bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic small extracellular vesicles promote microvascular endothelial hyperpermeability during NAFLD via novel-miRNA-7
Authors: Zuo Rui , Ye Li-Feng , Huang Yi , Song Zi-Qing , Wang Lei , Zhi Hui , Zhang Min-Yi , Li Jie-Yi , Zhu Li , Xiao Wen-Jing , Shang Hong-Cai , Zhang Yang , He Rong-Rong , Chen Yang
Published: November 2021

Background

A recent study has reported that patients with nonalcoholic fatty liver disease (NAFLD) are more susceptible to coronary microvascular dysfunction (CMD), which may predict major adverse cardiac events. However, little is known regarding the causes of CMD during NAFLD. In this study, we aimed to explore the role of hepatic small extracellular vesicles (sEVs) in regulating the endothelial dysfunction of coronary microvessels during NAFLD.

Results

We established two murine NAFLD models by feeding mice a methionine-choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 16 weeks. We found that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent endothelial hyperpermeability occurred in coronary microvessels during both MCD diet and HFD-induced NAFLD. The in vivo and in vitro experiments proved that novel-microRNA(miR)-7-abundant hepatic sEVs were responsible for NLRP3 inflammasome-dependent endothelial barrier dysfunction. Mechanistically, novel-miR-7 directly targeted lysosomal associated membrane protein 1 (LAMP1) and promotes lysosomal membrane permeability (LMP), which in turn induced Cathepsin B-dependent NLRP3 inflammasome activation and microvascular endothelial hyperpermeability. Conversely, a specific novel-miR-7 inhibitor markedly improved endothelial barrier integrity. Finally, we proved that steatotic hepatocyte was a significant source of novel-miR-7-contained hepatic sEVs, and steatotic hepatocyte-derived sEVs were able to promote NLRP3 inflammasome-dependent microvascular endothelial hyperpermeability through novel-miR-7.

Conclusions

Hepatic sEVs contribute to endothelial hyperpermeability in coronary microvessels by delivering novel-miR-7 and targeting the LAMP1/Cathepsin B/NLRP3 inflammasome axis during NAFLD. Our study brings new insights into the liver-to-microvessel cross-talk and may provide a new diagnostic biomarker and treatment target for microvascular complications of NAFLD.

Graphical Abstract
M2 macrophage microvesicle-inspired nanovehicles improve accessibility to cancer cells and cancer stem cells in tumors
Authors: Wang Yuqi , Gong Xiang , Li Jie , Wang Hong , Xu Xiaoxuan , Wu Yao , Wang Jiaoying , Wang Siling , Li Yaping , Zhang Zhiwen
Published: November 2021

Cancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy.

Graphical Abstract
Association between supportive supervision and performance of community health workers in India: a longitudinal multi-level analysis
Authors: Gopalakrishnan Lakshmi , Diamond-Smith Nadia , Avula Rasmi , Menon Purnima , Fernald Lia , Walker Dilys , Patil Sumeet
Published: November 2021

Introduction

Community health workers (CHWs) deliver services at-scale to reduce maternal and child undernutrition, but often face inadequate support from the health system to perform their job well. Supportive supervision is a promising intervention that strengthens the health system and can enable CHWs to offer quality services.

Objectives

We examined if greater intensity of supportive supervision as defined by monitoring visits to Anganwadi Centre, CHW-supervisor meetings, and training provided by supervisors to CHWs in the context of Integrated Child Services Development (ICDS), a national nutrition program in India, is associated with higher performance of CHWs. Per program guidelines, we develop the performance of CHWs measure by using an additive score of nutrition services delivered by CHWs. We also tested to see if supportive supervision is indirectly associated with CHW performance through CHW knowledge.

Methods

We used longitudinal survey data of CHWs from an impact evaluation of an at-scale technology intervention in Madhya Pradesh and Bihar. Since the inception of ICDS, CHWs have received supportive supervision from their supervisors to provide services in the communities they serve. Mixed-effects logistic regression models were used to test if higher intensity supportive supervision was associated with improved CHW performance. The model included district fixed effects and random intercepts for the sectors to which supervisors belong.

Results

Among 809 CHWs, the baseline proportion of better performers was 45%. Compared to CHWs who received lower intensity of supportive supervision, CHWs who received greater intensity of supportive supervision had 70% higher odds (AOR 1.70, 95% CI 1.16, 2.49) of better performance after controlling for their baseline performance, CHW characteristics such as age, education, experience, caste, timely payment of salaries, Anganwadi Centre facility index, motivation, and population served in their catchment area. A test of mediation indicated that supportive supervision is associated indirectly with CHW performance through improvement in CHW knowledge.

Conclusion

Higher intensity of supportive supervision is associated with improved CHW performance directly and through knowledge of CHWs. Leveraging institutional mechanisms such as supportive supervision could be important in improving service delivery to reach beneficiaries and potentially better infant and young child feeding practices and nutritional outcomes.

Trial registration : Trial registration number: https://doi.org/10.1186/ISRCTN83902145
Factors influencing the performance of community health volunteers working within urban informal settlements in low- and middle-income countries: a qualitative meta-synthesis review
Authors: Ogutu Michael , Muraya Kui , Mockler David , Darker Catherine
Published: November 2021

Background

There is limited information on community health volunteer (CHV) programmes in urban informal settlements in low- and middle-income countries (LMICs). This is despite such settings accounting for a high burden of disease. Many factors intersect to influence the performance of CHVs working in urban informal settlements in LMICs. This review was conducted to identify both the programme level and contextual factors influencing performance of CHVs working in urban informal settlements in LMICs.

Methods

Four databases were searched for qualitative and mixed method studies focusing on CHVs working in urban and peri-urban informal settlements in LMICs. We focused on CHV programme outcome measures at CHV individual level. A total of 13 studies met the inclusion criteria and were double read to extract relevant data. Thematic coding was conducted, and data synthesized across ten categories of both programme and contextual factors influencing CHV performance. Quality was assessed using both the Critical Appraisal Skills Programme (CASP) and the Mixed Methods Assessment Tool (MMAST); and certainty of evidence evaluated using the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach.

Results

Key programme-level factors reported to enhance CHV performance in urban informal settlements in LMICs included both financial and non-financial incentives, training, the availability of supplies and resources, health system linkage, family support, and supportive supervision. At the broad contextual level, factors found to negatively influence the performance of CHVs included insecurity in terms of personal safety and the demand for financial and material support by households within the community. These factors interacted to shape CHV performance and impacted on implementation of CHV programmes in urban informal settlements.

Conclusion

This review identified the influence of both programme-level and contextual factors on CHVs working in both urban and peri-urban informal settlements in LMICs. The findings suggest that programmes working in such settings should consider adequate remuneration for CHVs, integrated and holistic training, adequate supplies and resources, adequate health system linkages, family support and supportive supervision. In addition, programmes should also consider CHV personal safety issues and the community expectations.
The State of the World’s Midwifery 2021 report: findings to drive global policy and practice
Authors: Nove Andrea , ten Hoope-Bender Petra , Boyce Martin , Bar-Zeev Sarah , de Bernis Luc , Lal Geeta , Matthews Zoë , Mekuria Million , Homer Caroline S. E.
Published: November 2021

The third global State of the World’s Midwifery report (SoWMy 2021) provides an updated evidence base on the sexual, reproductive, maternal, newborn and adolescent health (SRMNAH) workforce. For the first time, SoWMy includes high-income countries (HICs) as well as low- and middle-income countries. This paper describes the similarities and differences between regions and income groups, and discusses the policy implications of these variations. SoWMy 2021 estimates a global shortage of 900,000 midwives, which is particularly acute in low-income countries (LICs) and in Africa. The shortage is projected to improve only slightly by 2030 unless additional investments are made. The evidence suggests that these investments would yield important returns, including: more positive birth experiences, improved health outcomes, and inclusive and equitable economic growth. Most HICs have sufficient SRMNAH workers to meet the need for essential interventions, and their education and regulatory environments tend to be strong. Upper-middle-income countries also tend to have strong policy environments. LICs and lower-middle-income countries tend to have a broader scope of practice for midwives, and many also have midwives in leadership positions within national government. Key regional variations include: major midwife shortages in Africa and South-East Asia but more promising signs of growth in South-East Asia than in Africa; a strong focus in Africa on professional midwives (rather than associate professionals: the norm in many South-East Asian countries); heavy reliance on medical doctors rather than midwives in the Americas and Eastern Mediterranean regions and parts of the Western Pacific; and a strong educational and regulatory environment in Europe but a lack of midwife leaders at national level. SoWMy 2021 provides stakeholders with the latest data and information to inform their efforts to build back better and fairer after COVID-19. This paper provides a number of policy responses to SoWMy 2021 that are tailored to different contexts, and suggests a variety of issues to consider in these contexts. These suggestions are supported by the inclusion of all countries in the report, because it is clear which countries have strong SRMNAH workforces and enabling environments and can be viewed as exemplars within regions and income groups.
Associations of neighborhood built, safety, and social environment with walking to and from school among elementary school-aged children in Chiba, Japan
Authors: Hino Kimihiro , Ikeda Erika , Sadahiro Saiko , Inoue Shigeru
Published: November 2021

Background

Although it is globally known that Japan has high prevalence of active school travel among children, there are few international studies on Japanese children’s school travel. Moreover, only few studies have focused on the differences in their mode of travel between to-school and from-school. This study examined the associations of neighborhood built, safety, and social environments with walking to/from school among elementary school-aged children in Chiba, Japan.

Methods

We conducted an online survey with 1545 parents of children aged 6–12 years residing in Chiba between 25 and 27 November 2020 during the COVID-19 pandemic. A neighborhood was defined as the area of a postcode provided by the participants. Each neighborhood environment was assessed based on the built environment (new town designation, walkability, distance to school, population density), social environment (neighborhood cohesion and connection), and safety (CCTVs, a road section for walking alone, safety volunteers). Neighborhood walkability was measured using subscales of the Neighborhood Environment Walkability Scale (youth and abbreviated versions) including crime safety and traffic safety. Parents’ perceived influence of COVID-19 on school commuting and after-school activities were also included in the model as covariates. Walking to and from school were separately analyzed using multinomial logistic regressions, where new towns and walkability were computed separately as explanatory variables.

Results

Four fifths of children walked to and from school daily. Walking to school was positively associated with crime safety, neighborhood connections, and schools sited in new towns. Walking from school had positive associations with traffic safety, neighborhood cohesion, and CCTVs, but negative associations with safety volunteers and after-school activities. The presence of a section for walking alone and perceived influence of COVID-19 had negative associations with walking to and from school.

Conclusions

Recent social changes such as declining birthrate, decline in public elementary schools, and increasing after-school activities may change parental attitudes toward children’s walking to/from school, and subsequently, their mode of school travel over time. To maintain the high prevalence of walking to/from school in Japan, multidisciplinary approaches involving different stakeholders from education, public health, and urban planning are required to overcome sectionalism and support this behavior in the long term.
Mediterranean diet and depression: a population-based cohort study
Authors: Yin Weiyao , Löf Marie , Chen Ruoqing , Hultman Christina M. , Fang Fang , Sandin Sven
Published: November 2021

Background

Depression imposes immense public health burden, demonstrating an urgent need of the identification of modifiable risk factors. Only a few cohort studies have analyzed the association between Mediterranean dietary pattern (MDP) and depression but with mixed results. We examined the impact of MDP on clinically ascertained depression in a large population-based dataset.

Methods

In 1991/92, detailed information on diet, using a food frequency questionnaire, and potential confounding factors (body weight, height, educational attainment, smoking, previous diabetes and hypertension, and physical activity) was collected, in a random sample of 49,261 Swedish women aged 29-49. Adherence to MDP was calculated. Clinical depression was extracted from the National Patient Register. Study participants were followed up through 2012.

Results

During an average follow-up of 20.4 years, 1677 incident cases of depression were diagnosed. We observed a lower risk of depression for medium (score 4-5) and high (6-9) adherence to MDP, compared with low (0-3) adherence (Medium: hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.81-1.00; High: HR = 0.82, 95%CI = 0.71-0.94). Per unit increase of adherence, the risk of depression was reduced by 5% (HR = 0.95, 95%CI = 0.92-0.98). The association became stronger when restricting to severe form of depression (HR = 0.51, 95%CI = 0.33-0.76). The HRs were higher from age 50 onward both over the first and the second 10-year follow-up period, compared with before age 50, indicating stronger association with increasing age. Results remained after extensive sensitivity analyses.

Conclusion

Higher adherence to a Mediterranean diet at middle age was associated with a lower risk of depression later in life among Swedish women.
Barriers to translational research in Windsor Ontario: a survey of clinical care providers and health researchers
Authors: Senecal Justin B. , Metcalfe Karen , Wilson Kaila , Woldie Indryas , Porter Lisa A.
Published: November 2021

Background

Translational research is an ideology focussed on streamlining the transition of novel research into clinical practice to ultimately benefit populations. Central to this approach is overcoming barriers to research involvement and interdisciplinary collaboration. Identifying barriers has been the subject of several studies focused on communities with large academic hospitals. The Windsor-Essex region is currently built around community hospitals which have less of an emphasis on research, employ fewer physicians holding academic appointments and generally do not provide incentivised time for research and training. In this study, we surveyed clinicians and researchers working in Windsor-Essex to gain insight into barriers to translational research important to those working in smaller sized, community-based research networks.

Methods

Using an anonymous close-ended Qualtrics survey distributed via email, we surveyed faculty members from The University of Windsor and clinical care providers from Windsor-Essex (n = 68). This included 24 physicians, 14 allied health professionals, and 30 non-clinician researchers.

Results

Managing competing interests, lack of time, funding, infrastructure, and networks were identified by greater than 75% of participants as barriers to research involvement. 62% of physicians identified the lack of permanent post-graduate medical trainees as a barrier. Clinicians were consistently less experienced in research skills compared to others; particularly in publishing results and applying for funding (p < 0.001). Schedule incompatibility, funding issues and identifying interested collaborators with overlapping interests were identified as barriers to interdisciplinary collaboration by 80% of participants. Moreover, 46% of those surveyed were unhappy with their research involvement and these individuals were 13% more likely to perceive research as important for their career progression (p = 0.244).

Conclusions

This study identifies several important barriers to translational research in Windsor-Essex and suggests that many motivated researchers are unhappy with their current involvement. These results will inform decision making in the research community of Windsor-Essex and provides insight for communities of similar size and research capacity. Ultimately, enabling the translation of clinical research in all communities is required to ensure equitable access to cutting edge care.
The tumor immune microenvironment of primary and metastatic HER2− positive breast cancers utilizing gene expression and spatial proteomic profiling
Authors: Schlam Ilana , Church Sarah E. , Hether Tyler D. , Chaldekas Krysta , Hudson Briana M. , White Andrew M. , Maisonet Emily , Harris Brent T. , Swain Sandra M.
Published: November 2021

Background

The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies.

Methods

We examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM). Using molecular profiling by bulk gene expression TME signatures, including the Tumor Inflammation Signature (TIS) and PAM50 subtyping, as well as spatial characterization of immune hot, warm, and cold regions in the stroma and tumor epithelium using 64 protein targets on the GeoMx Digital Spatial Profiler.

Results

PBT had higher infiltration of immune cells relative to metastatic sites and higher protein and gene expression of immune activation markers when compared to metastatic sites. TIS scores were lower in metastases, particularly in BM. BM also had less immune infiltration overall, but in the stromal compartment with the highest density of immune infiltration had similar levels of T cells that were less activated than PBT stromal regions suggesting immune exclusion in the tumor epithelium.

Conclusions

Our findings show stromal and tumor localized immune cells in the TME are more active in primary versus metastatic disease. This suggests patients with early HER2+ breast cancer could have more benefit from immune-targeting therapies than patients with advanced disease.
CRISPR/Cas9-mediated TGFβRII disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells in vitro
Authors: Alishah Khadijeh , Birtel Matthias , Masoumi Elham , Jafarzadeh Leila , Mirzaee Hamid Reza , Hadjati Jamshid , Voss Ralf-Holger , Diken Mustafa , Asad Sedighe
Published: November 2021

Background

CAR T-cell therapy has been recently unveiled as one of the most promising cancer therapies in hematological malignancies. However, solid tumors mount a profound line of defense to escape immunosurveillance by CAR T-cells. Among them, cytokines with an inhibitory impact on the immune system such as IL-10 and TGFβ are of great importance: TGFβ is a pleiotropic cytokine, which potently suppresses the immune system and is secreted by a couple of TME resident and tumor cells.

Methods

In this study, we hypothesized that knocking out the TGFβ receptor II gene, could improve CAR T-cell functions in vitro and in vivo. Hereby, we used the CRISPR/Cas9 system, to knockout the TGFβRII gene in T-cells and could monitor the efficient gene knock out by genome analysis techniques. Next, Mesothelin or Claudin 6 specific CAR constructs were overexpressed via IVT-RNA electroporation or retroviral transduction and the poly-functionality of these TGFβRII KO CAR T-cells in terms of proliferation, cytokine secretion and cytotoxicity were assessed and compared with parental CAR T-cells.

Results

Our experiments demonstrated that TGFβRII KO CAR T-cells fully retained their capabilities in killing tumor antigen positive target cells and more intriguingly, could resist the anti-proliferative effect of exogenous TGFβ in vitro outperforming wild type CAR T-cells. Noteworthy, no antigen or growth factor-independent proliferation of these TGFβRII KO CAR T-cells has been recorded. TGFβRII KO CAR T-cells also resisted the suppressive effect of induced regulatory T-cells in vitro to a larger extent. Repetitive antigen stimulation demonstrated that these TGFβRII KO CAR T-cells will experience less activation induced exhaustion in comparison to the WT counterpart.

Conclusion

The TGFβRII KO approach may become an indispensable tool in immunotherapy of solid tumors, as it may surmount one of the key negative regulatory signaling pathways in T-cells.
Phospholipase A2 group IIA correlates with circulating high-density lipoprotein cholesterol and modulates cholesterol efflux possibly through regulation of PPAR-γ/LXR-α/ABCA1 in macrophages
Authors: Liang Ling , Xie Qiang , Sun Changqing , Wu Yuanhui , Zhang Wei , Li Weihua
Published: November 2021

Background

Secretory phospholipase A2 group IIA (sPLA2-IIA) is an independent risk factor for cardiovascular disease, but its role on high-density lipoprotein cholesterol (HDL-C) level has not been clarified. The aim of the present study was to explore the association between circulating sPLA2-IIA and HDL-C, and to evaluate if sPLA2-IIA enhances cholesterol efflux capacity through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ), liver X receptor α (LXR-α), and ATP-binding cassette A1 (ABCA1).

Methods

131 patients with coronary artery disease were enrolled. The plasma level of sPLA2-IIA was tested with enzyme-linked immunosorbent assay kit, and serum lipids were assessed by biochemical analyzer. Human monocyte-macrophage cell line THP-1 was co-incubated with sPLA2-IIA in the presence/absence of selective PPAR-γ antagonist GW9662 in vitro. Real-time PCR and Western-blot were employed to measure the mRNA and protein expressions of PPAR-γ, LXR-α, and ABCA1, respectively. The cholesterol efflux was evaluated by using an assay kit.

Results

In subjects, circulating level of sPLA2-IIA was positively related with that of HDL-C (r = 0.196, p = 0.024). The plasma level of sPLA2-IIA was significantly higher in the high HDL-C (≥ 1.04 mmol/L) group (7477.828 pg/mL) than that in low HDL-C (< 1.04 mmol/L) group (5836.92 pg/mL, p = 0.004). For each increase of 1 pg/μl in sPLA2-IIA level, the adjusted odds ratio for HDL-C ≥ 1.04 mmol/L was 1.143. Co-incubation of THP-1 cells with sPLA2-IIA resulted in increased expressions of PPAR-γ, LXR-α, and ABCA1, as well as enhanced cholesterol efflux capacity, that were all reversed by administration of GW9662.

Conclusions

Circulating sPLA2-IIA was positively associated with HDL-C. PPAR-γ/LXR-α/ABCA1 might be responsible for sPLA2-IIA-regulated cholesterol efflux in macrophages.
Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
Authors: Savarraj Jude , Park Eun S. , Colpo Gabriela D. , Hinds Sarah N. , Morales Diego , Ahnstedt Hilda , Paz Atzhiry S. , Assing Andres , Liu Fudong , Juneja Shivanki , Kim Eunhee , Cho Sung-min , Gusdon Aaron M. , Dash Pramod , McCullough Louise D. , Choi H. Alex
Published: November 2021

Objective

Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes.

Methods

Plasma samples from 57 subjects at < 48 h of COVID-19 hospitalization, and 20 matched controls were interrogated for the levels of six BIMs—including GFAP, S100B, Syndecan-1, UCHLI, MAP2 and NSE, two EIMs—including sICAM1 and sVCAM1. Additionally, several cytokines/chemokines were analyzed by multiplex. Statistical and bioinformatics methods were used to measure differences in the marker profiles across (a) COVID-19 vs. controls and (b) men vs. women.

Results

Three BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (p < 0.05) elevated in the COVID-19 cohort compared to controls. Bioinformatics analysis reveal a stronger positive association between BIM/CC/EIMs in the COVID-19 cohort. Analysis across sex revealed that several BIMs and CCs including NSE, IL10, IL15 and IL8 were significantly (p < 0.05) higher in men compared to women. Men also expressed a more robust BIM/ EIM/CC association profile compared to women.

Conclusion

The acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization are suggestive of brain and endothelial injury. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Authors: Chu Erskine , Mychasiuk Richelle , Hibbs Margaret L. , Semple Bridgette D.
Published: November 2021

Microglia are integral mediators of innate immunity within the mammalian central nervous system. Typical microglial responses are transient, intending to restore homeostasis by orchestrating the removal of pathogens and debris and the regeneration of damaged neurons. However, prolonged and persistent microglial activation can drive chronic neuroinflammation and is associated with neurodegenerative disease. Recent evidence has revealed that abnormalities in microglial signaling pathways involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) may contribute to altered microglial activity and exacerbated neuroimmune responses. In this scoping review, the known and suspected roles of PI3K-AKT signaling in microglia, both during health and pathological states, will be examined, and the key microglial receptors that induce PI3K-AKT signaling in microglia will be described. Since aberrant signaling is correlated with neurodegenerative disease onset, the relationship between maladapted PI3K-AKT signaling and the development of neurodegenerative disease will also be explored. Finally, studies in which microglial PI3K-AKT signaling has been modulated will be highlighted, as this may prove to be a promising therapeutic approach for the future treatment of a range of neuroinflammatory conditions.
Period poverty: menstrual health hygiene issues among adolescent and young Venezuelan migrant women at the northwestern border of Brazil
Authors: Soeiro Rachel E. , Rocha Leila , Surita Fernanda G. , Bahamondes Luis , Costa Maria L.
Published: November 2021

Background

Adolescent and young women (10–24 years old) are habitually a neglected group in humanitarian settings. Menstrual hygiene management (MHM) is an unmet aspect of sexual and reproductive health (SRH) and an additional challenge if lack of hygiene products, inadequate access to safe, clean, and private toilets identified as period poverty. Our objective was to provide an overview of the main MHM issues affecting Venezuelan migrant adolescents and young women in the north-western border of Venezuela-Brazil.

Method

A cross-sectional study was conducted, early in 2021, with the use of a self-responded questionnaire, in Spanish, adapted from the Menstrual Practice Needs Scale (MPNS-36). All identified adolescents and young women aged between 12 and 24 years old were invited to participate (convenience sample-167 women). Women with complete questionnaires and who menstruate were included. Information on access to and quality of hygiene kits and toilets were retrieved, and a descriptive analysis performed, with an evaluation of frequencies for categorical variables (n, %) and mean (± SD-standard deviation) for continuous variables. In addition to the open-ended questions, we included one open question about their personal experience with menstruation.

Results

According to official reports, at the moment of the interviews, there were 1.603 Venezuelans living on the streets in Boa Vista. A total of 167 young women were invited, and 142 further included, mean age was 17.7 years, almost half of the participants who menstruate (46.4%) did not receive any hygiene kits, 61% were not able to wash their hands whenever they wanted, and the majority (75.9%) did not feel safe to use the toilets. Further, menstruation was often described with negative words.

Conclusions

Migrant Venezuelan adolescents and young women have their MHM needs overlooked, with evident period poverty, and require urgent attention. It is necessary to assure appropriate menstrual materials, education, and sanitation facilities, working in partnership among governmental and non-governmental organizations to guarantee menstrual dignity to these young women.
Association between experience of specific side-effects and contraceptive switching and discontinuation in Uganda: results from a longitudinal study
Authors: Zimmerman Linnea A. , Sarnak Dana O. , Karp Celia , Wood Shannon N. , Ahmed Saifuddin , Makumbi Fredrick , Kibira Simon P. S.
Published: November 2021

Background

There is substantial evidence that contraceptive side-effects are a major deterrent to consistent use of contraception but few studies in low- or middle-income countries explore the role of specific side-effects on contraceptive use dynamics. This study used population-based, longitudinal data to explore the effect of specific side-effects on contraceptive continuation, discontinuation, and switching in Uganda.

Methods

Data for this study come from two rounds of survey data collection in Uganda: PMA2020’s sixth cross-sectional survey and a follow-up survey conducted 1 year later. The main outcomes of interest were discontinuation and switching among users of hormonal contraceptive methods (implants, injectables and oral pill) and the IUD at baseline (n = 560). Multivariable logistic regressions assessed the association of experiencing specific side-effects (more bleeding, less bleeding, irregular bleeding, increased dryness/reduced libido, and physical discomfort) with discontinuation and switching 1 year later, adjusting for socio-demographic characteristics, type of method, and length of use. We also examined the differential effects of side-effects between discontinuation and switching risks.

Results

About 23% of hormonal and IUD contraceptive users reported experiencing side-effects at baseline survey. Overall, discontinuation and switching were higher among injectables and pill users, compared to IUD and implants users. Reporting more bleeding or less bleeding increased the odds of discontinuation and switching by 2.74 (95% CI 1.00–7.51) and 1.86 (1.04–3.34), respectively. There was no significant difference in discontinuation and switching by side-effects.

Conclusions

Greater attention should be paid to understanding the unique contributions of side-effects to contraceptive behavior using population-based data. While about a quarter of women reported experiencing side effects, those who experienced bleeding specific side effects were at higher risk of contraceptive discontinuation and switching. Providing greater individualized care that includes information and counseling about common side-effects, how they may impact daily life, and how tolerable these effects may be is necessary.
Determinants of women’s preferred and actual abortion provision locations in Nigeria
Authors: Byrne Meagan E. , Omoluabi Elizabeth , OlaOlorun Funmilola M. , Moreau Caroline , Bell Suzanne O.
Published: November 2021

Background

Unsafe abortion remains a leading cause of maternal mortality globally. Many factors can influence women’s decisions around where to seek abortion care; however, little research has been done on abortion care decisions at a population-level in low-resource settings, particularly where abortion is legally restricted.

Methods

This analysis uses data from a 2019–2020 follow-up survey of 1144 women in six Nigerian states who reported an abortion experience in a 2018 cross-sectional survey. We describe women’s preferred and actual primary abortion care provider/location by distinguishing clinical, pharmacy/chemist, or other non-clinical providers or locations. We also examine factors that influence women’s decisions about where to terminate their pregnancy and identify factors hindering women’s ability to operationalize their preferences. We then examine the characteristics of women who were not able to use their preferred provider/location.

Results

Non-clinical providers (55.0%) were more often used than clinical providers (45.0%); however, clinical providers were preferred by most women (55.6%). The largest discrepancies in actual versus preferred abortion provider/location were private hospitals (7.6% actual versus 37.2% preferred), government hospitals (4.3% versus 22.6%), chemists (26.5% versus 5.9%) and pharmacies (14.9% versus 6.6%). “Privacy/confidentiality” was the most common main reason driving women’s abortion provider/location choice (20.7%), followed by “convenience” (16.9%) and “recommended” by someone (12.3%), most often a friend (60.8%), although top reasons differed by type of provider/location. Cost and distance were the two most common reasons that women did not use their preferred provider/location (46.1% and 21.9%, respectively). There were no statistically significant differences in the sociodemographic characteristics between women who were able to use their preferred provider/location and those who were not able to implement their preferred choice, with the exception of state of residence.

Conclusions

These findings provide insights on barriers to abortion care in Nigeria, suggesting discretion is key to many women’s choice of abortion location, while cost and distance prevent many from seeking their preferred care provider/location. Results also highlight the diversity of women’s abortion care preferences in a legally restrictive environment.
A novel upper-limb tracking system in a virtual environment for stroke rehabilitation
Authors: Cha Kuan , Wang Jinying , Li Yan , Shen Longbin , Chen Zhuoming , Long Jinyi
Published: November 2021

Background

The transfer of the behaviors of a human’s upper limbs to an avatar is widely used in the field of virtual reality rehabilitation. To perform the transfer, movement tracking technology is required. Traditionally, wearable tracking devices are used for tracking; however, these devices are expensive and cumbersome. Recently, non-wearable upper-limb tracking solutions have been proposed, which are less expensive and more comfortable. However, most products cannot track the upper limbs, including the arms and all the fingers at the same time, which limits the limb parts for tracking in a virtual environment and may lead to a limited rehabilitation effect.

Methods

In this paper, a novel virtual reality rehabilitation system (VRRS) was developed for upper-limb rehabilitation. The VRRS could track the motion of both upper limbs, integrate fine finger motion and the range of motion of the entire arm and map the motion to an avatar. To test the performance of VRRS, two experiments were designed. In the first experiment, we investigated the effect of VRRS on virtual body ownership, agency and location of the body and usability in 8 healthy participants by comparing it with a partial upper-limb tracking method based on a Leap Motion controller (LP) in the same virtual environments. In the second experiment, we examined the feasibility of VRRS in upper-limb rehabilitation with 27 stroke patients.

Results

VRRS improved the users’ senses of body ownership, agency, and location of the body. The users preferred using the VRRS to using the LP. In addition, we found that although the upper limb motor function of patients from all groups was improved, the difference between the FM scores tested on the first day and the last day of the experimental group was more significant than that of the control groups.

Conclusions

A VRRS with motion tracking of the upper limbs and avatar control including the arms and all the fingers was developed. It resulted in an improved user experience of embodiment and effectively improved the effects of upper limb rehabilitation in stroke patients.

Trial registration

The study was registered at the First Affiliated Hospital of Jinan University Identifier: KY-2020–036; Date of registration: June 01, 2020.
Detection and phylogenetic analysis of a novel tick-borne virus in Haemaphysalis longicornis ticks and sheep from Shandong, China
Authors: Shao Lijun , Chang Ruiheng , Liu Lin , Wang Yongjin , Gao Yun , Wang Shaoqing , Sun Hengyi , Niu Guoyu
Published: November 2021

Dabieshan tick virus (DTV) was first identified in Haemaphysalis longicornis from Hubei Province, China in 2015. However, its pathogenic potential to animals and human remains to be further explored. In this study, a total of 170 engorged ticks and 22 sheep serum samples were collected from Taian and Yantai city, Shandong Province to investigate the presence of DTV. The results of qRT-PCR revealed the positive rate of 13.6% (3/22) in sheep serum and 8.2% (14/170) in attached ticks, respectively. Phylogenetic analysis demonstrated a close evolutionary relationship among those DTV isolates from animal and ticks, and DTV might be relatively conservative in evolution. These findings are the first to demonstrate molecular evidence of DTV in domestic animals. Nonetheless, whether or not causing disease in animals, DTV deserves further investigation.
The effect of dietary lipid quality in early life on serum LysoPC(18:2) levels and their association with adult blood glucose levels in intrauterine growth restricted rats
Authors: Kodde Andrea , Mischke Mona , Rakhshandehroo Maryam , Voggel Jenny , Fink Gregor , Nüsken Eva , Rauh Manfred , van der Beek Eline M. , Dötsch Jörg , Nüsken Kai-Dietrich
Published: November 2021

Being born small-for-gestational-age, especially with subsequent catch-up growth, is associated with impaired metabolic health in later-life. We previously showed that a postnatal diet with an adapted lipid droplet structure can ameliorate some of the adverse metabolic consequences in intrauterine growth-restricted (IUGR) rats. The aim of the present work was to explore possible underlying mechanism(s) and potential biomarkers. To this end, serum metabolomics was performed in postnatal day (PN) 42 and PN96 samples of the above-mentioned rat offspring, born after uterine vasculature ligation. Blood samples were collected at PN42, directly after a postnatal dietary intervention with either complex lipid matrix (CLM) or control (CTRL) diet, and at PN96 after a subsequent western-style diet (WSD). Offspring of Non-operated (NOP) dams fed CTRL in early life were included as control group. In the PN42 metabolomics data, 11 co-abundance modules of metabolites were identified, of which four were significantly correlated to adult blood glucose levels at PN96. Further analyses showed that Lysophosphatidylcholine(18:2) (LysoPC(18:2)) levels were reduced by ligation (p < 0.01) and restored in CLM fed animals (p < 0.05). LysoPC(18:2) levels at PN42 correlated inversely with adult blood glucose levels. These data indicate that early-life LysoPC(18:2) blood levels may predict adult blood glucose levels and are affected by a postnatal diet with an adapted lipid droplet structure in IUGR offspring.
Papua New Guinea agri-food trade and household consumption trends point towards dietary change and increased overweight and obesity prevalence
Authors: Schmidt Emily , Fang Peixun
Published: November 2021

Background

Papua New Guinea (PNG) experienced positive GDP growth at approximately 4.3% per year during the last decade. With increases in overall wealth within the country, PNG is facing a double burden of malnutrition: comparatively high child stunting rates and a growing overweight and obesity epidemic. We focus on the latter by evaluating trends in agri-food import data from 2001 to 2018 and household consumption data from 2018 and 2009/10.

Results

The analysis presented in this paper raises three red flags. First, international food import data suggest that the demand for ultra-processed, sugar-sweetened beverages and food have increased substantially over time in PNG. Sugar-sweetened beverages dominated the largest growth in processed food imports, increasing by 23% per capita per year between 2001 and 2018. Second, households across the country with a greater food expenditure on sugar-sweetened beverages have a higher probability of an overweight child (under 5 years old). Last, the probability of soft-drink consumption in PNG increases with greater income acquisition and improved market access. While the price of a soft drink is negatively correlated with the quantity consumed, analysis suggests that total household income has a quantitatively larger (and positive) association with soft drink consumption.

Conclusions

Taxing (or increasing taxes on) sugar-sweetened beverages may not be a sufficient policy mechanism to curb overconsumption of soft drinks in PNG. Education and advocacy programs should be fostered that integrate improved dietary information on packaging, as well as greater access to and understanding of nutrition and diet information of common household consumption items. While increases in household income and market access are crucial to economic growth and transformation, PNG’s economic transition must be dovetailed with programs that expand and enhance health and nutrition information and education to improve household consumption decisions and overall household wellbeing.
Barriers and facilitators to the introduction of import duties designed to prevent noncommunicable disease in Tonga: a case study
Authors: Bell Colin , Latu Catherine , Na’ati Elisiva , Snowdon Wendy , Moodie Marj , Waqa Gade
Published: November 2021

Background

In Tonga, import duties were lowered on tinned fish and seafood in 2013 and raised on soft drinks, dripping and other animal fats. Additional import duties were applied to soft drinks and dripping and other fats in 2016 and duties were also applied to high fat meats, mutton flaps and turkey tails. The objective of this study was to describe barriers to and facilitators of these import duties from a policy-maker perspective.

Methods

A case study was conducted to analyse implementation of policies originally modelled by the Pacific Obesity Prevention in Communities project to reduce mortality in the Kingdom of Tonga. Policymakers (n = 15) from the Ministries of Revenue, Health, Finance and Labour and Commerce involved in the development and implementation of Tonga’s food-related policies participated in key-informant interviews.

Results

The main facilitator of import duties were strong leadership and management, cross-sector collaboration, awareness raising and advocacy, nature of the policy, and the effective use of data to model policy impacts and inform the general public. The absence of clear lines of responsibility and a decline in collaboration over time were identified as barriers to implementation of the import duties.

Conclusion

In a small Island state implementing import duties to prevent non-communicable disease can be straight forward providing policymakers and the community have a shared understanding of the health and economic costs of NCDs.
Spindle cell variant of medullary thyroid carcinoma: a clinicopathologic study of four cases
Authors: Wang Yan Xia , Yang Shou Jing
Published: November 2021

Background

Medullary thyroid carcinoma (MTC) is a malignant tumor derived from C cells. It accounts for about 10% of all thyroid malignancies. More than 14 histological variants have been described. Among them, spindle cell variant is extremely rare.

Case presentation

Here we describe 4 cases of spindle cell variant of MTC collected from 2012 to 2019. Ultrasound showed solid and hypoechoic nodules. Three patients underwent total thyroidectomy and regional lymph node dissection, and 1 patient underwent thyroid mass resection. Histologically, the tumors showed spindle shaped cells in bundles or interlaced arrangement, separated by hyalinised fibrous stroma that contained amyloid deposits. Immunohistochemistry showed that the tumor cells were positive for calcitonin, chromogranin A, synaptophysin, CD56, and TTF-1, but negative for other lineage-specific markers.

Conclusions

We report 4 rare cases of spindle cell variant of MTC. Due to its rarity and special morphology, the diagnosis of spindle cell variant MTC relies on its morphology and immunohistochemical markers to avoid misdiagnosis.