bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium isoglycyrrhizinate attenuates acute alcohol-induced hepatic steatosis in a zebrafish model by regulating lipid metabolism and ER stress
Authors: Dai Wencong , Wang Kunyuan , Zhen Xinchun , Huang Zhibin , Liu Li
Published: March 2022

Background

Alcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish model.

Methods

Alcohol was administered directly to embryo medium at 5 days post-fertilization (dpf) for up to 32 h. MgIG was given to the larvae 2 h before the administration of alcohol and then cotreated with alcohol starting at 5 dpf. Oil red O staining was used to determine the incidence of steatosis, and pathological features of the liver were assessed by hematoxylin–eosin staining. Biological indexes, total cholesterol (TC) and triacylglycerol (TG) were detected in the livers of zebrafish larvae. Morphological changes in the livers of zebrafish larvae were observed using liver-specific EGFP transgenic zebrafish (Tg(lfabp10a:eGFP)). The expression levels of critical molecules related to endoplasmic reticulum (ER) stress and lipid metabolism were detected by qRT–PCR, whole-mount in situ hybridization and western blotting.

Results

Alcohol-treated larvae developed hepatomegaly and steatosis after 32 h of exposure. We found that MgIG improved hepatomegaly and reduced the incidence of steatosis in a dose-dependent manner by oil red O staining and diminished deposits of alcohol-induced fat droplets by histologic analysis. Moreover, MgIG significantly decreased the levels of TC and TG in the livers of zebrafish larvae. Furthermore, the expression levels of critical genes involved in ER stress (atf6, irela, bip, chop) and the key enzymes regulating lipid metabolism (acc1, fasn, hmgcs1 and hmgcra) were significantly higher in the alcohol-treated group than in the control group. However, in the MgIG plus alcohol-treated group, the expression of these genes was markedly decreased compared with that in the alcohol-treated group. Whole-mount in situ hybridization and western blotting also showed that MgIG had an effect on the expression levels of critical genes and proteins involved in lipid metabolism and ER stress. Our results revealed that MgIG could markedly regulate these genes and protect the liver from ER stress and lipid metabolism disorders.

Conclusions

Our study is the first to demonstrate that MgIG could protect the liver from acute alcohol stimulation by ameliorating the disorder of lipid metabolism and regulating ER stress in zebrafish larvae.
High fructose induces dysfunctional vasodilatation via PP2A-mediated eNOS Ser1177 dephosphorylation
Authors: Jin Jiaqi , Liu Jingya , Luo Yong , He Hong , Zheng Xinyue , Zheng Chaoyang , Huang Yi , Chen Yang
Published: March 2022

Background

Processed foods are popular and contain large amounts of industrial fructose, which changes people’s diet and exacerbates the negative health effects of high fructose. Several studies have shown that excessive intake of fructose has a major impact on vascular disease. However, the mechanism of the effect of high fructose on blood vessels is currently unclear.

Methods

The effect of fructose on the vasodilatation of isolated thoracic aortic rings was observed by using wire myography in wild-type (WT) mice. Cell viability and nitric oxide (NO) production were assessed by the corresponding kits in mouse vascular endothelial cells. The effect of fructose on endothelial nitric oxide synthase (eNOS) and protein phosphatase 2A (PP2A) and their changes in phosphorylation were detected by using Western blots. Moreover, a PP2A inhibitor (okadaic acid, OA) was used to evaluate the relationship between fructose and PP2A. Furthermore, PP2ACα endothelial-specific knockout (PP2A cKO) mice were used to detect the vasodilatation of in vitro fructose-incubated thoracic aortic rings by using wire myography.

Results

High fructose induced endothelium-dependent dysfunctional vasodilatation. High fructose reduced acetylcholine (Ach)-induced vasodilation but did not affect sodium nitroprusside (SNP)-induced vasodilation. Accordingly, NO production and the phosphorylation level of eNOS at serine (Ser) 1177 (P-eNOS) in vascular endothelial cells were remarkably reduced without changes in cell viability. The expression of protein phosphatase 2A catalytic subunit (PP2AC) was increased and the expression of phosphorylated PP2AC (P-PP2A, tyrosine [Tyr] 307) was significantly decreased. Nevertheless, these effects were reversed by OA. Moreover, knockout of the PP2A gene could recover the response of vessels to Ach under high fructose stimulation.

Conclusions

Our observations demonstrate an underlying mechanism of fructose-induced dysfunctional vasodilatation. Fructose could activate PP2A, which leads to decrease in the phosphorylation of eNOS at Ser1177 and the reduction of NO release, thus leading to the occurrence of endothelium-dependent dysfunctional vasodilatation.
Effects of subchronic dietary exposure to the engineered nanomaterials SiO2 and CeO2 in C57BL/6J and 5xFAD Alzheimer model mice
Authors: Sofranko Adriana , Wahle Tina , Kolling Julia , Heusinkveld Harm J. , Stahlmecke Burkhard , Rosenbruch Martin , Albrecht Catrin , Schins Roel P. F.
Published: March 2022

Background

There is an increasing concern about the neurotoxicity of engineered nanomaterials (NMs). To investigate the effects of subchronic oral exposures to SiO2 and CeO2 NMs on Alzheimer’s disease (AD)-like pathology, 5xFAD transgenic mice and their C57BL/6J littermates were fed ad libitum for 3 or 14 weeks with control food pellets, or pellets dosed with these respective NMs at 0.1% or 1% (w/w). Behaviour effects were evaluated by X-maze, string suspension, balance beam and open field tests. Brains were analysed for plaque load, beta-amyloid peptide levels, markers of oxidative stress and neuroinflammation.

Results

No marked behavioural impairments were observed in the mice exposed to SiO2 or CeO2 and neither treatment resulted in accelerated plaque formation, increased oxidative stress or inflammation. In contrast, the 5xFAD mice exposed to 1% CeO2 for 14 weeks showed significantly lower hippocampal Aβ plaque load and improved locomotor activity compared to the corresponding controls.

Conclusions

The findings from the present study suggest that long-term oral exposure to SiO2 or CeO2 NMs has no neurotoxic and AD-promoting effects. The reduced plaque burden observed in the mice following dietary CeO2 exposure warrants further investigation to establish the underlying mechanism, given the easy applicability of this administration method.
Circ_0043947 contributes to interleukin 1β-induced injury in chondrocytes by sponging miR-671-5p to up-regulate RTN3 expression in osteoarthritis pathology
Authors: He Min , Jia Zhihe , Wen Yiying , Chen Xiaolin
Published: March 2022

Objective

Osteoarthritis (OA) is a chronic joint disease featured by articular cartilage degeneration and damage. Accumulating evidence have demonstrated the pivotal regulatory roles of circular RNAs in OA pathology. However, the role of circ_0043947 in OA progression and its associated mechanism remain largely unknown.

Methods

The expression of RNA and protein was determined by reverse transcription-quantitative polymerase chain reaction and Western blot assay. Cell viability was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was analyzed by 5-Ethynyl-2′-deoxyuridine (EdU) assay and flow cytometry. Cell apoptosis was assessed by flow cytometry. Enzyme linked immunosorbent assay was conducted to analyze the release of pro-inflammatory cytokines. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to confirm the target interaction between microRNA-671-5p (miR-671-5p) and circ_0043947 or reticulon 3 (RTN3).

Results

Interleukin 1β (IL-1β) stimulation up-regulated the expression of circ_0043947 in chondrocytes. IL-1β treatment restrained the viability and proliferation and induced the apoptosis, extracellular matrix degradation and inflammatory response of chondrocytes partly by up-regulating circ_0043947. Circ_0043947 interacted with miR-671-5p, and miR-671-5p silencing largely reversed circ_0043947 knockdown-mediated protective effects in IL-1β-induced chondrocytes. miR-671-5p interacted with the 3′ untranslated region (3′UTR) of RTN3. miR-671-5p overexpression attenuated IL-1β-induced injury in chondrocytes, and these protective effects were largely overturned by the overexpression of RTN3. Circ_0043947 acted as a molecular sponge for miR-671-5p to up-regulate RTN3 level in chondrocytes.

Conclusion

Circ_0043947 silencing alleviated IL-1β-induced injury in chondrocytes by targeting miR-671-5p/RTN3 axis.
Zone 2 hybrid thoracic endovascular aortic repair: Is it a good option for all types of thoracic aortic disease?
Authors: Sohn Bongyeon , Lee Jae Hang , Jung Joon Chul , Chang Hyoung Woo , Kim Dong Jung , Kim Jun Sung , Lim Cheong , Park Kay-Hyun
Published: March 2022

Background

Zone 2 thoracic endovascular aortic repair (TEVAR) is performed for the treatment of various thoracic aortic diseases involving the left subclavian artery. This study aimed to analyze the late clinical outcomes of zone 2 hybrid TEVAR according to the various indications.

Methods

A total of 48 patients who underwent zone 2 TEVAR at our institution between December, 2010 and July, 2020 were enrolled. The indications were aortic aneurysm (AA, n = 15), acute type B aortic dissection (AD, n = 14), penetrating aortic ulcer (PAU, n = 8), traumatic aortic injury (TAI, n = 8), and others (n = 3). The clinical outcomes including early complications and mid-term aortic measurements were retrospectively reviewed.

Results

The technical success rate was 100% and in-hospital mortality occurred in one patient. The early postoperative complications included stroke (n = 1), transient spinal cord ischemia (n = 1), neck wound hematoma (n = 1), and left phrenic or vagus nerve injury (n = 9). In patients with AD, positive remodeling was observed in ten patients (76.9%) (false lumen regression in the entire or thoracic aorta [n = 9], false lumen thrombosis in the thoracic aorta [n = 1]). However, in patients with AA, increased aneurysm was found in six patients (40%). Persistent aneurysmal growth was found in patients with a maximal aortic diameter of > 60 mm on initial imaging (4/6, 50%). No aortic expansion was observed in those with TAI or PAU. Endoleak was noted in five patients (10.4%), and among them, aortic reintervention was required only in patients with large AAs.

Conclusions

Zone 2 hybrid TEVAR was associated with an acceptable early complication rate and provided acceptable mid-term aortic results for patients with AD, PAU, and TAI. However, patients with large AAs were at increased risk of aortic reintervention. In cases of large AA, clinicians should carefully consider whether zone 2 hybrid TEVAR or open surgical repair will be more effective for the patient.
A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds
Authors: Fathi-Karkan Sonia , Banimohamad-Shotorbani Behnaz , Saghati Sepideh , Rahbarghazi Reza , Davaran Soodabeh
Published: March 2022

Certain polymeric materials such as polyurethanes (PUs) are the most prevalent class of used biomaterials in regenerative medicine and have been widely explored as vascular substitutes in several animal models. It is thought that PU-based biomaterials possess suitable hemo-compatibility with comparable performance related to the normal blood vessels. Despite these advantages, the possibility of thrombus formation and restenosis limits their application as artificial functional vessels. In this regard, various surface modification approaches have been developed to enhance both hemo-compatibility and prolong patency. While critically reviewing the recent advances in vascular tissue engineering, mainly PU grafts, this paper summarizes the application of preferred cell sources to vascular regeneration, physicochemical properties, and some possible degradation mechanisms of PU to provide a more extensive perspective for future research.
The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing
Authors: Kleber Christian , Sablotzki Armin , Casu Sebastian , Olivieri Martin , Thoms Kai-Martin , Horter Johannes , Schmitt Felix C. F. , Birschmann Ingvild , Fries Dietmar , Maegele Marc , Schöchl Herbert , Wilhelmi Michaela
Published: March 2022

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60–70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.
Silver and gold nanoparticles induced differential antimicrobial potential in calli cultures of Prunella vulgaris
Authors: Ahmad Nisar , Muhammad Jan , Khan Khalil , Ali Wajid , Fazal Hina , Ali Mohammad , Rahman Latif-ur , Khan Hayat , Uddin Muhammad Nazir , Abbasi Bilal Haider , Hano Christophe
Published: March 2022

Background

Prunella vulgaris is medicinally important plant containing high-valued chemical metabolites like Prunellin which belong to family Lamiaceae and it is also known as self-heal. In this research, calli culture were exposed to differential ratios of gold (Au) and silver (Ag) nanoparticles (1:1, 1:2, 1:3, 2:1 and 3:1) along with naphthalene acetic acid (2.0 mg NAA) to investigate its antimicrobial potential. A well diffusion method was used for antimicrobial properties.

Results

Here, two concentrations (1 and 2 mg/6 µl) of all treated calli cultures and wild plants were used against Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Bacillus atrophaeus, Bacillus subtilis, Agrobacterium tumefaciens, Erwinia caratovora and Candida albicans. Dimethyl sulfoxide (DMSO) and antibiotics were used as negative and positive controls. Here, the calli exposed to gold (Au) nanoparticles (NPs) and 2.0 mg naphthalene acetic acid (NAA) displayed the highest activity (25.7 mm) against Salmonella typhi than other extracts, which was considered the most susceptible species, while Agrobacterium tumefaciens and Candida albicans was the most resistance species. A possible mechanism of calli induced nanoparticles was also investigated for cytoplasmic leakage.

Conclusion

From the above data it is concluded that Prunella vulgaris is medicinally important plant for the development of anti-microbial drugs using nanotechnology and applicable in various pharmaceutical research.
Differences in topographical location of sacroiliac joint MRI lesions in patients with early axial spondyloarthritis and mechanical back pain
Authors: Kiil Rosa Marie , Mistegaard Clara E. , Loft Anne Gitte , Zejden Anna , Hendricks Oliver , Jurik Anne Grethe
Published: March 2022

Background

Early diagnostics of axial spondyloarthritis (axSpA) remains a challenge. Traditional imaging one-plane sacroiliac joint (SIJ) MRI assessment is used. By introducing a two-plane assessment system, the objective was to analyse the differences in SIJ MRI changes in early axSpA compared with changes in patients with mechanical back pain (MBP) by exploring the differences in volume and location.

Methods

MRIs in the early diagnostic state of 25 axSpA patients (mean age 31.3 years) and 59 MBP patients (mean age 32.3 years) were included. The MRIs were assessed by two readers regarding the distribution of bone marrow edema (BME) in 14 joint portions and structural changes in six joint portions in addition to SIJ anatomical variations and lumbar spine disc degeneration.

Results

AxSpA patients had a significantly higher overall BME sumscore (volume) of 25.1 compared to MBP patients 6.8, p < 0.005. The MBP group had the highest prevalence (66%) and sumscore (5.7) in the middle anterior sacrum. The axSpA group had significantly higher prevalence and sumscores in all joint portions except the three cartilaginous anterior sacral joint portions, including the ligamentous compartments (prevalence 40–60% compared to 8–15%, p both < 0.005). The axSpA group had also a significantly higher prevalence of erosions and fatty marrow disposition, but there were no differences in the prevalence of anatomical variations except the bipartite iliac bony plate.

Conclusions

AxSpA patients demonstrated a widespread distribution of both inflammatory and structural changes, including high BME occurrence in the ligamentous joint portions whereas patients with MBP had the highest occurrence of BME in the middle anterior sacrum. These findings may help differentiate axSpA patients from other back pain conditions in the early diagnostic phase.
Exosomal CagA from Helicobacter pylori aggravates intestinal epithelium barrier dysfunction in chronic colitis by facilitating Claudin-2 expression
Authors: Guo Yinjie , Xu Canxia , Gong Renjie , Hu Tingzi , Zhang Xue , Xie Xiaoran , Chi Jingshu , Li Huan , Xia Xiujuan , Liu Xiaoming
Published: March 2022

Background

The chronic infection with Helicobacter pylori (H. pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various extragastric disorders. Evaluating the potential impacts of virulence factor CagA on intestine may provide a better understanding of H. pylori pathogenesis such as colitis. The intestinal mucosal barrier is essential for maintaining its integrity and functions. However, how persistent CagA+H. pylori colonization influences barrier disruption and thereby affects chronic colitis is not fully understood.

Results

Chronic colitis models of CagA+H. pylori-colonized mice treated with 2% Dextran sulphate sodium (DSS) were established to assess the disease activity and pertinent expression of tight junction proteins closely related to mucosal integrity. The aggravating effect of CagA+H. pylori infection on DSS-induced chronic colitis was confirmed in mouse models. In addition, augmented Claudin-2 expression was detected in CagA+H. pylori infection conditions and selected for mechanistic analysis. Next, GES-1 human gastric epithelial cells were cultured with CagA+H. pylori or a recombinant CagA protein, and exosomes isolated from conditioned media were then identified. We assessed the Claudin-2 levels after exposure to CagA+ exosomes, CagA− exosomes, and IFN-γ incubation, revealing that CagA+H. pylori compromised the colonic mucosal barrier and facilitated IFN-γ-induced intestinal epithelial destruction through CagA-containing exosome-mediated mechanisms. Specifically, CagA upregulated Claudin-2 expression at the transcriptional level via a CDX2-dependent mechanism to slow the restoration of wounded mucosa in colitis in vitro.

Conclusions

These data suggest that exosomes containing CagA facilitate CDX2-dependent Claudin-2 maintenance. The exosome-dependent mechanisms of CagA+H. pylori infection are indispensable for damaging the mucosal barrier integrity in chronic colitis, which may provide a new idea for inflammatory bowel disease (IBD) treatment.
Ethical implications of epigenetics in the era of personalized medicine
Authors: Santaló Josep , Berdasco María
Published: March 2022

Given the increasing research activity on epigenetics to monitor human diseases and its connection with lifestyle and environmental expositions, the field of epigenetics has attracted a great deal of interest also at the ethical and societal level. In this review, we will identify and discuss current ethical, legal and social issues of epigenetics research in the context of personalized medicine. The review covers ethical aspects such as how epigenetic information should impact patient autonomy and the ability to generate an intentional and voluntary decision, the measures of data protection related to privacy and confidentiality derived from epigenome studies (e.g., risk of discrimination, patient re-identification and unexpected findings) or the debate in the distribution of responsibilities for health (i.e., personal versus public responsibilities). We pay special attention to the risk of social discrimination and stigmatization as a consequence of inferring information related to lifestyle and environmental exposures potentially contained in epigenetic data. Furthermore, as exposures to the environment and individual habits do not affect all populations equally, the violation of the principle of distributive justice in the access to the benefits of clinical epigenetics is discussed. In this regard, epigenetics represents a great opportunity for the integration of public policy measures aimed to create healthier living environments. Whether these public policies will coexist or, in contrast, compete with strategies reinforcing the personalized medicine interventions needs to be considered. The review ends with a reflection on the main challenges in epigenetic research, some of them in a technical dimension (e.g., assessing causality or establishing reference epigenomes) but also in the ethical and social sphere (e.g., risk to add an epigenetic determinism on top of the current genetic one). In sum, integration into life science investigation of social experiences such as exposure to risk, nutritional habits, prejudice and stigma, is imperative to understand epigenetic variation in disease. This pragmatic approach is required to locate clinical epigenetics out of the experimental laboratories and facilitate its implementation into society.
Robotic pyelolithotomy in a solitary pelvic kidney complicated with fulminant Clostridium difficile: a case report
Authors: Kerr Preston S. , Nguyen Nga T. , Martinez Andrew , Srinivasan Aditya , Kosarek Christopher D. , Sreshta Joseph Nicholas
Published: March 2022

Background

Robotic-assisted surgeries have gradually become the standard of care for many procedures, especially in the field of urology. Despite the widespread use of robotic assistance in surgeries, data on its postoperative complications are extremely limited. We detail a rare presentation of fulminant Clostridium difficile colitis requiring surgical intervention in a patient with a solitary ectopic pelvic kidney who underwent a robotic-assisted pyelolithotomy. Highlights of the most recent management recommendations for C. difficile infection are also presented.

Case presentation

A 26-year-old Caucasian woman who underwent a robot-assisted pyelolithotomy of a pelvic kidney developed tachycardia, leukocytosis, and severe diarrhea 2 days following surgery. Because of her long history of antibiotic use, her severe symptoms were concerning for C. difficile colitis. This was confirmed by a C. difficile toxin test and a computed tomography scan. She was given recommended antibiotics, but her condition progressively deteriorated. The patient developed fulminant colitis and toxic megacolon, for which she underwent an exploratory laparotomy with subtotal abdominal colectomy and ileostomy creation on the twelfth day of her hospitalization. She fully recovered and was discharged 3 weeks after her subtotal colectomy.

Conclusion

Although robotic surgeries have been shown to have several advantages, risk of postsurgical complications remains. We present a rare case of fulminant C. difficile colitis that complicated a robotic-assisted pyelolithotomy. Active prevention, early detection, and optimization of management are essential to preventing unfavorable outcomes.
Herpetic anterior uveitis following Pfizer–BioNTech coronavirus disease 2019 vaccine: two case reports
Authors: Ortiz-Egea José Manuel , Sánchez Cristina Gómez , López-Jiménez Andrés , Navarro Olga Diego
Published: March 2022

Purpose

To describe two cases of herpetic anterior uveitis after inoculation of the first dose of Pfizer–BioNTech coronavirus disease 2019 vaccine.

Methods

Case 1: a healthy 92-year-old Caucasian woman developed symptomatic unilateral anterior uveitis for 3 days after Pfizer–BioNTech coronavirus disease 2019 vaccination (Pfizer Inc.). The episode fully resolved with topical and oral antiviral treatment. Case 2: a previously healthy 85-year-old Caucasian woman with left hemicranial signs of herpes zoster infection, associated with herpetic keratouveitis for 3 days after Pfizer–BioNTech coronavirus disease 2019 vaccination. Treatment with topical antibiotics and both oral and topical antiherpetic medication was administered, and she recovered successfully in 5 weeks.

Conclusion

Clinicians should be aware of the possibility of eye inflammation in the form of herpetic reactivation after coronavirus disease 2019 vaccination.
A multifunctional enolase mediates cytoadhesion and interaction with host plasminogen and fibronectin in Mycoplasma hyorhinis
Authors: Wang Jia , Yu Yanfei , Li Yao , Li Shiyang , Wang Li , Wei Yanna , Wu Yuzi , Pillay Bala , Olaniran Ademola Olufolahan , Chiliza Thamsanqa E. , Shao Guoqing , Feng Zhixin , Xiong Qiyan
Published: March 2022

Mycoplasma hyorhinis may cause systemic inflammation of pigs, typically polyserositis and arthritis, and is also associated with several types of human cancer. However, the pathogenesis of M. hyorhinis colonizing and breaching the respiratory barrier to establish systemic infection is poorly understood. Glycolytic enzymes are important moonlighting proteins and virulence-related factors in various bacteria. In this study, we investigated the functions of a glycolytic critical enzyme, enolase in the infection and systemic spread of M. hyorhinis. Bacterial surface localization of enolase was confirmed by flow cytometry and colony hybridization assay. Recombinant M. hyorhinis enolase (rEno) was found to adhere to pig kidney (PK-15) cells, and anti-rEno serum significantly decreased adherence. The enzyme was also found to bind host plasminogen and fibronectin, and interactions were specific and strong, with dissociation constant (KD) values of 1.4 nM and 14.3 nM, respectively, from surface plasmon resonance analysis. Activation of rEno-bound plasminogen was confirmed by its ability to hydrolyze plasmin-specific substrates and to degrade a reconstituted extracellular matrix. To explore key sites during these interactions, C-terminal lysine residues of enolase were replaced with leucine, and the resulting single-site and double-site mutants show significantly reduced interaction with plasminogen in far-Western blotting and surface plasmon resonance tests. The binding affinities of all mutants to fibronectin were reduced as well. Collectively, these results imply that enolase moonlights as an important adhesin of M. hyorhinis, and interacts with plasminogen and fibronectin. The two lysine residues in the C-terminus are important binding sites for its multiple binding activities.
Computation bits maximization in backscatter-assisted wireless-powered NOMA-MEC networks
Authors: Zheng Chuangming , Zhou Wengang
Published: March 2022

In the field of Internet-of-Things (IoT), how to enhance the computation capacity and prolong the life span of massive smart IoT nodes is becoming a more practically important but challenging problem. In this paper, we propose a backscatter-assisted wireless-powered non-orthogonal multiple access (NOMA)-mobile edge computing (MEC) network, where IoT nodes harvest energy from signals transmitted by a dedicated energy source and then offload data to the MEC server via backscattering and uplink NOMA. To exploit its potential performance, we formulate a non-convex problem to maximize the total computation bits of all the IoT nodes by jointly optimizing the communication resource of each IoT node and the computation resource of both the IoT nodes and the MEC server. By introducing a slack variable and a series of auxiliary variables as well as using the contradiction and inequality transformation approaches, we transform the original non-convex problem into a convex one and devise an iterative algorithm to optimally solve it. Simulation results are provided to demonstrate the quick convergence of the proposed iterative algorithm and to confirm the superiority of the proposed scheme over the existing benchmark schemes.
New Hadamard-type inequalities for E-convex functions involving generalized fractional integrals
Authors: Latif Asia , Hussain Rashida
Published: March 2022

In this article, we establish some new Hadamard-type inequalities for E-convex functions involving generalized fractional integrals. These inequalities include a generalized Hadamard-type inequality and the corresponding right Hadamard-type inequalities for E-convex functions. The results presented here are generalizations of some of the results discussed in the recent literature.
HIV prevalence and risk behaviors among female sex workers in Togo in 2017: a cross-sectional national study
Authors: Bitty-Anderson Alexandra M. , Gbeasor-Komlanvi Fifonsi A. , Tchankoni Martin Kouame , Sadio Arnold , Salou Mounerou , Coffie Patrick A. , Dagnra Claver A. , Ekouevi Didier K.
Published: March 2022

Background

The HIV epidemic remains an important public health challenge for the sub-Saharan region. Female Sex Workers (FSW) in this region are among the most vulnerable of the key population groups with HIV prevalence as high as twice that of the general population. The aim of this study was to estimate HIV prevalence and explore sexual risk behaviors among FSW in Togo.

Methods

A cross-sectional study using a Respondent Driven Sampling method was conducted across the six regions of country among FSW in 2017. A comprehensive questionnaire was used to explore socio-demographic characteristics, sexual history, HIV knowledge, and sexual behaviors. HIV rapid tests were used to assess HIV infection.

Results

A total of 1,036 FSW, with a median age of 26 years old [interquartile range (IQR): 22–33], participated in the study, with 49.2% (n = 510) of them having reached secondary school. Median age at first sexual intercourse was 20 years old [IQR: 17–25] and estimated number of clients per week was of 5 [IQR: 3–10]. A total of 936 (95.6%) reported the use of a condom during last sexual intercourse with a client and 493 (47.6%) reported the use of a condom during their last sexual intercourse with a partner or husband. HIV prevalence was 13.2% [95% CI: 11.2 – 15.4], and was associated with age (being between 26 and 32 years old; aOR = 4.5; 95% CI: [2.4 – 9.1], p < 0.0001) and ≥ 33 years old; aOR = 6.4; 95% CI [3.5 – 12.7], p < 0.0001), education level (being in primary school or less; aOR = 1.7; 95% CI: [1.1–2.6]; p = 0.012) and the number of partners per week (more than 2 and 3 partners; aOR = 2.5; 95% CI [1.2—5.2]; p = 0.014).

Conclusions

HIV prevalence and sexual risk behaviors remain high among FSW in Togo, despite prevention efforts aimed at curbing this trend. Other factors, such as access and availability of condoms, the social and legal environment in which FSW operate, should be considered for HIV prevention strategies in this population.
A systematic literature review of disability weights measurement studies: evolution of methodological choices
Authors: Charalampous Periklis , Polinder Suzanne , Wothge Jördis , von der Lippe Elena , Haagsma Juanita A.
Published: March 2022

Background

The disability weight is an essential factor to estimate the healthy time that is lost due to living with a certain state of illness. A 2014 review showed a considerable variation in methods used to derive disability weights. Since then, several sets of disability weights have been developed. This systematic review aimed to provide an updated and comparative overview of the methodological design choices and surveying techniques that have been used in disability weights measurement studies and how they evolved over time.

Methods

A literature search was conducted in multiple international databases (early-1990 to mid-2021). Records were screened according to pre-defined eligibility criteria. The quality of the included disability weights measurement studies was assessed using the Checklist for Reporting Valuation Studies (CREATE) instrument. Studies were collated by characteristics and methodological design approaches. Data extraction was performed by one reviewer and discussed with a second.

Results

Forty-six unique disability weights measurement studies met our eligibility criteria. More than half (n = 27; 59%) of the identified studies assessed disability weights for multiple ill-health outcomes. Thirty studies (65%) described the health states using disease-specific descriptions or a combination of a disease-specific descriptions and generic-preference instruments. The percentage of studies obtaining health preferences from a population-based panel increased from 14% (2004–2011) to 32% (2012–2021). None of the disability weight studies published in the past 10 years used the annual profile approach. Most studies performed panel-meetings to obtain disability weights data.

Conclusions

Our review reveals that a methodological uniformity between national and GBD disability weights studies increased, especially from 2010 onwards. Over years, more studies used disease-specific health state descriptions in line with those of the GBD study, panel from general populations, and data from web-based surveys and/or household surveys. There is, however, a wide variation in valuation techniques that were used to derive disability weights at national-level and that persisted over time.
Dexmedetomidine reduces propofol-induced hippocampal neuron injury by modulating the miR-377-5p/Arc pathway
Authors: Chen Zong , Ding Yong , Zeng Ying , Zhang Xue-Ping , Chen Jian-Yan
Published: March 2022

Background

Propofol and dexmedetomidine (DEX) are widely used in general anesthesia, and exert toxic and protective effects on hippocampal neurons, respectively. The study sought to investigate the molecular mechanisms of DEX-mediated neuroprotection against propofol-induced hippocampal neuron injury in mouse brains.

Methods

Hippocampal neurons of mice and HT22 cells were treated with propofol, DEX, and propofol+DEX. In addition, transfection of miR-377-5p mimics or inhibitors was performed in HT22 cells. Neuronal apoptosis was evaluated by a means of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) or Hochest 33,258 staining; Arc positive expression in hippocampus tissues was detected using a microscope in immunohistochemistry assays; miRNA-377-5p expression was quantified by RT-qPCR; the protein levels of Arc, DNMT3A, and DNMT3B were determined using western blot; Cell Counting Kit-8 (CCK-8) assay was used to detect the viability and apoptotic rate of the neurons; methylation analysis in the miR-377-5p promoter was performed through methylated DNA immunoprecipitation (MeDIP) assay; dual luciferase reporter assay was performed to confirm whether Arc was under targeted regulation of miR-377-5p.

Results

In the current study, both in vitro and in vivo, propofol treatment induced hippocampal neuron apoptosis and suppressed cell viability. DNMT3A and DNMT3B expression levels were decreased following propofol treatment, resulting in lowered methylation in the miR-377-5p promoter region and then enhanced expression of miR-377-5p, leading to a decrease in the expression of downstream Arc. Conversely, the expression levels of DNMT3A and DNMT3B were increased following DEX treatment, thus methylation in miR-377-5p promoter region was improved, and miR-377-5p expression was decreased, leading to an increase in the expression of downstream Arc. Eventually, DEX pretreatment protected hippocampal neurons against propofol-induced neurotoxicity by recovering the expression levels of DNMT3A, miR-377-5p, and Arc to the normal levels. Additionally, DNMT3A knockdown improved miR-377-5p expression but reduced Arc expression, and DNMT3A overexpression exerted the opposite effects. Dual luciferase reporter assay revealed a binding target between miR-377-5p and Arc 3’UTR. The neuroprotective effect of DEX against propofol-induced neuronal apoptosis was diminished after Arc knockdown. Silencing Arc independently triggered the apoptosis of HT22 cells, which was alleviated through transfection of miR-377-5p inhibitors.

Conclusions

DEX reduced propofol-induced hippocampal neuron injury via the miR-377-5p/Arc signaling pathway.
Estimating errors in autocorrelation functions for reliable investigations of reflection profiles
Authors: Maeda Yuta , Watanabe Toshiki
Published: March 2022

Autocorrelation functions (ACFs) of vertically incident seismic waves are used to image subsurface reflectors. However, the reflection responses derived from ACFs usually contain many false signals. We present a method to quantify the errors in ACFs and extract true reflectors with high reliability. We estimated the errors for each earthquake at each station as follows. We calculated the amplitude of the observed waveform within the noise window and generated 1000 random noise traces that have this amplitude. By subtracting the random noise traces from the observed waveform, we created 1000 candidate earthquake waveforms. We computed the ACF for each of the 1000 waveforms and calculated the ensemble average and standard deviation of the 1000 different ACF amplitudes at each lag time. Then, we applied weighted stacking to the ACFs of many earthquakes to obtain the reflection response at the station. We calculated the standard deviation of the weighted stack to estimate errors in the reflection response. We evaluated the method by applying it to seismic data from the metropolitan area of Japan. The subsurface structure of the study area has been studied extensively and consists of a strong velocity discontinuity between sedimentary and basement layers. Following our method, the discontinuity was imaged as a clear reflector with an amplitude that was substantially greater than three times the standard deviation, which corresponds to statistical significance at the 99% confidence level. At other depths where reflectors are not expected to be present, the amplitudes of the peaks were less than or close to three times the standard deviation. The signal of the discontinuity was clearly visible at frequencies below 10 Hz and was less prominent at higher frequencies.

Graphical Abstract
Specialised early intervention for recent-onset psychosis
Authors: Butt Harun S.
Published: March 2022

Specialised early intervention (SEI) services have seen significant investment and expansion in the UK, aiming to improve long-term outcomes for psychotic disorders. This commentary discusses a recent Cochrane review that examines the evidence for SEI services delivered within the first 3 years of onset of psychotic illness. From a small number of studies conducted in high-income countries, the review draws the conclusion that there is low- to moderate-certainty evidence that SEI services improve recovery and reduce disengagement.
Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: A Randomized Clinical Trial
Authors: Kim Young-Woo , Min Jae-Seok , Yoon Hong Man , An Ji Yeong , Eom Bang Wool , Hur Hoon , Lee Young Joon , Cho Gyu Seok , Park Young-Kyu , Jung Mi Ran , Park Ji-Ho , Hyung Woo Jin , Jeong Sang-Ho , Kook Myeong-Cherl , Han Mira , Nam Byung-Ho , Ryu Keun Won
Published: March 2022

PURPOSE

To compare postoperative complications, long-term survival, and quality of life (QOL) after laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG).

METHODS

Five hundred eighty patients with preoperatively diagnosed stage IA gastric adenocarcinoma (≤ 3 cm) were assigned to undergo either LSG or LSNNS. Observers were not blinded to patient grouping. The primary outcome was 3-year disease-free survival (3y-DFS). Secondary outcomes included postoperative complications, QOL, 3-year disease-specific survival (3y-DSS), and 3-year overall survival (3y-OS).

RESULTS

In total, 527 patients were included in the modified intention-to-treat analysis population for the primary outcome (LSG, 269; LSNNS, 258). Stomach-preserving surgery was performed in 210 patients (81%) in the LSNNS group. During the median follow-up duration, the 3y-DFS rates in the LSG and LSNNS groups were 95.5% and 91.8%, respectively (difference: 3.7%; 95% CI, –0.6 to 8.1). Three patients with recurrence and five with metachronous gastric cancer in the LSNNS group underwent standard surgery. Two patients with distant metastasis in both groups were treated with palliative chemotherapy. The 3y-DSS and 3y-OS rates in the LSG and LSNNS groups were 99.5% and 99.1% ( P = .59) and 99.2% and 97.6% ( P = .17), respectively. Postoperative complications occurred in 19.0% of the LSG group and 15.5% of the LSNNS group ( P = .294). The LSNNS group showed better physical function ( P = .015), less symptoms ( P < .001), and improved nutrition than the LSG group.

CONCLUSION

LSNNS did not show noninferiority to LSG for 3y-DFS, with a 5% margin. However, the 3y-DSS and 3y-OS were not different after rescue surgery in cases of recurrence/metachronous gastric cancer, and LSNNS had better long-term QOL and nutrition than LSG.
Multilevel Factors for Adiposity Change in a Population-Based Prospective Study of Black Breast Cancer Survivors
Authors: Qin Bo , Kim Kate , Goldman Noreen , Rundle Andrew G. , Chanumolu Dhanya , Zeinomar Nur , Xu Baichen , Pawlish Karen S. , Ambrosone Christine B. , Demissie Kitaw , Hong Chi-Chen , Lovasi Gina S. , Bandera Elisa V.
Published: March 2022

PURPOSE

Unfavorable weight change after breast cancer diagnosis increases the risk of mortality, but individual and neighborhood risk factors affecting postdiagnosis weight and body fat changes are unclear among Black women, who have higher rates of obesity and mortality than any other racial/ethnic group.

METHODS

Adiposity changes during the period approximately 10 months-24 months after diagnosis were evaluated among 785 women diagnosed between 2012 and 2018 and enrolled in the Women's Circle of Health Follow-Up Study, a population-based prospective cohort of Black breast cancer survivors in New Jersey. Multilevel factors for weight and fat mass change (with gain or loss defined as a relative difference of 3% or more, and considering whether changes were intentional or unintentional) were estimated using multivariable polytomous logistic regressions and multilevel models.

RESULTS

Adiposity gain was prevalent: 28% and 47% gained weight and body fat, respectively, despite a high baseline prevalence of overweight or obesity (86%). Risk factors for fat mass gain included receiving chemotherapy (relative risk ratio: 1.59, 95% CI, 1.08 to 2.33) and residing in neighborhoods with a greater density of fast-food restaurants (relative risk ratio comparing highest with lowest tertile: 2.18, 95% CI, 1.38 to 3.46); findings were similar for weight gain. Only 9% of women had intentional weight loss, and multilevel risk factors differed vastly from unintentional loss.

CONCLUSION

Both individual and neighborhood factors were associated with adiposity change among Black breast cancer survivors. Residential environment characteristics may offer clinically meaningful information to identify cancer survivors at higher risk for unfavorable weight change and to address barriers to postdiagnosis weight management.
Coupling-induced periodic windows in networked discrete-time systems
Authors: Hallier Leonard , Medeiros Everton S. , Mihara Antonio , Medrano-T Rene O. , Zakharova Anna
Published: March 2022

Networked nonlinear systems present a variety of emergent phenomena as a result of the mutual interactions between their units. An interesting feature of these systems is the presence of stable periodic behavior even when each unit oscillates chaotically if in isolation. Surprisingly, the mechanism in which the network interaction replaces chaos by periodicity is still poorly understood. Here, we show that such an onset of regularity can occur via replication of periodic windows. This phenomenon multiplies the stability domains in the system parameter space, not only suppressing chaos but also making the network less vulnerable to external disturbances such as shocks and noise. Moreover, we observe that the network cluster synchronizes for the parameters corresponding to the replica periodic windows. To confirm these observations, we employ the formalism of the master stability function demonstrating that the complete synchronized state is indeed transversally unstable in the replica windows.
Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans
Authors: Hoskova Katerina , Kayton Bryant Nora , Chen Margaret E , Nachtigall Lisa B , Lippincott Margaret F , Balasubramanian Ravikumar , Seminara Stephanie B
Published: March 2022

Context

Hyperprolactinemia suppresses gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) pulses. The hypothalamic neuropeptide kisspeptin potently stimulates the secretion of GnRH. The effects of exogenous kisspeptin administration on GnRH pulse generation in the setting of hyperprolactinemia have not previously been explored.

Objective

This work aimed to examine the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in women with hyperprolactinemia.

Methods

Women with hyperprolactinemia (n = 11) participated in two 12-hour visits. Before study visits, participants underwent washout of dopamine agonist and/or combined oral contraceptive. Frequent blood sampling was performed (1 sample was collected every 10 minutes). Visit 1 involved no intervention, to examine baseline LH pulsatility. During visit 2, kisspeptin 112–121 (0.24 nmol/kg) was administered every 1 hour, for 10 hours. At hour 11, one intravenous bolus of GnRH (75 ng/kg) was administered.

Results

Repetitive intravenous bolus kisspeptin administration increased the total number of LH pulses in the setting of hyperprolactinemia. The interpulse interval declined during the same time frames. LH pulse amplitude did not change, but the mean LH rose. In 6 participants with progesterone levels suggestive of an anovulatory state, mean LH and estradiol levels increased significantly at visit 2. In the entire cohort, follicle-stimulating hormone and prolactin levels did not change significantly across the 2 visits. A total of 73% of subjects exhibited an LH pulse within 30 minutes of first kisspeptin dose.

Conclusion

Kisspeptin is capable of stimulating hypothalamic GnRH-induced LH pulses in the setting of hyperprolactinemia.