bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of four hub genes as promising biomarkers to evaluate the prognosis of ovarian cancer in silico
Authors: Chen Jingxuan , Cai Yun , Xu Rui , Pan Jiadong , Zhou Jie , Mei Jie
Published: June 2020

Background

Ovarian cancer (OvCa) is one of the most fatal cancers among females in the world. With growing numbers of individuals diagnosed with OvCa ending in deaths, it is urgent to further explore the potential mechanisms of OvCa oncogenesis and development and related biomarkers.

Methods

The gene expression profiles of GSE49997 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to explore the most potent gene modules associated with the overall survival (OS) and progression-free survival (PFS) events of OvCa patients, and the prognostic values of these genes were exhibited and validated based on data from training and validation sets. Next, protein–protein interaction (PPI) networks were built by GeneMANIA. Besides, enrichment analysis was conducted using DAVID website.

Results

According to the WGCNA analysis, a total of eight modules were identified and four hub genes (MM > 0.90) in the blue module were reserved for next analysis. Kaplan–Meier analysis exhibited that these four hub genes were significantly associated with worse OS and PFS in the patient cohort from GSE49997. Moreover, we validated the short-term (4-years) and long-term prognostic values based on the GSE9891 data, respectively. Last, PPI networks analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed several potential mechanisms of four hub genes and their co-operators participating in OvCa progression.

Conclusion

Four hub genes (COL6A3, CRISPLD2, FBN1 and SERPINF1) were identified to be associated with the prognosis in OvCa, which might be used as monitoring biomarkers to evaluate survival time of OvCa patients.
β-catenin promotes MTX resistance of leukemia cells by down-regulating FPGS expression via NF-κB
Authors: Liu Shu-Guang , Yue Zhi-Xia , Li Zhi-Gang , Zhang Rui-Dong , Zheng Hu-Yong , Zhao Xiao-Xi , Gao Chao
Published: June 2020

Background

Aberrant activation of β-catenin has been shown to play important roles in the chemoresistance of acute lymphoblastic leukemia (ALL), but the involvement and mechanism of β-catenin in methotrexate (MTX) resistance is poorly understood. In the present study, we demonstrate a critical role of β-catenin-NF-κB-FPGS pathway in MTX resistance in the human T-lineage ALL cell lines.

Methods

Lentivirus sh-β-catenin was used to silence the expression of β-catenin. Flow cytometry was performed to detect apoptosis after MTX treatment. Western blot, real-time PCR, Co-immunoprecipitation (Co-IP), Chromatin immunoprecipitation (ChIP), Re-ChIP, and Luciferase assay were utilized to investigate the relationship among β-catenin, nuclear factor (NF)-κB, and folypoly-γ-glutamate synthetase (FPGS).

Results

Depletion of β-catenin significantly increased the cytotoxicity of MTX. At the molecular level, knockdown of β-catenin caused the increase of the protein level of FPGS and NF-κB p65. Furthermore, β-catenin complexed with NF-κB p65 and directly bound to the FPGS promoter to regulate its expression. In addition, β-catenin repression prolonged the protein turnover of FPGS.

Conclusions

Taken together, our results demonstrate that β-catenin may contribute to MTX resistance in leukemia cells via the β-catenin-NF-κB-FPGS pathway, posing β-catenin as a potential target for combination treatments during ALL therapy.
Activation of the LINC00242/miR-141/FOXC1 axis underpins the development of gastric cancer
Authors: Zhong Xiongdong , Yu Xianchang , Wen Xiaoyan , Chen Lei , Gu Ni
Published: June 2020

Background

Long non-coding RNAs (LncRNAs) are a class of newly identified transcripts recognized as critical governors of gene expression during human carcinogenesis, whereas their tumor-suppressive or tumor-promoting effects on gastric cancer (GC) are required for further investigation. In the study, we identify the expression pattern of a novel lncRNA LINC00242 in GC and its possible permissive role in the development of GC.

Methods

The study included 68 pairs of GC and adjacent normal gastric tissue samples. The viability, migration, and invasion of cultured human GC cells HGC27 were evaluated by CCK-8 and Transwell chamber assays. In vitro tube formation of human brain microvascular endothelial cells (HBMVECs) in HGC27 cell coculture was detected. The regulatory network of LINC00242/miR-141/FOXC1 was verified using dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Subcutaneous xenografts of HGC27 cells were performed in nude mice.

Results

LINC00242 was highly expressed in GC tissues and cells and contributed to poor prognosis. LINC00242 knockdown inhibited HGC27 cell viability, migration and invasion, and tube formation of HBMVECs. LINC00242 interacted with miR-141 and positively regulated FOXC1, a target gene of miR-141. LINC00242 knockdown was partially lost in HGC27 cells upon miR-141 inhibition or FOXC1 overexpression. The tumor-promoting effect of LINC00242 on GC was demonstrated in nude mice.

Conclusion

Taken together, the present study demonstrates the oncogenic role of the LINC00242/miR-141/FOXC1 axis in GC, highlighting a theoretical basis for GC treatment.
Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer
Authors: Jin Xiao , Dai Lu , Ma Yilan , Wang Jiayan , Liu Zheng
Published: June 2020

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1 alpha (HIF-1α) is a major regulator of cellular response to changes in oxygen concentration, supporting the adaptation of tumor cells to hypoxia in an oxygen-deficient tumor microenvironment. Numerous studies revealed the central role of HIF-1α in the carcinogenesis and progression of pancreatic cancer. This article reviewed the molecular mechanisms of how HIF-1α regulated tumorigenesis and progression of pancreatic cancer and suggested that targeting HIF-1α and its signaling pathways could be promising therapeutics for pancreatic cancer.
Efficacy and safety of artesunate–amodiaquine and artemether–lumefantrine and prevalence of molecular markers associated with resistance, Guinea: an open-label two-arm randomised controlled trial
Authors: Beavogui Abdoul Habib , Camara Alioune , Delamou Alexandre , Diallo Mamadou Saliou , Doumbouya Abdoulaye , Kourouma Karifa , Bouedouno Patrice , Guilavogui Timothée , dos Santos Souza Samaly , Kelley Julia , Talundzic Eldin , Fofana Aissata , Plucinski Mateusz M.
Published: June 2020

Background

Anti-malarial resistance is a threat to recent gains in malaria control. This study aimed to assess the efficacy and safety of artesunate–amodiaquine (ASAQ) and artemether–lumefantrine (AL) in the management of uncomplicated malaria and to measure the prevalence of molecular markers of resistance of Plasmodium falciparum in sentinel sites in Maferinyah and Labé Health Districts in Guinea in 2016.

Methods

This was a two-arm randomised controlled trial of the efficacy of AL and ASAQ among children aged 6–59 months with uncomplicated Plasmodium falciparum malaria in two sites. Children were followed for 28 days to assess clinical and parasitological response. The primary outcome was the Kaplan–Meier estimate of Day 28 (D28) efficacy after correction by microsatellite-genotyping. Pre-treatment (D0) and day of failure samples were assayed for molecular markers of resistance in the pfk13 and pfmdr1 genes.

Results

A total of 421 participants were included with 211 participants in the Maferinyah site and 210 in Labé. No early treatment failure was observed in any study arms. However, 22 (5.3%) participants developed a late treatment failure (8 in the ASAQ arm and 14 in the AL arm), which were further classified as 2 recrudescences and 20 reinfections. The Kaplan–Meier estimate of the corrected efficacy at D28 was 100% for both AL and ASAQ in Maferinyah site and 99% (95% Confidence Interval: 97.2–100%) for ASAQ and 99% (97.1–100%) for AL in Labé. The majority of successfully analysed D0 (98%, 380/389) and all day of failure (100%, 22/22) samples were wild type for pfk13. All 9 observed pfk13 mutations were polymorphisms not associated with artemisinin resistance. The NFD haplotype was the predominant haplotype in both D0 (197/362, 54%) and day of failure samples (11/18, 61%) successfully analysed for pfmdr1.

Conclusion

This study observed high efficacy and safety of both ASAQ and AL in Guinea, providing evidence for their continued use to treat uncomplicated malaria. Continued monitoring of ACT efficacy and safety and molecular makers of resistance in Guinea is important to detect emergence of parasite resistance and to inform evidence-based malaria treatment policies.
Caregiver and community perceptions and experiences participating in an infant malaria prevention trial of PfSPZ Vaccine administered by direct venous inoculation: a qualitative study in Siaya County, western Kenya
Authors: Achieng Florence , Rosen Joseph G. , Cherop Reuben Yego , Kariuki Simon , Hoffman Stephen L. , Seder Robert , Oneko Martina , Steinhardt Laura C.
Published: June 2020

Background

Despite available control strategies, malaria morbidity and mortality, especially in infants and young children in sub-Saharan Africa, remain intractable. Malaria vaccination could substantially reduce malaria episodes and deaths. One vaccine candidate is the whole sporozoite PfSPZ Vaccine, consisting of irradiated cryopreserved sporozoites administered by direct venous inoculation (DVI). DVI may be less acceptable than more familiar administration routes, particularly intramuscular. As part of a PfSPZ Vaccine trial among infants in western Kenya, a qualitative study was conducted to explore caregiver and community perceptions of the malaria vaccine trial, including the unique DVI administration procedure.

Methods

Twelve focus groups and 28 in-depth interviews explored perceptions of the DVI procedure in infants, factors influencing trial acceptability, and barriers to sustained trial participation. Purposively sampled participants included mothers of enrolled children, fathers and mothers who withdrew their children from the trial, village elders, and study clinicians from two trial enrollment sites. An iterative, multi-stage analytic approach, adapted from the Framework Method, was used to synthesize and interpret textual data.

Results

Desires to prevent malaria and participation incentives (e.g., free consultations and medication) motivated caregivers to enroll their children in the trial. However, numerous factors also demotivated trial participation. Family members’ (i.e., fathers') objections to required blood draws were cited most frequently as drivers of early trial withdrawal, in many cases prior to receiving any vaccine. Among mothers whose children received PfSPZ Vaccine (or placebo), many spoke favourably of DVI administration, describing improved tolerability relative to intramuscularly administered immunizations. Other trial-related challenges cited by caregivers included negative interactions with study clinicians and perceived delays in administering trial procedures.

Conclusions

Despite high acceptance of DVI among caregivers whose children received PfSPZ Vaccine (or placebo), objections to trial procedures from other non-sensitized household and family members prompted early trial withdrawal and inhibited successful completion of trial procedures for some infants. Implications for future trials include targeting heads of household during sensitization and recruitment activities, as well as equipping trial staff to effectively respond to participant and community concerns regarding trial procedures.
The impact of gravidity, symptomatology and timing of infection on placental malaria
Authors: Tran Erin E. , Cheeks Morgan L. , Kakuru Abel , Muhindo Mary K. , Natureeba Paul , Nakalembe Miriam , Ategeka John , Nayebare Patience , Kamya Moses , Havlir Diane , Feeney Margaret E. , Dorsey Grant , Gaw Stephanie L.
Published: June 2020

Background

Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria.

Methods

The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection.

Results

Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34–18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69–3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02–1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23–28.43, p < 0.001).

Conclusions

Total number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.
Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer
Authors: Li Yaqing , Tian Zhenfeng , Tan Ying , Lian Guoda , Chen Shangxiang , Chen Shaojie , Li Jiajia , Li Xuanna , Huang Kaihong , Chen Yinting
Published: June 2020

Background

We previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP.

Methods

Microarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.

Results

The downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155.

Conclusions

Bmi-1 was proven to induce the expression of miR-27a and miR-155 and thus promote tumor metastasis and chemoresistance by targeting RKIP in GC. Overall, miR-27a and miR-155 might be promising targets for the screening, diagnosis, prognosis, treatment and disease monitoring of GC.
Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation
Authors: Han Min , Chen Xiao-Cui , Sun Ming-Hui , Gai Min-Tao , Yang Yi-Ning , Gao Xiao-Ming , Ma Xiang , Chen Bang-Dang , Ma Yi-Tong
Published: June 2020

Background

Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway.

Methods

The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins.

Results

IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation.

Conclusion

IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.
NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway
Authors: Tang Biao , Liu Dan , Chen Lingyu , Liu Yu
Published: June 2020

Background

Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear.

Methods

To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, 30 female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis.

Results

MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF2α and PGE2, and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus.

Conclusions

MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.
Sociodemographic determinants of maternal health service use in rural China: a cross-sectional study
Authors: Jiang Kexin , Liang Libo , Wang Haifeng , Li Jingqun , Li Yuze , Jiao Mingli , Mao Jingfu , Wu Qunhong
Published: June 2020

Objective

This study examined the relationship between sociodemographic characteristics and maternal health use from a policy perspective. It aimed to provide an overview of maternal health in Heilongjiang’s rural provinces and its implications on rural areas in countries with low and middle income gross domestic products.

Design, setting, and participants

This cross-sectional study used data from the Fifth Health Service Survey of Heilongjiang Province. Participants included 481 mothers who delivered a baby after August 15, 2008. Trained investigators collected data on their family and sociodemographic characteristics, antenatal care, delivery at specialised obstetric institutions (e.g. hospitals, clinics, other medical institutions), and postnatal care services.

Results

The number of women with more than five antenatal care visits and the delivery rate at specialised obstetric institutions were high. Approximately 50% of the participants had three or more postnatal care visits. Maternal healthcare use among women less than 20 years old and those with natural deliveries were higher. There were fewer antenatal care visits among women who had been pregnant once or twice before.

Conclusions

Delivery rates at specialised obstetric institutions and the number of antenatal care visits were higher than the World Health Organization requirements, while the frequency of postnatal care visits were better than most countries. This study identified several demographic characteristics that influenced maternal health service use. Policymakers should consider these findings when developing maternal health policies that protect women’s interests and expand free services. Additional resources should be given to increase the postnatal care capacity and quality of maternal healthcare.
Correction to: The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus
Authors: Xu Lili , Bao Linlin , Deng Wei , Zhu Hua , Chen Ting , Lv Qi , Li Fengdi , Yuan Jing , Xiang Zhiguang , Gao Kai , Xu Yanfeng , Huang Lan , Li Yanhong , Liu Jiangning , Yao Yanfeng , Yu Pin , Yong Weidong , Wei Qiang , Zhang Lianfeng , Qin Chuan
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Early life high-fat diet exposure evokes normal weight obesity
Authors: Maejima Yuko , Yokota Shoko , Horita Shoichiro , Shimomura Kenju
Published: June 2020

Obesity is becoming one of the most severe global health problems. However, risk of developing normal weight obesity, where an individual has a high percentage of body fat despite a normal body mass index, is gaining attention since such individuals also develop systemic inflammation and metabolic dysregulation.

In this study, juvenile (3-week-old) and adult (8-week-old) rats were fed a high fat diet (HFD) for 9 weeks and compared them with normal chow diet (NCD) fed rats. The HFD fed adult group showed increase in energy intake, body weight (BW), total fat, visceral fat and subcutaneous fat compared with an age-matched NCD group. In addition, the percentage of muscle mass to BW in the adult HFD group was significantly lower compared with the NCD group. When HFD feeding was started from the juvenile stage, there were almost no differences in energy intake and BW between the HFD and NCD groups. However, the juvenile HFD group showed a 1.7-fold increase in total fat, visceral fat and subcutaneous fat compared with their age-matched NCD group. The percentage of muscle mass to BW was significantly lower in the juvenile HFD group compared with the NCD group. In addition, increased plasma insulin levels and decreased insulin sensitivity was observed only in juvenile HFD group, but not in adult HFD group. These results suggest that HFD feeding in growth period induces insulin resistance and normal weight obesity.

Here we show a method for generating a normal weight obesity model, as well as raising the alarm for developing normal weight obesity when children are exposed to high-fat meals.
Globalisation in the time of COVID-19: repositioning Africa to meet the immediate and remote challenges
Authors: Yaya Sanni , Otu Akaninyene , Labonté Ronald
Published: June 2020

The COVID-19 pandemic has ushered in a new climate of uncertainty which is fuelling protectionism and playing into nationalist narratives. Globalisation is under significant threat as governments scramble to reduce their vulnerability to the virus by limiting global trade and flows of people. With the imposition of border closures and strict migration measures, there have been major disruptions in Africa’s global supply chains with adverse impacts on employment and poverty. The African economies overly reliant on single export-orientated industries, such as oil and gas, are expected to be severely hit. This situation is further aggravated by tumbling oil prices and a lowered global demand for African non-oil products. The agricultural sector, which should buffer these shocks, is also being affected by the enforcement of lockdowns which threaten people’s livelihoods and food security. Lockdowns may not be the answer in Africa and the issue of public health pandemic response will need to be addressed by enacting context-specific policies which should be implemented in a humane way. In addressing the socioeconomic impact of COVID-19 on African nations, we argue that governments should prioritize social protection programmes to provide people with resources to maintain economic productivity while limiting job losses. International funders are committing assistance to Africa for this purpose, but generally as loans (adding to debt burdens) rather than as grants. G20 agreement so suspend debt payments for a year will help, but is insufficient to fiscal need. Maintaining cross-border trade and cooperation to continue generating public revenues is desirable. New strategies for diversifying African economies and limiting their dependence on external funding by promoting trade with a more regionalised (continental) focus as promoted by the African Continental Free Trade Agreement, while not without limitations, should be explored. While it is premature to judge the final economic and death toll of COVID-19, African leaders’ response to the pandemic, and the support they receive from wealthier nations, will determine its eventual outcomes.
The enclosed ward management strategies in psychiatric hospitals during COVID-19 outbreak
Authors: Chen Jiajia , Xiong Maoxiang , He Zongling , Shi Wen , Yue Yuchuan , He Manxi
Published: June 2020

During the COVID-19 pandemic, as a large city located in Southwest China, Chengdu was mainly affected by imported cases. For a psychiatric hospital, the enclosed management model, the crowded wards and the uncooperative patients are the risk factors of nosocomial infection. Admitting new patients while preventing the COVID-19 outbreak within the institutions was a crucial challenge. The Mental Health Centre of Chengdu proposed a series of effective management strategies to deal with the rapidly evolving situation during the COVID-19 pandemic which included regulation for the inpatients, their families and staff, and achieved Zero infection in our hospital.
The use of fish and herptiles in traditional folk therapies in three districts of Chenab riverine area in Punjab, Pakistan
Authors: Altaf Muhammad , Abbasi Arshad Mehmood , Umair Muhammad , Amjad Muhammad Shoaib , Irshad Kinza , Khan Abdul Majid
Published: June 2020

Background

Like botanical taxa, various species of animals are also used in traditional and modern health care systems. Present study was intended with the aim to document the traditional uses of herptile and fish species among the local communities in the vicinity of the River Chenab, Punjab Pakistan.

Method

Data collected by semi-structured interviews and questionnaires were subsequently analyzed using relative frequency of citation (FC), fidelity level (FL), relative popularity level (RPL), similarity index (SI), and rank order priority (ROP) indices.

Results

Out of total 81 reported species, ethnomedicinal uses of eight herptiles viz. Aspideretes gangeticus, A. hurum, Eublepharis macularius, Varanus bengalensis, Python molurus, Eryx johnii, Ptyas mucosus mucosus, Daboia russelii russelii and five fish species including Hypophthalmichthys molitrix, Cirrhinus reba, Labeo dero, Mastacembelus armatus, and Pethia ticto were reported for the first time from this region. Fat, flesh, brain, and skin were among the commonly utilized body parts to treat allergy, cardiovascular, nervous and respiratory disorders, sexual impotency, skin infections, and as antidote and anti-diabetic agents. Hoplobatrachus tigerinus, Duttaphrynus stomaticus, and Ptyas mucosus mucosus (herptiles), as well as Labeo rohita, Wallago attu, and Cirrhinus reba (fish) were top ranked with maximum informant reports, frequency of citations, and rank order priority. Uromastyx hardwickii, Ctenopharyngodon idella, H. molitrix, Cirrhinus mrigala, C. reba, L. rohita, L. calbasu, L. dero, and Pethia ticto were the species with 100% fidelity level. Furthermore, medicinal uses of Aspideretes gangeticus, Aspideretes hurum, Calotes versicolor, Daboia russelii russelii, Hypophthalmichthys molitrix, Cirrhinus reba, Labeo dero, Mastacembelus armatus, Pethia ticto, and Gagata cenia were reported for the first time.

Conclusion

About half of the reported species depicted zero similarity index with previously reported literature, which indicates strong associations of local inhabitants with animal species, particularly for therapeutic purpose. Inclusive studies on composition and bioactivities of the species with maximum use reports may contribute significantly in animal-based novel drugs discovery.
Mental health problems among young people in substance abuse treatment in Sweden
Authors: Richert Torkel , Anderberg Mats , Dahlberg Mikael
Published: June 2020

Background

Young people with substance use problems face a high risk of co-occurring mental health problems, something that may involve a more difficult life situation, social problems as well as worse treatment outcomes. The aim of this study is to analyse self-reported mental health problems among young people receiving outpatient treatment for substance use problems in Sweden. We explore what types of mental health problems are more or less predominant, and whether there are significant differences between boys and girls. In addition, we analyse how various mental health problems covary with indicators of substance abuse severity.

Methods

The study is based on structured interviews with 1970 young people enrolled at outpatient clinics in 11 Swedish cities. The data was analysed through frequency- and averages-calculations, Chi-square tests and multivariate logistic regression analyses.

Results

Self-reported mental health problems were common among the young people in the study. A relatively large percentage of the total group (34–54%) reported problems such as concentration difficulties, sleeping difficulties, anxiety and depression. At the same time, many of the young people did not report any symptoms and only a small group, about 20%, reported diagnosed mental health disorders. The results show substantial gender differences, with girls reporting significantly higher levels of mental health problems.

Multivariate logistic regression analyses demonstrated significant associations between severity of drug use problems and anxiety, concentration difficulties, aggression, hallucinations and mental stress caused by experiences of trauma.

Conclusions

Treatment needs are diverse within this group of young people who use drugs. Since girls report higher levels of all mental health problems, and a larger burden of psychosocial risk factors than boys, they are likely to require more comprehensive treatment interventions. The link between more severe drug problems and mental health problems points to the importance of exploring this relationship in treatment. A multidisciplinary approach, in which co-occurring problems can be addressed simultaneously, may be the best treatment form for many young people with drug problems.
Prevention of health care associated venous thromboembolism through implementing VTE prevention clinical practice guidelines in hospitalized medical patients: a systematic review and meta-analysis
Authors: Abboud Juliana , Abdel Rahman Abir , Kahale Lara , Dempster Martin , Adair Pauline
Published: June 2020

Background

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. Numerous VTE prevention clinical practice guidelines are available but not consistently implemented. This systematic review explored effectiveness of implementing VTE prevention clinical practice guidelines on VTE risk assessment and appropriateness of prophylaxis in hospitalized adult medical patients and identified the interventions followed to improve the adherence to these guidelines.

Methods

Six electronic databases were searched for randomized controlled trials, clinical controlled trials, or pre/post evaluation studies up to January 2019. Studies identified were screened for eligibility by two reviewers independently. Data were extracted by two reviewers using a standardized form. Risk of bias was assessed using MINORS and the certainty of evidence for each outcome using the GRADE approach.

Results

Of the 3537 records identified, 36 were eligible; eight studies were included for qualitative synthesis and four for meta-analysis. The meta-analysis of the studies assessing the impact of implementing VTE clinical practice guidelines favored appropriate prophylaxis (RR 1.67, 95% CI 1.41 to 1.97, 552 patients). Potential risk of bias was assessed to be low for 28% of the studies. However, using GRADE, the certainty of the evidence of all outcomes was rated very low quality.

Conclusions

The lack of randomized controlled trials in this area reduces the quality of the evidence available. The evidence from before-after studies suggests that the implementation of VTE clinical practice guidelines may increase the practice of VTE risk assessment and appropriate prophylaxis in hospitalized medical patients.

Trial registration

PROSPEROCRD42018085506
Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia
Authors: Worth Chris , Hashmi Laila Al , Yau Daphne , Salomon-Estebanez Maria , Ruiz Diego Perez , Hall Caroline , O’Shea Elaine , Stokes Helen , Foster Peter , Flanagan Sarah E. , Cosgrove Karen E , Dunne Mark J , Banerjee Indraneel
Published: June 2020

Background

Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology.

Aim

We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years.

Method

We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset.

Results

Seventy patients were recruited to the study. Mean weight at birth was − 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was − 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009).

Conclusion

In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.
Prevalence and association of Epstein-Barr virus infection with sinonasal inverted papilloma and sinonasal squamous cell carcinoma in the northeastern Thai population
Authors: Nukpook Thawaree , Ekalaksananan Tipaya , Teeramatwanich Watchareporn , Patarapadungkit Natcha , Chaiwiriyakul Surachat , Vatanasapt Patravoot , Aromseree Sirinart , Pientong Chamsai
Published: June 2020

Aims

Sinonasal inverted papillomas (SIP) and sinonasal squamous cell carcinomas (SNSCC) are sinonasal tumors with unclear etiology and pathogenesis. Epstein-Barr virus (EBV) has been detected in these tumors but information concerning their association is still limited. This study aimed to investigate the prevalence in, and association of EBV infection with SIP and SNSCC in northeastern Thailand.

Methods

DNA was extracted from 226 formalin-fixed, paraffin-embedded tissues including 80 nasal polyps (NP; the control group), 64 SIP and 82 SNSCC samples. Presence of EBV in these tissues was investigated using real-time PCR and their localization within tissues was confirmed using in situ hybridization (ISH). Characteristics of patients and the association of EBV prevalence with sinonasal tumors were analyzed.

Results

SIP and SNSCC were frequently found in people aged > 50 years and more often in males than in females (3:1 ratio). EBV infection was detected in 33.75, 64.06 and 37.80% of NP, SIP and SNSCC tissues, respectively, by real-time PCR. There was a statistically significant association between EBV infection and SIP (odds ratio [OR] = 3.52). This was not the case for SNSCC when compared to the NP group (OR = 1.83). Interestingly, EBV infection tended to be associated with inflammation and dysplasia in SIP. In SNSCC, EBV was mostly found in samples with undifferentiated or poorly differentiated cell types as well as in recurrent cases and lymph-node metastasis. Using ISH, EBV was detected only in infiltrating lymphocytes within the tumor stroma, not in the tumor epithelial cells.

Conclusions

Infiltrating lymphocytes containing EBV in the tumor microenvironment might enhance tumorigenesis of SIP and SNSCC. The mechanism by which EBV promotes development of SIP and SNSCC needs to be elucidated in the future.
A descriptive study of acute outbreaks of respiratory disease in Norwegian fattening pig herds
Authors: Cohen Liza Miriam , Grøntvedt Carl Andreas , Klem Thea B. , Gulliksen Stine Margrethe , Ranheim Birgit , Nielsen Jens Peter , Valheim Mette , Kielland Camilla
Published: June 2020

Background

Respiratory diseases are major health concerns in the pig production sector worldwide, contributing adversely to morbidity and mortality. Over the past years there was a rise in reported incidents of respiratory disease in pigs in Norway, despite population wide freedom from Aujeszky´s disease, porcine reproductive and respiratory syndrome, porcine respiratory corona virus and enzootic pneumonia. The main objective of this study was to investigate acute outbreaks of respiratory disease in conventional Norwegian fattening pig herds. The study included 14 herds. In seven herds with reported outbreaks of acute respiratory disease, data on clinical signs was recorded and samples for laboratory examination were collected. Diagnostic protocols were compared by parallel analysis of clinically healthy pigs from seven non-outbreak herds.

Results

The most commonly reported clinical signs were sudden deaths and dyspnea. An average compartment morbidity of 60%, mortality of 4% and case fatality of 9% was recorded in the outbreak herds. Post-mortem examinations revealed acute lesions resembling porcine pleuropneumonia in all 28 pigs investigated from the outbreak herds and in 2 of the 24 (8%) pigs from the non-outbreak herds. Chronic lesions were recorded in another 2 pigs (8%) from the non-outbreak herds.Actinobacillus pleuropneumoniaeserovar 8 was isolated from lungs and/or pleura from all tested pigs (n = 28) in the outbreak herds, and from 2 out of 24 pigs (8%) in the non-outbreak herds, one pig with an acute and another pig with a chronic infection. No other significant bacterial findings were made. Seroconversion toA. pleuropneumoniaeantibodies was detectable in all outbreak herds analyzed and in six out of seven non-outbreak herds, but the risk ratio for seroconversion of individual pigs was higher (risk ratio 2.3 [1.50- 3.43 95% CI; P < 0.001]) in the outbreak herds. All herds tested positive for porcine circovirus type 2 and negative for influenza A viruses on oral fluid RT-qPCR.

Conclusion

The main etiological pathogen found during acute outbreaks of respiratory disease wasA. pleuropneumoniaeserovar 8. All pigs from outbreak herds had typical lesions of acute porcine pleuropneumonia, and onlyA. pleuropneumoniaeserovar 8 was identified. Co-infections were not found to impact disease development.
Streptococcus suis in Swedish grower pigs: occurrence, serotypes, and antimicrobial susceptibility
Authors: Werinder Anna , Aspán Anna , Backhans Annette , Sjölund Marie , Guss Bengt , Jacobson Magdalena
Published: June 2020

Background

Streptococcus suisis a major cause of meningitis, arthritis, and pneumonia in pigs worldwide, and an emerging pathogen in humans. In Sweden,S. suishas previously received little attention but has in recent years become increasingly recognized as affecting the pig production. The aim of the present study was to investigate the occurrence, serotypes and antimicrobial susceptibility ofS. suisin Swedish grower pigs from herds with and without reportedS. suisassociated disease, as well as possible associations betweenS. suisassociated disease and selected environmental and production factors. Swab samples were taken from the tonsils of clinically healthy 8–13-week-old grower pigs from ten case herds and ten control herds. Isolates were cultured, identified using MALDI–TOF MS, and serotyped using latex agglutination. The antimicrobial susceptibility of 188 isolates was tested using broth microdilution. Production data was gathered and environmental parameters were measured on the farms.

Results

Streptococcus suiswas isolated from 95% of the sampled pigs in both the case and the control herds. Serotypes 3, 4, 5, 7, 9, 10, 11, 15, 16, and 17–34 were detected, although a majority of the isolates (81.5%) were non-typeable. There was less diversity among the serotypes isolated from the case herds than among those from the control herds; four and nine different serotypes, respectively. Isolates resistant to penicillin (3.8%) were reported for the first time in Sweden. Tetracycline resistance was common (88.4%). No association was noted between the production and the environmental factors investigated, and the carriership ofS. suis.

Conclusions

The carriership ofS. suiswas found to be higher in clinically healthy Swedish pigs than previously estimated, and for the first time, the presence of Swedish isolates resistant to penicillin was reported. Many of the most commonly disease-associated serotypes, e.g. serotypes 2, 9, 3, and 7, were detected in healthy grower pigs although further studies are needed to investigate the virulence of these isolates.
A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis
Authors: Ma M. H. Y. , Defranoux N. , Li W. , Sasso E. H. , Ibrahim F. , Scott D. L. , Cope A. P.
Published: June 2020

Background

Reliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission.

Methods

RA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as ‘low disease activity state’ (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as ‘persistent disease activity’ (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test.

Results

Of 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68–0.75) and IR/SR (AUROCs 0.65–0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65–0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year.

Conclusions

This study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.