bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the suction device Nimble for the assessment of skin fibrosis in systemic sclerosis
Authors: Müller Bettina , Ruby Lisa , Jordan Suzana , Rominger Marga B. , Mazza Edoardo , Distler Oliver
Published: June 2020

Objectives

Skin fibrosis is a main hallmark of systemic sclerosis (SSc). Clinical assessment is done semi-quantitatively using the modified Rodnan skin score (mRSS). Objective measurements for quantifying skin fibrosis could complement the mRSS to achieve higher reproducibility. The aim of this study was to explore the potential of suction measurements to detect structural changes in the skin that are associated with skin fibrosis.

Methods

This clinical trial included 30 SSc patients and 30 healthy volunteers (HC). We validated a novel suction device—the Nimble—to quantify skin stiffness in comparison to the Cutometer using the OMERACT filter.

Results

A significant difference (p < 0.05) between the skin stiffness of HC and SSc patient groups was found for each location measured. The correlation between the measurements of forearm skin stiffness and the mRSS values was high for the Nimble (r = 0.82) and moderate for the Cutometer (r = 0.58). A ROC analysis showed good ability for the Nimble to distinguish between SSc patients with and without skin involvement (AUC = 0.82). Both suction devices provided excellent reliability in all measurements on HC and SSc patients and proved face validity and feasibility.

Conclusion

Suction devices assessing skin stiffness, such as the Nimble, show clear potential to objectively quantify skin fibrosis in SSc patients and might be promising outcome measures complementing established methods such as the mRSS.

Trial registration

Clinicaltrials.gov, NCT03644225, Registered 23 August 2018—Retrospectively registered, http://www.clinicaltrials.gov
Gender discrepancy of incidence and risk factors of metabolic syndrome among rural Chinese from 2012–2013 to 2015–2017
Authors: Yu Shasha , Guo Xiaofan , Li GuangXiao , Yang Hongmei , Sun Guozhe , Zheng Liqiang , Sun Yingxian
Published: June 2020

Background

We reported a relatively high rate of MetS in rural Northeast residents in 2012–2013. Many strategies like health knowledge propagation and lifestyle modification have been taken to help rural residents decrease metabolic disorders. Hence, we held the present follow-up study in order to figure the changes of metabolic parameters and the possible reasons together with the evaluation of MetS incidence and associated risk factors.

Methods

A population-based sample of 8147 rural Northeast Chinese residents aged ≥ 35 years at baseline were followed up from 2012–2013 to 2015–2017. MetS was diagnosed following the unify criteria in 2009 using the Asian specific criteria.

Results

Among residents with MetS at baseline, value of systolic, diastolic blood pressure, total cholesterol, HDL-C decreased while waist circumference increased in both genders in follow-up. Discrepancy of trend in body mass index, LDL-C and estimated GFR existed between male and female. Besides, triglyceride increased, and fast glucose decreased in female only. The alterations of dietary pattern might be accountable for those changes. Among residents without MetS at baseline, the cumulative incidence of newly diagnosed MetS was 24.0% (25.8% for male; 22.3% for female). As the number of metabolic disorders increased at baseline, the incidence of MetS also increased (zero metabolic disorder: 8.3%; one metabolic disorder: 17.1%; two metabolic disorders: 35.4%). In male residents, bad living habits like smoking and drinking were associated with increasing risk of Mets while in female, higher risk of MetS was more likely relevant to dietary pattern.

Conclusion

Metabolic parameters changes during the past years and seem to be associated with alteration of diet pattern. Incidence of MetS still high among rural Northeast Chinese. The risk factors of higher incidence of MetS show gender discrepancy which make the prophylaxis and control of MetS more effective and directive in rural residents.
Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter
Authors: Sandoval-Sierra Jose Vladimir , Salgado García Francisco I. , Brooks Jeffrey H. , Derefinko Karen J. , Mozhui Khyobeni
Published: June 2020

Background

A long-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here, we examine whether we can detect DNA methylation changes associated with a few days’ use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5 days (visit 2), and 39 ± 10 days (visit 3) after the discontinuation of opioid analgesics.

Results

The perioperative methylome underwent significant changes over the three visits that were primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was a significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5–210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: < 25 MME, 25–90 MME, and ≥ 90 MME. Using mixed-effects modeling, 4 CpGs had significant positive associations with opioid dose at two-tailed p value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, one-tailed p value = 0.02) and duration of opioid use (regression coefficient = 0.003, one-tailed p value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RAS-related signaling gene, RASL10A, that may be predictive of opioid dosage.

Conclusion

The present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use and that epigenetic differences in OPRM1 and other sites are associated with a short-term use of therapeutic opioids.
Reproducibility of EEG functional connectivity in Alzheimer’s disease
Authors: Briels Casper T. , Schoonhoven Deborah N. , Stam Cornelis J. , de Waal Hanneke , Scheltens Philip , Gouw Alida A.
Published: June 2020

Background

Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer’s disease (AD) compared to healthy subjects, there is no general consensus on the methodology of estimating functional connectivity in AD. Inconsistent results are reported due to multiple methodological factors such as diagnostic criteria, small sample sizes and the use of functional connectivity measures sensitive to volume conduction. We aimed to investigate the reproducibility of the disease-associated effects described by commonly used functional connectivity measures with respect to the amyloid, tau and neurodegeneration (A/T/N) criteria.

Methods

Eyes-closed task-free 21-channel EEG was used from patients with probable AD and subjective cognitive decline (SCD), to form two cohorts. Artefact-free epochs were visually selected and several functional connectivity measures (AEC(-c), coherence, imaginary coherence, PLV, PLI, wPLI) were estimated in five frequency bands. Functional connectivity was compared between diagnoses using AN(C)OVA models correcting for sex, age and, additionally, relative power of the frequency band. Another model predicted the Mini-Mental State Exam (MMSE) score of AD patients by functional connectivity estimates. The analysis was repeated in a subpopulation fulfilling the A/T/N criteria, after correction for influencing factors. The analyses were repeated in the second cohort.

Results

Two large cohorts were formed (SCD/AD;n = 197/214 andn = 202/196). Reproducible effects were found for the AEC-c in the alpha and beta frequency bands (p = 6.20 × 10−7, Cohen’sd = − 0.53;p = 5.78 × 10−4,d = − 0.37) and PLI and wPLI in the theta band (p = 3.81 × 10−8,d = 0.59;p = 1.62 × 10−8,d = 0.60, respectively). Only effects of the AEC-c remained significant after statistical correction for the relative power of the selected bandwidth. In addition, alpha band AEC-c correlated with disease severity represented by MMSE score.

Conclusion

The choice of functional connectivity measure and frequency band can have a large impact on the outcome of EEG studies in AD. Our results indicate that in the alpha and beta frequency bands, the effects measured by the AEC-c are reproducible and the most valid in terms of influencing factors, correlation with disease severity and preferable properties such as correction for volume conduction. Phase-based measures with correction for volume conduction, such as the PLI, showed reproducible effects in the theta frequency band.
Effects of MP-AzeFlu enhanced by activation of bitter taste receptor TAS2R
Authors: Ekstedt Sandra , Kumlien Georén Susanna , Cardell Lars Olaf
Published: June 2020

MP-AzeFlu is relatively new a pharmaceutical drug used in the treatment of allergic rhinitis. It is comprised of azelastine hydrochloride (AZE), a potent histamine-H1-receptor antagonist and fluticasone propionate (FP), corticosteroid. It’s somewhat bitter taste (often considered a disadvantage) can be attributed to AZE. We here hypothesize that MP-AzeFlu may induce some of its beneficial effects through activation of bitter taste receptors (Tas2R), which have recently been described in human airways. In the nose Tas2Rs induce secretion of antimicrobial peptides and increase ciliary activity, while in the lung they cause airway smooth muscle relaxation. The mechanisms behind Tas2R-mediated effects are not yet fully known. In order to evaluate the role of Tas2R in the effects induced by MP-AzeFlu the dilatory response of pre-contracted isolated airways from Balb/c mice was investigated in tissue bath myographs in the presence or absence of various well-characterized pharmacological antagonists or their corresponding vehicles. MP-AzeFlu caused a potent dose-dependent relaxation of pre-contracted airways, an effect probably mediated by its AZE component. The dilatory effect of MP-AzeFlu and AZE both mimicked the response induced by the Tas2R agonist, chloroquine, but was independent of histamine receptor (H1-, H2- and H3-), prostaglandins, cAMP and cGMP involvement, all known to be common pathways for airway dilation. Other bitter-tasting antihistamines (i.e. olopatadine and desloratadine) also relaxed airway segments. These data support the notion that MP-AzeFlu has the ability to activate Tas2R in the same way as chloroquine. The effect appears to be mediated by AZE, but not via the histamine receptor. Activation of Tas2R by MP-AzeFlu may contribute to its superior efficacy over FP observed in controlled clinical trials in patients with moderate/severe allergic rhinitis.
Which stem cells will eventually translate to the clinics for treatment of diabetes?
Authors: Bhartiya Deepa , Mohammad Subhan Ali
Published: June 2020

Human embryonic stem (hES) cells have been around for more than two decades now. It was expected that hES/iPS (induced pluripotent stem) cells will quickly translate to the clinics to treat diabetic patients and to obtain gametes in vitro for infertile couples. However, there is no breakthrough yet in either of the fields although considerable progress has been made. Research efforts are ongoing to obtain an insight into the gene expression changes associated with directed differentiation of hES/iPS cells. Autologous bone marrow/cord blood mononuclear cells’ therapy has also failed to show any regenerative potential and only remains as a standard method of care for blood diseases. Only mesenchymal stem cells (MSCs) have shown promise in the clinics to alleviate diabetic symptoms. But MSCs are stromal cells with no regenerative properties; rather “paracrine providers”, pericytes/stromal cells, better known for their trophic, immuno-modulatory, and anti-inflammatory properties and thus best termed as mesenchymal stromal cells (MSCs). Autologus bone marrow cells enriched for hematopoietic stem cells have no potential to cross boundaries and transdifferentiate into other lineages including endodermal pancreatic cells. Endogenous, pluripotent, very small embryonic-like stem cells (VSELs) emerge as the most likely endogenous stem cell candidates to regenerate adult diabetic pancreas. Transplanted MSCs provide a healthy paracrine support required for endogenous/ resident VSELs to differentiate into acinar cells and islets in a diabetic pancreas to enable restoration of homeostasis. Our recently published study shows that VSELs exist and can be enriched from intact mouse pancreas as well as from the islets and increase in numbers in diabetic pancreas. Providing “regenerative pressure” by subjecting diabetic mice to partial pancreatectomy stimulated the VSELs to undergo differentiation into various cell types in an attempt to restore homeostasis. Double-blinded, placebo controlled clinical trials need to be undertaken to evaluate the efficacy of transplanting MSCs in diabetic patients with conviction since now underlying fine play of endogenous VSELs and niche providing MSCs has emerged.
Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis
Authors: Alvarez-Palomo Belén , Sanchez-Lopez Luis Ignacio , Moodley Yuben , Edel Michael J. , Serrano-Mollar Anna
Published: June 2020

Background

Idiopathic pulmonary fibrosis is a chronic, progressive, and severe disease with a limited response to currently available therapies. Epithelial cell injury and failure of appropriate healing or regeneration are central to the pathogenesis of idiopathic pulmonary fibrosis. The purpose of this study is to investigate whether intratracheal transplantation of alveolar type II-like cells differentiated from induced pluripotent stem cells can stop and reverse the fibrotic process in an experimental model of bleomycin-induced lung fibrosis in rats.

Methods

Human induced pluripotent stem cells were differentiated to alveolar type II-like cells and characterized. Lung fibrosis was induced in rats by a single intratracheal instillation of bleomycin. Animals were transplanted with human induced pluripotent stem cells differentiated to alveolar type II-like cells at a dose of 3 × 106 cells/animal 15 days after endotracheal bleomycin instillation when the animal lungs were already fibrotic. Animals were sacrificed 21 days after the induction of lung fibrosis. Lung fibrosis was assessed by hydroxiprolin content, histologic studies, and the expression of transforming growth factor-β and α-smooth muscle actin.

Results

Cell transplantation of alveolar type II-like cells differentiated from induced pluripotent stem cells can significantly reduce pulmonary fibrosis and improve lung alveolar structure, once fibrosis has already formed. This is associated with the inhibition of transforming growth factor-β and α-smooth muscle actin in the damaged rat lung tissue.

Conclusion

To our knowledge, this is the first data to demonstrate that at the fibrotic stage of the disease, intratracheal transplantation of human induced pluripotent differentiated to alveolar type II-like cells halts and reverses fibrosis.
Resource allocation for virtual reality content sharing based on 5G D2D multicast communication
Authors: Yang Yang , Feng Lei , Zhang Cheng , Ou Qinghai , Li Wenjing
Published: June 2020

As the development of wireless virtual reality (VR), a great disparity exists among the huge content transmission, rigorous QoS guarantees and the limited bandwidth of cellular networks. With the increasing of cache capacity on user devices, direct content sharing between user devices is a promising solution to solve this problem. To meet the quality of service (QoS) requirement of wireless VR transmission, this paper proposes a content sharing scheme based on 5G device-to-device (D2D) Multicast Communication. In this way, some adjacent VR users can form multicasting clustering to share VR content by working on D2D communication mode. The VR D2D multicasting clusters reuse the uplink channel resource of ordinary VR cellular users in the same cell. The basic prerequisite is that the degrading on QoS of these ordinary VR cellular users can be affordable. We design a two-step scheme to solve this radio resource allocation problem for VR content sharing. Firstly, we find out the optimal transmitting power for each VR user devices by geometric proximity, which metrics are affected by wireless VR throughput, tracking accuracy and delay. In the second step, we transform the channel allocation problem into a bipartite graph matching problem based on the transmitting power metrics, which is optimally solved by the Hungarian algorithm. The simulation results show that the VR content sharing based on 5G D2D communication technology can achieve larger system throughput gain and lower transmission delay. Compared with heuristic scheme and stochastic scheme, the proposed scheme can increase the throughput of the overall network by about 50% and 12%, respectively.
Complete moment convergence of extended negatively dependent random variables
Authors: Song Mingzhu , Zhu Quanxin
Published: June 2020

In this paper, some results on the complete moment convergence of extended negatively dependent (END) random variables are established. The results in the paper improve and extend the corresponding ones of Qiu et al. (Acta Math. Appl. Sin. 40(3):436–448, 2017) under some weaker conditions. Our results also improve and extend the related known works in the literature.
Some inequalities obtained by fractional integrals of positive real orders
Authors: Gürbüz Mustafa , Taşdan Yakup , Set Erhan
Published: June 2020

The primary objective of this study is to handle new generalized Hermite–Hadamard type inequalities with the help of the Katugampola fractional integral operator, which generalizes the Hadamard and Riemann–Liouville fractional integral operators into one system. In order to do this, a new fractional integral identity is obtained. Then, by using this identity, some inequalities for the class of functions whose derivatives in absolute values at certain powers are ρ-convex are derived. It is observed that the obtained inequalities are generalizations of some results in the literature.
Tykhonov well-posedness of split problems
Authors: Shu Qiao-yuan , Sofonea Mircea , Xiao Yi-bin
Published: June 2020

In (J. Optim. Theory Appl. 183:139–157, 2019) we introduced and studied the concept of well-posedness in the sense of Tykhonov for abstract problems formulated on metric spaces. Our aim of this current paper is to extend the results in (J. Optim. Theory Appl. 183:139–157, 2019) to a system which consists of two independent problems denoted by P and Q, coupled by a nonlinear equation. Following the terminology used in literature we refer to such a system as a split problem. We introduce the concept of well-posedness for the abstract split problem and provide its characterization in terms of metric properties for a family of approximating sets and in terms of the well-posedness for the problems P and Q, as well. Then we illustrate the applicability of our results in the study of three relevant particular cases: a split variational–hemivariational inequality, an elliptic variational inequality and a history-dependent variational inequality. We describe each split problem and clearly indicate the family of approximating sets. We provide necessary and sufficient conditions which guarantee the well-posedness of the split variational–hemivariational inequality. Moreover, under appropriate assumptions on the data, we prove the well-posedness of the split elliptic variational inequality as well as the well-posedness of the split history-dependent variational inequality. We illustrate our abstract results with various examples, part of them arising in contact mechanics.
Stability analysis of imitative dynamics in two-community with multiple delays
Authors: Hu Wenjun , Zhang Gang
Published: June 2020

Evolutionary game dynamics has become a hot topic in recent years. In this paper, we combine game theory and dynamical systems to investigate the stability of imitative dynamics in two-community with different kinds of delays. First, we establish a new model of imitative dynamics in two-community. Then, three sufficient conditions of the asymptotical stability for the neutrally stable strategy of the imitative dynamics are obtained. Finally, numerical simulations are consistent with the theoretical analysis.
Evidence that cultural food practices of Adi women in Arunachal Pradesh, India, improve social-ecological resilience: insights for Sustainable Development Goals
Authors: Singh Ranjay K. , Kumar Arvind , Singh Anshuman , Singhal Poonam
Published: June 2020

Introduction

Sustainable use of biocultural diversity can help achieve Sustainable Development Goals (SDGs) in many ways. The tribal communities of bio-culturally rich Northeastern India rely heavily on local food resources and knowledge for livelihood security. In this study with Adi women of East Siang district, Arunachal Pradesh, India, we aimed to understand (i) access and use patterns for biocultural plants and animal species from diverse ecosystems and (ii) species diversity and conservation strategies deployed by Adis. We employed a novel participatory approach called “recipe contest” to mobilize Adi women from 15 randomly selected remote and transitional villages. Data collected through interviews, focus group discussions and transect walks from 75 women, were analyzed using qualitative and quantitative methods.

Results

We found that traditional local food was linked intricately with women’s knowledge, access patterns, and socio-cultural institutions. From an end-user perspective, remote Adi villages had more widespread use of plant species (14 as food; 34 as food-cum-ethnomedicine and 13 as income-generating species) and animal (17) as food in remote than in transitional villages. Further, there were significant differences (p < 0.000; 0244 and 0.000, respectively) across the social groups for use of plant- and animal-derived food and ethnomedicine. Among different land use systems (i.e., Jhum lands, home gardens, and morang forests), the highest diversity for food plant was found in home gardens while that for food-cum-ethnomedicinal plants and animal species was observed in morang forests. Adi women apply traditional agronomic, cultural, and harvest strategies, based on local knowledge and institutions and varying with social systems, to conserve their key local resources. Significant correlations (r = 0.63 to 0.92) were seen between conservation and use of food and animal species. Traditional knowledge on these aspects was linked intricately to the socio-cultural milieu and is transmitted inter-generationally through various social institutions.

Conclusions

Cultural food practices, crucial to social-ecological resilience and livelihood security of Adi and similar indigenous communities confronting global environmental challenges, need to be mainstreamed with relevant policies for achieving some targets of SDGs.
Why women are not small men: sex-related differences in perioperative cardiopulmonary exercise testing
Authors: Thomas G. , West M. A. , Browning M. , Minto G. , Swart M. , Richardson K. , McGarrity L. , Jack S. , Grocott M. P. W. , Levett D. Z. H.
Published: June 2020

Background

The use of preoperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative outcomes is increasingly prevalent. CPET-derived information enables personalised perioperative care and enhances shared decision-making. Sex-related differences in physical fitness are reported in non-perioperative literature. However, little attention has been paid to sex-related differences in the context of perioperative CPET.

Aim

We explored differences in the physical fitness variables reported in a recently published multi-centre study investigating CPET before colorectal surgery. We also report the inclusion rate of females in published perioperative CPET cohorts that are shaping guidelines and clinical practice.

Methods

We performed a post hoc analysis of the trial data of 703 patients who underwent CPET prior to major elective colorectal surgery. We also summarised the female inclusion rate in peer-reviewed published reports of perioperative CPET.

Results

Fitness assessed using commonly used perioperative CPET variables—oxygen consumption at anaerobic threshold (AT) and peak exercise—was significantly higher in males than in females both before and after correction for body weight. In studies contributing to the development of perioperative CPET, 68.5% of the participants were male.

Conclusion

To our knowledge, this is the first study to describe differences between males and females in CPET variables used in a perioperative setting. Furthermore, there is a substantial difference between the inclusion rates of males and females in this field. These findings require validation in larger cohorts and may have significant implications for both sexes in the application of CPET in the perioperative setting.
18β-Glycyrrhetinic acid induces human HaCaT keratinocytes apoptosis through ROS-mediated PI3K-Akt signaling pathway and ameliorates IMQ-induced psoriasis-like skin lesions in mice
Authors: Gao Jintao , Guo Junfan , Nong Yuejuan , Mo Wenfei , Fang Huanan , Mi Jing , Qi Qi , Yang Mengjuan
Published: June 2020

Background

Psoriasis is a chronic inflammatory skin disease affecting 2–3% of the population worldwide. Hyperproliferative keratinocytes were thought to be an amplifier of inflammatory response, thereby sustaining persistence of psoriasis lesions. Agents with the ability to inhibit keratinocyte proliferation or induce apoptosis are potentially useful for psoriasis treatment. 18β-Glycyrrhetinic acid (GA), an active metabolite of glycyrrhizin, exhibits diverse pharmacological activities, including anti-inflammatory, anti-bacteria and anti-proliferation. The current study aims to evaluate the effects of GA on the proliferation and apoptosis of human HaCaT keratinocytes in vitro and investigate the effects of GA on the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model in vivo.

Methods

Cell viability was assayed by CCK-8. Flow cytometry was performed to measure apoptosis and reactive oxygen species (ROS), with Annexin V-FITC/PI detection kit and DCFH-DA probe respectively. Caspase 9/3 activities were measured using caspase activity assay kits. The protein levels of Akt and p-Akt were determined using Western blotting. IMQ was applied to induce psoriasis-like skin lesions in mice. The histological change in mouse skin lesions was detected using hematoxylin and eosin (H&E) staining. The severity of skin lesions was scored based on Psoriasis Area Severity Index (PASI). RT-PCR was employed to examine the relative expression of TNF-α, IL-22 and IL-17A in mouse skin lesions.

Results

GA decreased HaCaT keratinocytes viability and induced cell apoptosis in a dose-dependent manner. In the presence of GA, intracellular ROS levels were significantly elevated. NAC, a ROS inhibitor, attenuated GA-mediated HaCaT keratinocytes growth inhibition and apoptosis. In addition, GA treatment remarkably decreased p-Akt protein level, which could be restored partially when cells were co-treated with GA and NAC. LY294002 (a PI3K inhibitor) treatment significantly enhanced GA-mediated cytotoxicity. Moreover, GA ameliorated IMQ-induced psoriasis-like skin lesions in mice.

Conclusions

GA inhibits proliferation and induces apoptosis in HaCaT keratinocytes through ROS-mediated inhibition of PI3K-Akt signaling pathway, and ameliorates IMQ-induced psoriasis-like skin lesions in mice.
UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases
Authors: Lee Wonwoong , Um Jinhee , Ko Keon-hee , Lee Yong Chan , Chung Bong Chul , Hong Jongki
Published: June 2020

Bile acids (BAs) are synthesized in the liver and can mediate homeostasis and various metabolism processes in the human body. Their levels in the gastrointestinal tract are closely related to various gastrointestinal diseases. In particular, farnesoid X receptor activated by free BAs is associated with overexpression of histidine decarboxylase in tumorigenesis. Therefore, comprehensive profiling of histamine (HIST), histidine (His), and BAs in biological samples can provide insight into the pathological mechanisms of gastrointestinal diseases. However, development of an analytical platform to profile HIST, His, and BAs in biological samples has several challenges such as highly different polarities between acidic and basic targets, low physiological concentrations of analytes, and high matrix interference of biological samples. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method combined with serial derivatization was developed to simultaneously determine HIST, His, and 5 BAs (cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid) in human gastric fluid. In serial derivatization, benzoyl chloride (BzCl) and N,N-dimethylethylenediamine (DMED) were used to selectively derivatize amino and carboxyl groups of analytes, respectively. After serial derivatization, all target derivatives were determined using a reverse-phase C18 LC column and positive multiple reaction monitoring (MRM) mode, with reasonable chromatographic separation and sensitive MS detection. To accurately quantify target metabolites, 7 stable isotope-labeled internal standards were used. The MS/MS spectra of DMED and Bz derivatives exhibited specific fragments via loss of a neutral molecule (dimethylamine; 45 Da) and inductive cleavage (benzoyl; m/z 105) from protonated molecules, enabling selection of appropriate MRM transition ions for selective and sensitive detection. The developed method was validated with respect to limits of detection and quantification, linearity, precision, accuracy, stability, and matrix effect. The established method was successfully applied to human gastric fluid samples. This method provides reliable quantification of HIST, His, and BAs in human gastric fluid and will be helpful to understand pathophysiological mechanisms of gastric diseases.
Retraction Note: Successful clavicle fracture surgery performed under selective supraclavicular nerve block using the new subclavian approach
Authors: Ueshima Hironobu , Otake Hiroshi
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Retraction Note: Who performs the preoperative examination?
Authors: Ueshima Hironobu , Otake Hiroshi
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
The failure of two major formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/6 mice
Authors: Nakamura Jun , Holley Darcy W. , Kawamoto Toshihiro , Bultman Scott J.
Published: June 2020

Background

Exogenous formaldehyde is classified by the IARC as a Category 1 known human carcinogen. Meanwhile, a significant amount of endogenous formaldehyde is produced in the human body; as such, formaldehyde-derived DNA and protein adducts have been detected in animals and humans in the absence of major exogenous formaldehyde exposure. However, the toxicological effects of endogenous formaldehyde on individuals with normal DNA damage repair functions are not well understood. In this study, we attempted to generate C57BL/6 mice deficient in both Adh5 and Aldh2, which encode two major enzymes that metabolize endogenous formaldehyde, in order to understand the effects of endogenous formaldehyde on mice with normal DNA repair function.

Results

Due to deficiencies in both ADH5 and ALDH2, few mice survived past post-natal day 21. In fact, the survival of pups within the first few days after birth was significantly decreased. Remarkably, two Aldh2−/−/Adh5−/− mice survived for 25 days after birth, and we measured their total body weight and organ weights. The body weight of Aldh2−/−/Adh5−/− mice decreased significantly by almost 37% compared to the Aldh2−/−/Adh5+/− and Aldh2−/−/Adh5+/+ mice of the same litter. In addition, the absolute weight of each organ was also significantly reduced.

Conclusion

Mice deficient in both formaldehyde-metabolizing enzymes ADH5 and ALDH2 were found to develop partial synthetic lethality and mortality shortly after birth. This phenotype may be due to the accumulation of endogenous formaldehyde. No serious phenotype has been reported in people with dysfunctional, dominant-negative ALDH2*2 alleles, but it has been reported that they may be highly susceptible to osteoporosis and neurodegenerative diseases. It is important to further investigate these diseases in individuals with ALDH2*2 alleles, including an association with decreased metabolism, and thus accumulation, of formaldehyde.
Cutaneous leishmaniasis in north-central Ethiopia: trend, clinical forms, geographic distribution, and determinants
Authors: Eshetu Belayneh , Mamo Hassen
Published: June 2020

Background

Cutaneous leishmaniasis (CL), being among the neglected tropical diseases, catches little attention despite its considerable influence. This study aimed at estimating the prevalence and associated factors of CL in Boru Meda Hospital, Dessie town, north-central Ethiopia.

Methods

Medical records of patients who attended the Dermatology Department of the Hospital in 2012–May 2018 were assessed. In addition, dermatological patients who were visiting the hospital during the data collection period (November 2017–May 2018) were interviewed to capture socio-demographic, environmental variables, and related factors. The source population was individuals who visited the hospital for skin problems in the stated years and CL positives were the targets. The association between CL and its determinants was tested by logistic regression.

Results

CL prevalence was 1.5% showing increasing trend with the year of examination. Localized, diffused, and mucosal CL was evident across the years. Dessie town had the highest prevalence, 291 (32.8%) patients out of 888 cases. The number of examined (29,701) and positives (543, 1.8%) for males was comparable with females, 28,459 and 345 (1.2%), respectively, increasing with age but without significant difference. Dessie town residence (adjusted odds ratio (AOR) 12.2, 95% confidence interval (CI) 2.2–18.6, p = 0.01), no bed net (AOR 9.9, 95% CI 2.7–16.7, p < 0.01), nearby irrigation (AOR 8.1, 95% CI 1.9–12.4, p < 0.01), and travel to CL endemic areas (AOR 13.9, 95% CI 4.4–14.3, p < 0.01) were significantly associated with CL.

Conclusion

CL is a growing health problem in Dessie and its surroundings. Known risk factors prevail. Comprehensive parasitological, entomological, and social studies are warranted to better manage the disease.
Complimentary code keying of spectral amplitude coding signals in optical buffering with increased capacity
Authors: Chen Kai-Sheng , Hong Wien
Published: June 2020

Signal buffering services such as contention resolution and congestion avoidance are essential in optical packet switching networks. In this paper, an optical memory scheme based on spectral amplitude coding (SAC) and complementary code keying (CCK) is proposed to increase the buffer capacity. CCK is applied to packet buffering by selecting an available code set and encoding the payload bits with either an SAC signal or its complementarity. The capacity constraint is effectively released, as the usable codes for queuing packets are twice those for the conventional code-domain buffers. To minimize system costs by reducing the codec number, a shared structure based on an arrayed waveguide grating (AWG), which is capable of processing both the typical and complimentary coded signals simultaneously, is also investigated.
Ultrasound-driven piezoelectric current activates spinal cord neurocircuits and restores locomotion in rats with spinal cord injury
Authors: Li Shuai , Alam Monzurul , Ahmed Rakib Uddin , Zhong Hui , Wang Xiao-Yun , Ng Serena , Zheng Yong-Ping
Published: June 2020

Background

Neuromodulation via electrical stimulation (ES) is a common technique to treat numerous brain and spinal cord related neurological conditions. In the present study, we examined the efficacy of piezoelectric stimulation (pES) by a custom miniature piezostimulator to activate the spinal cord neurocircuit in comparison with conventional epidural ES in rats.

Methods

Stimulation electrodes were implanted on L2 and S1 spinal cord and were connected to a head-plug for ES, and a piezostimulator for pES. EMG electrodes were implanted into hindlimb muscles. To generate piezoelectric current, an ultrasound beam was delivered by an external ultrasound probe. Motor evoked potentials (MEPs) were recorded during the piezoelectric stimulation and compared with the signals generated by the ES.

Results

Our results suggest that ultrasound intensity as low as 0.1 mW/cm2 could induce MEPs in the hindlimbs. No significant difference was found either in MEPs or in muscle recruitments for ES and pES. Similar to ES, pES induced by 22.5 mW/cm2 ultrasound restored locomotion in paralyzed rats with complete thoracic cord injury. Locomotion EMG signals indicated that pES works same as ES.

Conclusion

We propose piezoelectric stimulation as a new avenue of neuromodulation with features overtaking conventional electrical stimulation to serve future bioelectronic medicine.
Influence of foliar application with putrescine, salicylic, and ascorbic acid on the productivity and physical and chemical fruit properties of Picual olive trees
Authors: Hagagg Laila F. , Abd-Alhamid Nazmy , Hassan Hassan S. A. , Hassan Ahmed M. , Geanidy Esmail A. E.
Published: June 2020

Background and objective

Olive tree is very popular in the Mediterranean area because of its fruits and oil yields. Both of them are worldwide known by their beneficial health properties. Salicylic acid is naturally occurring as phenolic compound and endogenously synthesized as signaling molecule in plants and influences various physiological and biochemical functions in plants. Ascorbic acid is an antioxidant molecule and a key substrate for the detoxification of ROS. Putrescine participates in several processes of plant growth and development. Putrescine participates in several processes of plant growth and development. Therefore, the objective of this study is to determine the best concentrations of these substances to improve olive fruits yield and its chemical and physical properties.

Materials and methods

The field experiment was conducted during two seasons of 2017 and 2018 on adult olive trees of Picual cv. (8 years old) in a private orchard located in Ismailia Governorate, Egypt, to study the effect of foliar application with different concentrations of putrescine, salicylic, and ascorbic, in two dates of November and December. The effect of different concentrations and dates of spray under the conditions of the saline irrigation water (4.40 ds m−1) were evaluated on the fruit yield, fruit physical characteristics and fruit chemical properties of olive trees of Picual cv.

Results

In this study, all treatments were able to improve all studied characters compared with the control treatment in both spraying dates of November and December in both seasons, respectively. Moreover, the best yield of olive fruits in this study was recorded with the application of putrescine at 15 ppm + salicylic at 200 ppm + ascorbic at 2000 ppm in the first and second seasons, respectively.

Conclusion

Spraying Picual olive trees with putrescine, salicylic, and ascorbic acid in this study under the conditions of the saline irrigation water (4.40 ds m−1) was able to improve fruit yield and fruit physical and chemical properties of olive trees of Picual cv. compared with the control treatment in both spraying dates
Convergence analysis and parity conservation of a new form of a quadratic explicit spline with applications to integral equations
Authors: Ferrari Alberto José , Lara Luis Pedro , Santillan Marcus Eduardo Adrian
Published: June 2020

In this study, a new form of a quadratic spline is obtained, where the coefficients are determined explicitly by variational methods. Convergence is studied and parity conservation is demonstrated. Finally, the method is applied to solve integral equations.
Physiologically Based Dissolution Testing in a Drug Development Process—a Case Study of a Successful Application in a Bioequivalence Study of Trazodone ER Formulations Under Fed Conditions
Authors: Danielak Dorota , Milanowski Bartłomiej , Wentowski Krzysztof , Nogowska Maria , Kątny Michał , Rogowski Piotr , Konwicki Łukasz , Puk Ewa , Pieczuro Jarosław , Bawiec Marek , Garbacz Grzegorz , Lulek Janina
Published: June 2020

Development of generic extended-release (ER) formulations is challenging. Especially under fed conditions, the risk of failure in bioequivalence trials is high because of long gastric residence times and susceptibility to food effects. We describe the development of a generic trazodone ER formulation that was aided with a biorelevant dissolution evaluation. Trazodone hydrochloride 300-mg monolithic matrix tablets were dissolved both in USP and EMA compliant conditions and in the StressTest device that simulated both physicochemical and mechanical conditions of the gastrointestinal passage. The final formulation was tested against the originator, Trittico XR 300 mg, in a randomized cross-over bioequivalence trial with 44 healthy volunteers, in agreement with EMA guidelines. Initially developed formulations dissolved trazodone similarly to the originator under standard conditions (f2 factor above 50), but their dissolution kinetics differed significantly in the biorelevant tests. The formulation was optimized by the addition of low-viscosity hypromellose and mannitol. The final formulation was approved for the bioequivalence trial. Calculated Cmax were 1.92 ± 0.77 and 1.92 ± 0.63 [μg/mL], AUC0-t were 27.46 ± 8.39 and 29.96 ± 9.09 [μg∙h/mL], and AUC0-∞ were 28.22 ± 8.91 and 30.82 ± 9.41 [μg∙h/mL] for the originator and test formulations, respectively. The 90% confidence intervals of all primary pharmacokinetic parameters fell within the 80–125% range. In summary, biorelevant dissolution tests supported successful development of a generic trazodone ER formulation pharmaceutically equivalent with the originator under fed conditions. Employment of biorelevant dissolution tests may decrease the risk of failure in bioequivalence trials of ER formulations.
Associations of Perfluoroalkyl Substances with Incident Natural Menopause: The Study of Women’s Health Across the Nation
Authors: Ding Ning , Harlow Siobán D , Randolph John F , Calafat Antonia M , Mukherjee Bhramar , Batterman Stuart , Gold Ellen B , Park Sung Kyun
Published: June 2020

Context

Previous epidemiologic studies of per- and polyfluoroalkyl substances (PFASs) and menopausal timing conducted in cross-sectional settings were limited by reverse causation because PFAS serum concentrations increase after menopause.

Objectives

To investigate associations between perfluoroalkyl substances and incident natural menopause.

Design and Setting

A prospective cohort of midlife women, the Study of Women’s Health Across the Nation, 1999-2017.

Participants

1120 multiracial/ethnic premenopausal women aged 45-56 years.

Methods

Serum concentrations of perfluoroalkyls were quantified by high-performance liquid chromatography isotope dilution tandem mass spectrometry. Natural menopause was defined as the bleeding episode prior to at least 12 months of amenorrhea not due to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Participants contributed 5466 person-years of follow-up, and 578 had incident natural menopause. Compared with the lowest tertile, women at the highest tertile of baseline serum concentrations had adjusted HR for natural menopause of 1.26 (95% CI: 1.02-1.57) for n-perfluorooctane sulfonic acid (n-PFOS) (Ptrend = .03), 1.27 (95% CI: 1.01-1.59) for branched-PFOS (Ptrend = .03), and 1.31 (95% CI: 1.04-1.65) for n-perfluorooctanoic acid (Ptrend = .01). Women were classified into four clusters based on their overall PFAS concentrations as mixtures: low, low–medium, medium–high, and high. Compared with the low cluster, the high cluster had a HR of 1.63 (95% CI: 1.08-2.45), which is equivalent to 2.0 years earlier median time to natural menopause.

Conclusion

This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life.
Moderate-Intensity Exercise and High-Intensity Interval Training Affect Insulin Sensitivity Similarly in Obese Adults
Authors: Ryan Benjamin J , Schleh Michael W , Ahn Cheehoon , Ludzki Alison C , Gillen Jenna B , Varshney Pallavi , Van Pelt Douglas W , Pitchford Lisa M , Chenevert Thomas L , Gioscia-Ryan Rachel A , Howton Suzette M , Rode Thomas , Hummel Scott L , Burant Charles F , Little Jonathan P , Horowitz Jeffrey F
Published: June 2020

Objective

We compared the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on insulin sensitivity and other important metabolic adaptations in adults with obesity.

Methods

Thirty-one inactive adults with obesity (age: 31 ± 6 years; body mass index: 33 ± 3 kg/m2) completed 12 weeks (4 sessions/week) of either HIIT (10 × 1-minute at 90%HRmax, 1-minute active recovery; n = 16) or MICT (45 minutes at 70%HRmax; n = 15). To assess the direct effects of exercise independent of weight/fat loss, participants were required to maintain body mass.

Results

Training increased peak oxygen uptake by ~10% in both HIIT and MICT (P < 0.0001), and body weight/fat mass were unchanged. Peripheral insulin sensitivity (hyperinsulinemic-euglycemic clamp) was ~20% greater the day after the final exercise session compared to pretraining (P < 0.01), with no difference between HIIT and MICT. When trained participants abstained from exercise for 4 days, insulin sensitivity returned to pretraining levels in both groups. HIIT and MICT also induced similar increases in abundance of many skeletal muscle proteins involved in mitochondrial respiration and lipid and carbohydrate metabolism. Training-induced alterations in muscle lipid profile were also similar between groups.

Conclusion

Despite large differences in training intensity and exercise time, 12 weeks of HIIT and MICT induce similar acute improvements in peripheral insulin sensitivity the day after exercise, and similar longer term metabolic adaptations in skeletal muscle in adults with obesity. These findings support the notion that the insulin-sensitizing effects of both HIIT and MICT are mediated by factors stemming from the most recent exercise session(s) rather than adaptations that accrue with training.