bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in maternal characteristics and pregnancy outcomes between syphilitic women with and without partner coinfection
Authors: Zhang Xiao-hui , Chen Yan-min , Sun Yu , Qiu Li-qian , Chen Dan-qing
Published: November 2019

Background

Partner infection is a significant factor in preventing mother-to-child syphilis transmission. We compared pregnancy outcomes between syphilis discordant and syphilis concordant couples.

Methods

We conducted a retrospective study among 3076 syphilis-positive women who received syphilis screening together with their partners during pregnancy. Multivariate analysis was used to explore risks for abnormal outcomes in objects correcting for the major covariate factors. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated to compare pregnancy outcomes between syphilis concordant and syphilis discordant couples.

Results

Overall, 657 of the 3076 women were diagnosed with gestational syphilis and had a syphilis-positive partner, giving a partner concordance prevalence of 21.36%. Women in concordant couples were more likely to have higher parity, more children, late antenatal care and syphilis screening, a lower proportion of latent syphilis, and elevated serologic titers than women in discordant couples (P < 0.01 for all). Totally, 10.08% of women had adverse pregnancy outcomes. Multivariate analysis showed partners’ syphilis infection (ORadj = 1.44, 95% CI: 1.10–1.89), untreated pregnancy syphilis (ORadj = 1.67, 95% CI: 1.15–2.43), and higher maternal serum titers (> 1:8) (ORadj = 1.53, 95% CI: 1.17–2.00) increased the risks of adverse pregnancy outcomes. Concordance was associated with increased risk for stillbirth (ORadj = 2.86, 95%CI:1.36–6.00), preterm birth (PTB) (ORadj = 1.38,95%CI:1.02–1.87) and low birth weight (LBW) (ORadj = 1.55, 95%CI:1.13–2.11) compared with discordance. Even among treated women, concordance was associated with increased risk for stillbirth (ORadj = 3.26, 95%CI:1.45–7.31) and LBW (ORadj = 1.52, 95%CI:1.08–2.14). Among women with one treatment course, the risks for PTB(ORadj = 1.81, 95%CI:1.14–2.88) and LBW(ORadj = 2.08, 95%CI:1.28–3.38)were also higher among concordant couples than discordant couples. Nevertheless, there were no significant differences between concordant and discordant couples in risks of stillbirth (ORadj = 2.64, 95% CI: 0.98–7.05),PTB (ORadj = 1.15, 95% CI: 0.76–1.74), and LBW(ORadj = 1.21, 95% CI: 0.78–2.02) among women with two treatment courses.

Conclusion

Male partner coinfection increased the risks for stillbirth, PTB and LBW, particularly when gestational syphilis treatment was suboptimal. However, this risk could be reduced by adequate treatment.
Association of sleep quality during pregnancy with stress and depression: a prospective birth cohort study in China
Authors: Gao Ming , Hu Jiajin , Yang Liu , Ding Ning , Wei Xiaotong , Li Lin , Liu Lei , Ma Yanan , Wen Deliang
Published: November 2019

Background

The sleep quality of pregnant women in the third trimester is related to mental health. However, there is still a lack of large-scale cohort research exploring this relationship in the second trimester. Thus, we assessed the associations of sleep quality during the second trimester with antenatal stress and antenatal and postnatal depression.

Methods

We examined 1152 pregnant women from a prospective cohort study in China to assess the associations of sleep quality in the second trimester with antenatal stress, antenatal depression, and postnatal depression. We used linear regression models and logistic regression models to examine the associations of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) during pregnancy with perinatal stress (Pregnancy Pressure Scale [PPS]) and depression (Edinburgh Postnatal Depression Scale [EPDS]) status. We further assessed the relationship in groups divided according to maternal age.

Results

PSQI scores were positively associated with antenatal PPS scores (β: 1.52, 95% confidence interval [CI]: 1.28, 1.76), antenatal EPDS scores (β: 0.68, 95% CI: 0.58, 0.78), and postpartum EPDS scores (β: 0.51, 95% CI: 0.38, 0.64). Poor sleep quality (PSQI scores ≥5) was associated with antenatal stress status (odds ratio [OR]: 2.60, 95% CI: 1.79, 3.77), antenatal depression status (OR: 3.42, 95% CI: 2.48, 4.72), and postpartum depression status (OR: 2.40, 95% CI: 1.58, 3.64) after adjusting maternal age, BMI, gestational age, smoking, educational level, annual household income and social support. The association of poor sleep quality (PSQI scores ≥5) in the second trimester with postnatal depression status was significant among women more than or equal to 30 years old (OR: 4.12, 95% CI: 2.18, 7.78) but not among women less than 30 years old after adjusting covariates above.

Conclusion

Poor sleep quality in the second trimester among Chinese pregnant women is associated with stress and depression symptoms. Strategies to boost sleep quality should be considered during prenatal health care to improve women’s mental health status.
Pregnancy options counselling in Ghana: a case study of women with unintended pregnancies in Kumasi metropolis, Ghana
Authors: Agbeno Evans Kofi , Gbagbo Fred Yao , Morhe E. S. K. , Maltima Soale Issah , Sarbeng Kwadwo
Published: November 2019

Background

Pregnancy crisis mismanagement has contributed to maternal deaths and illnesses globally and in Ghana due to absence/inadequate pregnancy options counselling for clients to make informed decisions. This study examines options counselling for abortion seekers in health facilities in Ghana.

Methods

Analytical cross-sectional study design was done in selected specialised public and NGO health facilities within Kumasi Metropolis of Ghana, using self-administered structured questionnaires for data collection from 1st January to 30th April, 2014. Participants were 442 women with unintended pregnancies seeking abortion services. Data was analysed using Epi-Info (7.1.1.14) and STATA 12 to generate descriptive statistics, Pearson chi-square and multivariable logistic regressions. The Kwame Nkrumah University of Science and Technology approved the study.

Results

Respondents had divergent reproductive and socio-demographic profiles. Majority (about 58%) of them had been pregnant more than twice, but about 53% of this population had no biological children. (Although about 90% of respondents held perceptions that the index and previous pregnancies were mistimed/unintended, the majority (72%) had no induced abortion history. Induced abortion (208, 49%) and parenting (216, 51%) were mentioned as the only available options to unintended pregnancy in hospitals. Exposure to options counselling was observed to be significantly associated with parity (P = < 0.001), gestational age (P = < 0.001), previous induced abortions (P = < 0.001), perception of pregnancy at conception (P = < 0.001) and level of education (P = 0.002). The logistic regression analysis also shows that higher education has statistically significant effect on being exposed to options counselling (P = < 0.001). Majority of respondents (95%) were not aware that giving a child up for adoption is an option to abortion in Ghana.

Conclusions

Pregnancy options counselling remains a major challenge in comprehensive abortion care in Ghana. Although higher educational attainments significantly exposes women to options counselling for informed decisions, the less educated are disadvantaged in this regard. Further research on type and depth of counselling services provided to pregnant women in health facilities is required to inform health policy and program decisions.
Optic perineuritis secondary to hyaluronic acid injections: a case report
Authors: Hu Yanjun , Wang Yingjun , Tong Yuhua
Published: November 2019

Background

Although a safe, excellent administration method for hyaluronic acid derivatives has been documented; improper injections can lead to devastating and irreversible consequences. Here, we present the first known case of optic perineuritis caused by hyaluronic acid.

Case presentation

A young female experienced sudden orbital pain in the right eye after receiving hyaluronic acid injections to the eyebrows. She presented to the eye clinic two weeks later, after developing blurred vision in the right eye. Visual acuity was reduced significantly in the right eye. Automated visual field examination showed defects in both eyes. Fundus examination revealed bilateral swelling of optic discs. Magnetic resonance imaging of the brain demonstrated bilateral perineural enhancement consistent with optic perineuritis. The patient was treated with retrobulbar injection of hyaluronidase and oral prednisolone. Her vision improved with treatment.

Conclusions

The prognosis for visual outcomes in patients with optic perineuritis is generally excellent. However, a poor prognosis is associated with delays to the initiation of treatment. Recognizing this condition is important, and treatment with corticosteroids should be initiated early.
Correction to: Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation
Authors: Capozza Manuela , Chinellato Iolanda , Guarnieri Vito , Di Iorgi Natascia , Accadia Maria , Traggiai Cristina , Mattioli Girolamo , Di Mauro Antonio , Laforgia Nicola
Published: November 2019

In the published article [1], an error has been noticed in the author group section.
Dental caries experience and socio-economic status among Iranian children: a multilevel analysis
Authors: Ghasemianpour Majid , Bakhshandeh Soheila , Shirvani Armin , Emadi Naghmeh , Samadzadeh Hamid , Moosavi Fatemi Nadereh , Ghasemian Anoosheh
Published: November 2019

Background

Socio-economic factors are considered as main determinants causing disparities in oral health across different countries. The aim of the present study was to investigate the associations of social and economic factors with dental caries experience among 6- and 12-year-old Iranian children.

Methods

In this cross-sectional study, a total of 31,146 students, aged 6 and 12 years old, were enrolled from all (31) provinces in Iran. Based on the standardized World Health Organization (WHO) criteria for oral health surveys, dental caries indices in primary and permanent teeth were assessed by clinical examination in schools. Data on socio-economic status was obtained from the modified WHO questionnaire and national data bank. The decayed, missing and filled teeth (dmft/DMFT) indices for primary and permanent dentition were compared at the individual and provincial levels using multilevel regression analysis. Poisson regression analysis was used to evaluate the association of social (demographic and behavioral) determinants with dental caries indices among individuals. To assess the causes of difference in dental caries indices across provinces, justifiable economic factors were also analyzed using poisson regression analysis.

Results

The mean (SE) of dmft and DMFT were 5.84 (0.05) and 1.84 (0.03), for 6-and 12-year-old children, respectively. The differences of dental caries indices were statistically significant among provinces. Higher level of parental education was negatively related to dental caries indices of both age groups. Rural residency was positively and dental flossing was reversely associated with dmft index of 6-year-old children. Negative associations were found between frequency of tooth brushing and preventive dental utilization with dmft and DMFT indices. Gross Domestic Product (GDP) index had negative and Consumer Price Index (CPI) had positive associations with dmft and DMFT indices in both age groups. However, positive relationships were observed between Gini index with DMFT index among 12-year-old children; as well as between the number of dentists per capita with dmft index among 6-year-old children.

Conclusion

Socio-demographic and behavioral factors were found to be associated with dental caries experience. However, economic indicators had the greatest importance.
Assessing physical performance and physical activity in large population-based aging studies: home-based assessments or visits to the research center?
Authors: Portegijs Erja , Karavirta Laura , Saajanaho Milla , Rantalainen Timo , Rantanen Taina
Published: November 2019

Background

The current study aims to compare correlations between a range of measures of physical performance and physical activity assessing the same underlying construct in different settings, that is, in a home versus a highly standardized setting of the research center or accelerometer recording. We also evaluated the selective attrition of participants related to these different settings and how selective attrition affects the associations between variables and indicators of health, functioning and overall activity.

Methods

Cross-sectional analyses comprising population-based samples of people aged 75, 80, and 85 years living independently in Jyväskylä, Finland. The AGNES study protocol involved the following phases: 1) phone interview (n = 1886), 2) face-to-face at-home interview (n = 1018), 3) assessments in the research center (n = 910), and 4) accelerometry (n = 496). Phase 2 and 3 included walking and handgrip strength tests, and phase 4 a chest-worn and thigh-worn accelerometer estimating physical activity and assessing posture, respectively, for 3–10 days in free-living conditions.

Results

Older people with poorer health and functioning more likely refrained from subsequent study phases, each requiring more effort or commitment from participants. Paired measures of walking speed (R = 0.69), handgrip strength (R = 0.85), time in physical activity of at least moderate intensity (R = 0.42), and time in upright posture (R = 0.30) assessed in different settings correlated with each other, and they correlated with indicators of health, functioning and overall activity. Associations were robust regardless of limitations in health and functioning, and low overall activity.

Conclusions

Correlational analyses did not clearly reveal one superior setting for assessing physical performance or physical activity. Inclusion of older people with early declines in health, functioning and overall activity in studies on physical performance and physical activity is feasible in terms of study outcomes, but challenging for recruitment.
Context of water transport related drownings in Bangladesh: a qualitative study
Authors: Jagnoor Jagnoor , Lukaszyk Caroline , Baset Kamran ul , Ivers Rebecca , Easmin Shamima , Rahman Aminur
Published: November 2019

Background

Bangladesh has one of the highest drowning mortality rates in the world. The use of unregulated water transportation may contribute to this burden, with 38% of all passenger traffic occurring by water. The present study aims to identify provider and end user perception on water transport related drowning risk, and barriers and facilitators for improving water safety practices.

Methods

A qualitative study was conducted in a riverine area of Bangladesh, the Barishal division. Data was collected through 18 in-depth interviews, two small group discussions and six observations in February–March 2016. Content analysis was conducted, guided by domains of Haddon’s matrix for injury prevention.

Results

A range of unsafe behaviours, practices and conditions were identified at pre event, event and post event stages of water transport related drownings. It was also recognised it is not only the regulation of water transport but other factors such as occupational insecurities, poor access to rescue services and healthcare, migration and capacity for skill development among providers that contribute to unsafe water transport practices and drowning risk.

Conclusion

There are some immediate measures that can be implemented, with some monitoring and accountability processes for water transport safety. However, there is need for robust data to quantify transport related drowning, making a case for prioritization and action by relevant stakeholder such as government and transport providers.
Impact of global warming scenarios on life-history traits of Tetranychus evansi (Acari: Tetranychidae)
Authors: Ghazy Noureldin Abuelfadl , Gotoh Tetsuo , Suzuki Takeshi
Published: November 2019

Background

The tomato red spider mite,Tetranychus evansiBaker & Pritchard (Acari: Tetranychidae), is an agricultural pest of solanaceous crops. AlthoughT. evansiis of South American subtropical origin, it has recently expanded its distribution range to many tropical and temperate areas around the world. Its potential distribution range in response to scenarios of global warming was recently modeled, confirming its current and possible future distributions. Here, we experimentally investigated the biological traits ofT. evansiin the context of the current and future global warming (2100) scenarios. Using an environmental simulation system, we tested the life-history traits ofT. evansiunder current summer temperatures (as of June, July, and August 2016) and under expected temperature increases based on two IPCC scenarios: RCP2.6 (+ 1 °C) and RCP8.5 (+ 3.7 °C). The mites were introduced into each scenario on 1 June and their sequential progeny were used for testing in each following month.

Results

The mite could develop and reproduce under all scenarios. There was a decrease in the duration of lifespan and female fecundity at RCP8.5 during June and August, but this may be compensated for by the high intrinsic rate of increase, which implies faster population growth and shorter generation time.

Conclusion

Our study and other reports reveal the high adaptability ofT. evansito a wide range of summer temperatures; this may explain its current distribution. We anticipate that global warming will favor the spread ofT. evansiand may further expand its distribution to a large area of the globe. These findings should be of ecological and practical relevance for designing prevention and control strategies.
Chitosan oligosaccharide inhibits skull resorption induced by lipopolysaccharides in mice
Authors: Guo Ke , Liu Zong Lin , Wang Wen Chao , Xu Wei Feng , Yu Shi Qi , Zhang Shan Yong
Published: November 2019

Background

Low-molecular-weight chitosan oligosaccharide (LMCOS), a chitosan degradation product, is water-soluble and easily absorbable, rendering it a popular biomaterial to study. However, its effect on bone remodelling remains unknown. Therefore, we evaluated the effect of LMCOS on lipopolysaccharide (LPS)-induced bone resorption in mice.

Methods

Six-week-old male C57BL/6 mice (n = five per group) were randomly divided into five groups: PBS, LPS, LPS + 0.005% LMCOS, LPS + 0.05% LMCOS, and LPS + 0.5% LMCOS. Then, the corresponding reagents (300 μL) were injected into the skull of the mice. To induce bone resorption, LPS was administered at 10 mg/kg per injection. The mice were injected three times a week with PBS alone or LPS without or with LMCOS and sacrificed 2 weeks later. The skull was removed for micro-computed tomography, haematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. The area of bone damage and osteoclast formation were evaluated and recorded.

Results

LMCOS treatment during LPS-induced skull resorption led to a notable reduction in the area of bone destruction; we observed a dose-dependent decrease in the area of bone destruction and number of osteoclasts with increasing LMCOS concentration.

Conclusions

Our findings showed that LMCOS could inhibit skull bone damage induced by LPS in mice, further research to investigate its therapeutic potential for treating osteolytic diseases is required.
Annual alveolar bone loss in older adults taking oral bisphosphonate: a retrospective cohort study
Authors: Helmi Mohammad , AlOsaimy Sara , Goodson J. Max , Hasturk Hatice , Natto Zuhair S.
Published: November 2019

Background

Although several studies assessed the effect of bisphosphonate (BIS) administration on alveolar bone loss, this relationship has not been fully investigated using longitudinal analysis. The aim of the this article is to predict annual alveolar bone loss in a subpopulation of older adults patients who were taking oral bisphosphonate (BIS), adjusting for systemic diseases and associated risk factors.

Methods

This is a retrospective cohort study. We identified all subjects who reported receiving oral bisphosphonate from 2008 to 2015 (N = 30) using the electronic health records of each patient to identify suitable radiographs for analysis. For the longitudinal data analysis, 26 subjects were eligible for inclusion, having at least two exposures of the complete mouth set or repeated bitewing radiographs at least a one-year interval; they were then matched on age and sex to another 26 patients who did not report receiving bisphosphonate at any point of their life.

Results

Mild periodontitis was higher in the BIS group compared to the no BIS group; however, moderate periodontitis was higher in the no BIS group. For those who did not take oral BIS, change over time was not significant after the two-year period. However, the BIS group had experienced 0.088 mm more bone loss compared to the no BIS group (95% CI: 0.001, 0.176. P-value = 0.048), adjusting for all other variables included in the model.

Conclusion

The group that reported receiving oral bisphosphonates showed no improvement in maintaining alveolar bone level, and the use of oral BIS may not be effective in reducing annual alveolar bone loss; however, emerging evidence is promising for the use of bisphosphonate as an adjunctive local delivery medication for the management of periodontal diseases.
Randomized, double-blind, placebo-controlled phase I dose escalation study of Dan Qi Tong Mai tablet in healthy volunteers
Authors: Gou Zhong-ping , Zhang Wei , Liang Xiu-fang , Wang Ying , Mou Ju-hong , Li Mei , Zhang Ya , Feng Ping
Published: November 2019

Background

This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins.

Methods

A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events.

Results

No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools.

Conclusions

DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.
Comparative case studies in integrated care implementation from across the globe: a quest for action
Authors: Stadnick Nicole A. , Sadler Euan , Sandall Jane , Turienzo Cristina Fernandez , Bennett Ian M. , Borkan Jeffrey , Oladeji Bibilola , Gureje Oye , Aarons Gregory A. , Sklar Marisa
Published: November 2019

Background

Integrated care is the coordination of general and behavioral health and is a highly promising and practical approach to improving healthcare delivery and patient outcomes. While there is growing interest and investment in integrated care implementation internationally, there are no formal guidelines for integrated care implementation applicable to diverse healthcare systems. Furthermore, there is a complex interplay of factors at multiple levels of influence that are necessary for successful implementation of integrated care in health systems.

Methods

Guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework (Aarons et al., 2011), a multiple case study design was used to address two research objectives: 1) To highlight current integrated care implementation efforts through seven international case studies that target a range of healthcare systems, patient populations and implementation strategies and outcomes, and 2) To synthesize the shared and unique challenges and successes across studies using the EPIS framework.

Results

The seven reported case studies represent integrated care implementation efforts from five countries and continents (United States, United Kingdom, Vietnam, Israel, and Nigeria), target a range of clinical populations and care settings, and span all phases of the EPIS framework. Qualitative synthesis of these case studies illuminated common outer context, inner context, bridging and innovation factors that were key drivers of implementation.

Conclusions

We propose an agenda that outlines priority goals and related strategies to advance integrated care implementation research. These goals relate to: 1) the role of funding at multiple levels of implementation, 2) meaningful collaboration with stakeholders across phases of implementation and 3) clear communication to stakeholders about integrated care implementation.

Trial registration

Not applicable.
Comparative evaluation of drug information leaflets for non-steroidal anti-inflammatory drugs in Palestine: local versus imported products
Authors: Arandy Dina A. , Abu-Hashia Maysa W. , Al-hroub Bahaa M. , Qatmosh Sandra A. , Koni Amer A. , Qeeno Baraa G. , Al-Jabi Samah W. , Zyoud Sa’ed H.
Published: November 2019

Background

Drug information leaflets (DILs) are written for patients and health care providers to show how to use the medications safely and effectively, in order to reach the required therapeutics outcomes. This comparative study was conducted to evaluate various DILs of non-steroidal anti-inflammatory drugs (NSAIDs) that are produced in Palestine, along with their imported equivalents.

Methods

Thirty-five DILs of NSAIDs were analyzed and evaluated in a cross-sectional comparative study. Thirty-one statements were obtained from literature and used; evaluation was performed on basis of both any presence or absence of these statements in the leaflets. 23 of the 31 statements that were available in both local and imported DILs were also evaluated in terms of total word-counts: the median (interquartile range) word-count for each statement was determined separately for the two groups and then compared. For the remaining 8 statements, this was not performed,either because they were not present in any leaflet, or because counting the number of words would not be meaningful.

Results

A total of 35 DILs for nine different active ingredients of NSAIDs were analyzed. In 97% of leaflets, “Instructions to convert medication into liquid forms” were missing and 94% did not provide any information about “Pharmacokinetics”. 83% of DILs provided no information about “Mechanism of action” and 74% did not mention any reliable references. 66% of the analyzed inserts did not include any instruction about the possibility of a tablet splitting. And in 63%, the “Date of last revision” was missing. Further, “Duration of using” and “Inactive ingredients” were not found in 51% of leaflets. In terms of word-count, the related sections of the 23 selected criteria were expressed with more words by imported leaflets compared with the local ones, significant differences were found in 12 categories, the highest significance of > 42.4-fold difference was found in “Geriatric considerations” category whereas 1.4-fold difference was found in “Shelf life,” being the lowest one.

Conclusions

This study shows that local products provide less information than imported products, so we recommend that appropriate measurements be taken by both Palestinian authorities and manufacturers to improve both quantity and quality of local DILs.
The intestinal microbiota regulates host cholesterol homeostasis
Authors: Le Roy Tiphaine , Lécuyer Emelyne , Chassaing Benoit , Rhimi Moez , Lhomme Marie , Boudebbouze Samira , Ichou Farid , Haro Barceló Júlia , Huby Thierry , Guerin Maryse , Giral Philippe , Maguin Emmanuelle , Kapel Nathalie , Gérard Philippe , Clément Karine , Lesnik Philippe
Published: November 2019

Background

Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale.

Results

We depleted the intestinal microbiota of hypercholesterolemic femaleApoe−/−mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated toBetaproteobacteria,Alistipes,Bacteroides, andBarnesiellataxa.

Conclusions

These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.
Identification and ranking of recurrent neo-epitopes in cancer
Authors: Blanc Eric , Holtgrewe Manuel , Dhamodaran Arunraj , Messerschmidt Clemens , Willimsky Gerald , Blankenstein Thomas , Beule Dieter
Published: November 2019

Background

Immune escape is one of the hallmarks of cancer and several new treatment approaches attempt to modulate and restore the immune system’s capability to target cancer cells. At the heart of the immune recognition process lies antigen presentation from somatic mutations. These neo-epitopes are emerging as attractive targets for cancer immunotherapy and new strategies for rapid identification of relevant candidates have become a priority.

Methods

We carefully screen TCGA data sets for recurrent somatic amino acid exchanges and apply MHC class I binding predictions.

Results

We propose a method for in silico selection and prioritization of candidates which have a high potential for neo-antigen generation and are likely to appear in multiple patients. While the percentage of patients carrying a specific neo-epitope and HLA-type combination is relatively small, the sheer number of new patients leads to surprisingly high reoccurence numbers. We identify 769 epitopes which are expected to occur in 77629 patients per year.

Conclusion

While our candidate list will definitely contain false positives, the results provide an objective order for wet-lab testing of reusable neo-epitopes. Thus recurrent neo-epitopes may be suitable to supplement existing personalized T cell treatment approaches with precision treatment options.
Vitamin D deficiency exacerbates bleomycin-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated epithelial-mesenchymal transition
Authors: Li Se-Ruo , Tan Zhu-Xia , Chen Yuan-Hua , Hu Biao , Zhang Cheng , Wang Hua , Zhao Hui , Xu De-Xiang
Published: November 2019

Background

Our earlier report indicated that active vitamin D3 inhibited epithelial-mesenchymal transition (EMT) in bleomycin (BLM)-induced pulmonary fibrosis. The objective of this study was to further investigate whether vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis.

Methods

This study consists of two independent experiments. Experiment 1, male mice were fed with vitamin D deficient (VDD) fodder. Experiment 2, Cyp27b1+/+, Cyp27b1+/− and Cyp27b1−/− mice were fed with standard diet. For pulmonary fibrosis, mice were intratracheally instilled with a single dose of BLM (1.5 mg/kg). Serum 25(OH) D level was measured. Pulmonary collagen deposition was assessed by Sirius red staining. EMT was measured and transforming growth factor-beta (TGF-β)/Smad3 signaling was evaluated in the lungs of BLM-treated mice.

Results

The relative weight of lungs was elevated in BLM-treated mice. Col1α1 and Col1α2, two collagen protein genes, were upregulated, and collagen deposition, as determined by Sirius red staining, was observed in the lungs of BLM-treated mice. E-cadherin, an epithelial marker, was downregulated. By contrast, vimentin and α-SMA, two EMT markers, were upregulated in the lungs of BLM-treated mice. Pulmonary TGF-β/Smad3 signaling was activated in BLM-induced lung fibrosis. Further analysis showed that feeding VDD diet, leading to vitamin D deficiency, aggravated elevation of BLM-induced relative lung weight. Moreover, feeding VDD diet aggravated BLM-induced TGF-β/Smad3 activation and subsequent EMT in the lungs. In addition, feeding VDD diet exacerbated BLM-induced pulmonary fibrosis. Additional experiment showed that Cyp27b1 gene knockout, leading to active vitamin D3 deficiency, exacerbated BLM-induced pulmonary fibrosis. Moreover, Cyp27b1 gene knockout aggravated pulmonary TGF-β/Smad2/3 activation and subsequent EMT in BLM-induced lung fibrosis.

Conclusion

Vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated EMT in the lungs.
Effect of beta blocker use and type on hypoglycemia risk among hospitalized insulin requiring patients
Authors: Dungan Kathleen , Merrill Jennifer , Long Clarine , Binkley Philip
Published: November 2019

Background

Although beta blockers could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. This study sought to determine the relationship between type of beta blocker and incidence of hypoglycemia and mortality in hospitalized patients.

Methods

We retrospectively identified non-critically ill hospitalized insulin requiring patients who were undergoing bedside glucose monitoring and received either carvedilol or a selective beta blocker (metoprolol or atenolol). Patients receiving other beta blockers were excluded. Hypoglycemia was defined as any glucose < 3.9 mmol/L within 24 h of admission (Hypo1day) or throughout hospitalization (HypoT) and any glucose < 2.2 mmol/L throughout hospitalization (Hyposevere).

Results

There were 1020 patients on carvedilol, 886 on selective beta blockers, and 10,216 on no beta blocker at admission. After controlling for other variables, the odds of Hypo1day, HypoT and Hyposevere were higher for carvedilol and selective beta blocker recipients than non-recipients, but only in basal insulin nonusers. The odds of Hypo1day (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.28, 3.09, p = 0.0002) and HypoT (OR 1.38, 95% CI 1.02, 1.86, p = 0.03) but not Hyposevere (OR 1.90, 95% CI 0.90, 4.02, p = 0.09) were greater for selective beta blocker vs. carvedilol recipients in basal insulin nonusers. Hypo1day, HypoT, and Hyposevere were all associated with increased mortality in adjusted models among non-beta blocker and selective beta blocker recipients, but not among carvedilol recipients.

Conclusions

Beta blocker use is associated with increased odds of hypoglycemia among hospitalized patients not requiring basal insulin, and odds are greater for selective beta blockers than for carvedilol. The odds of hypoglycemia-associated mortality are increased with selective beta blocker use or nonusers but not in carvedilol users, warranting further study.
Phosphate regulator PhoP directly and indirectly controls transcription of the erythromycin biosynthesis genes in Saccharopolyspora erythraea
Authors: Xu Ya , You Di , Yao Li-li , Chu Xiaohe , Ye Bang-Ce
Published: November 2019

Background

The choice of phosphate/nitrogen source and their concentrations have been shown to have great influences on antibiotic production. However, the underlying mechanisms responsible for this remain poorly understood.

Results

We show that nutrient-sensing regulator PhoP (phosphate regulator) binds to and upregulates most of genes (ery cluster genes) involved in erythromycin biosynthesis in Saccharopolyspora erythraea, resulting in increase of erythromycin yield. Furthermore, it was found that PhoP also directly interacted with the promoter region of bldD gene encoding an activator of erythromycin biosynthesis, and induced its transcription. Phosphate limitation and overexpression of phoP increased the transcript levels of ery genes to enhance the erythromycin production. The results are further supported by observation that an over-producing strain of S. erythraea expressed more PhoP than a wild-type strain. On the other hand, nitrogen signal exerts the regulatory effect on the erythromycin biosynthesis through GlnR negatively regulating the transcription of phoP gene.

Conclusions

These findings provide evidence that PhoP mediates the interplay between phosphate/nitrogen metabolism and secondary metabolism by integrating phosphate/nitrogen signals to modulate the erythromycin biosynthesis. Our study reveals a molecular mechanism underlying antibiotic production, and suggests new possibilities for designing metabolic engineering and fermentation optimization strategies for increasing antibiotics yield.
Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway
Authors: Zhang Huan-yu , Xing Mao-qing , Guo Jing , Zhao Jin-chuan , Chen Xin , Jiang Zhong , Zhang Hong , Dong Qian
Published: November 2019

Background

Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.

Methods

Through mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.

Results

We identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.

Conclusion

Overall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.
Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway
Authors: Wu Shuai , Luo Chen , Li Fengjiao , Hameed N. U. Farrukh , Jin Qiuyan , Zhang Jie
Published: November 2019

Background

The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. Abnormal expression of PHF14 has been identified in various cancers and is known to be implicated in the pathogenesis of tumors. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme).

Methods

Tissue microarrays and public databases interrogation were used to explore the relationship between the expression of PHF14 and GBM. Three stable PHF14-silenced cell lines (U251, U87MG and A172) were constructed to assess the biological functions changes of GBM cells in vitro. In addition, tumorigenicity in vivo was also performed using U87MG cell line. To understand the mechanism of action of PHF14, RNA-Seq, qRT-PCR, Western blot, IC50 assay and subsequent pathway analysis were performed.

Results

Our results showed that the expression of PHF14 was upregulated in glioma, especially in GBM. Overexpression of PHF14 translated to poor prognosis in glioma patients. In vitro assays revealed that silencing expression of PHF14 in glioma cells inhibited migration, invasiveness and proliferation and promoted cell apoptosis. Animal assay further confirmed that over-expression of PHF14 was a dismal prognostic factor. Analysis based on RNA-Seq suggested a PHF14-dependent regulation of Wnt signaling networks, which was further validated by qRT-PCR, Western blot and IC50 analysis. In addition, the mRNA expression of several key markers of EMT (epithelial–mesenchymal transition) and angiogenesis was found to change upon PHF14 silencing.

Conclusions

Our data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.
Rubber plantations and drug resistant malaria: a cross-sectional survey in Cambodia
Authors: Thomson Rebecca , Sochea Phok , Sarath Mak , MacDonald Amanda , Pratt Abigail , Poyer Steve , Allen Henrietta , Kunthy Sok , Chamroeun Sok , Daro Kim , Samean Sourn , Panharith Nou , Ra Sok , Sovottha Chan , Mundy Gary , Yeung Shunmay
Published: November 2019

Background

The ongoing spread of artemisinin resistantPlasmodium falciparummalaria is a major threat to global health. In response, countries in the Greater Mekong Sub-region, including Cambodia, have declared ambitious goals to eliminate malaria. Major challenges include the lack of information on the at-risk population-individuals who live or work in or near the forest where the malaria vectors are found, including plantation workers. This study aimed to address this knowledge gap through a cross-sectional survey conducted in rubber plantations in Cambodia in 2014.

Methods

The survey was conducted in two rounds in four provinces and included a malaria prevalence survey, analysis for the K13 genetic mutation, and a comprehensive behavioural questionnaire. Forty plantations were included in each round, and 4201 interviews were conducted. An additional 701 blood samples were collected from family members of plantation workers.

Results

Overall malaria prevalence was relatively low with adjusted PCR prevalence rate of 0.6% forP. falciparumand 0.3% forPlasmodium vivax, and was very heterogenous between plantations. There was little difference in risk between permanent residents and temporary workers, and between the two rounds. The main risk factors forP. falciparuminfection were smaller plantations, age under 30 years, lack of self-reported use of a treated net and recent travel, especially to the Northeastern provinces. Proximity of plantations to the forest was also a risk factor for malaria in round one, while male gender was also a risk factor for malaria by either species.

Conclusions

With Cambodia’sP. falciparumelimination target on the horizon, identifying every single malaria case will become increasingly important. Plantations workers are relatively accessible compared to some other at-risk groups and will likely remain a high priority. Ongoing surveillance and adaptive strategies will be critical if malaria elimination is to be achieved in this setting.
Forest work and its implications for malaria elimination: a qualitative study
Authors: Sanann Nou , Peto Thomas J. , Tripura Rupam , Callery James J. , Nguon Chea , Bui Thanh Mai , Nofal Stephanie D. , von Seidlein Lorenz , Lek Dysoley , Dondorp Arjen M. , Cheah Phaik Yeong , Pell Christopher
Published: November 2019

Background

Over the last 20 years, malaria incidence has decreased across the Greater Mekong Sub-region (GMS) and the emergence of artemisinin resistance has stimulated efforts to accelerate regional elimination. In the GMS, the malaria transmission is focused increasingly in forested zones. This article describes forest-going activities and examines forest workers’ attitudes to and experiences of malaria prevention and control in north-eastern Cambodia.

Methods

In Stung Treng Province, Cambodia, 19 in-depth interviews were conducted in villages with participants recently diagnosed with uncomplicated falciparum malaria who reported working in forests. Two focus group discussions with respondents’ forest-working peers were held. Interviews and focus groups were audio-recorded transcribed, and translated for thematic analysis.

Results

Forest work is an essential source of income for respondents. Many combine it with farming, which influences the timing and duration of forest visits. Forest activities include logging and collecting other forest products, particularly malva nuts. Men log year-round, whereas gathering forest products is seasonal and can involve entire families. Forest workers sleep chiefly in unimpregnated hammock nets in make-shift encampments. Respondents are concerned about symptomatic malaria, but unfamiliar with the concept of asymptomatic infection. They view the forest as an area of potential malaria infection and seek to protect themselves from mosquito bites through wearing long-sleeved clothes, using repellents, and lighting fires. Forest workers express a willingness to self-test and self-administer anti-malarials.

Conclusions

Forest workers’ behaviour and perceptions of risk indicate that improvements are needed to current control measures. There is potential to: better target distribution of impregnated hammock nets; offer curative or presumptive treatment while in forests; and expand access to screening. Establishing the efficacy and feasibility of prophylaxis for forest workers in the GMS is a priority.
Tamoxifen activity against Plasmodium in vitro and in mice
Authors: Weinstock Ada , Gallego-Delgado Julio , Gomes Cláudia , Sherman Julian , Nikain Cyrus , Gonzalez Sandra , Fisher Edward , Rodriguez Ana
Published: November 2019

Background

Tamoxifen is an oestrogen receptor modulator that is widely used for the treatment of early stage breast cancer and reduction of recurrences. Tamoxifen is also used as a powerful research tool for controlling gene expression in the context of the Cre/loxP site-specific recombination system in conditional mutant mice.

Methods

To determine whether the administration of tamoxifen affects Plasmodium growth and/or disease outcome in malaria, in vitro studies assessing the effect of tamoxifen and its active metabolite 4-hydroxytamoxifen on Plasmodium falciparum blood stages were performed. Tamoxifen effects were also evaluated in vivo treating C57/B6 mice infected with Plasmodium berghei (ANKA strain), which is the standard animal model for the study of cerebral malaria.

Results

Tamoxifen and its active metabolite, 4-hydroxytamoxifen, show activity in vitro against P. falciparum (16.7 to 5.8 µM IC50, respectively). This activity was also confirmed in tamoxifen-treated mice infected with P. berghei, which show lower levels of parasitaemia and do not develop signs of cerebral malaria, compared to control mice. Mice treated with tamoxifen for 1 week and left untreated for an additional week before infection showed similar parasitaemia levels and signs of cerebral malaria as control untreated mice.

Conclusions

Tamoxifen and its active metabolite, 4-hydroxytamoxifen, have significant activity against the human parasite P. falciparum in vitro and the rodent parasite P. berghei in vivo. This activity may be useful for prevention of malaria in patients taking this drug chronically, but also represents a major problem for scientists using the conditional mutagenic Cre/LoxP system in the setting of rodent malaria. Allowing mice to clear tamoxifen before starting a Plasmodium infection allows the use the Cre/LoxP conditional mutagenic system to investigate gene function in specific tissues.