m of displacement postdates an early Holocene (ca. 10.5 ka) alluvial-fan surface. We document evidence of three surface-faulting earthquakes based on packages of scarp-derived colluvium that postdate the alluvial-fan units. Bayesian modeling of radiocarbon and luminescence ages yields earthquake times of ca. 9.9 ka, ca. 7.1 ka, and ca. 4.6 ka, forming the longest, most complete paleoseismic record of the Teton fault. We integrate these data with a displaced deglacial surface 4 km NE at Granite Canyon to calculate a postglacial to mid-Holocene (14.4–4.6 ka) slip rate of ∼1.1 mm/yr. Our analysis also suggests that the postglacial to early Holocene (14.4–9.9 ka) slip rate exceeds the Holocene (9.9–4.6 ka) rate by a factor of ∼2 (maximum of 3); however, a uniform rate for the fault is possible considering the 95% slip-rate errors. The ∼5 k.y. elapsed time since the last rupture of the southernmost Teton fault implies a current slip deficit of ∼4–5 m, which is possibly explained by spatially/temporally incomplete paleoseismic data, irregular earthquake recurrence, and/or variable per-event displacement. Our study emphasizes the importance of minimizing slip-rate uncertainties by integrating paleoseismic and geomorphic data sets and capturing multiple earthquake cycles.
Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial
Authors: Abbe Carmen , Roxby Alison C
Published: November 2019

Introduction

There is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs).

Methods

We examined the frequency of reported AEs by male research participants compared with AEs reported in prescribing information of approved female hormonal contraceptive methods. Published data from trials of the top five most-used female hormonal contraceptives, supplemented by contemporary contraceptive research, were compared with the frequency of AEs reported in a male injectable hormonal contraceptive trial.

Results

We observed similar frequencies of AEs reported by users of male contraceptives compared with those reported by female users. Among quantitatively comparable AEs, compared with men, women reported experiencing higher frequencies of headaches, pelvic pain, and weight gain and similar frequencies of decreased libido. Compared with women, men reported experiencing higher frequencies of acne and mood changes. Men discontinued participation due to AEs at a lower frequency than women.

Conclusions

Female hormonal methods generally have similar frequencies of AEs to those reported in a recent male hormonal contraceptive trial, and male users had lower rates of discontinuation due to AEs. There were fewer serious AEs of the male contraceptive than reported in contemporary female trials which resulted in FDA licensure. This suggests there may be implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods.
Impact of household composition and satisfaction with family life on self-reported sexual health outcomes of high-school students in Hong Kong
Authors: Wong William Chi Wai , Choi Edmond P H , Holroyd Eleanor , Ip Patrick , Fan Susan , Yip Paul S F
Published: November 2019

Background

The study aimed to examine the impact of household composition and satisfaction with family life on sexual behaviours among high school male and female students (aged 11–22 years) in Hong Kong.

Method

High schools were randomly selected, and the final sample comprised 25 schools. Students were divided into two groups ('living with both biological parents' vs 'not living with both biological parents'). Students were asked to rate their satisfaction with family life on a five-point Likert scale in a self-administered questionnaire. Dependent variables were sexual experience, sexual harassment, sexting and nude chats. Multiple logistic regression was used to analyse the results.

Results

3907 students were included in the analysis. 202 students (5.2%) were sexually active. 505 students had ever (13.0%) sexually harassed others and 303 students (7.8%) had ever been sexually harassed by others. 58 students (1.5%) had ever had nude chats. 1005 students (25.8%) had sexted in the last 12 months. Students who lived with both biological parents were less like to be sexually active, to sext and to have nude chats than those who did not. Students who had higher family life satisfaction were less likely to be sexually active, to sexually harass others, to be sexually harassed by others, to sext and to have nude chats than students who had lower satisfaction with their family life.

Conclusions

Sexual health programmes and interventions should consider family functioning. Students who have low family satisfaction and those who do not live with both their biological parents should be targeted for sexual health interventions.
Osler Centenary Papers: Would Sir William Osler be a role model for medical trainees and physicians today?
Authors: Murthy Vivek K , Wright Scott M
Published: November 2019

If Sir William Osler were alive and practising as one of our contemporary colleagues, would he be viewed as a role model by medical trainees and other physicians? Recently published literature has sought to define clinical excellence; this characterisation of physician performance establishes a context in which role models in medicine can be appraised. Building on this framework, we present rich anecdotes and quotes from Sir William Osler himself, his colleagues, and his students to consider whether Osler would have been regarded as a role model for clinical excellence today. This paper illustrates convincingly that William Osler indeed personified clinical excellence and would have been appreciated as a consummate role model if he were alive and on a medical school’s faculty today. However, a century has passed since his death, and he is not sufficiently visible today to serve as a role model to modern medical trainees and physicians. Moreover, we speculate that Osler himself would not have wanted to be a role model for today’s trainees, as he emphasised that medicine is best learned from teachers at the bedside—a place where he cannot be. Reanimating Osler through rich stories and inspiring quotes, and translating his example of clinical excellence into modern clinical practice, can remind us all to carry Oslerian virtues with us in our professional work.
10 Osler as a role model for today
Authors: Wright Scott
Published: November 2019

If Sir William Osler were alive and practicing as one of our contemporary colleagues, would he be viewed as a role model by medical trainees and other physicians? Recently published literature has sought to define clinical excellence; this characterization of physician performance establishes a context upon which role models in medicine can be appraised. Building on this framework, we present rich anecdotes and quotes from Sir William Osler himself, his colleagues, and his students to consider whether Osler would have been regarded as a role model for clinical excellence today.

This manuscript illustrates convincingly that William Osler indeed personified clinical excellence and would have been appreciated as a consummate role model if he were alive and on a medical school’s faculty today. However, a century has passed since his death, and he is not sufficiently visible today to serve as a role model to modern medical trainees and physicians. Moreover, we speculate that Osler himself would not want to be a role model for today’s trainees, as he emphasized that medicine is best learned from teachers at the bedside – a place where he cannot be. Reanimating Osler through rich stories and inspiring quotes, and translating his example of clinical excellence into modern clinical practice, can remind us all to carry Oslerian virtues with us in our professional work.
2 Advances in oral and insulin treatments for diabetes
Authors: Chowdhury Tahseen A
Published: November 2019

Prevalence of type 2 diabetes is rising worldwide, and adding significant burdens of morbidity, mortality and financial costs to healthcare systems worldwide. Whilst cardiovascular risk reduction is central to diabetes management, improved glycaemic control remains an important aim of management, in order to reduce the risk of microvascular complications.

In this presentation, I hope to remind the audience why diabetes is such an important condition, to review the evidence behind tight glucose control, and to assess the options and evidence behind newer oral and injectable therapies in the management of glucose in type 2 diabetes. I will also discuss recent studies concerning the prevention and remission of type 2 diabetes.

Finally, I hope to highlight the huge potential value of new technology in the management of Type 1 diabetes, which is set to change the treatment of this condition completely in the next few years.
8 General surgical foundation doctor optimisation of daily practice
Authors: Feldano Emmanuel , Ramasubbu Ben
Published: November 2019

Introduction

Traditionally the role of a surgical foundation year 1 (FY1s) doctors consisted of long working hours, multiple on call shifts and little to rest however, the introduction of European working time directive now means that FY1s are constricted to 48 hours per week on average and various other regulations that junior doctors should abide by yet the same quantity of daily tasks remains the same. In this study we looked at the difficulties FY1s now face in their daily working day and if some of these issues could be resolved by implementing some structural changes.

Methods

The study was conducted in three cycles, each lasting five days (Monday to Friday). Cycle 1 included shadowing of Surgical FY1s on wards for five consecutive days observing daily routine (arrival, lunch and departure time), task completion, communication and handovers. Following this multiple interventions were made to the structure of their daily practice to improve productivity and performance. These improvements were measured in cycle 2 (as the new model was scaffolded into place) and cycle 3 (strictly observed).

Results

In cycle 1 we observed that 100% of F1s arrived to work on time, there was no set times for lunch and all of the FY1s lunches were interrupted. There was no structure for handovers and 100% of F1s stayed at work beyond there contracted hours. In second cycle, 100% of F1s had lunch between the hours of 12pm-1PM on 3/5 days and 75% on the remaining two days. 75% of F1s had uninterrupted lunches on all 5 days. Morning and afternoon handovers were completed every day. In cycle 3 the results remained as high. There was no significant difference in number of tasks between week 1, 2 and 3.

Conclusion

Through the implementation of daily structure and other interventions involving the multidisciplinary team we improved the quality of F1s working day and increased the efficiency of service delivered on the surgical ward.
Effect of lidocaine cream analgesia for chest drain tube removal after video-assisted thoracoscopic surgery for lung cancer: a randomized clinical trial
Authors: Watanabe Shin-nosuke , Imai Kazuhiro , Kimura Tetsu , Saito Yoshitaro , Takashima Shinogu , Matsuzaki Ikuo , Kurihara Nobuyasu , Atari Maiko , Matsuo Tsubasa , Iwai Hidenobu , Sato Yusuke , Motoyama Satoru , Nomura Kyoko , Nishikawa Toshiaki , Minamiya Yoshihiro
Published: November 2019

Background and objectives

Pain management makes an important contribution to good respiratory care and early recovery after thoracic surgery. Although the development of video-assisted thoracoscopic surgery (VATS) has led to improved patient outcomes, chest tube removal could be distressful experience for many patients. The aim of this trial was to test whether the addition of lidocaine cream would have a signiﬁcant impact on the pain treatment during chest tube removal from patients who had undergone VATS for lung cancer.

Methods

This clinical trial was a double-blind randomized study. Forty patients with histologically confirmed lung cancer amenable to lobectomy/segmentectomy were enrolled. All patients had standard perioperative care. Patients were randomly assigned to receive either epidural anesthesia plus placebo cream (placebo, Group P) or epidural anesthesia plus 7% lidocaine cream cutaneously around the chest tube insertion site and on the skin over the tube’s course 20 min (Group L) before chest drain removal.

Results

Visual analog scale (VAS) scores were higher in Group P (median 5, IQR, 3.25-8) than in Group L (median 2, IQR, 1-3). Pain intensities measured using a PainVision system were also higher in Group P (median 296.7, IQR, 216.9–563.5) than Group L (median 41.2, IQR, 11.8–97.0). VAS scores and the pain intensity associated with chest drain removal were significantly lower in Group L than Group P (p=0.0002 vs p<0.0001).

Conclusion

Analgesia using lidocaine cream is a very simple way to reduce the pain of chest tube removal after VATS.

Trial registration number

UMIN000013824.
Effects on understory biomass and forage 8–10 years after precommercial thinning of Sitka spruce – western hemlock stands in southeast Alaska
Authors: Crotteau Justin S. , Rue-Johns Annelise Z. , Barnard Jeffrey C.
Published: November 2019

In southeast Alaska, United States, multiple-use forest management objectives include both timber production and wildlife habitat. Following stand-replacing disturbances such as clear-cutting, Sitka spruce (Picea sitchensis (Bong.) Carrière) and western hemlock (Tsuga heterophylla (Raf.) Sarg.) naturally regenerate and competitively dominate resources, excluding understory biomass and biodiversity. Thinning may mitigate the effects of canopy closure and permit understory development, but evidence of the effect on understories 8–10 years after thinning is lacking. We report results 4–5 and 8–10 years after thinning experiments on the Tongass National Forest to demonstrate the effects of precommercial thinning (thinned versus control), stand age (15–25, 25–35, and 35–50 years), and weather on understory dynamics and Sitka black-tailed deer (Odocoileus hemionus sitkensis Merriam, 1898) forage availability. Stand density negatively affected understory biomass, whereas temperature and precipitation positively interacted to increase biomass. Thinning had an enduring effect on understories, with biomass at least twice as great in thinned versus unthinned stands through year 10. We identified compositional differences from thinning as stand age class increased. Deer forage responded similarly to biomass, but thinning-induced differences faded with increased winter snowfall scenarios, especially in older stands. This study aids the understanding of stand overstory and understory development following silvicultural treatments in the coastal temperate rain forest of Alaska and suggests management implications and applications for balancing objectives throughout the forest type.
On stochastic effects and primordial black-hole formation
Authors: Kühnel Florian , Freese Katherine
Published: November 2019

The effect of large quantum fluctuations on primordial black-hole formation for inflationary models with a quasi-inflection point is investigated. By using techniques of stochastic inflation in combination with replica field theory and the Feynman–Jensen variational method, it is non-perturbatively demonstrated that the abundance of primordial black holes is amplified by several orders of magnitude as compared to the classical computation.
Soft fluorescent organic nanodots as nanocarriers for porphyrins
Authors: Sasaki Isabelle , Daniel Jonathan , Marais Sébastien , Verlhac Jean-Baptiste , Vaultier Michel , Blanchard-Desce Mireille
Published: November 2019

Novel fluorescent organic nanoparticles made from citric acid and diethylenetriamine were used as biocompatible and highly water-soluble nanocarriers for hydrophobic tetraphenylporphyrin (TPP). The tetraphenylporphyrin units were covalently attached to the nanoparticles, generating conjugated nanoparticles which retain water solubility and preserve the photophysical properties of monomeric TPP. The conjugated nanoparticles show two distinct fluorescence features: blue emission from the nanoparticle when excited in the near-UV (360 nm) and characteristic far-red emission of the TPP when excited in the visible (Soret band or Q bands). The uptake of the conjugated nanoparticles in live human neuroblastoma cancer cells was evidenced using two-photon microscopy. These experiments demonstrate that the fluorescent organic nanoparticles do act as efficient nanocarriers, allowing cell internalization of hydrophobic porphyrins. These conjugated nanoparticles appear as promising nanotools for theranostic (based on the combination of imaging and monitoring of the nanoparticle fluorescence) and therapeutic (photodynamic therapy by selectively exciting the grafted porphyrin units) modalities.
Fusion of Spatio-temporal Information for Indic Word Recognition Combining Online and Offline Text Data
Authors: Mukherjee Subham , Kumar Pradeep , Roy Partha Pratim
Published: November 2019

We present a novel Indic handwritten word recognition scheme by fusion of spatio-temporal information extracted from handwritten images. The main challenge in Indic word recognition lies in its complexity because of modifiers, touching characters, and compound characters. Hidden Markov Models (HMMs) are being used to model such data due to their ability to learn sequential data, however, the recognition performance is not satisfactory. We propose here a Long Short-Term Memory (LSTM)-based architecture for offline Indic word recognition. Offline recognition methods usually involve spatial data, whereas it has been observed that online recognition schemes show better performance than the offline methodologies. Online information usually refers to the temporal information obtained from the strokes of the pen tip while writing, which is missing in offline word images. In this article, an effort has been made to extract the online temporal information from offline images using stroke recovery and later it is combined with spatial information in LSTM architecture. During recognition, the character models are trained using both offline and extracted pseudo-online handwritten data separately. Finally, a novel fusion scheme has been used to combine them together. From the experiment, it is noted that recognition performance of handwritten Indic words improves considerably due to the fusion scheme of spatial and temporal data.
Robots aim to boost astronaut efficiency
Authors: Marks Paul
Published: November 2019

A multitude of robotic assistants for astronauts and rovers are in development to make space exploration more resource-efficient.
Uncertainty
Authors: Denning Peter J. , Lewis Ted G.
Published: November 2019

Considering how to best navigate stability and randomness.
Rapid hepatic metabolism blunts the endocrine action of portally infused GLP-1 in male rats
Authors: Aulinger Benedikt A. , Perabo Marta , Seeley Randy J. , Parhofer Klaus G. , D’Alessio David A.
Published: November 2019

Glucagon-like peptide-1 (GLP-1) is an enteral peptide that contributes to the incretin effect. GLP-1 action is typically described as endocrine, but this mechanism has been questioned because rapid inactivation in the circulation by dipeptidylpeptidase 4 (DPP4) results in a short half-life, limiting the amount of the hormone that can reach the pancreatic islet. An alternative mechanism for GLP-1 to regulate insulin secretion through neuroendocrine signaling originating from sensors in the portal vein has been proposed. We hypothesized that portal infusion of GLP-1 would cause greater glucose-stimulated insulin secretion than equimolar administration into the jugular vein. To test this, hyperglycemic clamps with superimposed graded infusions of GLP-1 into the jugular or portal veins of male rats were performed. These experiments were repeated with pharmacologic DPP4 inhibition to determine the effect of GLP-1 metabolism in the jugular and portal venous beds. Contrary to our hypothesis, we found a higher insulinotropic effect with jugular compared with portal GLP-1, which was associated with higher plasma concentrations of intact GLP-1. The greater insulinotropic effect of jugular venous GLP-1 persisted even with pharmacological DPP4 inhibition. These findings do not support an important role of portal vein GLP-1 signaling for the incretin effect but highlight the hepatoportal bed as a major site of GLP-1 degradation that persists even with pharmacological inhibition. Together, these results support rapid inactivation of enterally released GLP-1 in the liver as limiting endocrine actions on the β-cell and raise questions about the conventional endocrine model of pharmacologic effects of DPP4 inhibitors.
Obesity alters the topographical distribution of ventilation and the regional response to bronchoconstriction
Authors: Rutting S. , Mahadev S. , Tonga K. O. , Bailey D. L. , Dame Carroll J. R. , Farrow C. E. , Thamrin C. , Chapman D. G. , King G. G.
Published: November 2019

Obesity is associated with reduced operating lung volumes that may contribute to increased airway closure during tidal breathing and abnormalities in ventilation distribution. We investigated the effect of obesity on the topographical distribution of ventilation before and after methacholine-induced bronchoconstriction using single-photon emission computed tomography (SPECT)-computed tomography (CT) in healthy subjects. Subjects with obesity ( n = 9) and subjects without obesity ( n = 10) underwent baseline and postbronchoprovocation SPECT-CT imaging, in which Technegas was inhaled upright and followed by supine scanning. Lung regions that were nonventilated (Ventnon), low ventilated (Ventlow), or well ventilated (Ventwell) were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. To determine regional ventilation, lungs were divided into upper, middle, and lower thirds of axial length, derived from CT. At baseline, Ventnonand Ventlowfor the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Ventnon(17.5 ± 10.6% vs. 34.7 ± 7.8%, P < 0.001) and Ventlow(25.7 ± 6.3% vs. 33.6 ± 5.1%, P < 0.05) were decreased in subjects with obesity, with a consequent increase in Ventwell(56.8 ± 9.2% vs. 31.7 ± 10.1%, P < 0.001). The greater diversion of ventilation to the upper zone was correlated with body mass index ( rs = 0.74, P < 0.001), respiratory system resistance ( rs = 0.72, P < 0.001), and respiratory system reactance ( rs = −0.64, P = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Ventnonincreased similarly in both groups; however, in subjects without obesity, Ventnononly increased in the lower zone, whereas in subjects with obesity, Ventnonincreased more evenly across all lung zones. In conclusion, obesity is associated with altered ventilation distribution during baseline and following bronchoprovocation, independent of reduced lung volumes.

NEW & NOTEWORTHY Using ventilation SPECT-computed tomography imaging in healthy subjects, we demonstrate that ventilation in obesity is diverted to the upper lung zone and that this is strongly correlated with body mass index but is independent of operating lung volumes and of airway closure. Furthermore, methacholine-induced bronchoconstriction only occurred in the lower lung zone in individuals who were not obese, whereas in subjects who were obese, it occurred more evenly across all lung zones. These findings show that obesity-associated factors alter the topographical distribution of ventilation.
Diverse Linguistic Development in Prelingually Deaf Children with Cochlear Implants
Authors: De Stefano Pia , Pisani Francesco , Cossu Giuseppe
Published: November 2019

The advent of cochlear implants has enormously improved the quality of sensory perception in deaf children. Notwithstanding these advantages, the current literature shows a substantial variability in language proficiency among implanted children. This case series explores the variability of language acquisition in congenitally deaf children with cochlear implants. We report 4 prelingually deaf children (mean age=10.5; SD=1.08), affected by a genetically determined bilateral deafness, due to GJB2 gene mutation Cx26. Each implanted child underwent a systematic assessment of speech perception and production, as well as of lexical, morphologic, and syntactic skills in both comprehension and production. Notwithstanding similar clinical histories and similarly good postimplant pure-tone audiometry, two of the four children fared very poorly in speech audiometry, whereas the other two children gained very good results. We suggest that the language impairment detected in (some) implanted children may not be fully accounted for by pure auditory thresholds and that may be the outcome of concomitant damage to core components of the child’s linguistic brain.
Effects of Combined Treatment with Acupuncture and Chunggan Formula in a Mouse Model of Parkinson’s Disease
Authors: Hwang Tae-Yeon , Song Min-A , Ahn Sora , Oh Ju-Young , Kim Dong-hee , Liu Quan Feng , Lee Wonwoong , Hong Jongki , Jeon Songhee , Park Hi-Joon
Published: November 2019

Parkinson’s disease is the second most common neurodegenerative disease. Patients with Parkinson’s disease can be treated with a combination of acupuncture and herbal medicine, but studies on the synergistic effects of the combined treatment have not yet been conducted. Thus, we subjected an MPTP-induced Parkinson’s disease mouse model to the combined treatment. We used acupoint GB34 for acupuncture and modified Chunggantang (KD5040) as the herbal medicine, as they have been reported to be effective in Parkinson’s disease. We investigated the suboptimal dose of KD5040 and then used this dose in the combined treatment. The results showed that the combined treatment had a synergistic effect on improvements in abnormal motor function and neurodegeneration compared with the use of acupuncture or herbal medicine alone. The combined treatment also had a neuroprotective effect via the PI3K/AKT and MAPK/ERK signaling pathways. These findings suggest that the combined treatment with acupuncture and KD5040 can help improve the symptoms of Parkinson’s disease.
Acupuncture Differentially Affects the High-Frequency Spectral Energy in Radial Pulse Positions Depending on Type of Lower Back Pain
Authors: Ng Hui-Ping , Huang Chin-Ming , Ho Wen-Chao , Lee Yu-Chen
Published: November 2019

Acupuncture is a core discipline in traditional Chinese medicine (TCM) and has been practised in China for centuries. In traditional acupuncture, pulse palpation is an important clinical diagnostic technique that guides practitioners in their treatment strategies as they evaluate the effectiveness of the treatment. This paper provides the findings of our investigation of acupuncture’s effect on specific radial pulse spectral energies in 41 individuals with lower back pain (LBP), in response to a single acupuncture treatment delivered bilaterally at acupoints BL23, BL25, and BL40. Baseline assessments (vital signs and radial pulse diagnoses), primary outcome measures (radial pulse diagnoses), and secondary outcome measures (the Faces Pain Scale-Revised (FPS-R) and fingertip-to-floor (FTF) tests) were performed at specified intervals before and after the intervention. Our study provides novel information about the effects of acupuncture on the radial pulse spectral energy in individuals with different types of LBP. Our findings suggest that the right Chi pulse is an effective indicator to assess the effects of acupuncture in individuals with fixed, distended, or sharp pain, whereas the left Guan pulse is a potentially useful diagnostic technique to determine acupuncture’s effects in individuals with dull, aching pain. The acupoints BL23, BL25, and BL40 provide effective treatment for LBP. Study participants with dull, aching pain had a significant improvement in their lumbar ranges of motion, and their pain rating scores were markedly decreased after acupuncture treatment.
ALDH2 Overexpression Alleviates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation
Authors: Cao Ruiping , Fang Dian , Wang Jiahui , Yu Ying , Ye Hongwei , Kang Pinfang , Li Zhenghong , Wang Hongju , Gao Qin
Published: November 2019

Although the underlying mechanisms of diabetes-induced myocardial injury have not been fully illuminated, the inflammation reaction has been reported intently linked with diabetes. The nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, the key component of pyroptosis, is involved in inflammation reaction, which may be one of the important mechanisms in diabetes-induced myocardial injury. The purpose of this study was to investigate the changes of NLRP3 inflammasome and pyroptosis in high glucose-induced H9C2 cardiac cell injury and investigate whether overexpression of mitochondrial aldehyde dehydrogenase 2 (ALDH2) can reduce the occurrence of pyroptosis. The H9C2 cardiac cells were exposed to 35 mM glucose for 24 h to induce cytotoxicity. Mitochondrial ALDH2 overexpression cardiac cell line was constructed. The results showed in high glucose condition that ALDH2 overexpression significantly increased H9C2 cardiac cell viability, increased mitochondrial ALDH2 activity and protein expression, and reduced mitochondrial reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and lactate dehydrogenase (LDH) levels; meanwhile, the pyroptosis key components—NLRP3 inflammasome-related proteins, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteine-containing aspartate specific protease 1 (Caspase-1), and interleukin-18 (IL-18) protein expressions—were significantly decreased, and IL-18 and interleukin-1β (IL-1β) levels were also decreased. In high glucose-induced cardiac cell injury, ALDH2 overexpression may reduce ROS production, thereby inhibiting the activation of NLRP3 inflammation and cell pyroptosis. ALDH2 gene might play the potential role in the treatment of high glucose-induced H9C2 cardiac cell injury.
Silicone Plate for the Prevention of Postoperative Adhesions in Patients with Asherman Syndrome
Authors: Miyagi Maho , Mekaru Keiko , Oishi Sugiko , Urasoe Chiaki , Akamine Kozue , Aoki Yoichi
Published: November 2019

Purpose. Re-adhesion rates following hysteroscopic adhesiolysis have remained high. Accordingly, we present a case involving temporary placement of an intrauterine silicone plate to prevent re-adhesions following hysteroscopic adhesiolysis in a 36-year-old woman with Asherman syndrome. Methods. After hysteroscopic adhesiolysis, a silicone plate molded to the uterine cavity’s shape was inserted into the uterine cavity and left in place for 1 month. Results. The patient had a history of endometrial curettage for endometrial polyps. After the procedure, she developed amenorrhea and experienced infertility for 5 years despite four cycles of in vitro fertilization and embryo transfer. Following admission to our hospital, hysteroscopic examination showed a wide area of intrauterine adhesions for which hysteroscopic adhesiolysis and silicone plate insertion were performed. The silicone plate was removed after 1 month. No intrauterine adhesions were observed during the subsequent hysteroscopic examination. After a thawed embryo transfer, the patient became pregnant and delivered a healthy baby. Conclusions. A silicon plate may be considered a useful tool for preventing re-adhesion following hysteroscopic adhesiolysis without serious complications.
A MEMS Gyroscope Noise Suppressing Method Using Neural Architecture Search Neural Network
Authors: Zhu Zhenshu , Bo Yuming , Jiang Changhui
Published: November 2019

Inertial measurement unit (IMU) (an IMU usually contains three gyroscopes and accelerometers) is the key sensor to construct a self‐contained inertial navigation system (INS). IMU manufactured through the Micromechanics Electronics Manufacturing System (MEMS) technology becomes more popular, due to its smaller column, lower cost, and gradually improved accuracy. However, limited by the manufacturing technology, the MEMS IMU raw measurement signals experience complicated noises, which cause the INS navigation solution errors diverge dramatically over time. For addressing this problem, an advanced Neural Architecture Search Recurrent Neural Network (NAS‐RNN) was employed in the MEMS gyroscope noise suppressing. NAS‐RNN was the recently invented artificial intelligence method for time series problems in data science community. Different from conventional method, NAS‐RNN was able to search a more feasible architecture for selected application. In this paper, a popular MEMS IMU STIM300 was employed in the testing experiment, and the sampling frequency was 125 Hz. The experiment results showed that the NAS‐RNN was effective for MEMS gyroscope denoising; the standard deviation values of denoised three‐axis gyroscope measurements decreased by 44.0%, 34.1%, and 39.3%, respectively. Compared with the Long Short‐Term Memory Recurrent Neural Network (LSTM‐RNN), the NAS‐RNN obtained further decreases by 28.6%, 3.7%, and 8.8% in standard deviation (STD) values of the signals. In addition, the attitude errors decreased by 26.5%, 20.8%, and 16.4% while substituting the LSTM‐RNN with the NAS‐RNN.
Colony Formation, Migratory, and Differentiation Characteristics of Multipotential Stromal Cells (MSCs) from “Clinically Accessible” Human Periosteum Compared to Donor-Matched Bone Marrow MSCs
Authors: Owston Heather E. , Ganguly Payal , Tronci Giuseppe , Russell Stephen J. , Giannoudis Peter V. , Jones Elena A.
Published: November 2019

Periosteum is vital for fracture healing, as a highly vascular and multipotential stromal cell- (MSC-) rich tissue. During surgical bone reconstruction, small fragments of periosteum can be “clinically accessible,” yet periosteum is currently not ultilised, unlike autologous bone marrow (BM) aspirate. This study is aimed at comparing human periosteum and donor-matched iliac crest BM MSC content and characterising MSCs in terms of colony formation, growth kinetics, phenotype, cell migration patterns, and trilineage differentiation capacity. “Clinically accessible” periosteum had an intact outer fibrous layer, containing CD271+ candidate MSCs located perivasculary; the inner cambium was rarely present. Following enzymatic release of cells, periosteum formed significantly smaller fibroblastic colonies compared to BM (6.1 mm2 vs. 15.5 mm2, n=4, P=0.0006). Periosteal colonies were more homogenous in size (range 2-30 mm2 vs. 2-54 mm2) and on average 2500-fold more frequent (2.0% vs. 0.0008%, n=10, P=0.004) relative to total viable cells. When expanded in vitro, similar growth rates up to passage 0 (P0) were seen (1.8 population doublings (PDs) per day (periosteum), 1.6 PDs per day (BM)); however, subsequently BM MSCs proliferated significantly slower by P4 (4.3 PDs per day (periosteum) vs. 9.3 PDs per day (BM), n=9, P=0.02). In early culture, periosteum cells were less migratory at slower speeds than BM cells. Both MSC types exhibited MSC phenotype and trilineage differentiation capacity; however, periosteum MSCs showed significantly lower (2.7-fold) adipogenic potential based on Nile red : DAPI ratios with reduced expression of adipogenesis-related transcripts PPAR-γ. Altogether, these data revealed that “clinically accessible” periosteal samples represent a consistently rich source of highly proliferative MSCs compared to donor-matched BM, which importantly show similar osteochondral capacity and lower adipogenic potential. Live cell tracking allowed determination of unique morphological and migration characteristics of periosteal MSCs that can be used for the development of novel bone graft substitutes to be preferentially repopulated by these cells.
Post-TTM Rebound Pyrexia after Ischemia-Reperfusion Injury Results in Sterile Inflammation and Apoptosis in Cardiomyocytes
Authors: Tong Giang , von Garlen Nalina N. A. , Wowro Sylvia J. , Lam Phuong D. , Krech Jana , Berger Felix , Schmitt Katharina R. L.
Published: November 2019

Introduction. Fever is frequently observed after acute ischemic events and is associated with poor outcome and higher mortality. Targeted temperature management (TTM) is recommended for neuroprotection in comatose cardiac arrest survivors, but pyrexia after rewarming is proven to be detrimental in clinical trials. However, the cellular mechanisms and kinetics of post-TTM rebound pyrexia remain to be elucidated. Therefore, we investigated the effects of cooling and post-TTM pyrexia on the inflammatory response and apoptosis in a cardiomyocyte ischemia-reperfusion (IR) injury model. Methods. HL-1 cardiomyocytes were divided into the following groups to investigate the effect of oxygen-glucose deprivation/reperfusion (OGD/R), hypothermia (33.5°C), and pyrexia (40°C): normoxia controls maintained at 37°C and warmed to 40°C, OGD/R groups maintained at 37°C and cooled to 33.5°C for 24 h with rewarming to 37°C, and OGD/R pyrexia groups further warmed from 37 to 40°C. Caspase-3 and RBM3 were assessed by Western blot and TNF-α, IL-6, IL-1β, SOCS3, iNOS, and RBM3 transcriptions by RT-qPCR. Results. OGD-induced oxidative stress (iNOS) in cardiomyocytes was attenuated post-TTM by cooling. Cytokine transcriptions were suppressed by OGD, while reperfusion induced significant TNF-α transcription that was exacerbated by cooling. Significant inductions of TNF-α, IL-6, IL-1β, and SOCS3 were observed in noncooled, but not in cooled and rewarmed, OGD/R-injured cardiomyocytes. Further warming to pyrexia induced a sterile inflammatory response in OGD/R-injured groups that was attenuated by previous cooling, but no inflammation was observed in pyrexic normoxia groups. Moreover, cytoprotective RBM3 expression was induced by cooling but suppressed by pyrexia, correlating with apoptotic caspase-3 activation. Conclusion. Our findings show that maintaining a period of post-TTM “therapeutic normothermia” is effective in preventing secondary apoptosis-driven myocardial cell death, thus minimizing the infarct area and further release of mediators of the innate sterile inflammatory response after acute IR injury.
The Bioprotective Effects of Polyphenols on Metabolic Syndrome against Oxidative Stress: Evidences and Perspectives
Authors: Liu Kui , Luo Miao , Wei Shuang
Published: November 2019

Polyphenols are the general designation of various kinds of phytochemicals, mainly classified as flavonoids and nonflavonoids. Polyphenolic compounds have been confirmed to exhibit numerous bioactivities and potential health benefits both in vivo and in vitro. Dietary polyphenols have been shown to significantly alleviate several manifestations of metabolic syndrome, namely, central obesity, hypertension, dyslipidemia, and high blood sugar. This review is aimed at discussing the bioprotective effects and related molecular mechanisms of polyphenols, mainly by increasing antioxidant capacity or oxygen scavenging capacity. Polyphenols can exert their antioxidative activity by balancing the organic oxidoreductase enzyme system, regulating antioxidant responsive signaling pathways, and restoring mitochondrial function. These data are helpful for providing new insights into the potential biological effects of polyphenolic compounds and the development of future antioxidant therapeutics.