bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
Authors: Hou Lei , Xu Mingqing , Yu Yuanyuan , Sun Xiaoru , Liu Xinhui , Liu Lu , Li Yunxia , Yuan Tonghui , Li Wenchao , Li Hongkai , Xue Fuzhong
Published: January 2020

Background and purpose

Previous studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation.

Methods

Summary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect.

Results

Blood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10−5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke.

Conclusions

Our study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.
Association between standardized vitamin 25(OH)D and dyslipidemia: a community-based study in Riyadh, Saudi Arabia
Authors: AlQuaiz AlJohara M , Kazi Ambreen , Youssef Randa M. , Alshehri Norah , Alduraywish Shatha Ahmed
Published: January 2020

Background

Vitamin D deficiency associated with dyslipidemia can contribute towards cardiovascular diseases. Previous studies have found that Saudi Arabia has a high burden of vitamin D deficiency and cardiovascular disease risk factors. We aimed to explore the relationship between vitamin D deficiency and dyslipidemia, including total cholesterol, low-density lipids, high-density lipids (HDL), and triglycerides (TG) in apparently healthy Saudi male and female participants aged 30–75 years.

Methods

A cross-sectional study was conducted on 1717 apparently healthy Saudi participants from 18 primary health care centers in Riyadh. Data collectors conducted the interviews, took anthropometric measurements, and collected the blood samples. Serum 25-hydroxyvitamin vitamin D (25(OH)D) levels were measured using an electrochemiluminescence assay method. Lipid panel was measured by a fully automated analyzer using enzymatic methods.

Results

Multivariable logistic regression analysis revealed that the adjusted odds ratio (ORA) of low level of HDL cholesterol in association with 25(OH)D deficiency was 2.1 times higher in males (ORA = 2.1; 95% CI = 1.1, 3.9) and 1.3 times higher in females (ORA = 1.3; 95% CI = 0.9, 1.9). A significant excess odds ratio of high levels of TG in association with 25(OH) D deficiency was observed in females (ORA = 3.0; 95% CI = 1.1, 7.9) but not in males.

Conclusion

Vitamin D deficiency is highly prevalent in Saudi Arabia. Low levels of HDL cholesterol in men and high TG levels in women are associated with vitamin D deficiency. The results emphasize the importance of treating vitamin D deficiency in the general population.
The effects of the DNA Demethylating reagent, 5-azacytidine on SMCHD1 genomic localization
Authors: Massah S. , Jubene J. , Lee F. J. S. , Beischlag T. V. , Prefontaine G. G.
Published: January 2020

Background

DNA methylation is an epigenetic modification that mainly repress expression of genes essential during embryogenesis and development. There are key ATPase-dependent enzymes that read or write DNA methylation to remodel chromatin and regulate gene expression. Structural maintenance of chromosome hinge domain containing 1 (SMCHD1) is an architectural protein that regulates expression of numerous genes, some of which are imprinted, that are sensitive to DNA methylation. In addition, SMCHD1 germline mutations lead to developmental diseases; facioscapulohumoral muscular dystrophy (FSHD), bosma arhinia and micropthalmia (BAMS). Current evidence suggests that SMCHD1 functions through maintenance or de novo DNA methylation required for chromatin compaction. However, it is unclear if DNA methylation is also essential for genomic recruitment of SMCHD1 and its role as an architectural protein. We previously isolated SMCHD1 using a methylated DNA region from mouse pituitary growth hormone (Gh1) promoter, suggesting that methylation is required for SMCHD1 DNA binding. The goal of this study was to further understand DNA methylation directed role of SMCHD1 in regulating gene expression. Therefore, we profiled SMCHD1 genome wide occupancy in human neuroblastoma SH-SY5Y cells and evaluated if DNA methylation is required for SMCHD1 genomic binding by treating cells with the DNA demethylating reagent, 5-azacytidine (5-azaC).

Results

Our data suggest that the majority of SMCHD1 binding occurs in intron and intergenic regions. Gene ontology analysis of genes associated with SMCHD1 genomic occupancy that is sensitive to 5-azaC treatment suggests SMCHD1 involvement in central nervous system development. The potassium voltage-gated channel subfamily Q member1 (KCNQ1) gene that associates with central nervous system is a known SMCHD1 target. We showed SMCHD1 binding to an intronic region of KCNQ1 that is lost following 5-azaC treatment suggesting DNA methylation facilitated binding of SMCHD1. Indeed, deletion of SMCHD1 by CRISPR- Cas9 increases KCNQ1 gene expression confirming its role in regulating KCNQ1 gene expression.

Conclusion

These findings provide novel insights on DNA methylation directed function of SMCHD1 in regulating expression of genes associated with central nervous system development that impact future drug development strategies.
Transcriptome analysis of Clinopodium gracile (Benth.) Matsum and identification of genes related to Triterpenoid Saponin biosynthesis
Authors: Shan Chunmiao , Wang Chenkai , Zhang Shengxiang , Shi Yuanyuan , Ma Kelong , Yang Qingshan , Wu Jiawen
Published: January 2020

Background

Clinopodium gracile (Benth.) Matsum (C. gracile) is an annual herb with pharmacological properties effective in the treatment of various diseases, including hepatic carcinoma. Triterpenoid saponins are crucial bioactive compounds in C. gracile. However, the molecular understanding of the triterpenoid saponin biosynthesis pathway remains unclear.

Results

In this study, we performed RNA sequencing (RNA-Seq) analysis of the flowers, leaves, roots, and stems of C. gracile plants using the BGISEQ-500 platform. The assembly of transcripts from all four types of tissues generated 128,856 unigenes, of which 99,020 were mapped to several public databases for functional annotation. Differentially expressed genes (DEGs) were identified via the comparison of gene expression levels between leaves and other tissues (flowers, roots, and stems). Multiple genes encoding pivotal enzymes, such as squalene synthase (SS), or transcription factors (TFs) related to triterpenoid saponin biosynthesis were identified and further analyzed. The expression levels of unigenes encoding important enzymes were verified by quantitative real-time PCR (qRT-PCR). Different chemical constituents of triterpenoid saponins were identified by Ultra-Performance Liquid Chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS).

Conclusions

Our results greatly extend the public transcriptome dataset of C. gracile and provide valuable information for the identification of candidate genes involved in the biosynthesis of triterpenoid saponins and other important secondary metabolites.
Genome-resolved metagenomics analysis provides insights into the ecological role of Thaumarchaeota in the Amazon River and its plume
Authors: Pinto Otávio H. B. , Silva Thais F. , Vizzotto Carla S. , Santana Renata H. , Lopes Fabyano A. C. , Silva Bruno S. , Thompson Fabiano L. , Kruger Ricardo H.
Published: January 2020

Background

Thaumarchaeota are abundant in the Amazon River, where they are the only ammonia-oxidizing archaea. Despite the importance of Thaumarchaeota, little is known about their physiology, mainly because few isolates are available for study. Therefore, information about Thaumarchaeota was obtained primarily from genomic studies. The aim of this study was to investigate the ecological roles of Thaumarchaeota in the Amazon River and the Amazon River plume.

Results

The archaeal community of the shallow in Amazon River and its plume is dominated by Thaumarchaeota lineages from group 1.1a, which are mainly affiliated to Candidatus Nitrosotenuis uzonensis, members of order Nitrosopumilales, Candidatus Nitrosoarchaeum, and Candidatus Nitrosopelagicus sp. While Thaumarchaeota sequences have decreased their relative abundance in the plume, Candidatus Nitrosopelagicus has increased. One genome was recovered from metagenomic data of the Amazon River (ThauR71 [1.05 Mpb]), and two from metagenomic data of the Amazon River plume (ThauP25 [0.94 Mpb] and ThauP41 [1.26 Mpb]). Phylogenetic analysis placed all three Amazon genome bins in Thaumarchaeota Group 1.1a. The annotation revealed that most genes are assigned to the COG subcategory coenzyme transport and metabolism. All three genomes contain genes involved in the hydroxypropionate/hydroxybutyrate cycle, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation. However, ammonia-monooxygenase genes were detected only in ThauP41 and ThauR71. Glycoside hydrolases and auxiliary activities genes were detected only in ThauP25.

Conclusions

Our data indicate that Amazon River is a source of Thaumarchaeota, where these organisms are important for primary production, vitamin production, and nitrification.
Prevalence and antimicrobial susceptibility of enterotoxigenic extra-intestinal Bacteroides fragilis among 13-year collection of isolates in Kuwait
Authors: Jamal Wafaa , Khodakhast Fatima Bibi , AlAzmi Ameerah , Sόki Jόzsef , AlHashem Ghayda , Rotimi Vincent O.
Published: January 2020

Background

Some strains of Bacteroides fragilis species are associated with diarrhea as a result of enterotoxin production (bft or fragilysin). Fragilysin is activated by C11 protease (fpn) and together with C10 protease (bfp) play a significant role in its invasiveness. The objectives of this study were to investigate the proportion of clinical isolates from extra-intestinal sources that are toxin producers and characterize the genes mediating toxin production. Clinical isolates submitted to our reference laboratory over the last 13 years were screened for toxin production using PCR technique. All stool isolates were excluded. The isolates were tested for their susceptibility to 8 antimicrobial agents by E test. Carbapenem resistance gene cfiA was detected by PCR.

Results

A total of 421 B. fragilis isolates were viable. Out of these, bft was detected in 210 (49.9%) isolates. Of the 210 bft-positive isolates, 171 (81.4%), 33 (15.7%) and 6 (2.8%) harbored bft-1, bft-2, and bft-3 genes, respectively. Twenty (9.5%) of the bft-positive strains originated from bloodstream infections. Twenty-five, 20 and 9 strains harbored bfp-1, bfp-2 and bfp-3 gene, respectively. Two, 3, 4 bfp isotypes were detected simultaneously in some of strains. The resistance rates against amoxicillin-clavulanic acid was 32%, clindamycin 62%, cefoxitin 26%, imipenem 11%, meropenem 17%, metronidazole 4%, piperacillin 61% and tigecycline 14%. A chromosomally located cfiA gene that encode metallo-β-lactamase was identified in only 34 isolates (16.2%).

Conclusions

The prevalence of enterotoxin-producing B. fragilis was high among the extra-intestinal isolates. Metronidazole was the most active agent against all isolates. There was no statistically significance difference between resistance rates among bft-positive and bft-negative isolates except for clindamycin.
Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress
Authors: Zhou Yue , Cong Yu , Liu Huan
Published: January 2020

Background

Depression is characterized by significant and low mood. Classical antidepressants are still not adequate in treating depression because of undesirable side effects. Folic acid, a member of the vitamin B complex, in considered to be strongly associated with the function and development of the central nervous system. Thus, in this study, we established a model of depression through chronic unpredictable mild stress (CUMS) in rats and assessed the antidepressant effects and mechanisms of folic acid.

Methods

Sprague–Dawley rats were randomly divided into four groups: control, chronic unpredictable mild stress (CUMS), CUMS treated with folic acid, and CUMS treated with citalopram. Rats were assessed in terms of weight change, open-field test and sucrose preference. Homocysteine, monoamine neurotransmitters, interleukin-6, brain-derived neurotrophic factor (BDNF), β-endorphin levels in the serum and brains of rats were analysed.

Results

Folic acid exhibited antidepressant-like effects in open-field and sucrose preference tests. Folic acid treatment effectively increased the levels of monoamine neurotransmitters, BDNF and β-endorphin, interleukin-6 and homocysteine levels were also significantly suppressed by folic acid administration.

Conclusions

These findings serve as preclinical evidence that folic acid plays an antidepressant-like role in several pathways involving monoamine neurotransmitters. Thus, folic acid may be used as a potential antidepressant.
Full moonlight-induced circadian clock entrainment in Coffea arabica
Authors: Breitler J-C. , Djerrab D. , Leran S. , Toniutti L. , Guittin C. , Severac D. , Pratlong M. , Dereeper A. , Etienne H. , Bertrand B.
Published: January 2020

Background

It is now well documented that moonlight affects the life cycle of invertebrates, birds, reptiles, and mammals. The lunisolar tide is also well-known to alter plant growth and development. However, although plants are known to be very photosensitive, few studies have been undertaken to explore the effect of moonlight on plant physiology.

Results

Here for the first time we report a massive transcriptional modification in Coffea arabica genes under full moonlight conditions, particularly at full moon zenith and 3 h later. Among the 3387 deregulated genes found in our study, the main core clock genes were affected.

Conclusions

Moonlight also negatively influenced many genes involved in photosynthesis, chlorophyll biosynthesis and chloroplast machinery at the end of the night, suggesting that the full moon has a negative effect on primary photosynthetic machinery at dawn. Moreover, full moonlight promotes the transcription of major rhythmic redox genes and many heat shock proteins, suggesting that moonlight is perceived as stress. We confirmed this huge impact of weak light (less than 6 lx) on the transcription of circadian clock genes in controlled conditions mimicking full moonlight.
Job satisfaction, burnout, and turnover intention among primary care providers in rural China: results from structural equation modeling
Authors: Wang Haipeng , Jin Yinzi , Wang Dan , Zhao Shichao , Sang Xingang , Yuan Beibei
Published: January 2020

Background

Low job satisfaction, severe burnout and high turnover intention are found to be prevalent among the primary care providers (PCPs) in township health centers (THCs), but their associations have received scant attention in the literature. In light of this, this study aims to examine the relationships between job satisfaction, burnout and turnover intention, and explore the predictors of turnover intention with a view to retaining PCPs in rural China.

Methods

Using the multistage cluster sampling method, a cross-sectional survey was conducted in Shandong Province, China. 1148 PCPs from 47 THCs participated in this study. Job satisfaction, burnout and turnover intention were measured with a multifaceted instrument developed based on the existing literature, the Maslach Burnout Inventory and the participants’ responses to a Likert item drawn from the literature, respectively. The relationships of the three factors were examined using Pearson correlation and structural equation modeling, while the predictors of turnover intention were investigated using multivariate logistic regression.

Results

The subscale that the PCPs were most dissatisfied with was job rewards (95.12%), followed by working environment (49.65%) and organizational management (47.98%). The percentages of the PCPs reporting high-levels of emotional exhaustion, depersonalization and reduced personal accomplishment were 27.66, 6.06, and 38.74%, respectively. About 14.06% of the respondents had high turnover intention. There was a significant direct effect of job satisfaction on burnout (γ = − 0.52) and turnover intention (γ = − 0.29), a significant direct effect of burnout on turnover intention (γ = 0.28), and a significant indirect effect (γ = − 0.14) of job satisfaction on turnover intention through burnout as a mediator. Work environment satisfaction, medical practicing environment satisfaction, and organizational management satisfaction proved to be negative predictors of turnover intention (p < 0.05), whereas reduced personal accomplishment was identified as a positive predictor (p < 0.05).

Conclusions

Plagued by low job satisfaction and severe burnout, the PCPs in rural China may have high turnover intentions. Job satisfaction had not only negative direct effects on burnout and turnover intention, but also an indirect effect on turnover intention through burnout as a mediator. Targeted strategies should be taken to motivate and retain the PCPs.
The importance of different frailty domains in a population based sample in England
Authors:   on behalf of the Pre-FIT Study Group, Arnadottir Solveig A. , Bruce Julie , Lall Ranjit , Withers Emma J. , Underwood Martin , Shaw Fiona , Sheridan Ray , Hossain Anower , Lamb Sarah E.
Published: January 2020

Background

The aim was to estimate the prevalence of frailty and relative contribution of physical/balance, nutritive, cognitive and sensory frailty to important adverse health states (falls, physical activity levels, outdoor mobility, problems in self-care or usual activities, and lack of energy or accomplishment) in an English cohort by age and sex.

Methods

Analysis of baseline data from a cohort of 9803 community-dwelling participants in a clinical trial. The sample was drawn from a random selection of all people aged 70 or more registered with 63 general practices across England. Data were collected by postal questionnaire. Frailty was measured with the Strawbridge questionnaire. We used cross sectional, multivariate logistic regression to estimate the association between frailty domains and known correlates and adjusted for age. Some models were stratified by sex.

Results

Mean age of participants was 78 years (sd 5.7), range 70 to 101 and 47.5% (4653/9803) were men. The prevalence of overall frailty was 20.7% (2005/9671) and there was no difference in prevalence by sex (Odds Ratio 0.98; 95% Confidence Interval 0.89 to 1.08). Sensory frailty was the most common and this was reported by more men (1823/4586) than women (1469/5056; Odds Ratio for sensory frailty 0.62, 95% Confidence Interval 0.57 to 0.68). Men were less likely than women to have physical or nutritive frailty. Physical frailty had the strongest independent associations with adverse health states. However, sensory frailty was independently associated with falls, less frequent walking, problems in self-care and usual activities, lack of energy and accomplishment.

Conclusions

Physical frailty was more strongly associated with adverse health states, but sensory frailty was much more common. The health gain from intervention for sensory frailty in England is likely to be substantial, particularly for older men. Sensory frailty should be explored further as an important target of intervention to improve health outcomes for older people both at clinical and population level.

Trial registration

ISRCTN71002650.
Lymphedema in three previously Wuchereria bancrofti-endemic health districts in Mali after cessation of mass drug administration
Authors: Dolo Housseini , Coulibaly Yaya Ibrahim , Konipo Fatoumata Nene , Coulibaly Siaka Yamoussa , Doumbia Salif Seriba , Sangare Moussa Brema , Soumaoro Lamine , Coulibaly Michel Emmanuel , Diallo Abdallah Amadou , Diarra Yaye , Sangare Modibo , Doumbia Seydou , Colebunders Robert , Nutman Thomas B.
Published: January 2020

Background

Lymphedema is a public health problem in countries with lymphatic filariasis (LF) including Mali. We studied the epidemiology and clinical presentation of lymphedema in three previously LF-endemic health districts of Mali after at least five consecutive rounds of mass drug administration (MDA) with albendazole and ivermectin.

Methods

From 2016 to 2018, we used passive and active case finding methods to identify lymphedema cases in three health districts with high pre-MDA LF prevalence: Kolondieba (66%), Bougouni (44%) and Kolokani (34%).

Results

Three hundred and thirty nine cases of lymphedema were identified, 235 (69.32%) through active case finding. Their median age was 56 years (range 2–90) and 286 (84.36%) were women. Lymphedema was reported in 226 (78.5%) people aged 41 years and older compared to 73 (21.5%) people below the age of 41 years (Chi2 = 17.28, df = 5,p = 0.004). One hundred and seventy five cases of lymphedema were found in Kolondieba (66 per 100,000 people), 116 in Bougouni (19 per 100,000) and 48 in Kolokani (16 per 100,000). Stage III lymphedema was observed in 131 (38.64%), stage II in 108 (31.86%), stage IV in 46 (13.57%), stage I in 23 (6.78%), stage V in 21 (6.19%) and stage VI in ten (2.95%). In the three study districts, lymphedema affected the legs in 281 (82.89%), the arms in 42 (12.39%) and both in 16 (4.72%) (Chi2 = 13.63,p = 0.008).

Conclusion

Health districts in Mali with the highest pre-MDA LF prevalences had the highest prevalence of lymphedema. Efforts to actively identify lymphedema cases should be scaled up in previous LF-endemic areas, and should be supplemented by a morbidity management and disability prevention plan at the peripheral health system level.
Anticipated HIV stigma among HIV negative men who have sex with men in China: a cross-sectional study
Authors: Liu Chuncheng , Zhang Ye , Pan Stephen W. , Cao Bolin , Ong Jason J. , Fu Hongyun , Wu Dan , Fu Rong , Wei Chongyi , Tucker Joseph D. , Tang Weiming
Published: January 2020

Background

Anticipated HIV stigma, i.e., the expectation of adverse experiences from one’s seroconversion, is associated with both negative psychological and behavioral outcomes. We know little about anticipated HIV stigma’s relationship with emerging technologies, such as HIV self-testing (HIVST) and online sex-seeking platforms, that have become popular among populations that are disproportionately affected by HIV/AIDS. This study examined correlates of anticipated HIV stigma among Chinese men who have sex with men (MSM).

Methods

In July 2016, MSM, who were ≥ 16 years old and self-reported as HIV negative or unknown, were recruited from a gay mobile phone application in China. Information regarding socio-demographics, sexual behaviors, sexual health service utilization, and anticipated HIV stigma were collected. Anticipated HIV stigma (i.e., negative attitude toward future stigmatization of HIV seroconversion by others) was measured as the mean score from a 7-item Likert-scale ranging from 1 (low) to 4 (high). Generalized linear models were conducted to examine the factors associated with the anticipated HIV stigma scores.

Results

Overall, 2006 men completed the survey. Most men completed high school (1308/2006, 65.2%) and had an annual personal income of ≤9200 USD (1431/2006, 71.3%). The mean anticipated HIV stigma score for the participants was 2.98 ± 0.64. Using social media to seek sexual partners was associated with higher anticipated HIV stigma (Adjusted β = 0.11, 95% confidence interval (CI): 0.05 to 0.17,p = 0.001). HIV self-testing (Adjusted β = − 0.07, 95%CI: − 0.13 to − 0.01,p = 0.02) and having disclosed one’s sexual orientation to a healthcare provider (Adjusted β = − 0.16, 95%CI: − 0.22 to − 0.96,p < 0.001) were associated with lower anticipated HIV stigma.

Conclusion

Our data suggested that anticipated HIV stigma is still common among Chinese MSM not living with HIV. Tailored anti-HIV stigma campaigns on social media are especially needed, and the promotion of HIVST may be a promising approach.
Association analysis between the tag single nucleotide polymorphisms of DENND1A and the risk of polycystic ovary syndrome in Chinese Han women
Authors: Zhu Ya-nan , Zhang Yi-ting , Liu Qin , Shen Shan-mei , Zou Xiang , Cao Yun-xia , Wang Wen-jun , Yi Long , Gao Qian , Yang Wei-dong , Wang Yong
Published: January 2020

Background

The DENND1A gene is one of the most important sites associated with polycystic ovary syndrome (PCOS). We attempted to analyze the correlation between five single nucleotide polymorphisms (SNPs) in the DENND1A gene and the development of PCOS.

Methods

A total of 346 PCOS patients and 225 normal ovulatory women were involved in the case-control study. Clinical variables and hormones were recorded. According to the Hap Map database, five tagging SNPs (rs2479106, rs2768819, rs2670139, rs2536951 and rs2479102) in the DENND1A gene were identified. The TaqMan probe and the PCR–RFLP (restriction fragment length polymorphism) methods were used for revealing these genotypes. TaqMan Genotype Software was used to analyze the alleles of the five SNPs.

Results

Linkage disequilibrium and the gene frequency analysis demonstrated that the CCGGG haplotype might increase the risk of PCOS (P = 0.038, OR = 1.89, 95% CI = 1.027–3.481). Significant differences were found in genotypic and allelic distributions at the rs2536951 and rs2479102 loci between PCOS women and controls (P <  0.001). The LH levels and LH/FSH ratios were higher in PCOS patients than in the control group. A detailed analysis revealed that for the rs2479106 locus, these two values were significantly different in the control subjects who had AA, AG and GG genotypes (P = 0.013 and P = 0.007, respectively), and for the rs2468819 locus, these two values were significantly different among the PCOS patients with AA, AG and GG genotypes (P = 0.013 and 0.002, respectively).

Conclusions

The tagging SNPs rs2479106 and rs2468819 in the DENND1A gene are associated with PCOS in the Chinese population, whereas rs2670139, rs2536951 and rs2479102 are not correlated with PCOS in the same population.
C1GALT1 expression is associated with galactosylation of IgA1 in peripheral B lymphocyte in immunoglobulin a nephropathy
Authors: Xing Yue , Li Lina , Zhang Yaru , Wang Fanghao , He Dandan , Liu Youxia , Jia Junya , Yan Tiekun , Lin Shan
Published: January 2020

Background

More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of β1, 3-galactosyltransferase (β1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN.

Methods

Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to β1, 3Gal-T of IgA1, was also been compared.

Results

Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of β1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of β1, 3Gal-T in B cells, and the result showed the β1, 3Gal-T activity was decreased in B cells.

Conclusions

We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of β1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.
Definition of hourly urine output influences reported incidence and staging of acute kidney injury
Authors: Allen Jennifer C. , Gardner David S. , Skinner Henry , Harvey Daniel , Sharman Andrew , Devonald Mark A. J.
Published: January 2020

Background

Acute kidney injury (AKI) is commonly defined using the KDIGO system, which includes criteria based on reduced urine output (UO). There is no consensus on whether UO should be measured using consecutive hourly readings or mean output. This makes KDIGO UO definition and staging of AKI vulnerable to inconsistency which has implications both for research and clinical practice. The objective of this study was to investigate whether the way in which UO is defined affects incidence and staging of AKI.

Methods

We conducted a retrospective analysis of two single centre observational studies investigating (i) patients undergoing cardiac surgery and (ii) patients admitted to general intensive care units (ICU). AKI was identified using KDIGO serum creatinine (SCr) criteria and two methods of UO (UOcons: UO meeting KDIGO criteria in each consecutive hour; UOmean: mean hourly UO meeting KDIGO criteria).

Results

Data from 151 CICU and 150 ICU admissions were analysed. Incidence of AKI using SCr alone was 23.8% in CICU and 32% in ICU. Incidence increased in both groups when UO was considered, with inclusion of UOmeanmore than doubling reported incidence of AKI (CICU: UOcons39.7%, UOmean72.8%; ICU: UOcons51.3%, UOmean69.3%). In both groups UOconsled to a larger increase in KDIGO stage 1 but UOmeanincreased the incidence of KDIGO stage 2.

Conclusions

We demonstrate a serious lack of clarity in the internationally accepted AKI definition leading to significant variability in reporting of AKI incidence.
Prognostic factors of patients with Gliomas – an analysis on 335 patients with Glioblastoma and other forms of Gliomas
Authors: Liang Jianfeng , Lv Xiaomin , Lu Changyu , Ye Xun , Chen Xiaolin , Fu Jia , Luo Chenghua , Zhao Yuanli
Published: January 2020

Background

The prognosis of glioma is poor, despite recent advances in diagnosis and treatment of the disease. It is important to investigate the clinical characteristics and prognostic factors of glioma so as to provide basis for treatment and management of patients.

Method

A total of 335 patients with glioma were included in this study. These patients were admitted to the medical center between November 2015 and December 2018. The clinical data, including demographic data, tumor characteristics, treatment strategy, expression pattern of tumor markers, and survival data, were retrospectively reviewed. Survival data were analyzed using Kaplan-Meier curves with log-rank test, while multivariate analysis Cox regression model was used to investigate risk factors for mortality.

Results

In this patient cohort, glioblastoma (40%), diffuse glioma (14.6%) and oligodendroglioma (9.6%) were the most common pathological types. The expression of Ki-67 was associated with several clinicopathological parameters (e.g. tumor type, grade, and number of lesions). In addition, Ki-67 correlated with the mortality within the first year of the post-treatment follow-up (P <  0.001). Kaplan-Maier analysis revealed that older patients (≥ 45 years) displayed worse prognosis than those aged under 45 years (P = 0.038). Dismal prognosis was also associated with clinical parameters, including high tumor grade, multiple lesions, and Karnofsky performance score (KPS). Multivariate analysis showed that low KPS (< 85) increased the risk of mortality by 2.3 folds with a 95% CI of 1.141 to 4.776 (P = 0.020). Low tumor grade (grade 1–2) oppositely reduced the mortality risk by 0.22 folds (95% CI, 0.065 to 0.763,P = 0.0168).

Conclusion

KPS and tumor grade were independent prognostic factors in patients with gliomas.
Establishment and validation of a nomogram with intratumoral heterogeneity derived from 18F-FDG PET/CT for predicting individual conditional risk of 5-year recurrence before initial treatment of nasopharyngeal carcinoma
Authors: Gu Bingxin , Zhang Jianping , Ma Guang , Song Shaoli , Shi Liqun , Zhang Yingjian , Yang Zhongyi
Published: January 2020

Background

Intratumoral heterogeneity has an enormous effect on patient treatment and outcome. The purpose of the current study was to establish and validate a nomogram with intratumoral heterogeneity derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prognosis of 5-Year progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC).

Methods

A total of 171 NPC patients who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Data was randomly divided into training cohort (n = 101) and validation cohort (n = 70). The clinicopathologic parameters and the following PET parameters were analyzed: maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI, SUVmax/SUVmean) for primary tumor and maximal neck lymph node. Cox analyses were performed on PFS in the training cohort. A prognostic nomogram based on this model was developed and validated.

Results

For the primary tumor, MTV-2.5, TLG-2.5, MTV-70%, and TLG-70% were significantly correlated with PFS. For the maximal neck lymph node, short diameter and HI were significantly correlated with PFS. Among the clinicopathologic parameters, M stage was a significant prognostic factor for recurrence. In multivariate analysis, M stage (P = 0.006), TLG-T-70% (P = 0.002), and HI-N (P = 0.018) were independent predictors. Based on this prognostic model, a nomogram was generated. The C-index of this model was 0.74 (95% CI: 0.63–0.85). For the cross validation, the C-index for the model was 0.73 (95% CI: 0.62–0.83) with the validation cohort. Patients with a risk score of ≥111 had poorer survival outcomes than those with a risk score of 0–76 and 77–110.

Conclusions

Intratumoral heterogeneity derived from 18F-FDG PET/CT could predict long-term outcome in patients with primary NPC. A combination of PET parameters and the TNM stage enables better stratification of patients into subgroups with different PFS rates.
Ex vivo anti-microbial efficacy of various formaldehyde releasers against antibiotic resistant and antibiotic sensitive microorganisms involved in infectious keratitis
Authors: Amponin Daeryl E. , Przybek-Skrzypecka Joanna , Zyablitskaya Mariya , Takaoka Anna , Suh Leejee H. , Nagasaki Takayuki , Trokel Stephen L. , Paik David C.
Published: January 2020

Background

Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis.

Methods

In vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used.

Results

The results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%.

Conclusion

Our results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.
Health effects of nutrients and environmental pollutants in Baltic herring and salmon: a quantitative benefit-risk assessment
Authors: Tuomisto Jouni T. , Asikainen Arja , Meriläinen Päivi , Haapasaari Päivi
Published: January 2020

Background

Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion.

Methods

We performed an online survey investigating consumers’ fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life.

Results

Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic.

Conclusions

The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.
A good beginning: study protocol for a group-randomized trial to investigate the effects of sit-to-stand desks on academic performance and sedentary time in primary education
Authors: van Delden A. E. Q. , Band Guido P. H. , Slaets Joris P. J.
Published: January 2020

Background

Sedentary behavior is associated with health risks and academic under-achievement in children. Still, children spend a large part of their waking hours sitting at a desk at school. Recent short-term studies demonstrated the potential of sit-to-stand desks to reduce sitting time in primary education. The program of “A Good Beginning” was conceived to assess the long-term effects of sit-to-stand desks on sitting time in primary education, and to examine how sit-to-stand desks versus regular desks relate to academic performance, and measures of executive functioning, health and wellbeing. The present paper describes the design of this group-randomized trial, which started in 2017 and will be completed in 2019.

Methods

Children of two grade-three groups (age 8–9) following regular primary education in Leiden, The Netherlands, were recruited. A coin toss determined which group is the experimental group; the other group is the control group. All children in the experimental group received sit-to-stand desks. They are invited and motivated to reduce sedentary time at school, however, it is their own choice to sit or stand. Children in the control group use regular desks. Otherwise, both groups receive regular treatment. Outcomes are assessed at baseline (T0) and at five follow-up sessions (T1-T5) alternately in winter and summer seasons over three academic years. Primary outcome measures are academic performance, and the proportion of sitting time at school, measured with a 3D accelerometer. Secondary outcome measures are a number of measures related to executive functioning (e.g., N-back task for working memory), health (e.g., height and weight for BMI), and wellbeing (e.g., KIDSCREEN-52 for Quality of Life).

Discussion

A Good Beginning is a two-and-a-half-year research program, which aims to provide a better understanding of the long-term effects of sit-to-stand desks on sedentary time at school and the relation between sitting time reduction and academic performance, executive functioning, health and wellbeing. The findings may serve as useful information for policy making and practical decision making for school and classroom environments.

Trial registration

The program of “A Good Beginning” is registered at the Netherlands Trial Register (NTR, https://www.trialregister.nl), number NL6166, registration date 24 November 2016.
Maternal depression in rural Pakistan: the protective associations with cultural postpartum practices
Authors: LeMasters Katherine , Andrabi Nafeesa , Zalla Lauren , Hagaman Ashley , Chung Esther O. , Gallis John A. , Turner Elizabeth L. , Bhalotra Sonia , Sikander Siham , Maselko Joanna
Published: January 2020

Background

Traditional postpartum practices are intended to provide care to mothers, but there is mixed evidence concerning their impact on postpartum depression (PPD). It remains unknown if there is a unique impact of postpartum practices on PPD separately from other types of social support, or if practices differentially affect those with existing prenatal depression. In Pakistan, chilla (چله) is a traditional postpartum practice in which women receive relief from household work, additional familial support, and supplemental food for up to 40 days postpartum. This study aims to understand if chilla protects against PPD independent of other support and whether this relationship varies by prenatal depression status.

Methods

Data come from the Bachpan cohort study in rural Pakistan. Chilla participation and social support (Multidimensional Scale of Perceived Social Support) were assessed at 3 months postpartum. Women were assessed for major depressive episodes (MDE) with the Structured Clinical Interview, DSM-IV and for depression symptom severity with the Patient Health Questionnaire (PHQ-9) in their third trimester and at 6 months postpartum. Adjusted linear mixed models were used to assess the relationship between chilla participation and PPD.

Results

Eighty-nine percent of women (N = 786) participated in chilla and almost 70% of those that participated took part in all of chilla’s aspects. In adjusted models, chilla participation was inversely related to MDE (OR = 0.56;95%CI = 0.31,1.03) and symptom severity (Mean Difference (MD) = − 1.54;95%CI: − 2.94,-0.14). Chilla participation was associated with lower odds of MDE (OR = 0.44;95%CI = 0.20,0.97) among those not prenatally depressed and with lower symptom severity among those prenatally depressed (MD = -2.05;95%CI:-3.81,-0.49).

Conclusions

Chilla is inversely associated with both MDE and symptom severity at 6 months postpartum above and beyond social support. Specifically, chilla is inversely associated with MDE among those not prenatally depressed and with lower symptom severity among those prenatally depressed. This relationship signals an opportunity for interventions aimed at preventing and treating PPD in this region to draw upon chilla and similar traditional postpartum practices in creating community-based, low-cost, sustainable interventions for maternal mental health.

Trial registration

NCT02111915. Registered 18 September 2015. NCT02658994. Registered 22 January 2016. Both trials were prospectively registered.