bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade
Authors: Rampa Dileep Reddy , Murugesan Priya , Chao Honglu , Feng Huiying , Dai Wenxin , Lee Dongwon , Pekcec Anton , Doods Henri , Wu Dongmei
Published: October 2021

Background

This study examined whether BI113823, a novel selective kinin B1 receptor antagonist can reverse established pulmonary arterial hypertension (PAH), prevent right heart failure and death, which is critical for clinical translation.

Methods

Left pneumonectomized male Wistar rats were injected with monocrotaline to induce PAH. Three weeks later, when PAH was well established, the rats received daily treatment of BI113823 or vehicle for 3 weeks.

Results

Treatment with BI113823 from day 21 to day 42 after monocrotaline injection reversed established PAH as shown by normalized values of mean pulmonary arterial pressure (mPAP). BI113823 therapy reversed pulmonary vascular remodeling, pulmonary arterial neointimal formation, and heart and lung fibrosis, reduced right ventricular pressure, right heart hypertrophy, improved cardiac output, and prevented right heart failure and death. Treatment with BI113823 reduced TNF-α and IL-1β, and macrophages recruitment in bronchoalveolar lavage, reduced CD-68 positive macrophages and expression of proliferating cell nuclear antigen (PCNA) in the perivascular areas, and reduced expression of iNOS, B1 receptors, matrix metalloproteinase (MMP)-2 and MMP-9 proteins, and the phosphorylation of ERK1/2 and AKT in lung. Treatment with BI113823 reduced mRNA expression of ANP, BNP, βMHC, CGTF, collange-I and IV in right heart, compared to vehicle treated controls. In human monocytes cultures, BI113823 reduced LPS-induced TNF-α production, MMP-2 and MMP-9 expression, and reduced TNF-α-induced monocyte migration.

Conclusions

We conclude that BI113823 reverses preexisting severe experimental pulmonary hypertension via inhibition of macrophage infiltration, cytokine production, as well as down regulation of matrix metalloproteinase proteins.
Improving CoQ10 productivity by strengthening glucose transmembrane of Rhodobacter sphaeroides
Authors: Yang Yuying , Li Lu , Sun Haoyu , Li Zhen , Qi Zhengliang , Liu Xinli
Published: October 2021

Background

Several Rhodobacter sphaeroides have been widely applied in commercial CoQ10 production, but they have poor glucose use. Strategies for enhancing glucose use have been widely exploited in R. sphaeroides. Nevertheless, little research has focused on the role of glucose transmembrane in the improvement of production.

Results

There are two potential glucose transmembrane pathways in R. sphaeroides ATCC 17023: the fructose specific-phosphotransferase system (PTSFru, fruAB) and non-PTS that relied on glucokinase (glk). fruAB mutation revealed two effects on bacterial growth: inhibition at the early cultivation phase (12–24 h) and promotion since 36 h. Glucose metabolism showed a corresponding change in characteristic vs. the growth. For ΔfruAΔfruB, maximum biomass (Biomax) was increased by 44.39% and the CoQ10 content was 27.08% more than that of the WT. glk mutation caused a significant decrease in growth and glucose metabolism. Over-expressing a galactose:H+ symporter (galP) in the ΔfruAΔfruB relieved the inhibition and enhanced the growth further. Finally, a mutant with rapid growth and high CoQ10 titer was constructed (ΔfruAΔfruB/tac::galPOP) using several glucose metabolism modifications and was verified by fermentation in 1 L fermenters.

Conclusions

The PTSFru mutation revealed two effects on bacterial growth: inhibition at the early cultivation phase and promotion later. Additionally, biomass yield to glucose (Yb/glc) and CoQ10 synthesis can be promoted using fruAB mutation, and glk plays a key role in glucose metabolism. Strengthening glucose transmembrane via non-PTS improves the productivity of CoQ10 fermentation.
Kaposi’s sarcoma-associated herpesvirus infection promotes proliferation of SH-SY5Y cells by the Notch signaling pathway
Authors: Cao Dongdong , Wu Shuyuan , Wang Xiaolu , Li Ying , Xu Huiling , Pan Zemin , Wu Zhaofu , Yang Lei , Tan Xiaohua , Li Dongmei
Published: October 2021

Background

The cancer caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection is one of the major causes of death in AIDS patients. Some patients have neurological symptoms, which appear to be associated with KSHV infection, based on the neurotropic tendency of this virus in recent years. The objectives of this study were to investigate the effects of KSHV infection on neuronal SH-SY5Y cells and to identify differentially expressed genes.

Methods

KSHV was collected from islk.219 cells. Real-time PCR was used to quantify KSHV copy numbers. KSHV was used to infect SH-SY5Y cells. The KSHV copy number in the supernatants and mRNA levels of latency-associated nuclear antigen (LANA), ORF26, K8.1 A, and replication and transcriptional activator (RTA) were detected by real-time PCR. Proteins were detected by immunohistochemistry. The effect of KSHV infection on cell proliferation was detected by MTT and Ki-67 staining. Cell migration was evaluated by Transwell and wound healing assays. The cell cycle was analyzed by flow cytometry. The expression of CDK4, CDK5, CDK6, cyclin D1, and p27 were measured by western blotting. The levels of cell cycle proteins were re-examined in LANA-overexpressing SH-SY5Y cells. Transcriptome sequencing was used to identify differentially expressed genes in KSHV-infected cells. The levels of Notch signaling pathway proteins were measured by western blotting. RNA interference was used to silence Notch1 and proliferation were analyzed again.

Results

SH-SY5Y cells were successfully infected with KSHV, and they maintained the ability to produce virions. KSHV-infected SH-SY5Y expressed LANA, ORF26, K8.1 A, and RTA. After KSHV infection, cell proliferation was enhanced, but cell migration was suppressed. KSHV infection accelerated the G0/G1 phase. CDK4, CDK5, CDK6, and cyclin D1 expression was increased, whereas p27 expression was decreased. After LANA overexpression, CDK4, CDK6 and cyclin D1 expression was increased. Transcriptome sequencing showed that 11,258 genes were upregulated and 1,967 genes were downregulated in KSHV-infected SH-SY5Y. The Notch signaling pathway played a role in KSHV infection in SH-SY5Y, and western blots confirmed that Notch1, NICD, RBP-Jĸ and Hes1 expression was increased. After silencing of Notch1, the related proteins and cell proliferation ability were decreased.

Conclusions

KSHV infected SH-SY5Y cells and promoted the cell proliferation. KSHV infection increased the expression of Notch signaling pathway proteins, which may have been associated with the enhanced cell proliferation.
Effects of indoor air movement and ambient temperature on mosquito (Anopheles gambiae) behaviour around bed nets: implications for malaria prevention initiatives
Authors: Sutcliffe James F. , Yin Shaoman
Published: October 2021

Background

Until recently, relatively little research has been done on how mosquitoes behave around the occupied bed net in the indoor environment. This has been partly remedied in the last few years through laboratory and field studies, most of these using video methods and mosquito flight tracking. Despite these recent advances, understanding of the mosquito-bed net environment system, and the principles that underlie mosquito behaviour within it, is limited. This project aimed to further understand this system by studying the effects of gently moving air (such as might be introduced through room design to make the indoor environment more comfortable and conducive to ITN use) and warmer vs. cooler ambient conditions on mosquito activity around ITNs and other bed nets.

Methods

The activity of colonized femaleAnopheles gambiaearound an occupied untreated bed net set up in a mosquito-proof tent in a large laboratory space was recorded under different ambient conditions using a laser detection-video recording system. Conditions tested were ‘cool’ (23–25 °C) and ‘warm’ (27–30 °C) air temperatures and the presence or absence of a cross-flow produced by a small central processing unit (CPU) fan pointed at the side of the net so that it produced a ‘low-’ or ‘high-’ speed cross-draught (approx. 0.1 and 0.4 m/s, respectively). Near-net activity in recordings was measured using video image analysis.

Results

In cool, still air conditions, more than 80% of near-net activity byAn. gambiaeoccurred on the net roof. Introduction of the low-speed or high-speed cross-draught resulted in an almost total drop off in roof activity within 1 to 2 min and, in the case of the high-speed cross-draught, a complementary increase in activity on the net side. In warm, still conditions, near-net activity appeared to be lower overall than in cool, still air conditions and to be relatively less focussed on the roof. Introduction of the high-speed cross-draught in warm conditions resulted in a decrease in roof activity and increase in side activity though neither effect was statistically significant.

Conclusions

Results are interpreted in terms of the flow of the stimulatory odour plume produced by the net occupant which, consistent with established principles of fluid dynamics, appears to rise quickly and remain more intact above the net occupant in cool, still air than in warm, still air. Cross-draught effects are ascribed to the changes they cause in the flow of the host odour plume as opposed to mosquito flight directly. The implications of these results for house designs that promote indoor air movement, on bed net design, and on other vector control measures are discussed. How mosquitoes approach a net is influenced both by indoor temperature and ventilation and their interaction. This system is in need of further study.
Should commercial sex workers have unrestricted healthcare access across the world?
Authors: Taylor-Robinson Simon D. , De Souza Lopes Paulo A. , Zdravkov Jey , Harrison Rachel
Published: October 2021

We argue commercial sex workers have rights to healthcare and psychosocial support. While decriminalization is not legally enacted in most countries, we would suggest these workers rights include freedom from harassment and opportunities to lead healthy lives. The need for healthcare access for all is heightened in the COVID-19 pandemic where some people flout rules on lockdown by engaging with commercial sex workers and may unwittingly spread SARS-CoV-2 in so doing. Unrestricted healthcare access without stigma for commercial sex workers protects them, and has a beneficial societal effect on those who engage with them and on their contacts.
A scoping review on disparities in exposure to advertising for e-cigarettes and heated tobacco products and implications for advancing a health equity research agenda
Authors: Grilo Graziele , Crespi Elizabeth , Cohen Joanna E.
Published: October 2021

Background

Disparities in exposure to and density of tobacco advertising are well established; however, it is still unclear how e-cigarette and heated tobacco product (HTP) advertising vary by age, education, sex, gender identity, race/ethnicity, sexual orientation, socioeconomic status (SES), and/or urban/rural area. Through a scoping review, we sought to identify potential disparities in exposure to e-cigarette and HTP advertising and promotion across populations.

Methods

In January 2020, a systematic literature search was conducted in five databases: PubMed, Scopus, Embase, Web of Science, and the Cochrane Library. The search was updated in October 2020. Articles reporting on exposure to e-cigarette and/or HTP advertising and promotion across age, education, sex, gender identity, race/ethnicity, sexual orientation, SES, and/or urban/rural areas were included for full-text review (n = 25). Of those, 15 were deemed relevant for data extraction.

Results

The majority of the studies were from the U.S. (n = 12) and cross-sectional (n = 14). Studies were published between 2014 and 2020 and focused on determining causal relationships that underlie disparities; only one study assessed HTP advertising and promotion. Exposure to e-cigarette and HTP advertising was assessed at the individual-level (e.g., recall seeing ads on television) and at the neighborhood-level (e.g., ad density at the point-of-sale). Studies addressed differences across age (n = 6), education (n = 2), sex (n = 6), gender identity and sexual orientation (n = 3), race/ethnicity (n = 11), SES (n = 5), and urban/rural (n = 2). The following populations were more likely to be exposed to e-cigarette advertising: youth, those with more than a high school diploma, males, sexual and gender minorities, Whites, and urban residents. At the neighborhood-level, e-cigarette advertisements were more prevalent in non-White neighborhoods.

Conclusions

Exposure to e-cigarette/HTP advertising varies based on sociodemographic characteristics, although the literature is limited especially regarding HTPs. Higher exposure among youth might increase tobacco-related disparities since it can lead to nicotine/tobacco use. Research should incorporate and apply a health equity lens from its inception to obtain data to inform the elimination of those disparities.
Decreased plasma lipid levels in a statin-free Danish primary health care cohort between 2001 and 2018
Authors: Engell Anna E. , Jørgensen Henrik L. , Lind Bent S. , Pottegård Anton , Andersen Christen L. , Andersen John S. , Kriegbaum Margit , Grand Mia K. , Bathum Lise
Published: October 2021

Background

Lipid levels in blood have decreased considerably during the past decades in the general population partly due to use of statins. This study aims to investigate the trends in lipid levels between 2001 and 2018 in a statin-free population from primary health care, overall and by sex and age.

Methods

In a cohort of 634,119 patients from general practice with no diagnoses or medical treatments that affected lipid levels of total cholesterol (TC; n = 1,574,339) between 2001 and 2018 were identified. Similarly, measurements of low-density lipoprotein cholesterol (LDL-C; n = 1,302,440), high-density lipoprotein cholesterol (HDL-C; n = 1,417,857) and triglycerides (TG; n = 1,329,477) were identified.

Results

Mean TC decreased from 5.64 mmol/L (95% CI: 5.63–5.65) in 2001 to 5.17 mmol/L (95% CI: 5.16–5.17) in 2018 while LDL-C decreased from 3.67 mmol/L (95% CI: 3.66–3.68) to 3.04 mmol/L (95% CI: 3.03–3.04). Women aged 70–74 years experienced the largest decreases in TC levels corresponding to a decrease of 0.7 mmol/L. The decrease in LDL-C levels was most pronounced in men ≥85 years with a decrease of 0.9 mmol/L. For both genders, TC and LDL-C levels increased with advancing age until around age 50. After menopause the women had higher TC and LDL-C levels than the men. The median (geometric mean) TG level decreased by 0.4 mmol/L from 2001 to 2008, after which it increased slightly by 0.1 mmol/L until 2018. During life the TG levels of the men were markedly higher than the women’s until around age 65–70. HDL-C levels showed no trend during the study period.

Conclusions

The levels of TC and LDL-C decreased considerably in a statin-free population from primary health care from 2001 to 2018. These decreases were most pronounced in the elderly population and this trend is not decelerating. For TG, levels have started to increase, after an initial decrease.
Effects of dyslipidemia on E antigen seroconversion of patients with chronic hepatitis B treated by nucleoside (acid) analogs
Authors: Xia Ziqiang , Zheng Juzeng , Zheng Liang , Zheng Endian , Zou Zhuolin , Sheng Xiong , Wu Jinming
Published: October 2021

Background

The prevalence of dyslipidemia in China is increasing annually. Current studies suggest that dyslipidemia affects the antiviral efficacy of hepatitis C virus (HCV) therapies, while recent studies suggest that serum lipids influence the response rates of chronic hepatitis B (CHB) patients receiving PEGylated interferon-alpha (Peg IFN-α) treatment. However, the role of dyslipidemia in the efficacy of nucleoside (acid) analogues (NAs) in CHB patients remains unclear.

Methods

From January 2010 to December 2013, data from 179 treatment-naive patients with CHB who were hepatitis B e antigen (HBeAg)-positive and had visited the first affiliated hospital of Wenzhou Medical University were assessed. Of these patients, 68 were assigned to the dyslipidemia group (diagnosed with CHB complicated with dyslipidemia) and 111 to the normolipidemic group. The following 3 treatment strategies were performed for all CHB patients over a 5-year period: lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy, telbivudine (LdT) monotherapy, and entecavir (ETV) monotherapy. Serum assessments, blood biochemistry, HBV serological markers, HBV DNA before treatment and HBeAg serological conversion and virological responses at different timepoints after treatment were compared between the two groups. Measurement data were compared by τ tests and enumeration data by χ2 tests. Correlation analysis was performed using binary logistic regression analysis.

Results

The rates of HBeAg seroconversion in the dyslipidemia group at years 1, 2, 3, and 4 were 10.3, 13.2, 17.6, and 22.1%, respectively, which were not significantly lower than those of the normolipidemic group (11.7, 16.2, 18.0 and 33.3%; χ2 = 0.085, 0.293, 0.004, and 2.601, respectively; Ρ > 0.05). However, the rates of HBeAg seroconversion in the dyslipidemia group were significantly lower than those in the normolipidemic group at year 5 (27.9% vs. 43.2%, χ2 = 4.216, Ρ < 0.05). Univariate logistic regression analysis revealed significant differences in group, gender, PTA, ALT, AST, CR, and LDL-C between groups with and without seroconversion. Multivariate regression analysis demonstrated that dyslipidemia (OR = 1.993, Ρ = 0.038) and male gender (OR = 2.317, Ρ = 0.029) were risk factors associated with HBeAg seroconversion.

Conclusions

During antiviral therapy, dyslipidemia affects HBeAg seroconversion in CHB patients treated with NAs, but does not affect the virological response.
In vivo performance of electrospun tubular hyaluronic acid/collagen nanofibrous scaffolds for vascular reconstruction in the rabbit model
Authors: Niu Yuqing , Galluzzi Massimiliano , Fu Ming , Hu Jinhua , Xia Huimin
Published: October 2021

One of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction.

Graphical Abstract
Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing
Authors: Ao Mingtao , Yu Fei , Li Yixiang , Zhong Mengya , Tang Yonghe , Yang Hua , Wu Xiaojing , Zhuang Yifan , Wang Huiyun , Sun Xiaolian , Hong Xuehui , Chen Xiao Dong
Published: October 2021

Background

Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive.

Results

In this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug–drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy.

Conclusion

A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system.

Graphical Abstract
Predicting the impact of placing an overdose prevention site in Philadelphia: a mathematical modeling approach
Authors: Wares Joanna R. , Dong Jing , Gevertz Jana L. , Radunskaya Ami , Viner Kendra , Wiebe Doug , Solomon Sara
Published: October 2021

Background

Fatal overdoses from opioid use and substance disorders are increasing at an alarming rate. One proposed harm reduction strategy for reducing overdose fatalities is to place overdose prevention sites—commonly known as safe injection facilities—in proximity of locations with the highest rates of overdose. As urban centers in the USA are tackling legal hurdles and community skepticism around the introduction and location of these sites, it becomes increasingly important to assess the magnitude of the effect that these services might have on public health.

Methods

We developed a mathematical model to describe the movement of people who used opioids to an overdose prevention site in order to understand the impact that the facility would have on overdoses, fatalities, and user education and treatment/recovery. The discrete-time, stochastic model is able to describe a range of user behaviors, including the effects from how far they need to travel to the site. We calibrated the model to overdose data from Philadelphia and ran simulations to describe the effect of placing a site in the Kensington neighborhood.

Results

In Philadelphia, which has a non-uniform racial population distribution, choice of site placement can determine which demographic groups are most helped. In our simulations, placement of the site in the Kensington neighborhood resulted in White opioid users being more likely to benefit from the site’s services. Overdoses that occur onsite can be reversed. Our results predict that for every 30 stations in the overdose prevention site, 6 per year of these would have resulted in fatalities if they had occurred outside of the overdose prevention site. Additionally, we estimate that fatalities will decrease further when referrals from the OPS to treatment are considered.

Conclusions

Mathematical modeling was used to predict the impact of placing an overdose prevention site in the Kensington neighborhood of Philadelphia. To fully understand the impact of site placement, both direct and indirect effects must be included in the analysis. Introducing more than one site and distributing sites equally across neighborhoods with different racial and demographic characteristics would have the broadest public health impact. Cities and locales can use mathematical modeling to help quantify the predicted impact of placing an overdose prevention site in a particular location.
Challenges encountered in comparing international policy responses to COVID-19 and their effects
Authors: Riley Christine , Xie Bo , Khurshid Anjum
Published: October 2021

Background

A variety of policies have been implemented around the world in response to the COVID-19 pandemic. This study originally aimed to identify and compare policy responses of different countries and their effects on the pandemic. It quickly evolved into an identification of the heterogeneity among existing policies and the challenges in making meaningful comparisons of the impact of these policies.

Methods

The process of collecting and comparing data from different sources was analysed through inductive thematic analysis to understand the obstacles that impede research designed to compare COVID-19 data and related policies.

Results

We identified the following obstacles: (1) no single reputable source of information and too much noise; (2) a lack of standards for how to measure and report data across countries; (3) variations in the content, implementation and enforcement of policies; and (4) politics, instead of science, leading the efforts in pandemic management.

Conclusion

Heterogeneity in existing policies makes it challenging to compare the effects of various policies worldwide on the COVID-19 pandemic. Our findings call for an automatically updated informatics infrastructure across the globe for collecting and maintaining standardized data from multiple sources. There is a strong need for steadfast utilization of scientific and technical experts to inform and influence health policy. Increased investment in public health and emergency planning is essential to overcome the current pandemic, as well as future public health emergencies. Focused leadership and collaboration from world leaders in a unified mission to decrease the mortality and morbidity of the COVID-19 pandemic is imperative.
Combined cART including Tenofovir Disoproxil, Emtricitabine, and Dolutegravir has potent therapeutic effects in HIV-1 infected humanized mice
Authors: Weichseldorfer Matthew , Affram Yvonne , Heredia Alonso , Rikhtegaran-Tehrani Zahra , Sajadi Mohammad M. , Williams Sumiko P. , Tagaya Yutaka , Benedetti Francesca , Ramadhani Habib O. , Denaro Frank , Munawwar Arshi , Bryant Joseph , Zella Davide , Reitz Marvin , Romerio Fabio , Latinovic Olga S.
Published: October 2021

HIV-1 reservoirs persist in the presence of combined antiretroviral therapy (cART). However, cART has transformed HIV-1 infection into a chronic disease marked by control of HIV-1 viral load and mortality reduction. Major challenges remain, including viral resistance upon termination of cART and persistence and identification of tissue distribution of HIV-1 reservoirs. Thus, appropriate animal models that best mimic HIV-1 pathogenesis are important, and the current study complements our previously published validation of the CD34+ hematopoietic humanized mouse model for this purpose. Here we analyze viral suppression using the recently developed combination of antiretrovirals that include Tenofovir Disoproxil (TDF), Emtricitabine (FTC), and Dolutegravir (DTG), a choice based on recent clinical outcomes showing its improved antiretroviral potency, CD4+ T cell preservation, tolerability, and prevention of viral drug resistance compared to that of previous regimens. We used quantitative Airyscan-based super resolution confocal microscopy of selected mouse tissues. Our data allowed us to identify specific solid tissue reservoirs of human T cells expressing the HIV-1 core protein p24. In particular, lymph node, brain, spleen, and liver were visualized as reservoirs for residual infected cells. Marked reduction of viral replication was evident. Considering that detection and visualization of cryptic sites of HIV-1 infection in tissues are clearly crucial steps towards HIV-1 eradication, appropriate animal models with pseudo-human immune systems are needed. In fact, current studies with humans and non-human primates have limited sample availability at multiple stages of infection and cannot easily analyze the effects of differently administered combined antiretroviral treatments on multiple tissues. That is easier to manage when working with humanized mouse models, although we realize the limitations due to low human cell recovery and thus the number of cells available for thorough and comprehensive analyses. Nonetheless, our data further confirm that the CD34+ humanized mouse model is a potentially useful pre-clinical model to study and improve current anti-HIV-1 therapies.
A case report of a severe neonatal systemic vasculitis on the first day of life
Authors: Wong Stephanie , Demirkaya Erkan , Berard Roberta
Published: October 2021

Background

Neonatal systemic vasculitis syndromes have been reported in infants born to mothers with systemic lupus erythematosus, Sjögren’s syndrome, Behҫet’s disease, cutaneous polyarteritis nodosa and anti-neutrophil cytoplasmic antibody-associated vasculitides. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate.

Case presentation

In the first 24 h of life, a preterm Caucasian baby boy was noted to have blue discoloration to all four extremities. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Intravenous immunoglobulin (IVIG) was given with short-term improvement. Initial echocardiogram showed enlarged coronary arteries with normalization on repeat 1 week later. Clinical signs and symptoms responded to high dose oral steroid administration. MRI angiography (MRA) of the body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred.

He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. This was presumed a reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy.

The mother was weaned off prednisone, treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development.

Conclusion

This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.
Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Authors: Cui Yu , Zhang Zhaolong , Zhou Xin , Zhao Zhiyuan , Zhao Rui , Xu Xiangyu , Kong Xiangyi , Ren Jinyang , Yao Xujin , Wen Qian , Guo Feifei , Gao Shengli , Sun Jiangdong , Wan Qi
Published: October 2021

Abstracts

Background

Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis.

Methods

Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions.

Results

We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions.

Conclusions

These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.
T-cell dysregulation is associated with disease severity in Parkinson’s Disease
Authors: Bhatia Divisha , Grozdanov Veselin , Ruf Wolfgang P. , Kassubek Jan , Ludolph Albert C. , Weishaupt Jochen H. , Danzer Karin M.
Published: October 2021

The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemagglutinin that also correlated with disease severity. In summary, our data suggest that the consequences of disease severity account for the changes in PD T cells, rather than age, age of onset, duration or the disease progression rate.
Comparability of family planning quality of care measurement tools in low-and-middle income country settings: a systematic review
Authors: Hazel Elizabeth , Mohan Diwakar , Gross Margaret , Kattinakere Sreedhara Sushama , Shrestha Prakriti , Johnstone Maia , Marx Melissa
Published: October 2021

Background

In low-and-middle income countries (LMICs), accurate measures of the elements of quality care provided by a health worker through family planning services (also known as process quality) are required to ensure family’s contraceptives needs are being met. There are many tools used to assess family planning process quality of care (QoC) but no one standardized method. Those measuring QoC in LMICs should select an appropriate tool based the program context and financial/logistical parameters, but they require data on how well each tool measures routine clinical care. We aim to synthesize the literature on validity/comparability of family planning process QoC measurement tools through a quantitative systematic review with no meta-analysis.

Methods

We searched six literature databases for studies that compared quality measurements from different tools using quantitative statistics such as sensitivity/specificity, kappa statistic or absolute difference. We extracted the comparative measure along with other relevant study information, organized by quality indicator domain (e.g. counseling and privacy), and then classified the measure by low, medium, and high agreement.

Results

We screened 8172 articles and identified eight for analysis. Studies comparing quality measurements from simulated clients, direct observation, client exit interview, provider knowledge quizzes, and medical record review were included. These eight studies were heterogenous in their methods and the measurements compared. There was insufficient data to estimate overall summary measures of validity for the tools. Client exit interviews compared to direct observation or simulated client protocols had the most data and they were a poor proxy of the actual quality care received for many measurements.

Conclusion

To measure QoC consistently and accurately in LMICs, standardized tools and measures are needed along with an established method of combining them for a comprehensive picture of quality care. Data on how different tools proxy quality client care will inform these guidelines. Despite the small number of studies found during the review, we described important differences on how tools measure quality of care.
Decomposing the urban–rural inequalities in the utilisation of maternal health care services: evidence from 27 selected countries in Sub-Saharan Africa
Authors: Samuel Oduse , Zewotir Temesgen , North Delia
Published: October 2021

Background

There has been a substantial improvement in reducing maternal mortality in the Sub-Saharan African region. The vast rural-urban gap in maternal health outcomes, however, is obscured by this average achievement. This study attempts to measure the contribution of identified risk factors to describe the average rural-urban difference in the use of antenatal care, health facilities for delivery, and health professional assistance at delivery.

Method

To achieve this objective, we used descriptive analysis and Fairlie non-linear decomposition method to quantify covariates’ contribution in explaining the urban–rural difference in maternal healthcare services utilisation.

Result

The study’s finding shows much difference between urban and rural areas in the use of maternal healthcare services. Socio-economic factors such as household wealth index, exposure to media, and educational level of women and their husbands/partners contributed the most in explaining the gap between urban and rural areas in healthcare services utilisation.

Conclusions

Interventions to bridge the gap between urban and rural areas in maternal healthcare services utilisation in Sub-Saharan Africa should be centred towards socio-economic empowerment. Government can enforce targeted awareness campaigns to encourage women in rural communities in Sub-Sharan Africa to take the opportunity and use the available maternal health care services to be at par with their counterparts in urban areas.
Human cytomegalovirus inhibits the proliferation and invasion of extravillous cytotrophoblasts via Hippo-YAP pathway
Authors: Kong Qiaoqiao , Li Jing , Zhao Li , Shi Peng , Liu Xiaobei , Bian Cailing , Liu Jing , Liu Tao
Published: October 2021

Background

Human cytomegalovirus (HCMV) infection in utero is very common during pregnancy, which can lead to adverse outcomes in both pregnancy and progeny, but its pathogenesis has not been fully clarified. The decrease of extravillous cytotrophoblasts (EVT) invasion is an essential pathophysiological process of some pregnancy complications. Hippo-YAP signaling pathway plays an important role in regulating cell proliferation and apoptosis. However, whether YAP is involved in HCMV uterine infection remains to be studied.

Methods

The primary EVT was cultured and infected by the HCMV strain AD169 virus in vitro. Immunofluorescence staining of HCMVpp65 antigen was conducted afterward to confirm the establishment of an infection model. The optimal virus infection dose was determined by the EVT proliferation status in vitro. Real-time PCR was performed to examine the mRNA level of major genes involved in the Hippo pathway in EVT after HCMV infection. The effect of HCMV on the expression of YAP protein in EVT was evaluated by Immunofluorescence staining and Western blot. An in vitro cell invasion assay was carried out to analyze the influence of HCMV on EVT invasion. The changes of EVT invasion was accessed by establishing YAP silencing and over-expression models using YAP1 specific siRNA and plasmid pcDH.

Results

The optimal HCMV infection dose was 282.5TCID50/ml. Compared to the control group, the infection of HCMV significantly reduced the mRNA expression of Mst1, Mst2, SAV, Lats1, Lats2, Mob1, YAP1, TAZ, TEAD1-4 genes and YAP protein expression in the Hippo-YAP pathway. HCMV infection also decreased the EVT invasion. In non-infected EVT, the number of transmembrane EVT cells was significantly reduced when YAP1 gene was silenced, while it was significantly increased when YAP1 gene was over-expressed. In the HCMV-infected EVT, the number of transmembrane EVT cells significantly increased when over-expressed and eventually recovered to the level of NC.

Conclusions

HCMV may decrease EVT invasion by inhibiting the expression of mRNA and protein of YAP in the Hippo-YAP signaling pathway. HCMV eventually reduces the invasion ability of EVT by inhibiting multiple genes in the Hippo-YAP signaling pathway, especially inhibiting YAP which serves as the downstream effector.
Dietary curcumin supplementation promotes browning and energy expenditure in postnatal overfed rats
Authors: Zhu Xiaolei , Du Susu , Yan Qinhui , Min Cuiting , Zhou Nan , Zhou Wei , Li Xiaonan
Published: October 2021

Background

Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats.

Methods and results

This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.

Conclusion

Dietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.
Prevalence of exclusive breastfeeding practice and its association with maternal employment in Ethiopia: a systematic review and meta-analysis
Authors: Wake Getu Engida , Mittiku Yohannes Moges
Published: October 2021

Background

Exclusive breastfeeding is defined as the practice of providing only breast milk for an infant for the first 6 months of life without the addition of any other food or water, except for vitamins, mineral supplements, and medicines. Findings are inconsistent regarding the prevalence of exclusive breastfeeding in Ethiopia. Full-time maternal employment is an important factor contributing to the low rates of practice of exclusive breastfeeding. Empowering women to exclusively breastfeed, by enacting 6 months’ mandatory paid maternity leave can increase the rate of exclusive breastfeeding in the first 6 months of life up to 50%. The purpose of this review was to estimate the pooled prevalence of exclusive breastfeeding and its association with full-time maternal employment in the first 6 months of life for infants in the context of Ethiopia.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in this systematic review and meta-analysis. All observational studies reporting the prevalence of exclusive breastfeeding and its association with maternal employment in Ethiopia were considered. The search was conducted from 6 November 2020 to 31 December 2020 and all papers published in the English language from 1 January 2015 to 31 December 2020 were included in this review.

Results

Forty-five studies were included in the final analysis after reviewing 751 studies in this meta-analysis yielding the pooled prevalence of EBF 60.42% (95% CI 55.81, 65.02) at 6 months in Ethiopia. Those full-time employed mothers in the first 6 months were 57% less likely to practice exclusive breastfeeding in comparison to mothers not in paid employment in Ethiopia (OR 0.43; 95% CI 0.31, 0.61).

Conclusions

Full-time maternal employment was negatively associated with the practice of exclusive breastfeeding in comparison to unemployed mothers. The prevalence of exclusive breastfeeding in Ethiopia is low in comparison to the global recommendation. The Ethiopian government should implement policies that empower women. The governmental and non-governmental organizations should create a conducive environment for mothers to practice exclusive breastfeeding in the workplace.