bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function
Authors: Cho Youngkyung , Kim Sang Bum , Kim Jiyoon , Pham An Vuong Quynh , Yoon Min Ji , Park Jeong Hwan , Hwang Ki-Tae , Park Dongeun , Cho Yongcheol , Kim Moon Gyo , Kim Chungho
Published: June 2020

Background

Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein.

Results

In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b.

Conclusions

These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.
Routine data for malaria morbidity estimation in Africa: challenges and prospects
Authors: Alegana Victor A. , Okiro Emelda A. , Snow Robert W.
Published: June 2020

Background

The burden of malaria in sub-Saharan Africa remains challenging to measure relying on epidemiological modelling to evaluate the impact of investments and providing an in-depth analysis of progress and trends in malaria response globally.

In malaria-endemic countries of Africa, there is increasing use of routine surveillance data to define national strategic targets, estimate malaria case burdens and measure control progress to identify financing priorities. Existing research focuses mainly on the strengths of these data with less emphasis on existing challenges and opportunities presented.

Conclusion

Here we define the current imperfections common to routine malaria morbidity data at national levels and offer prospects into their future use to reflect changing disease burdens.
Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020
Authors: Tariq Amna , Lee Yiseul , Roosa Kimberlyn , Blumberg Seth , Yan Ping , Ma Stefan , Chowell Gerardo
Published: June 2020

Background

As of March 31, 2020, the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued.

Methods

Here we estimate the effective reproduction number,Rt, of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts.

Results

The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI 0.3, 1.0) during the first transmission wave by February 14, 2020, while the overall R based on the cluster size distribution as of March 17, 2020, was estimated at 0.6 (95% CI 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test,p < 0.001).

Conclusion

The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.
Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study
Authors: Shi Jichan , Li Yang , Zhou Xian , Zhang Qiran , Ye Xinchun , Wu Zhengxing , Jiang Xiangao , Yu Hongying , Shao Lingyun , Ai Jing-Wen , Zhang Haocheng , Xu Bin , Sun Feng , Zhang Wenhong
Published: June 2020

Background

Coronavirus disease 2019 (COVID-19) has infected more than 4 million people within 4 months. There is an urgent need to properly identify high-risk cases that are more likely to deteriorate even if they present mild diseases on admission.

Methods

A multicenter nested case-control study was conducted in four designated hospitals in China enrolling confirmed COVID-19 patients who were mild on admission. Baseline clinical characteristics were compared between patients with stable mild illness (stable mild group) and those who deteriorated from mild to severe illness (progression group).

Results

From Jan 17, 2020, to Feb 1, 2020, 85 confirmed COVID-19 patients were enrolled, including 16 in the progression group and 69 in the stable mild group. Compared to stable mild group (n = 69), patients in the progression group (n = 16) were more likely to be older, male, presented with dyspnea, with hypertension, and with higher levels of lactase dehydrogenase and c-reactive protein. In multivariate logistic regression analysis, advanced age (odds ratio [OR], 1.012; 95% confidence interval [CI], 1.020–1.166; P = 0.011) and the higher level of lactase dehydrogenase (OR, 1.012; 95% CI, 1.001–1.024; P = 0.038) were independently associated with exacerbation in mild COVID-19 patients.

Conclusion

Advanced age and high LDH level are independent risk factors for exacerbation in mild COVID-19 patients. Among the mild patients, clinicians should pay more attention to the elderly patients or those with high LDH levels.
Exploiting bacterial outer membrane vesicles as a cross-protective vaccine candidate against avian pathogenic Escherichia coli (APEC)
Authors: Hu Rujiu , Li Jing , Zhao Yuezhen , Lin Hua , Liang Liu , Wang Mimi , Liu Haojing , Min Yuna , Gao Yupeng , Yang Mingming
Published: June 2020

Background

The well-known fact that avian pathogenic Escherichia coli (APEC) is harder to prevent due to its numerous serogroups has promoted the development of biological immunostimulatory materials as new vaccine candidates in poultry farms. Bacterial outer membrane vesicles (OMVs), known as spherical nanovesicles enriched with various immunostimulants, are naturally secreted by Gram-negative bacteria, and have gained much attention for developing effective vaccine candidates. Recent report has demonstrated that OMVs of APEC O78 can induce protective immunity in chickens. Here, a novel multi-serogroup OMVs (MOMVs) vaccine was developed to achieve cross-protection against APEC infection in broiler chickens.

Results

In this study, OMVs produced by three APEC strains were isolated, purified and prepared into MOMVs by mixing these three OMVs. By using SDS-PAGE and LC–MS/MS, 159 proteins were identified in MOMVs and the subcellular location and biological functions of 20 most abundant proteins were analyzed. The immunogenicity of MOMVs was evaluated, and the results showed that MOMVs could elicit innate immune responses, including internalization by chicken macrophage and production of immunomodulatory cytokines. Vaccination with MOMVs induced specific broad-spectrum antibodies as well as Th1 and Th17 immune responses. The animal experiment has confirmed that immunization with an appropriate dose of MOMVs could not cause any adverse effect and was able to reduce bacteria loads and pro-inflammatory cytokines production, thus providing effective cross-protection against lethal infections induced by multi-serogroup APEC strains in chickens. Further experiments indicated that, although vesicular proteins were able to induce stronger protective efficiency than lipopolysaccharide, both vesicular proteins and lipopolysaccharide are crucial in MOMVs-mediated protection.

Conclusions

The multi-serogroup nanovesicles produced by APEC strains will open up a new way for the development of next generation vaccines with low toxicity and broad protection in the treatment and control of APEC infection.
DSG2 expression is correlated with poor prognosis and promotes early-stage cervical cancer
Authors: Qin Shuhang , Liao Yuandong , Du Qiqiao , Wang Wei , Huang Jiaming , Liu Pan , Shang Chunliang , Liu Tianyu , Xia Meng , Yao Shuzhong
Published: June 2020

Background

The pathogenesis and developmental mechanism of early-stage (FIGO 2009 IA2-IIA2) cervical cancer (CC) remain unclear. Seeking novel molecular biomarkers based on The Cancer Genome Atlas (TCGA) will facilitate the understanding of CC pathogenesis and help evaluate early-stage CC prognosis.

Methods

To identify prognosis-related genes in early-stage CC, we analyzed TCGA mRNA-seq data and clinical data by univariate Cox and Kaplan–Meier plotter analyses. Differential expression analysis identified upregulated genes in early-stage CC. Combined with the genes correlated with unfavorable prognosis, we selected desmoglein-2 (DSG2) for further investigation. To detect DSG2 expression in early-stage CC, we used immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blotting. The relationship between the expression of DSG2 and clinical features was analyzed by the Chi square test. Cox analysis was applied to assess the relationship between CC overall survival (OS) and risk factors. The correlations between DSG2 expression and CC cell line proliferation and migration were investigated with Cell Counting Kit-8 (CCK-8) and migration assays.

Results

There were 416 prognosis-related genes in early-stage CC. DSG2, matrix metallopeptidase 1 (MMP1), carbonic anhydrase IX (CA9), homeobox A1 (HOXA1), and serine protease inhibitor B3 (SERPINB3) were upregulated in early-stage CC compared with adjacent noncancerous tissue (ANT) and correlated with unfavorable prognosis. Among them, DSG2 was most significantly correlated with patient survival. Coexpression analysis indicated that DSG2 was probably involved in cell division, positive regulation of transferase activity, positive regulation of cell migration, EGFR upregulation pathway and regulation of lymphangiogenesis. IHC, qRT-PCR and western blotting showed that DSG2 expression was higher in CC than in normal tissue. Significant correlations were identified between DSG2 expression and several aggressive clinical features, including pelvic lymph node metastasis (PLNM). Multivariate Cox analysis showed that DSG2 and PLNM were independent prognostic factors for OS. DSG2 knockdown inhibited CC cell proliferation and migration.

Conclusions

DSG2 is a biomarker that promotes tumor proliferation and metastasis and is correlated with poor prognosis in early-stage CC.
Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma
Authors: Lv Lei , Zhao Yujia , Wei Qinqin , Zhao Ye , Yi Qiyi
Published: June 2020

Background

Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC).

Methods

Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR.

Results

HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1.

Conclusions

This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.
Circular RNA and tumor microenvironment
Authors: Song Huixin , Liu Qiaofei , Liao Quan
Published: June 2020

Circular RNAs (circRNAs) are small non-coding RNAs with a unique ring structure and play important roles as gene regulators. Disturbed expressions of circRNAs is closely related to varieties of pathological processes. The roles of circRNAs in cancers have gained increasing concerns. The communications between the cancer cells and tumor microenvironment (TME) play complicated roles to affect the malignant behaviors of cancers, which potentially present new therapeutic targets. Herein, we reviewed the roles of circRNAs in the TME.
The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells
Authors: Yuan Yin , Li Bo , Kuang Yanbin , Ni Shuo , Zhuge Aoxiang , Yang Jing , Lv Longxian , Gu Silan , Yan Ren , Li Yating , Wang Kaicen , Yang Liya , Zhu Xueling , Wu Jingjing , Bian Xiaoyuan , Li Lanjuan
Published: June 2020

Background

Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug.

Methods

In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro.

Results

Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5.

Conclusions

The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.
Impacts of skull stripping on construction of three-dimensional T1-weighted imaging-based brain structural network in full-term neonates
Authors: Wang Geliang , Hu Yajie , Li Xianjun , Wang Miaomiao , Liu Congcong , Yang Jian , Jin Chao
Published: June 2020

Background

Skull stripping remains a challenge for neonatal brain MR image analysis. However, little is known about the accuracy of how skull stripping affects the neonatal brain tissue segmentation and subsequent network construction. This paper therefore aimed to clarify this issue by comparing two automatic (FMRIB Software Library’s Brain Extraction Tool, BET; Infant Brain Extraction and Analysis Toolbox, iBEAT) and a semiautomatic (iBEAT with manual correction) processes in constructing 3D T1-weighted imaging (T1WI)-based brain structural network.

Methods

Twenty-two full-term neonates (gestational age, 37–42 weeks; boys/girls, 13/9) without abnormalities on MRI who underwent brain 3D T1WI were retrospectively recruited. Two automatic (BET and iBEAT) and a semiautomatic preprocessing (iBEAT with manual correction) workflows were separately used to perform the skull stripping. Brain tissue segmentation and volume calculation were performed by a Johns Hopkins atlas-based method. Sixty-four gray matter regions were selected as nodes; volume covariance network and its properties (clustering coefficient,Cp; characteristic path length,Lp; local efficiency,Elocal; global efficiency,Eglobal) were calculated by GRETNA. Analysis of variance (ANOVA) was used to compare the differences in the calculated volume between three workflows.

Results

There were significant differences in volumes of 50 brain regions between the three workflows (P < 0.05). Three neonatal brain structural networks presented small-world topology. The semiautomatic workflow showed remarkably decreased Cp, increased Lp, decreasedElocal, and decreasedEglobal, in contrast to the two automatic ones.

Conclusions

Imperfect skull stripping indeed affected the accuracy of brain structural network in full-term neonates.
Automatic group-wise whole-brain short association fiber bundle labeling based on clustering and cortical surface information
Authors: Vázquez Andrea , López-López Narciso , Houenou Josselin , Poupon Cyril , Mangin Jean-François , Ladra Susana , Guevara Pamela
Published: June 2020

Background

Diffusion MRI is the preferred non-invasive in vivo modality for the study of brain white matter connections. Tractography datasets contain 3D streamlines that can be analyzed to study the main brain white matter tracts. Fiber clustering methods have been used to automatically group similar fibers into clusters. However, due to inter-subject variability and artifacts, the resulting clusters are difficult to process for finding common connections across subjects, specially for superficial white matter.

Methods

We present an automatic method for labeling of short association bundles on a group of subjects. The method is based on an intra-subject fiber clustering that generates compact fiber clusters. Posteriorly, the clusters are labeled based on the cortical connectivity of the fibers, taking as reference the Desikan–Killiany atlas, and named according to their relative position along one axis. Finally, two different strategies were applied and compared for the labeling of inter-subject bundles: a matching with the Hungarian algorithm, and a well-known fiber clustering algorithm, called QuickBundles.

Results

Individual labeling was executed over four subjects, with an execution time of 3.6 min. An inspection of individual labeling based on a distance measure showed good correspondence among the four tested subjects. Two inter-subject labeling were successfully implemented and applied to 20 subjects and compared using a set of distance thresholds, ranging from a conservative value of 10 mm to a moderate value of 21 mm. Hungarian algorithm led to a high correspondence, but low reproducibility for all the thresholds, with 96 s of execution time. QuickBundles led to better correspondence, reproducibility and short execution time of 9 s. Hence, the whole processing for the inter-subject labeling over 20 subjects takes 1.17 h.

Conclusion

We implemented a method for the automatic labeling of short bundles in individuals, based on an intra-subject clustering and the connectivity of the clusters with the cortex. The labels provide useful information for the visualization and analysis of individual connections, which is very difficult without any additional information. Furthermore, we provide two fast inter-subject bundle labeling methods. The obtained clusters could be used for performing manual or automatic connectivity analysis in individuals or across subjects.
Salutogenic model of health to identify turning points and coping styles for eating practices in type 2 diabetes mellitus
Authors: Polhuis C. M. M. , Vaandrager L. , Soedamah-Muthu S. S. , Koelen M. A.
Published: June 2020

Background

It is important for people with Type 2 Diabetes Mellitus (T2DM) to eat healthily. However, implementing dietary advice in everyday life is difficult, because eating is not a distinguishable action, but a chain of activities, embedded in social practices and influenced by previous life experiences. This research aims to understand why and how eating practices are developed over the life-course by investigating influential life experiences – turning points – and coping strategies for eating practices of people with T2DM.

Methods

The Salutogenic Model of Health guided the study’s objective, study design and analysis. Seventeen interviews were performed and analysed based on the principles of interpretative phenomenological analysis. Narrative inquiry and the creation of timelines and food boxes were used as tools to facilitate reflection on turning points and eating practices.

Results

Turning points for unhealthier eating were experiences that strongly disturbed the participants’ emotional stability. These experiences included psychosocial trauma, physical health disorders, job loss, and smoking cessation. Turning points for healthier eating were experiences that significantly changed participants views on life and made participants reflective about the effects of current eating practices on future health and life goals. These turning points included confrontation with ill-health, becoming a parent, psychosocial therapy, and getting married. Notably, turning points for healthier eating seemed only to happen when life was relatively stress-free. All participants experienced turning points for healthier eating, yet, not all participants succeeded in improving their diets. Two coping styles were distinguished: active and passive coping. Active coping individuals were able to act in line with their personal intentions, whereas passive coping individuals could not. Differences between active and passive coping styles seemed to be explained by differences in available resources important for adapting and maintaining a healthy diet.

Conclusion

Disadvantaged childhood and later life adversities together with the inability to manage the mental stress explained the development unhealthier eating practices. All participants experienced turning points for healthier eating that caused eating to become a priority in their life. Yet, the fact that not all were able to eat as they intended, advocates for nutritional guidance for people with T2DM, with a greater emphasis on reflexivity, psycho-social well-being and social support.
Inequalities in access to water and soap matter for the COVID-19 response in sub-Saharan Africa
Authors: Jiwani Safia S. , Antiporta Daniel A.
Published: June 2020

The COVID-19 pandemic has spread rapidly since the first case notification of the WHO in December 2019. Lacking an effective treatment, countries have implemented non-pharmaceutical interventions including social distancing measures and have encouraged maintaining adequate and frequent hand hygiene to slow down the disease transmission. Although access to clean water and soap is universal in high-income settings, it remains a basic need many do not have in low- and middle-income settings.

We analyzed data from Demographic and Health Surveys (DHS) of 16 countries in sub-Saharan Africa, using the most recent survey since 2015. Differences in the percentage of households with an observed handwashing place with water and soap were estimated by place of residence and wealth quintiles. Equiplots showed wide within-country disparities, disproportionately affecting the poorest households and rural residents, who represent the majority of the population in most of the countries.

Social inequalities in access to water and soap matter for the COVID-19 response in sub-Saharan Africa. Interventions such as mass distribution of soap and ensuring access to clean water, along with other preventive strategies should be scaled up to reach the most vulnerable populations.
Indoor air pollution concentrations and cardiometabolic health across four diverse settings in Peru: a cross-sectional study
Authors: Kephart Josiah L. , Fandiño-Del-Rio Magdalena , Koehler Kirsten , Bernabe-Ortiz Antonio , Miranda J. Jaime , Gilman Robert H. , Checkley William
Published: June 2020

Background

Indoor air pollution is an important risk factor for health in low- and middle-income countries.

Methods

We measured indoor fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations in 617 houses across four settings with varying urbanisation, altitude, and biomass cookstove use in Peru, between 2010 and 2016. We assessed the associations between indoor pollutant concentrations and blood pressure (BP), exhaled carbon monoxide (eCO), C-reactive protein (CRP), and haemoglobin A1c (HbA1c) using multivariable linear regression among all participants and stratifying by use of biomass cookstoves.

Results

We found high concentrations of indoor PM2.5 across all four settings (geometric mean ± geometric standard deviation of PM2.5 daily average in μg/m3): Lima 41.1 ± 1.3, Tumbes 35.8 ± 1.4, urban Puno 14.1 ± 1.7, and rural Puno 58.8 ± 3.1. High indoor CO concentrations were common in rural households (geometric mean ± geometric standard deviation of CO daily average in ppm): rural Puno 4.9 ± 4.3. Higher indoor PM2.5 was associated with having a higher systolic BP (1.51 mmHg per interquartile range (IQR) increase, 95% CI 0.16 to 2.86), a higher diastolic BP (1.39 mmHg higher DBP per IQR increase, 95% CI 0.52 to 2.25), and a higher eCO (2.05 ppm higher per IQR increase, 95% CI 0.52 to 3.57). When stratifying by biomass cookstove use, our results were consistent with effect measure modification in the association between PM2.5 and eCO: among biomass users eCO was 0.20 ppm higher per IQR increase in PM2.5 (95% CI − 2.05 to 2.46), and among non-biomass users eCO was 5.00 ppm higher per IQR increase in PM2.5 (95% CI 1.58 to 8.41). We did not find associations between indoor air concentrations and CRP or HbA1c outcomes.

Conclusions

Excessive indoor concentrations of PM2.5 are widespread in homes across varying levels of urbanisation, altitude, and biomass cookstove use in Peru and are associated with worse BP and higher eCO.
Alveolar lipids in pulmonary disease. A review
Authors: Agudelo Christina W. , Samaha Ghassan , Garcia-Arcos Itsaso
Published: June 2020

Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.
High fat diet altered cardiac metabolic gene profile in Psammomys obesus gerbils
Authors: Sahraoui Abdelhamid , Dewachter Céline , Vegh Grégory , Mc Entee Kathleen , Naeije Robert , Bouguerra Souhila Aouichat , Dewachter Laurence
Published: June 2020

Background

In metabolic disorders, myocardial fatty infiltration is critically associated with lipotoxic cardiomyopathy.

Methods

TwentyPsammomys obesusgerbils were randomly assigned to normal plant or high fat diet. Sixteen weeks later, myocardium was sampled for pathobiological evaluation.

Results

A sixteen-week high fat diet resulted in myocardial structure disorganization, with collagen deposits, lipid accumulation, cardiomyocyte apoptosis and inflammatory cell infiltration. Myocardial expressions of glucose transporter GLUT1 and pyruvate dehydrogenase (PDH) inhibitor, PDH kinase (PDK)4 increased, while insulin-regulated GLUT4 expression remained unchanged. Myocardial expressions of molecules regulating fatty acid transport, CD36 and fatty acid binding protein (FABP)3, were increased, while expression of rate-controlling fatty acid β-oxidation, carnitine palmitoyl transferase (CPT)1B decreased. Myocardial expression of AMP-activated protein kinase (AMPK), decreased, while expression of peroxisome proliferator activated receptors (PPAR)-α and -γ did not change.

Conclusion

In high fat diet fedPsammomys obesus, an original experimental model of nutritionally induced metabolic syndrome mixing genetic predisposition and environment interactions, a short period of high fat feeding was sufficient to induce myocardial structural alterations, associated with altered myocardial metabolic gene expression in favor of lipid accumulation.
Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway
Authors: Zhang Shun , Tu Haoyan , Yao Jun , Le Jianghua , Jiang Zhengxu , Tang Qianqian , Zhang Rongrong , Huo Peng , Lei Xiaocan
Published: June 2020

Background

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disease with unknown pathogenesis. However, the treatment of Diane-35 combined with metformin can improve the endocrine and ovulation of PCOS. In this study, we investigated the effects of Diane-35 combined with metformin (DM) treatment on ovulation and glucose metabolism in a PCOS rat model.

Methods

Sprague Dawley rats were divided into 3 groups, control group, model group (PCOS group) and Diane-35 combined with metformin (PCOS + DM group). The mRNA expression levels were determined by qRT-PCR. The hormone levels were determined by enzyme-linked immunosorbent assay. Immunostaining detected the protein levels of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2) and sirtuin 1 (SIRT1) in the ovarian tissues. TNUEL assay was performed to determine cell apoptosis in the PCOS rats. The metabolites in the ovarian tissues were analyzed by liquid chromatography with tandem mass spectrometry.

Results

PCOS rats showed an increased in body weight, levels of luteinizing hormone and testosterone and insulin resistance, which was significantly attenuated by the DM treatment. The DM treatment improved disrupted estrous cycle and increased the granulosa cells of the ovary in the PCOS rats. The decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats were significantly reversed by the DM treatment. The analysis of metabolics revealed that ATP and lactate levels were significantly decreased in PCOS rats, which was recovered by the DM treatment. Furthermore, the expression of LDH-A, PKM2 and SIRT1 was significantly down-regulated in ovarian tissues of the PCOS rats; while the DM treatment significantly increased the expression of LDH-A, PKM2 and SIRT1 in the ovarian tissues of the PCOS rats.

Conclusion

In conclusion, our study demonstrated that Diane-35 plus metformin treatment improved the pathological changes in the PCOS rats. Further studies suggest that Diane-35 plus metformin can improve the energy metabolism of the ovary via regulating the glycolysis pathway. The mechanistic studies indicated that the therapeutic effects of Diane-35 plus metformin treatment in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A and SIRT1.
Policy context, coherence and disjuncture in the implementation of the Ideal Clinic Realisation and Maintenance programme in the Gauteng and Mpumalanga provinces of South Africa
Authors: Muthathi Immaculate Sabelile , Rispel Laetitia C.
Published: June 2020

Background

Universal health coverage is a key target of the Sustainable Development Goals and quality of care is fundamental to its attainment. In South Africa, the National Health Insurance (NHI) system is a major health financing reform towards universal health coverage. The Ideal Clinic Realisation and Maintenance (ICRM) programme aims to improve the quality of care at primary healthcare level in preparation for NHI system implementation. This study draws on Bressers’ Contextual Interaction Theory to explore the wider, structural and specific policy context of the ICRM programme and the influence of this context on policy actors’ motivation, cognition and perceived power.

Methods

This was a nested qualitative study, conducted in two NHI pilot districts in the Gauteng and Mpumalanga Provinces of South Africa. Following informed consent, we conducted in-depth interviews with key informants involved in the conceptualisation and implementation of the ICRM programme. The questions focused on ICRM policy context, rationale and philosophy, intergovernmental relationships, perceptions of roles and responsibilities in implementation, ICRM programme resourcing, and implementation progress, challenges and constraints. We used thematic analysis, informed by Bressers’ theory, to analyse the data.

Results

A total of 36 interviews were conducted with key informants from national, provincial and local government. The wider context of the ICRM programme implementation was the drive to improve the quality of care at primary healthcare level in preparation for NHI. However, the context was characterised by contestations about the roles and responsibilities of the three government spheres and weak intergovernmental relationships. Notwithstanding examples of strong local leadership, the disjuncture between two national quality of care initiatives and resource constraints influenced policy actors’ experiences and perceptions of the ICRM programme. They expressed frustrations about the lack of or diffuse accountability and their lack of involvement in decision-making, thus questioning the sustainability of the ICRM programme.

Conclusions

National health sector reforms should consider the context of policy implementation and potential impact on actors’ motivation, cognition and power. All relevant policy actors should be involved in policy design and implementation. A clear communication strategy and ongoing monitoring and evaluation are prerequisites for implementation success.
Adolescent health programming in India: a rapid review
Authors: Barua Alka , Watson Katherine , Plesons Marina , Chandra-Mouli Venkatraman , Sharma Kiran
Published: June 2020

Background

Recognizing the potential of the country’s large youth population and the importance of protecting and supporting its health and well-being, the Government of India committed to strengthening its programmes and systems for adolescents, initially through the Adolescent Reproductive and Sexual Health Strategy (ARSH) launched in 2005 and, subsequently, through the National Adolescent Health Programme (Rashtriya Kishore Swaasthya Karyakram or RKSK) launched in 2014. In 2016, in response to a request from the Government of India, the World Health Organisation undertook a rapid programme review of ARSH and RKSK at the national level and in four states (Haryana, Madhya Pradesh, Maharashtra and Uttarakhand) to identify and document lessons learnt in relation to four domains of the programmes (governance, implementation, monitoring and linkages) that could be used to enhance current and future adolescent health programming in India.

Methodology and findings

A rapid programme review methodology was utilised to gain an overview of the successes and challenges of the two adolescent health programmes. A desk review of policy statements, Program Implementation Plans (PIPs) (Program Implementation Plan (PIP) is an annual process of planning, approval and allocation of budgets of various programmes under the National Health Mission (NHM). It is also used for monitoring of physical and financial progress made against the approved activities and budget.

), reports and data provided by the four State governments was conducted alongside 70 semi-structured interviews with health, education and NGO officials at national, state, district and block levels. Data showed that the ARSH Strategy put adolescent health on the agenda for the first time in India, though insufficient human and financial resources were mobilised to ensure maximum impact. Further, the Strategy’s focus on clinical service provision in a limited number of health facilities with a complementary focus on promoting community support and adolescent demand for them meant that services were not as easily accessible to adolescents in their communities, and in addition many were not even aware of them. Under RKSK, significant investment has been made in adequate management structures, as well as in community engagement and clinical service delivery at all levels of the health system. Monitoring the quality of service delivery remains a challenge in all four of the states, as does training of counsellors, nodal officers and other implementing partners. Additionally, further thought and action are required to ensure that peer educators are properly trained, supported and retained for the programme.

Conclusions

India’s RKSK clearly integrated learning from the earlier ARSH Strategy. The findings of this review present an opportunity for the government and its partners to ensure that future investment in adolescent health programming continues to be framed around lessons learnt across India.
The process of risky sexual behaviors formation in women drug users: a protocol for a grounded theory study
Authors: Sourinejad Hadis , Noroozi Mahnaz , Taleghani Fariba , Kheirabadi Gholam Reza
Published: June 2020

Background

Drug use is an important underlying factor in risky sexual behaviors. Risky sexual behaviors can lead to STIs and HIV/AIDS, especially in women. For better understanding of the relationship between drug use and risky sexual behaviors in women, it is necessary to identify the process of the formation of these behaviors that is a multidimensional process influenced by multiple socio-cultural factors. Therefore, the present study aims to explore the process of risky sexual behaviors formation in women drug users.

Methods

This is a grounded theory qualitative study with Corbin and Strauss approach. The participants of the study are women drug users with risky sexual behaviors who, using purposeful sampling method, will be selected from the Counseling and Harm Reduction centers for vulnerable women, the Drug Rehabilitation centers affiliated to the Isfahan University of Medical Sciences, Therapeutic Community Rehabilitation centers, Drop in Centers affiliated to the Welfare Organization, Medium-term Residential centers (women’s camps), and Women’s Empowerment centers in Isfahan, Iran. Sampling will continue using snowball method and the strategy of maximum variation in terms of the age, occupation, education, duration of the drug use, and type of the drug. During the sampling process, theoretical sampling will gradually replace purposeful sampling, so that sampling will proceed based on the emergence of the theory and for understanding of the concept and, then, the next participants will be selected. Sampling will continue until data saturation is reached. Data will be collected using individual semi-structured in-depth interviews, observation, field notes, and memo writing. Data will be coded as they are collected, and the analysis will be performed at three levels of open, axial, and selective coding and based on the constant comparative analysis. The four criteria of credibility, dependability, transferability and confirmability will be used to ensure the trustworthiness of the data.

Discussion

The findings of the present study are expected to provide a better understanding of the process of risky sexual behaviors formation in women drug users. The findings may also lead to the identification of the barriers and factors contributing to the formation of such behaviors and, finally, will promote the reproductive and sexual health of these women. This study can also provide the guide and the ground for designing and conducting further studies in the related areas through using various qualitative and quantitative methods.
Providers’ perceptions of communication and women’s autonomy during childbirth: a mixed methods study in Kenya
Authors: Afulani Patience A. , Buback Laura , Kelly Ann Marie , Kirumbi Leah , Cohen Craig R. , Lyndon Audrey
Published: June 2020

Background

Effective communication and respect for women’s autonomy are critical components of person-centered care. Yet, there is limited evidence in low-resource settings on providers’ perceptions of the importance and extent of communication and women’s autonomy during childbirth. Similarly, few studies have assessed the potential barriers to effective communication and maintenance of women’s autonomy during childbirth. We sought to bridge these gaps.

Methods

Data are from a mixed-methods study in Migori County in Western Kenya with 49 maternity providers (32 clinical and 17 non-clinical). Providers were asked structured questions on various aspects of communication and autonomy followed by open ended questions on why certain practices were performed or not. We conducted descriptive analysis of the quantitative data and thematic analysis of the qualitative data.

Results

Despite acknowledging the importance of various aspects of communication and women’s autonomy, providers reported incidences of poor communication and lack of respect for women’s autonomy: 57% of respondents reported that providers never introduce themselves to women and 38% reported that women are never able to be in the birthing position of their choice. Also, 33% of providers reported that they did not always explain why they are doing exams or procedures and 73% reported that women were not always asked for permission before exams or procedures. The reasons for lack of communication and autonomy fall under three themes with several sub-themes: (1) work environment—perceived lack of time, language barriers, stress and burnout, and facility culture; (2) provider knowledge, intentions, and assumptions—inadequate provider knowledge and skill, forgetfulness and unconscious behaviors, self-protection and comfort, and assumptions about women’s knowledge and expectations; and (3) women’s ability to demand or command effective communication and respect for their autonomy—women’s lack of participation, women’s empowerment and provider bias.

Conclusions

Most providers recognize the importance of various aspects of communication and women’s autonomy, but they fail to provide it for various reasons. To improve communication and autonomy, we need to address the different factors that negatively affect providers’ interactions with women.
Augmenting propulsion demands during split-belt walking increases locomotor adaptation of asymmetric step lengths
Authors: Sombric Carly J. , Torres-Oviedo Gelsy
Published: June 2020

Background

Promising studies have shown that the gait symmetry of individuals with hemiparesis due to brain lesions, such as stroke, can improve through motor adaptation protocols forcing patients to use their affected limb more. However, little is known about how to facilitate this process. Here we asked if increasing propulsion demands during split-belt walking (i.e., legs moving at different speeds) leads to more motor adaptation and more symmetric gait in survivors of a stroke, as we previously observed in subjects without neurological disorders.

Methods

We investigated the effect of propulsion forces on locomotor adaptation during and after split-belt walking in the asymmetric motor system post-stroke. To test this, 12 subjects in the chronic phase post-stroke experienced a split-belt protocol in a flat and incline session so as to contrast the effects of two different propulsion demands. Step length asymmetry and propulsion forces were used to compare the motor behavior between the two sessions because these are clinically relevant measures that are altered by split-belt walking.

Results

The incline session resulted in more symmetric step lengths during late split-belt walking and larger after-effects following split-belt walking. In both testing sessions, subjects who have had a stroke adapted to regain speed and slope-specific leg orientations similarly to young, intact adults. Importantly, leg orientations, which were set by kinetic demands, during baseline walking were predictive of those achieved during split-belt walking, which in turn predicted each individual’s post-adaptation behavior. These results are relevant because they provide evidence that survivors of a stroke can generate the leg-specific forces to walk more symmetrically, but also because we provide insight into factors underlying the therapeutic effect of split-belt walking.

Conclusions

Individuals post-stroke at a chronic stage can adapt more during split-belt walking and have greater after-effects when propulsion demands are augmented by inclining the treadmill surface. Our results are promising since they suggest that increasing propulsion demands during paradigms that force patients to use their paretic side more could correct gait asymmetries post-stroke more effectively.
Three kinds of treatment with Homoharringtonine, Hydroxychloroquine or shRNA and their combination against coronavirus PEDV in vitro
Authors: Li Cui-Cui , Wang Xiao-Jia
Published: June 2020

Background

Porcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There’s currently no specific drug available for treatment of coronaviruses or PEDV.

Method

In the current study, we use coronavirus PEDV as a model to study antiviral agents. Briefly, a fusion inhibitor tHR2, recombinant lentivirus-delivered shRNAs targeted to conserved M and N sequences, homoharringtonine (HHT), and hydroxychloroquine (HCQ) were surveyed for their antiviral effects.

Results

Treatment with HCQ at 50 μM and HHT at 150 nM reduced virus titer in TCID50 by 30 and 3.5 fold respectively, and the combination reduced virus titer in TCID50 by 200 fold.

Conclusion

Our report demonstrates that the combination of HHT and HCQ exhibited higher antiviral activity than either HHT or HCQ exhibited. The information may contribute to the development of antiviral strategies effective in controlling PEDV infection.