bluuebunny/crossref_metadata_2025 huggingface dataset:
“I can make more from selling medicine when breaking the rules” – understanding the antibiotic supply network in a rural community in Viet Nam
Authors: Nguyen Hong Hanh , Ho Dang Phuc , Vu Thi Lan Huong , Tran Khanh Toan , Tran Thanh Do , Nguyen Thi Kim Chuc , van Doorn H. Rogier , Nadjm Behzad , Kinsman John , Wertheim Heiman
Published: November 2019

Background

As in many other low and middle income countries (LIMCs), Vietnam has experienced a major growth in the pharmaceutical industry, with large numbers of pharmacies and drug stores, and increasing drug expenditure per capita over the past decade. Despite regulatory frameworks that have been introduced to control the dispensing and use of prescription-only drugs, including antibiotics, compliance has been reported to be strikingly low particularly in rural parts of Vietnam. This qualitative study aimed to understand antibiotic access and use practices in the community from both supplier and consumer perspectives in order to support the identification and development of future interventions.

Methods

This qualitative study was part of a project on community antibiotic access and use (ABACUS) in six LMICs. The focus was Ba Vi district of Hanoi capital city, where we conducted 16 indepth interviews (IDIs) with drug suppliers, and 16 IDIs and 6 focus group discussions (FGDs) with community members. Drug suppliers were sampled based on mapping of all informal and formal antibiotic purchase or dispensing points in the study area. Community members were identified through local networks and relationships with the field collaborators. All IDIs and FGDs were audio-taped, transcribed and analysed using content analysis.

Results

We identified a large number of antibiotic suppliers in the locality with widespread infringements of regulatory requirements. Established reciprocal relationships between suppliers and consumers in drug transactions were noted, as was the consumers’ trust in the knowledge and services provided by the suppliers. In addition, antibiotic use has become a habitual choice in most illness conditions, driven by both suppliers and consumers.

Conclusions

This study presents an analysis of the practices of antibiotic access and use in a rural Vietnamese setting. It highlights the interactions between antibiotic suppliers and consumers in the community and identifies possible targets for interventions.
Nearly three in every five prisoners experience common mental disorders (CMDs) in Jimma correctional institution; south-West Ethiopia
Authors: Adraro Wasihun , Kerebih Habtamu , Tesema Workinesh , Abamecha Fira , Hailesilassie Hailemariam
Published: November 2019

Background

Millions of people are currently suffering from some form of mental disorders. The prevalence of common disorders is twofold higher in prison than general population and the condition is found to be worst in African in general and Ethiopia in particular. The aim of this study was to assess the prevalence of common mental disorders and its correlates among prisoners in Jimma town correctional institution; Ethiopia.

Methods

A cross sectional quantitative study was conducted enrolling 300 prisoners. The participants were recruited using systematic random sampling technique. The World health organization Self Reporting Questionnaire (SRQ-20) scale; was adapted to assess prevalence of mental disorders. Data were collected on interviewer administered basis by trained personnel. Statistical package for social sciences (SPSS) version 20 for widows was used for data analysis. Multivariate logistic regression modelling was conducted to identify the independent predictors of common mental disorders. P-value less than 5% was considered to indicate significant associations.

Results

The prevalence of common mental disorder was found to be 62.70, 95% CI; [57.30, 68.50]. Prisoners who had monthly income of 1500-3000birr, AOR = 3.30, 95% CI; [1.25, 8.69] and above 3000birr; AOR = 4.75, 95% CI; [1.57, 14.33], family history of mental illness; AOR = 6.14, 95% CI; [1.65, 22.79] and who ever used Khat; AOR = 4.33, 95% CI; [2.02, 9.27] were more likely to experience common mental disorders. Conversely; having some sort of work in prison; AOR = 0.25, 95% CI; [0.12, 0.54], perceived moderate social support; AOR = 0.094, 95% CI; [0.04–0.215] and perceived moderate strong; AOR = 0.025, 95% CI; [0.009, 0.07] were found to be protective factors.

Conclusion

Prevalence of common mental disorder was considerably high as nearly more than three in every five prisoner experience some form of the disorder. Early screening of prisoners up on their arrival, appropriate treatment and follow up should be done. Furthermore; creating prison based jobs that could bring prisoners together and encouraging positive relationships to build social supports as coping strategy is required.
Knowledge, attitudes and practices relating to antibiotic use among community members of the Rupandehi District in Nepal
Authors: Nepal Anant , Hendrie Delia , Robinson Suzanne , Selvey Linda A.
Published: November 2019

Background

The development of antibiotic resistance is one of the biggest threats to global public health. Inappropriate use of antibiotics is recognised as a leading cause of antibiotic resistance. The aim of this study was to explore the knowledge, attitudes and practices (KAP) towards antibiotic use among adults in Nepal.

Methods

A quantitative survey was conducted with 220 community members of the Rupandehi district of Nepal, with cluster sampling techniques applied to select households. Interviews were carried out face-to-face using a structured questionnaire. Responses were presented using descriptive analysis, with chi-squared tests and regression analysis applied to identify factors associated with KAP about antibiotic use and the Spearman’s rank order correlation coefficient calculated to examine the relationship between responses to the KAP questions.

Results

The sample comprised more females (54%) than males, the average age of respondents was 38.5 years and almost 60% of respondents lived in rural areas. Respondents had relatively good knowledge about aspects of antibiotic use other than identifying antibiotics. The concept of antibiotic resistance was well known but imperfectly understood. Half of respondents (50.9%) were unsure whether skipping doses would contribute to the development of antibiotic resistance, 88.2% indicated they would go to another doctor if not prescribed an antibiotic when they thought one was needed and nearly half (47.7%) believed antibiotics helped them get better more quickly if they had a fever. Most respondents reported correct practices accessing and using antibiotics, however, 84.6% at least sometimes preferred an antibiotic when they have a cough and sore throat.

Logistic regression showed respondents with higher levels of education tended to have better knowledge, more appropriate attitudes and better practices about antibiotic use. Rural respondents were less likely to have better knowledge about antibiotic use, while females were more likely to report better practices.

Conclusion

The study provides baseline evidence about the knowledge, attitudes and practices regarding antibiotic use among the population of the Rupandehl district. Its findings will be useful in designing effective and targeted interventions to decrease misconceptions about antibiotic use and to increase awareness about the risks of inappropriate use of antibiotics in the community.
The ameliorative effect of monotropein, astragalin, and spiraeoside on oxidative stress, endoplasmic reticulum stress, and mitochondrial signaling pathway in varicocelized rats
Authors: Karna Keshab Kumar , Choi Bo Ram , You Jae Hyung , Shin Yu Seob , Cui Wan Shou , Lee Sung Won , Kim Ji Hoon , Kim Chul Young , Kim Hye Kyung , Park Jong Kwan
Published: November 2019

Background

Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS.

Methods

Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays.

Results

Parameters such as sperm motility and count, Johnsen’s scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio.

Conclusion

This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.
Peripheral cathepsin L inhibition induces fat loss in C. elegans and mice through promoting central serotonin synthesis
Authors: Lin Yan , Bao Bin , Yin Hao , Wang Xin , Feng Airong , Zhao Lin , Nie Xianqi , Yang Nan , Shi Guo-Ping , Liu Jian
Published: November 2019

Background

Cathepsin L and some other cathepsins have been implicated in the development of obesity in humans and mice. The functional inactivation of the proteases reduces fat accumulation during mammalian adipocyte differentiation. However, beyond degrading extracellular matrix protein fibronectin, the molecular mechanisms by which cathepsins control fat accumulation remain unclear. We now provide evidence fromCaenorhabditis elegansand mouse models to suggest a conserved regulatory circuit in which peripheral cathepsin L inhibition lowers fat accumulation through promoting central serotonin synthesis.

Results

We established aC. elegansmodel of fat accumulation using dietary supplementation with glucose and palmitic acid. We found that nutrient supplementation elevated fat storage inC. elegans, and along with worm fat accumulation, an increase in the expression ofcpl-1was detected using real-time PCR and western blot. The functional inactivation ofcpl-1reduced fat storage inC. elegansthrough activating serotonin signaling. Further, knockdown ofcpl-1in the intestine and hypodermis promoted serotonin synthesis in worm ADF neurons and induced body fat loss inC. elegansvia central serotonin signaling. We found a similar regulatory circuit in high-fat diet-fed mice. Cathepsin L knockout promoted fat loss and central serotonin synthesis. Intraperitoneal injection of the cathepsin L inhibitor CLIK195 similarly reduced body weight gain and white adipose tissue (WAT) adipogenesis, while elevating brain serotonin level and WAT lipolysis and fatty acid β-oxidation. These effects of inhibiting cathepsin L were abolished by intracranial injection of p-chlorophenylalanine, inhibitor of a rate-limiting enzyme for serotonin synthesis.

Conclusion

This study reveals a previously undescribed molecular mechanism by which peripheral CPL-1/cathepsin L inhibition induces fat loss inC. elegansand mice through promoting central serotonin signaling.
Challenges in management and prevention of ischemic heart disease in low socioeconomic status people in LLMICs
Authors: Gupta Rajeev , Yusuf Salim
Published: November 2019

Background

Cardiovascular diseases, principally ischemic heart disease (IHD), are the most important cause of death and disability in the majority of low- and lower-middle-income countries (LLMICs). In these countries, IHD mortality rates are significantly greater in individuals of a low socioeconomic status (SES).

Main text

Three important focus areas for decreasing IHD mortality among those of low SES in LLMICs are (1) acute coronary care; (2) cardiac rehabilitation and secondary prevention; and (3) primary prevention. Greater mortality in low SES patients with acute coronary syndrome is due to lack of awareness of symptoms in patients and primary care physicians, delay in reaching healthcare facilities, non-availability of thrombolysis and coronary revascularization, and the non-affordability of expensive medicines (statins, dual anti-platelets, renin-angiotensin system blockers). Facilities for rapid diagnosis and accessible and affordable long-term care at secondary and tertiary care hospitals for IHD care are needed. A strong focus on the social determinants of health (low education, poverty, working and living conditions), greater healthcare financing, and efficient primary care is required. The quality of primary prevention needs to be improved with initiatives to eliminate tobacco and trans-fats and to reduce the consumption of alcohol, refined carbohydrates, and salt along with the promotion of healthy foods and physical activity. Efficient primary care with a focus on management of blood pressure, lipids and diabetes is needed. Task sharing with community health workers, electronic decision support systems, and use of fixed-dose combinations of blood pressure-lowering drugs and statins can substantially reduce risk factors and potentially lead to large reductions in IHD. Finally, training of physicians, nurses, and health workers in IHD prevention should be strengthened.

Conclusion

The management and prevention of IHD in individuals with a low SES in LLMICs are poor. Greater availability, access, and affordability for acute coronary syndrome management and secondary prevention are important. Primary prevention should focus on tackling the social determinants of health as well as policy and individual interventions for risk factor control, supported by task sharing and use of technology.
The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway
Authors: Guo Jinan , Chen Zhixin , Jiang Hongtao , Yu Zhou , Peng Junming , Xie Jing , Li ZaiShang , Wu Weiqing , Cheng Zhiqiang , Xiao Kefeng
Published: November 2019

Background

Bladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression.

Methods

Gene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model.

Results

Our results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues.

Conclusion

Collectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.
Evaluation of malaria microscopy diagnostic performance at private health facilities in Tanzania
Authors: Ngasala Billy , Bushukatale Samweli
Published: November 2019

Background

The World Health Organization (WHO) recommends use of parasitological diagnosis of malaria for all age groups in all malaria transmission settings. Many private health facilities rely on malaria microscopy for malaria diagnosis. However, quality of malaria microscopy is affected by number of factors including availability of skilled laboratory microscopists and lack of quality assurance systems in many malaria endemic countries. This study was carried out to assess quality of malaria microscopy in selected private health facilities in Tanzania.

Methods

A cross sectional study was conducted from August to September, 2017. A total of 40 private health laboratories in five regions were invited to participate in the study. Data were collected by distributing standardized pre-validated malaria slide-panels to each health facility. Sensitivity, specificity, and strength of agreement (with kappa score) were calculated to assess performance in detecting and quantification of Plasmodium species.

Results

Among the 40 health facilities, 31 (77.5%) returned their results to the reference centre (Muhimbili University of Health and Allied Sciences). Overall, the measures of malaria diagnostic accuracy were high, i.e. the sensitivity and specificity of malaria parasite detection by microscopy in the health facilities were 84.3% (95% CI 77–90) and 90.8% (95% CI 83.3–95.7), respectively. There was substantial agreement in parasite detection with (Kappa value: 0.74 (95% 0.65–0.83). However, only 17.8% (24 of 134) of blood slides were interpreted correctly at the health facilities in terms of parasite density counts.

Conclusion

Although there was substantial agreement between the private health microscopists and experienced microscopists in malaria parasite detection, there was poor performance in parasite counts. This calls for regular in-service training and external quality assessments at private health facilities to enhance the skills of private health facility microscopists in malaria microscopy.
A Phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) in patients with advanced high-grade ovarian serous carcinoma
Authors: Sarivalasis Apostolos , Boudousquié Caroline , Balint Klara , Stevenson Brian J. , Gannon Philippe O. , Iancu Emanuela Marina , Rossier Laetitia , Martin Lluesma Silvia , Mathevet Patrice , Sempoux Christine , Coukos George , Dafni Urania , Harari Alexandre , Bassani-Sternberg Michal , Kandalaft Lana E.
Published: November 2019

Background

Most ovarian cancer patients are diagnosed at a late stage with 85% of them relapsing after surgery and standard chemotherapy; for this reason, new treatments are urgently needed. Ovarian cancer has become a candidate for immunotherapy by reason of their expression of shared tumor-associated antigens (TAAs) and private mutated neoantigens (NeoAgs) and the recognition of the tumor by the immune system. Additionally, the presence of intraepithelial tumor infiltrating lymphocytes (TILs) is associated with improved progression-free and overall survival of patients with ovarian cancer. The aim of active immunotherapy, including vaccination, is to generate a new anti-tumor response and amplify an existing immune response. Recently developed NeoAgs-based cancer vaccines have the advantage of being more tumor specific, reducing the potential for immunological tolerance, and inducing robust immunogenicity.

Methods

We propose a randomized phase I/II study in patients with advanced ovarian cancer to compare the immunogenicity and to assess safety and feasibility of two personalized DC vaccines. After standard of care surgery and chemotherapy, patients will receive either a novel vaccine consisting of autologous DCs pulsed with up to ten peptides (PEP-DC), selected using an agnostic, yet personalized, epitope discovery algorithm, or a sequential combination of a DC vaccine loaded with autologous oxidized tumor lysate (OC-DC) prior to an equivalent PEP-DC vaccine. All vaccines will be administered in combination with low-dose cyclophosphamide. This study is the first attempt to compare the two approaches and to use NeoAgs-based vaccines in ovarian cancer in the adjuvant setting.

Discussion

The proposed treatment takes advantage of the beneficial effects of pre-treatment with OC-DC prior to PEP-DC vaccination, prompting immune response induction against a wide range of patient-specific antigens, and amplification of pre-existing NeoAgs-specific T cell clones.

Trial registration This trial is already approved by Swissmedic (Ref.: 2019TpP1004) and will be registered at http://www.clinicaltrials.gov before enrollment opens.
Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis
Authors: Sun Yufeng , Li Wenchao , Shen Shiqi , Yang Xuejing , Lu Bing , Zhang Xiaojing , Lu Peng , Shen Yi , Ji Juling
Published: November 2019

Background

Accumulated studies reported abnormal gene expression profiles of hepatocellular carcinoma (HCC) by cDNA microarray. We tried to merge cDNA microarray data from different studies to search for stably changed genes, and to find out better diagnostic and prognostic markers for HCC.

Methods

A systematic review was performed by searching publications indexed in Pubmed from March 1, 2001 to July 1, 2016. Studies that reporting cDNA microarray profiles in HCC, containing both tumor and nontumor data and published in English-language were retrieved. The differentially expressed genes from eligible studies were summarized and ranked according to the frequency. High frequency genes were subjected to survival analyses. The expression and prognostic value of alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT) was further evaluated in HCC datasets in Oncomine and an independent HCC tissue array cohort. The role of AGXT in HCC progression was evaluated by proliferation and migration assays in a human HCC cell line.

Results

A total of 43 eligible studies that containing 1917 HCC patients were included, a list of 2022 non redundant abnormally expressed genes in HCC were extracted. The frequencies of reported genes were ranked. We finally obtained a list of only five genes (AGXT; ALDOB; CYP2E1; IGFBP3; TOP2A) that were differentially expressed in tumor and nontumor tissues across studies and were significantly correlated to HCC prognosis. Only AGXT had not been reported in HCC. Reduced expression of AGXT reflected poor differentiation of HCC and predicts poor survival. Knocking down of AGXT enhanced cell proliferation and migration of HCC cell line.

Conclusions

The present study supported the feasibility and necessity of systematic review on discovering new and reliable biomarkers for HCC. We also identified a list of high frequency prognostic genes and emphasized a critical role of AGXT deletion during HCC progression.
The role of Toll-like receptor 4 in apoptosis of brain tissue after induction of intracerebral hemorrhage
Authors: Fei Xiaowei , He Yeting , Chen Jia , Man Weitao , Chen Chen , Sun Kai , Ding Boyun , Wang Chongwu , Xu Ruxiang
Published: November 2019

Background

Inflammation and apoptosis caused by intracerebral hemorrhage (ICH) are two important factors that affect patient prognosis and survival. Toll-like receptor 4 (TLR4) triggers activation of the inflammatory pathway, causing synthesis and release of inflammatory factors. The inflammatory environment also causes neuronal apoptosis. However, no studies have reported the role of TLR4 in inflammation and apoptosis.

Methods

We performed survival curve analysis and behavioral scores on TLR4 knockout mice and wild-type mice after inducing ICH. We used TLR4 knockout mice and wild-type mice to make ICH models with type VII collagenase and explored the link between TLR4 in inflammation and apoptosis. We used Western blot to detect the expression of apoptosis-related proteins, inflammatory factors, and their receptors at different time points after ICH induction. The effects of TLR4 on apoptosis were observed by TUNEL, Hoechst, and HE staining techniques. The association with TLR4 in inflammation and apoptosis was explored using IL-1β and TNF-α antagonists. Data conforming to a normal distribution are expressed as mean ± standard deviation. Grade and quantitative data were compared with rank sum test and t test between two groups. P < 0.05 was considered statistically significant.

Results

TLR4 knockout significantly increased the survival rate of ICH mice. The scores of TLR4 knockout mice were significantly lower than those of wild-type mice. We found that TLR4 knockout mice significantly inhibited apoptosis and the expression of inflammatory factors after the induction of ICH. The apoptosis of ICH-induced mice was significantly improved after injecting IL-1β and TNF-α antagonists. Moreover, the anti-apoptotic effect of the antagonist in wild-type mice is more pronounced. A single injection of the antagonist failed to improve apoptosis in TLR4 knockout mice.

Conclusions

We conclude that TLR4-induced inflammation after ICH promotes neuronal apoptosis. IL-1β and TNF-α antagonists attenuate this apoptotic effect. Therefore, targeting TLR4 in patients with clinical ICH may attenuate inflammatory response, thereby attenuating apoptosis and improving prognosis.
Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension
Authors: Eftekhari Sajedeh , Westgate Connar Stanley James , Uldall Maria Schmidt , Jensen Rigmor Hoejland
Published: November 2019

Background

Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of unknown cause with significant morbidity and limited therapeutic options. In this review, special focus is put on the preclinical research performed in order to understand the pathophysiology behind ICP regulation and IIH. This includes cerebrospinal fluid dynamics, molecular mechanisms underlying disturbances in brain fluids leading to elevated ICP, role of obesity in IIH, development of an IIH model and ICP measurements in rodents. The review also discusses existing and new drug targets for IIH that have been evaluated in vivo.

Conclusions

ICP monitoring in rodents is challenging and different methods have been applied. Some of these methods are invasive, depend on use of anesthesia and only allow short-term monitoring. Long-term ICP recordings are needed to study IIH but existing methods are hampered by several limitations. As obesity is one of the most common risk factors for IIH, a rodent obese model has been developed that mimics some key aspects of IIH. The most commonly used drugs for IIH have been evaluated in vivo for their efficacy at lowering ICP in the existing animal models. These studies suggest these drugs, including acetazolamide, might have limited or no reducing effect on ICP. Two drug targets that can impact ICP in healthy rodents are topiramate and a glucagon-like peptide-1 receptor (GLP-1R) agonist. However, it remains to evaluate their effect in an IIH model with more precise and valid ICP monitoring system. Therefore, continued evaluation in the preclinical research with refined tools is of great importance to further understand the pathophysiology behind disorders with raised ICP and to explore new drug targets.
Correction to: Knowledge of psychosocial factors associated with low back pain amongst health science students: a scoping review
Authors: Lewis Kelsey L. , Battaglia Patrick J.
Published: November 2019

Following publication of the original article [1], we have been notified that one of the author names was incorrect.
Chronic abdominal pain after laparoscopic hernia repair due to mesh graft migration to the cecum: a case report
Authors: AlShammari Abdullah , Alyousef Fatima , Alyousif Amal , Alsulabi Zainab , AlJishi Fatimah , Siraj Isra , Alotaibi Hissah , Aburahmah Mohammad
Published: November 2019

Background

Hernia repair with mesh graft is one of the most common procedures in general surgery. Mesh graft repair is the treatment of choice for umbilical and periumbilical hernias to minimize recurrence. One of the rare but serious complications is mesh graft migration to viscus. These complications can occur months to years after repair and their diagnosis can be challenging as they may present as vague abdominal pain only.

Case presentation

A 74-year-old gentleman with multiple medical comorbidities was diagnosed with a para-umbilical hernia after which he underwent a laparoscopic hernia repair at our hospital using a mesh graft with no complications. On postoperative day 10, he presented to the emergency room (ER) complaining of colicky abdominal pain in the right iliac fossa for 1 day associated with diarrhea. A Computed Tomography (CT) scan of the abdomen and pelvis showed diffuse wall thickening of the cecum and terminal ileum with small free air worrisome for perforation. The decision was made in the ER to discharge him home on antibiotics. The patient then returned back multiple times to the ER for the same complaint along with bleeding per rectum for which he underwent further investigations. Months later, the patient presented again with the same symptoms. A CT scan revealed recurrence of a periumbilical hernia and thickening of the medial wall of the cecum with mesh graft material. The patient was then taken to surgery and intra-operative findings revealed migration of almost 50% of the mesh graft size to the cecum and part of the mesh graft was eroding the distal part of ileum just proximal to the ileocecal junction. Adhesolysis and limited right hemicolectomy with ileocolic anastomosis was done. The patient had an uneventful recovery after revisions surgery without any perioperative complications. He was discharged home on postoperative readmission day 5 and followed up at 2 weeks and 3 months without any delayed complications or subjective complaints.

Conclusion

It is important to consider mesh graft migration to viscus as a cause of persistent abdominal pain and bleeding per rectum irrespective of the time of presentation post hernia repair.
Immune receptor repertoires in pediatric and adult acute myeloid leukemia
Authors: Zhang Jian , Hu Xihao , Wang Jin , Sahu Avinash Das , Cohen David , Song Li , Ouyang Zhangyi , Fan Jingyu , Wang Binbin , Fu Jingxin , Gu Shengqing , Sade-Feldman Moshe , Hacohen Nir , Li Wuju , Ying Xiaomin , Li Bo , Liu X. Shirley
Published: November 2019

Background

Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized.

Methods

In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples.

Results

We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival.

Conclusions

Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.
Heat shock pretreatment improves mesenchymal stem cell viability by heat shock proteins and autophagy to prevent cisplatin-induced granulosa cell apoptosis
Authors: Wang Qing , Li Xinran , Wang Qingru , Xie Jiaxin , Xie Chuhai , Fu Xiafei
Published: November 2019

Background

Bone marrow mesenchymal stem cells (BMSCs) can partially repair chemotherapy-induced ovarian damage. However, low survival rate after transplantation hampers the therapeutic efficiency of BMSCs. Heat shock pretreatment (HSP) effectively improves the cell survival. This study attempted to investigate the mechanisms of HSP on BMSCs survival and the effects of heat shock-pretreated BMSCs (HS-MSCs) on cisplatin-induced granulosa cell (GC) apoptosis.

Methods

BMSCs were isolated, cultured, and identified. After receiving HSP for different duration times in a 42 °C water bath, the apoptotic rates of BMSCs were detected by Annexin V-FITC/PI to determine the optimal condition of HSP. Cisplatin was added to the medium of HS-MSCs to simulate chemotherapy environment. The proliferative curve, apoptotic rate, and viability of HS-MSCs were determined by CCK-8, Annexin V-FITC/PI, and Hoechst33342/PI respectively to explore the alteration of biological characteristics. The levels of heat shock protein 70 and 90 (HSP70 and HSP90) and the expressions of autophagy-related markers (Beclin1 and LC3B) were detected by Western blot. In addition, the autophagosomes were observed by transmission electronic microscopy to discuss the possible mechanisms. The GCs were isolated, cultured, and identified. The HS-MSCs were co-cultured with GCs before and after the addition of cisplatin. Then, the apoptotic rate and viability of GCs were detected to investigate the therapeutic and preventive effects of HS-MSCs on GC apoptosis.

Results

After receiving HSP at 42 °C for 1 h, BMSCs represented the lowest apoptotic rate. After the addition of cisplatin, the apoptotic rate of HS-MSCs (11.94% ± 0.63%) was lower than that of BMSCs (14.30% ± 0.80%) and the percentage of HS-MSCs expressing bright blue/dull red fluorescence was lower than that of BMSCs. The expression of HSP70 and HSP90 increased, while the number of autophagosomes, the expression of Beclin1, and the LC3BII/LC3BI ratio decreased in HS-MSCs. The apoptotic rates of GCs co-cultured with HS-MSCs before and after the addition of cisplatin were 39.88% ± 1.65% and 36.72% ± 0.96%, both lower than those of cisplatin-induced GCs (53.81% ± 1.89%).

Conclusion

HSP can alleviate the apoptosis and improve the survival of BMSCs under chemotherapy environment. The mechanism may be associated with the elevated expression of HSP70 and HSP90 and the attenuation of autophagy. Moreover, HS-MSCs have both therapeutic and preventive effects on cisplatin-induced GC apoptosis.
Factors associated with childhood influenza vaccination in Israel: a cross-sectional evaluation
Authors: Glatman-Freedman Aharona , Amir Kanar , Dichtiar Rita , Zadka Hila , Vainer Ifat , Karolinsky Dolev , Enav Teena , Shohat Tamy
Published: November 2019

Background

Vaccinating children against influenza has shown both direct and indirect beneficial effects. However, despite being offered free of charge, childhood influenza vaccine coverage in Israel has been low. Our objective was to evaluate the factors associated with childhood influenza vaccination in Israel.

Methods

A cross-sectional language-specific telephone survey was conducted among adults 18 years or older, to examine childhood influenza vaccination practices and their associations with socio-demographic and relevant health variables. We further explored the reasons for these practices among parents. Multivariate logistic regression was used to identify factors associated with childhood influenza vaccine acceptance.

Results

Of a total of 6518 individuals contacted by mobile phone, 1165 eligible parents, ≥18 years old with children 1–18 years of age, were interviewed, and 1040 of them completed the survey successfully. Overall, factors associated with childhood influenza vaccination were younger child’s age, influenza vaccination of other family members and belonging to the Arab population group. No association was found between childhood influenza vaccination and routine childhood vaccine uptake. Several of the parents’ reasons for vaccine acceptance - preventing influenza or its transmission, awareness regarding the need for influenza vaccination and receipt of invitation to get vaccinated - differed significantly between Jewish and Arab parents. Several reasons reported by parents for not vaccinating children against influenza, indicated a likelihood to accept influenza vaccine outreach efforts. Such reasons were reported by 27.5% of Jewish parents and 37.5% of Arab parents.

Conclusions

We found that certain demographic factors were associated with childhood influenza vaccination in Israel. Several reasons described by the parent for not vaccinating their children indicate that outreach efforts are likely to increase childhood influenza vaccination. Addressing population group-specific needs is recommended to optimize the success of influenza vaccine outreach efforts.
Instrument-based tests for quantifying aqueous humour protein levels in uveitis: a systematic review protocol
Authors: McNally Thomas W. , Liu Xiaoxuan , Beese Sophie , Keane Pearse A. , Moore David J. , Denniston Alastair K.
Published: November 2019

Background

Inflammation in anterior uveitis is characterised by breakdown of the blood-ocular barrier, which allows leakage of blood constituents of higher molecular weight into the aqueous humour. In routine clinical care, increase in aqueous protein levels can be observed at the slit lamp as ‘flare’ and the severity can be graded using various clinical grading systems, of which the Standardization of Uveitis Nomenclature (SUN) grading system is most commonly used. Alternative instrument-based technologies are available, which can detect aqueous protein levels in an objective and quantifiable way. This review will identify instruments capable of measuring anterior chamber inflammation in this way, their level of reliability, and how well the measurements correlate with clinical grading and/or actual aqueous protein concentration.

Methods

Standard systematic review methodology will be used to identify, select and extract data from studies that report the use of any instrument-based technology in the assessment of aqueous protein levels. Searches will be conducted through bibliographic databases (MEDLINE, EMBASE and Cochrane Library), clinical trial registries and the grey literature. No restrictions will be placed on language or year of publication. The outcomes of interest are the level of correlation between identified instrument-based test measurements, clinical grading and/or actual aqueous protein concentration, as well as the reliability of each index test identified. Study quality assessment will be based on QUADAS2. Correlation and reliability outcomes will be pooled and meta-analysed if appropriate.

Discussion

The assessment of inflammation in anterior chamber protein levels currently relies on crude and subjective clinical examination. The findings of this review will identify non-invasive technologies which show good correlation with actual protein concentration, which could be used in routine clinical practice for objective monitoring of AC inflammation.

Systematic review registration

PROSPERO CRD42017084167. Study screening stage has just been completed.
Bombyx mori gloverin A2 alleviates enterotoxigenic Escherichia coli-induced inflammation and intestinal mucosa disruption
Authors: Lin Qian , Su Guoqi , Wu Aimin , Chen Daiwen , Yu Bing , Huang Zhiqing , Luo Yuheng , Mao Xiangbing , Zheng Ping , Yu Jie , Luo Junqiu , He Jun
Published: November 2019

Background

EnterotoxigenicEscherichia coli(ETEC) is one of the leading bacterial causes of intestinal inflammation and diarrhea. However, the ETEC is frequently resistant to common antibiotics. In this study, we explored the role of a novel antibacterial peptideBombyx morigloverin A2 (BMGlvA2) in alleviating ETEC-induced inflammation and intestinal epithelium disruption in mice.

Methods

An ETEC-challenged mice model was used, and the ETEC-challenged mice and non-challenged mice were treated by the BMGlvA2 at different doses.

Results

ETEC challenge not only elevated the concentrations of serum inflammatory cytokines such as the IL-6 and TNF-α (P < 0.01), but also elevated the concentrations of serum creatinine and urea (P < 0.05). However, BMGlvA2 attenuated the inflammatory responses by decreasing the serum inflammatory cytokines and improving the metabolisms in ETEC-challenged mice, and alleviated the ETEC-induced tissue damage in spleen. Moreover, BMGlvA2 treatment significantly elevated the duodenum villus height and decreased the crypt depth in the duodenum and ileum in ETEC-challenged mice (P < 0.05). Interestingly, BMGlvA2 improved the distribution and abundance of tight-junction protein ZO1 in duodenum and ileum epithelium after ETEC-challenge. Moreover, BMGlvA2 significantly down-regulated the expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and the apoptosis-related genes (Caspase 8 and Caspase 9) in jejunal mucosa (P < 0.05) in the TETC-challenged mice. Importantly, BMGlvA2 significantly elevated the expression levels of critical genes related to mucosal barrier functions such as the mucins (MUC1 and MUC2) and glucose transporter (GLUT2) in the intestinal mucosa (P < 0.05).

Conclusion

Our results suggested a novel function of the conventional antibacterial peptides, and the anti-bacterial and anti-inflammatory properties of BMGlvA2 may allow it a potential substitute for conventionally used antibiotics or drugs.
MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction
Authors: Guo Hailei , Tang Liying , Xu Jianjun , Lin Cai , Ling Xiangwei , Lu Caijiao , Liu Zhengjun
Published: November 2019

Background

Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction.

Methods

105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495.

Results

MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dtmax, and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection.

Conclusions

MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.
Food choice patterns of long-haul truck drivers driving through Germany, a cross sectional study
Authors: Bschaden Andreas , Rothe Siegfried , Schöner Anja , Pijahn Nina , Stroebele-Benschop Nanette
Published: November 2019

Background

Long-haul truck drivers are exposed to unfavorable working conditions affecting their health but information on truck drivers travelling through Europe is missing. The study aimed to describe the populations’ characteristics and food choice patterns while working compared with eating patterns at home, taking weight status into account.

Methods

A cross-sectional survey using questionnaires in 12 languages conducted at two truck stops in Germany.

Results

Among 404 truck drivers of 24 nationalities, only 24% were normal weight while 46% were considered overweight and 30% obese. In regards to their health, more than half reported that they smoked and 32% reported at least one chronic disease. 37% ate their meals often or always at truck stops, while 6% never did so. The most common food items brought from home were fruits (62%) followed by sausages (50.6%), sandwiches (38.7%), self-cooked meals (37%), sweets (35.4%), and raw vegetables (31%). Bivariate analyses revealed differences in food choices during work and at home with more sausages, energy drinks and soft drinks, and canned foods eaten during trips. Fresh vegetables, legumes and fish were more often chosen at home. Available food appliances in trucks appeared to be associated with food choice patterns. Interestingly, food choice patterns and food preparation did not differ significantly across weight categories.

Conclusions

The working conditions of professional truck drivers make a healthy lifestyle difficult to follow and appear to influence food choices while working. Particular effort should be taken to improve food choice patterns, food preparation and purchasing possibilities during trips.