bluuebunny/crossref_metadata_2025 huggingface dataset:
No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study
Authors: Miao Liu , Deng Guo-Xiong , Yin Rui-Xing , Nie Rong-Jun , Yang Shuo , Wang Yong , Li Hui
Published: December 2019

Background

Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction.

Methods

A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” (n = 184,305) and “acute myocardial infarction” (n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable.

Results

None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction (p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy (p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction.

Conclusions

The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.
miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation
Authors: Moimas Silvia , Salton Francesco , Kosmider Beata , Ring Nadja , Volpe Maria C. , Bahmed Karim , Braga Luca , Rehman Michael , Vodret Simone , Graziani Maria Laura , Wolfson Marla R. , Marchetti Nathaniel , Rogers Thomas J. , Giacca Mauro , Criner Gerard J. , Zacchigna Serena , Confalonieri Marco
Published: December 2019

Rationale

Alveolar type II (ATII) cells act as adult stem cells contributing to alveolar type I (ATI) cell renewal and play a major role in idiopathic pulmonary fibrosis (IPF), as supported by familial cases harbouring mutations in genes specifically expressed by these cells. During IPF, ATII cells lose their regenerative potential and aberrantly express pathways contributing to epithelial–mesenchymal transition (EMT). The microRNA miR-200 family is downregulated in IPF, but its effect on human IPF ATII cells remains unproven. We wanted to 1) evaluate the characteristics and transdifferentiating ability of IPF ATII cells, and 2) test whether miR-200 family members can rescue the regenerative potential of fibrotic ATII cells.

Methods

ATII cells were isolated from control or IPF lungs and cultured in conditions promoting their transdifferentiation into ATI cells. Cells were either phenotypically monitored over time or transfected with miR-200 family members to evaluate the microRNA effect on the expression of transdifferentiation, senescence and EMT markers.

Results

IPF ATII cells show a senescent phenotype (p16 and p21), overexpression of EMT (ZEB1/2) and impaired expression of ATI cell markers (AQP5 and HOPX) after 6 days of culture in differentiating medium. Transfection with certain miR-200 family members (particularly miR-200b-3p and miR-200c-3p) reduced senescence marker expression and restored the ability to transdifferentiate into ATI cells.

Conclusions

We demonstrated that ATII cells from IPF patients express senescence and EMT markers, and display a reduced ability to transdifferentiate into ATI cells. Transfection with certain miR-200 family members rescues this phenotype, reducing senescence and restoring transdifferentiation marker expression.
Primary headache disorders among the adult population of Mongolia: prevalences and associations from a population-based survey
Authors: Luvsannorov Otgonbayar , Tsenddorj Byambasuren , Baldorj Dorjkhand , Enkhtuya Selenge , Purev Delgermaa , Thomas Hallie , Steiner Timothy J.
Published: December 2019

Background

In the ongoing Global Campaign endeavour to improve knowledge and awareness of headache prevalence worldwide, Mongolia is a country of interest. It sits between Russia and China, in which prevalence is, respectively, much higher and much lower than the estimated global mean. We conducted a population-based study in Mongolia both to add to knowledge and to inform local health policy.

Methods

Using standardized methodology with cluster random sampling, we selected Mongolian adults (aged 18–65 years) from five regions reflecting the country’s diversities. They were interviewed by trained researchers, cold-calling at their homes, using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire following pilot-testing. ICHD-3 beta diagnostic criteria were applied.

Results

N = 2043 (mean age 38.0 [±13.4] years, 40% urban-dwelling and 60% rural), with a non-participation proportion of 1.7%. Males were somewhat underrepresented, for which corrections were made. The crude 1-year prevalence of any headache was 66.1% (95% CI: 64.0–68.2%), with a strong female preponderance (OR: 2.2; p < 0.0001). Age- and gender-adjusted prevalences were: migraine 23.1% (for females, OR = 2.2; p < 0.0001); tension-type headache (TTH) 29.1% (no gender difference); probable medication-overuse headache (pMOH) 5.7% (trending towards higher in females); other headache on ≥15 days/month 5.0% (for females, OR = 2.2; p = 0.0008). Unclassified cases were only 35 (1.7%). Any headache yesterday was reported by 410 (20.1%; for females, OR = 2.4; p < 0.0001). Only pMOH showed a strong association with age, peaking in middle years with a 5-fold increase in prevalence. Migraine showed a consistent association with educational level, while pMOH showed the reverse, and was also more common among other groups than among participants who were single (never married). Migraine was less common among rural participants than urban (OR: 0.80; p = 0.0326), while pMOH again showed the reverse (OR: 2.4; p < 0.0001). Finally, pMOH (but not migraine or TTH) was significantly associated with obesity (OR: 1.8; p = 0.0214).

Conclusion

Headache disorders are common in Mongolia, with, most notably, a very high prevalence of headache on ≥15 days/month corroborated by the high prevalence of headache yesterday. The picture is very like that in Russia, and dissimilar to China. There are messages for national health policy.
The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex
Authors: Wong Michael
Published: December 2019

Background

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, different types of glial cells have been increasingly recognized to play important roles in the phenotypes of TSC.

Main body

This review summarizes the literature supporting glial dysfunction from both mouse models and clinical studies of TSC. In particular, evidence for the role of astrocytes, microglia, and oligodendrocytes in the pathophysiology of epilepsy and TAND in TSC is analyzed. Therapeutic implications of targeting glia cells in developing novel treatments for the neurological manifestations of TSC are also considered.

Conclusions

Different types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients.
Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder
Authors:   on behalf of the TACERN Study Group, Prohl Anna K. , Scherrer Benoit , Tomas-Fernandez Xavier , Davis Peter E. , Filip-Dhima Rajna , Prabhu Sanjay P. , Peters Jurriaan M. , Bebin E. Martina , Krueger Darcy A. , Northrup Hope , Wu Joyce Y. , Sahin Mustafa , Warfield Simon K.
Published: December 2019

Background

Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants.

Methods

TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD.

Results

Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups.

Conclusions

Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.
The impact of expressive language development and the left inferior longitudinal fasciculus on listening and reading comprehension
Authors: Del Tufo Stephanie N. , Earle F. Sayako , Cutting Laurie E.
Published: December 2019

Background

During the first 3-years of life, as the brain undergoes dramatic growth, children begin to develop speech and language. Hallmarks of this progression are seen when children reach developmental milestones, forming the foundation of language. Expressive language milestones, such as the production of a child’s first word, are delayed in 5–8% of children. While for some children delays in reaching these milestones are harbingers of developmental disorders, for others expressive language delays appear to resolve. Regardless of whether or not early language skills appear resolved, difficulty with later comprehension is a likely outcome. Whether this heightened risk for poor comprehension differs based on text features, individual characteristics, or receipt of intervention remains unknown. Moreover, this relationship between expressive language development and comprehension is not yet linked to neurobiology, though the inferior longitudinal fasciculus (ILF) is a potential neurobiological correlate. Therefore, we investigated the impact of, and interactions between, expressive language development, early intervention, and the ILF on comprehension.

Methods

Longitudinal recurrent survival analyses predicted the risk of answering a comprehension question incorrectly. Predictors of comprehension included expressive language development, passage features, participant characteristics, fractional anisotropy, receipt of early intervention, and later diagnosis of speech or language disorders.

Results

Children with later expressive language milestones had poorer comprehension. When comprehension text features were examined, children with later milestones had poorer listening and reading comprehension, and poorer narrative and expository comprehension. The left ILF acted as a neurodevelopmental correlate, one that moderated the relationship between expressive language milestones and comprehension. Specifically, the left ILF exacerbated the relationship for those who did not receive early intervention and buffered the relationship for those who received intervention services. Early intervention decreased the risk of poor comprehension by 39% for children later diagnosed with a speech or language disorder.

Conclusions

Early intervention should be provided for children with delayed expressive language milestones, particularly those who are at risk for speech or language disorders. The ILF plays a critical role in the relationship between expressive language development and comprehension, which may be that of a protective factor for children with the most severe early issues with speech and language.
Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain
Authors: Zanno Allison E. , Romer Micah A. , Fox Lauren , Golden Thea , Jaeckle-Santos Lane , Simmons Rebecca A. , Grinspan Judith B.
Published: December 2019

Background

Intrauterine growth restriction (IUGR) is a common complication of pregnancy and is associated with significant neurological deficits in infants, including white matter damage. Previous work using an animal model of IUGR has demonstrated that IUGR rats exhibit neurobehavioral deficits and developmental delays in oligodendrocyte maturation and myelination, but the mechanisms which cause this delay are unknown. Inflammation may be an important etiological factor in IUGR and has been recognized as playing a fundamental role in the pathogenesis of myelin disorders, including cerebral palsy.

Methods

To create the model, the uterine arteries of pregnant rats were ligated at embryonic day 15. Rats delivered spontaneously. Cytokine and chemokine expression was evaluated at one prenatal and three postnatal time points, and myelin protein expression and oligodendrocyte cell numbers were evaluated by several methods at postnatal day 14. IL-4 was identified as a potential inhibitor of myelination, and rat pups were injected with IL-4 function blocking antibody from postnatal days 1–5 and myelination was assessed.

Results

Here, we show a novel mechanism of white matter injury. IUGR induces an exaggerated Th2 response in the developing rat brain, including upregulation of several Th2 cytokines. Of these, IL-4 is significantly increased during the period corresponding to robust developmental myelination. We show that neutralizing IL-4 antibody therapy given in the newborn period ameliorates inflammation and restores myelin protein expression and oligodendrocyte cell number in the IUGR brain to control levels, demonstrating a novel role for Th2 responses and IL-4 in IUGR and white matter injury. In addition, IL-4 directly affects oligodendrocytes in vitro decreasing differentiation.

Conclusions

In this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a potential therapeutic target.
Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome
Authors: Lessov-Schlaggar Christina N. , del Rosario Olga L. , Morris John C. , Ances Beau M. , Schlaggar Bradley L. , Constantino John N.
Published: December 2019

Background

Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients.

Methods

We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR—a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven’s Progressive Matrices to estimate IQ.

Results

Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults.

Conclusions

The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores.
The Rice G Protein γ Subunit DEP1/qPE9–1 Positively Regulates Grain-Filling Process by Increasing Auxin and Cytokinin Content in Rice Grains
Authors: Zhang Dongping , Zhang Minyan , Zhou Yong , Wang Yuzhu , Shen Jinyu , Chen Hongyingxue , Zhang Lin , Lü Bing , Liang Guohua , Liang Jiansheng
Published: December 2019

Heterotrimeric G protein-mediated signal transduction is one of the most important and highly conserved signaling pathways in eukaryotes, which involves in the regulation of many important biological processes. As compared with those in mammals and Arabidopsis thaliana, the functions of rice heterotrimeric G protein and their molecular mechanisms are largely unknown. The rice genome contains a single Gα (RGA1) and Gβ (RGB1), and five Gγ (RGG1, RGG2, GS3, DEP1/qPE9–1, and GGC2) subunits. Recent genetic studies have shown that DEP1/qPE9–1, an atypical putative Gγ protein, is responsible for the grain size as well as the dense and erect panicles, but the biochemical and molecular mechanisms underlying the control of grain size are not well understood. Here, we report that rice plants carrying DEP1/qPE9–1 have more endosperm cells per grain than plants contain the dep1/qpe9–1 allele. The DEP1/qPE9–1 line has a higher rate and more prolonged period of starch accumulation than the dep1/qpe9–1 line. Additionally, the expression of several essential genes encoding enzymes catalyzing sucrose metabolism and starch biosynthesis is higher in the DEP1/qPE9–1 line than in the dep1/qpe9–1 line, especially from the mid to late grain-filling stage. Grains of the DEP1/qPE9–1 line also have higher contents of three phytohormones, ABA, auxin and cytokinin. Exogenous application of auxin or cytokinin enhanced the starch accumulation and the expression of genes encoding grain-filling-related enzymes in the grains of dep1/qpe9–1, whereas ABA produced no effects. Based on these results, we conclude that DEP1/qPE9–1 positively regulates starch accumulation primarily through auxin and cytokinin, which enhance the expression of genes encoding starch biosynthesis during the mid to late grain-filling stage, resulting in increased duration of the grain-filling process.
Comparison of prostate size and anthropometric parameters between diabetic and non-diabetic Congolese patients who underwent transurethral prostate resection in the Democratic Republic of Congo
Authors: Mubenga L. E. , Chimanuka D. , De Groote P. , Bwenge E. , Hermans M. P. , Tombal B.
Published: December 2019

Background

Benign prostate hyperplasia (BPH) and type 2 diabetes mellitus are prevalent in older men, and both represent a challenge to public health. Prior studies reported a correlation between BPH and (hyper)glycaemia, a component of the metabolic syndrome, which is on the increase in sub-Saharan Africa (SSA) due to rapid modernization. This study was designed to evaluate the association of prostate volume and anthropometric parameters among diabetic and non-diabetic patients who had transurethral resection of the prostate (TURP) for BPH.

Results

We analyzed data of 159 selected patients who had TURP over a three-year period (February 2014–January 2017) for histologically confirmed BPH. Mean age in the entire cohort was 68 ± 8.5 years. Out of the 159 patients, 94 (59.1%) were non-diabetics and 65 (40.9%) were diabetics. International Prostate Symptom Score (IPSS) and fasting blood glucose were significantly higher in diabetic than in non-diabetic group (28.6 ± 4.3 vs 25.6 ± 6.4, andp0.005; 121.7 ± 45.7 vs 85.4 ± 11.7 mg/dl, andp < 0.001, respectively). BMI and waist circumference were statistically greater in non-diabetics than in diabetics (25.1 ± 3.3 kg/m2vs 23.6 ± 3.5 kg/m2, andp0.008; 94.6 cm ± 10.3 vs 90.6 ± 10.4 cm, andp0.018). Diabetic patients had larger prostate volume than non-diabetic in the working age subgroup only (< 65 years of age); beyond 65 years, this difference was not consistent (62.6 ± 23.1 cc vs 50.1 ± 20.7 cc, andp0.027; 56.2 ± 23.7 cc vs 49 ± 20.2 cc, andp0.15, respectively). Prostate size was significantly associated with fasting blood glucose (p = 0.002) and PSA (p = 0.027). However, prostate size was not related to age, presence of diabetes, BMI, waist circumference, IPSS, quality of life score, and duration of symptoms.

Conclusion

Prostate volume is not correlated with anthropometric parameters in diabetic and non-diabetic Congolese patients who had TURP in South Kivu. Diabetics were not obese and yet had larger prostate volume than non-diabetics < 65 years of age. It is hoped that these results would form groundwork for further studies on this topic in SSA region.
Danaparoid sodium-based anticoagulation therapy for portal vein thrombosis in cirrhosis patients
Authors: Hayashi Takehiro , Takatori Hajime , Horii Rika , Nio Kouki , Terashima Takeshi , Iida Noriho , Kitahara Masaaki , Shimakami Tetsuro , Arai Kuniaki , Kitamura Kazuya , Kawaguchi Kazunori , Yamashita Taro , Sakai Yoshio , Yamashita Tatsuya , Mizukoshi Eishiro , Honda Masao , Toyama Tadashi , Okumura Kenichiro , Kozaka Kazuto , Kaneko Shuichi
Published: December 2019

Background

Portal vein thrombosis (PVT) is a common complication of cirrhosis. However, in patients with PVT and cirrhosis, there is no clear evidence supporting effective treatment modalities. In this study, we examined the effectiveness and safety of anticoagulation therapy using danaparoid sodium for PVT in patients with cirrhosis.

Methods

This retrospective study assessed 52 cirrhotic patients with PVT treated with danaparoid sodium for 2 weeks between November 2008 and September 2018. The primary outcome measure was the post-treatment status of PVT assessed by reduction in thrombus volume and safety of the therapeutic intervention. PVT status was evaluated with contrast-enhanced computed tomography (CECT). All patients received 1250 units of danaparoid sodium twice daily by intravenous injection for 14 days. Patients on antithrombin III (AT-III) combination therapy were additionally administered 1500 units of AT-III on days 1–5 and days 8–12. Effectiveness was evaluated by CECT from between days 13 and 18. The secondary outcome measure was the prognosis of PVT.

Results

All patients showed reduction in PVT volume without complications. Return of plasma AT-III level to > 70% during the treatment period contributes to ≥75% reduction of PVT volume. The prognosis in PVT patients depends on hepatic reserve capacity. When limited to Child-Pugh B and C liver cirrhosis patients, a ≥ 75% reduction of PVT volume improved the prognosis.

Conclusions

Danaparoid sodium-based anticoagulation therapy was effective and safe for PVT in patients with cirrhosis. Return of plasma AT-III level to the normal range during the treatment period contributes to reduction of PVT volume. A reduction of ≥75% in PVT volume may improve the prognosis of Child-Pugh B and C decompensated cirrhosis patients with PVT.
Effect of epidural analgesia in trial of labor after cesarean on maternal and neonatal outcomes in China: a multicenter, prospective cohort study
Authors: Sun Jing , Yan Xuetao , Yuan Aiwu , Huang Xiaolei , Xiao Yuci , Zou Liwei , Liu Danyong , Huang Ting , Zheng Zhao , Li Yuantao
Published: December 2019

Background

The trial of labor after cesarean section (TOLAC) is a relatively new technique in mainland of China, and epidural analgesia is one of the risk factors for uterine rupture. This study aimed to evaluate the effect of epidural analgesia on primary labor outcome [success rate of vaginal birth after cesarean (VBAC)], parturient complications and neonatal outcomes after TOLAC in Chinese multiparas based on a strictly uniform TOLAC indication, management and epidural protocol.

Methods

A total of 423 multiparas undergoing TOLAC were enrolled in this study from January 2017 to February 2018. Multiparas were divided into two groups according to whether they received epidural analgesia (study group, N = 263) or not (control group, N = 160) during labor. Maternal delivery outcomes and neonatal characteristics were recorded and evaluated using univariate analysis, multivariable logistic regression and propensity score matching (PSM).

Results

The success rate of VBAC was remarkably higher (85.55% vs. 69.38%, p < 0.01) in study group. Epidural analgesia significantly shortened initiating lactation period and declined Visual Analogue Score (VAS). It also showed more superiority in neonatal umbilical arterial blood pH value. After matching by PSM, multivariable logistic regression revealed that the correction of confounding factors including epidural analgesia, cervical Bishop score at admission and spontaneous onset of labor were still shown as promotion probability in study group (OR = 4.480, 1.360, and 10.188, respectively; 95%CI = 2.025–10.660, 1.113–1.673, and 2.875–48.418, respectively; p < 0.001, p = 0.003, and p < 0.001, respectively).

Conclusions

Epidural analgesia could reduce labor pain, and no increased risk of postpartum bleeding or uterine rupture, as well as adverse effects in newborns were observed. The labor duration of multiparas was increased, but within acceptable range. In summary, epidural analgesia may be safe for both mother and neonate in the three studied hospitals.

Trial registration

Chineses Clinical Trial Register, ChiCTR-ONC-17010654. Registered February 16th, 2017.
Heart rate agreement between the 20-meter shuttle run test and virtual system in healthy children: a cross-sectional study
Authors: Moran Cristiane A. , Corso Simone Dal , Bombig Maria Teresa , Serra Andrey Jorge , Pereira Silvana Alves , Peccin Maria Stella
Published: December 2019

Background

Earlier studies evaluated the physiological responses to video games in children with different clinical conditions; however, no study has compared active video games with an incremental field test in healthy children. The purpose of this study was to verify the agreement between the 20-m shuttle run test (20 m-SRT) and virtual system (VS).

Methods

This is a cross-sectional study of 235 children (9.0 ± 0.8 years, 109 boys). The two tests were performed one week apart and the children were instructed not to engage in any physical exercise or sports in the 24 h preceding each test. Their resting heart rate was monitored for one minute and then throughout the tests. To evaluate the influence of motivation on the 20 m SRT and (VS), at the end of the tests the children were asked to rate their motivation on a scale of zero to 10, zero being “not cool” and 10 “awesome”. Perceived exertion at the end of the tests was assessed using the modified Borg scale.

Results

Maximum heart rate (HRmax) did not differ between the 20 m-SRT and VS (194.4 ± 10.2 bpm vs. 193.2 ± 13.8 bpm, respectively). Both tests were similar for intensity > and < 96% HRmax. The children showed greater exertion on the Borg scale and motivation during the VS. The multiple logistic regression model showed that motivation (p = 0.98), sex (p = 0.53), age (p = 0.61), nutritional status (p = 0.65), and speed (p = 0.18) were not predictive factors of the child’s reaching HRmax.

Conclusion

VS can be used as a tool to evaluate the intensity of maximal exercise tests, given that the percentage of children who achieved HRmax did not differ between the VS and 20 m SRT. The perceived exertion scales were correlated, but only the modified Borg scale correlated with HRmax in the 20 m SRT. The tests are motivational, and most children obtained the maximum VS score.
Comparison of open liver resection and RFA for the treatment of solitary 3–5-cmhepatocellular carcinoma: a retrospective study
Authors:   Liver Surgery Group, Jianyong Lei , Lunan Yan , Dajiang Li , Wentao Wang
Published: December 2019

Background

The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3–5 cm).

Patients and methods

We retrospectively collected 122 cases of small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3–5 cm. According to the treatment program received at our center, the patients were divided into liver resection (72 patients) and RFA (50 patients) groups.

Result

In comparison with the RFA group, the resection group had a longer operative time, greater intraoperative blood loss (P < 0.01), more hepatic inflow occlusion, and a longer postoperative hospital stay (P < 0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that neither resection nor RFA was a significant risk factor for overall or tumor-free survival in HCC.

Conclusions

For solitary HCC of 3–5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes than resection and can be considered for wide application, especially for central-location cases.
Engaging people with lived experience in the grant review process
Authors: Rittenbach Katherine , Horne Candice G. , O’Riordan Terence , Bichel Allison , Mitchell Nicholas , Fernandez Parra Adriana M. , MacMaster Frank P.
Published: December 2019

People with lived experience are individuals who have first-hand experience of the medical condition(s) being considered. The value of including the viewpoints of people with lived experience in health policy, health care, and health care and systems research has been recognized at many levels, including by funding agencies. However, there is little guidance or established best practices on how to include non-academic reviewers in the grant review process. Here we describe our approach to the inclusion of people with lived experience in every stage of the grant review process. After a budget was created for a specific call, a steering committee was created. This group included researchers, people with lived experience, and health systems administrators. This group developed and issued the call. After receiving proposals, stage one was scientific review by researchers. Grants were ranked by this score and a short list then reviewed by people with lived experience as stage two. Finally, for stage three, the Steering Committee convened and achieved consensus based on information drawn from stages one and two. Our approach to engage people with lived experience in the grant review process was positively reviewed by everyone involved, as it allowed for patient perspectives to be truly integrated. However, it does lengthen the review process. The proposed model offers further practical insight into including people with lived experience in the review process.
Implementation of machine learning algorithms to create diabetic patient re-admission profiles
Authors: Alloghani Mohamed , Aljaaf Ahmed , Hussain Abir , Baker Thar , Mustafina Jamila , Al-Jumeily Dhiya , Khalaf Mohammed
Published: December 2019

Background

Machine learning is a branch of Artificial Intelligence that is concerned with the design and development of algorithms, and it enables today’s computers to have the property of learning. Machine learning is gradually growing and becoming a critical approach in many domains such as health, education, and business.

Methods

In this paper, we applied machine learning to the diabetes dataset with the aim of recognizing patterns and combinations of factors that characterizes or explain re-admission among diabetes patients. The classifiers used include Linear Discriminant Analysis, Random Forest, k–Nearest Neighbor, Naïve Bayes, J48 and Support vector machine.

Results

Of the 100,000 cases, 78,363 were diabetic and over 47% were readmitted.Based on the classes that models produced, diabetic patients who are more likely to be readmitted are either women, or Caucasians, or outpatients, or those who undergo less rigorous lab procedures, treatment procedures, or those who receive less medication, and are thus discharged without proper improvements or administration of insulin despite having been tested positive for HbA1c.

Conclusion

Diabetic patients who do not undergo vigorous lab assessments, diagnosis, medications are more likely to be readmitted when discharged without improvements and without receiving insulin administration, especially if they are women, Caucasians, or both.
Peste des petits ruminants pathogenesis on experimental infected goats by the Moroccan 2015 isolate
Authors: Bamouh Z. , Fakri F. , Jazouli M. , Safini N. , Omari Tadlaoui K. , Elharrak M.
Published: December 2019

Background

Peste des petits ruminants (PPR) is a viral disease of major economic importance on small ruminants. Goats are usually known to be more susceptible to the disease. Infection chronology, virus circulation, and the disease early detection need to be better understood. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of goats using a lineage IV virus, the most dominant in the world originated from Asia. PPRV infection was experimentally induced in 4 six-month-old goats by intra-nasal and intravenous route of cell virus suspension and from infectious mashed tissue. The clinical signs were observed and goats were euthanized at predetermined clinical score level for post-mortem examinations and PPRV detection by RT-PCR. Clinical signs of infection were present, pyrexia, serous-mucopurulent nasal discharges, coughing, diarrhea and asthenia, for both cell virus suspension and infectious mashed tissue. PPRV genome was highly detected in swabs and tissues with clinical signs dominated by pulmonary attack and digestive symptoms secondary.

Results

Results of this study indicates that PPRV is an invasive infection in animals that in a short period, less than 10 days, invade all vital organs. On live animals, early diagnostic may be easily done on lacrimal and rectal swabs.

Conclusion

The experimental PPRV-infection model using the cell virus suspension is suitable for vaccine evaluation as a standard model.
A diagnostic approach for differentiating abdominal tuberculosis from ovarian malignancy: a case series and literature review
Authors: Fahmi Moh Nailul , Harti Annisaa Pelita
Published: December 2019

Background

Abdominal tuberculosis is an uncommon variant of extrapulmonary tuberculosis. It accounts for 3.5% of extrapulmonary tuberculosis. Diagnosis of abdominal tuberculosis is still a challenge due to its non-specific symptoms. Abdominal tuberculosis and ovarian cancer may show similar symptoms, laboratory and imaging features. The goal of our report is to emphasize for the need of a diagnostic approach based on clinical manifestations, laboratory, imaging findings, and additional tests for considering a diagnosis of abdominal tuberculosis rather than ovarian cancer.

Case presentation

We report 3 cases of abdominal tuberculosis in our Onco-gynaecology Division, Department of Obstetrics and Gynaecology, Sardjito Hospital, Yogyakarta, Indonesia in 2018 which were previously diagnosed as ovarian malignancy and managed surgically. All of our patients experienced abdominal pain and enlargement but only two of them had significant weight loss. The general symptoms were typically found in onco-gynaecology patients, especially in those with ovarian malignancy. Ultrasound examination showed multilocular masses, 2 of them with solid parts and ascites. Cancer antigen 125 (CA-125) levels were found increasing in those three patients. All of them were treated surgically and diagnosis of abdominal tuberculosis was established through the histopathological result of tissue biopsy. Based on our cases and literature, we consider the need of a diagnostic approach to differentiate abdominal tuberculosis from ovarian malignancy, an attempt to avoid unnecessary invasive procedures that put burden risk for the patients.

Conclusion

Minimally invasive tests to establish the diagnosis of abdominal tuberculosis should be optimized to reduce the burden risk of laparotomy. Careful diagnostic steps should be followed to avoid wrong diagnosis.
High-throughput RNA sequencing from paired lesional- and non-lesional skin reveals major alterations in the psoriasis circRNAome
Authors: Moldovan Liviu-Ionut , Hansen Thomas Birkballe , Venø Morten Trillingsgaard , Okholm Trine Line Hauge , Andersen Thomas Levin , Hager Henrik , Iversen Lars , Kjems Jørgen , Johansen Claus , Kristensen Lasse Sommer
Published: December 2019

Background

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. It is one of the most prevalent chronic inflammatory skin conditions in adults worldwide, with a considerable negative impact on quality of life. Circular RNAs (circRNAs) are a recently identified type of non-coding RNA with diverse cellular functions related to their exceptional stability. In particular, some circRNAs can bind and regulate microRNAs (miRNAs), a group of RNAs that play a role in the pathogenesis of psoriasis. The aim of this study was to characterize the circRNAome in psoriasis and to assess potential correlations to miRNA expression patterns.

Methods

We used high-throughput RNA-sequencing (RNA-seq), NanoString nCounter technology and RNA chromogenic in situ hybridization (CISH) to profile the circRNA expression in paired lesional and non-lesional psoriatic skin from patients with psoriasis vulgaris. In addition, 799 miRNAs were profiled using NanoString nCounter technology and laser capture microdissection was used to study the dermis and epidermis separately.

Results

We found a substantial down-regulation of circRNA expression in lesional skin compared to non-lesional skin. We observed that this mainly applies to the epidermis by analyzing laser capture microdissected tissues. We also found that the majority of the circRNAs were downregulated independently of their corresponding linear host genes. The observed downregulation of circRNAs in psoriasis was neither due to altered expression levels of factors known to affect circRNA biogenesis, nor because lesional skin contained an increased number of inflammatory cells such as lymphocytes. Finally, we observed that the overall differences in available miRNA binding sites on the circRNAs between lesional and non-lesional skin did not correlate with differences in miRNA expression patterns.

Conclusions

We have performed the first genome-wide circRNA profiling of paired lesional and non-lesional skin from patients with psoriasis and revealed that circRNAs are much less abundant in the lesional samples. Whether this is a cause or a consequence of the disease remains to be revealed, however, we found no evidence that the loss of miRNA binding sites on the circRNAs could explain differences in miRNA expression between lesional and non-lesional skin.
Correction to: Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
Authors: Nijsingh Niels , Munthe Christian , Larsson D. G. Joakim
Published: December 2019

Following publication of the original article [1], the author explained that there are multiple errors in the original article
Non-invasive quantification of cardiac stroke volume in the edible crab Cancer pagurus
Authors: Maus Bastian , Gutsfeld Sebastian , Pörtner Hans-Otto , Bock Christian
Published: December 2019

Background

Brachyuran crabs can effectively modulate cardiac stroke volume independently of heart rate in response to abiotic drivers. Non-invasive techniques can help to improve the understanding of cardiac performance parameters of these animals. This study demonstrates the in vivo quantification of cardiac performance parameters through magnetic resonance imaging (MRI) on the edible crabCancer pagurus. Furthermore, the suitability of signal integrals of infra-red photoplethysmographs as a qualitative tool is assessed under severe hypoxia.

Results

Multi-slice self-gated cardiac cinematic (CINE) MRI revealed the structure and motion of the ventricle to quantify heart rates, end-diastolic volume, end-systolic volume, stroke volume and ejection fraction. CINE MRI showed that stroke volumes increased under hypoxia because of a reduction of end-systolic volumes at constant end-diastolic volumes. Plethysmograph recordings allowed for automated heart rate measurements but determination of a qualitative stroke volume proxy strongly depended on the position of the sensor on the animal. Both techniques revealed a doubling in stroke volumes after 6 h under severe hypoxia (waterPO2 = 15% air saturation).

Conclusions

MRI has allowed for detailed descriptions of cardiac performance in intact animals under hypoxia. The temporal resolution of quantitative non-invasive CINE MRI is limited but should encourage further refining. The stroke volume proxy based on plethysmograph recordings is feasible to complement other cardiac measurements over time. The presented methods allow for non-destructive in vivo determinations of multiple cardiac performance parameters, with the possibility to study neuro-hormonal or environmental effects on decapod cardio physiology.
Effects of relaxation therapy on maternal psychological state, infant growth and gut microbiome: protocol for a randomised controlled trial investigating mother-infant signalling during lactation following late preterm and early term delivery
Authors: Yu Jinyue , Wells Jonathan , Wei Zhuang , Fewtrell Mary
Published: December 2019

Background

Breastfeeding is of great importance for infant health both short and long term, especially for those born preterm. Apart from the socio-economic and cultural factors which may influence a mother’s decision on breastfeeding, lactation performance is also influenced by maternal physiological and psychological condition, as well as infant behavioural factors. The aim of this project is to investigate physiological, psychological and anthropological aspects of ‘signalling’ between mother and infant during lactation in a stressful situation, following late preterm delivery, using an experimental approach.

Method

A single blind parallel randomised controlled trial will be conducted in Chinese primiparous mothers who deliver a infant (34 0/7–37 6/7) weeks and plan to exclusively breastfeed. Mothers will be recruited from four local community clinics attached to Beijing Children Hospital. Two home visits will be arranged at one week and eight weeks postpartum. Participants will be randomly assigned to either intervention arm or control (no intervention) before the first home visit. Mothers from the intervention group will be asked to listen to an audio recording with relaxation meditation daily during breastfeeding. Maternal stress and anxiety will be measured at one week and eight week postpartum using Chinese version of Cohen’s Perceived Stress Scale (PSS) and Beck Anxiety Inventory (BAI). Infant weight and length gain (as SD scores) from one to eight week will be measured using anthropometry. Milk volume will be measured using 48-h test-weighing method. Breast milk samples and mother and infant’s stool samples will be collected to measure macronutrient and microbiome content. Anthropometric measurements (weight, length and head circumference) will be performed during all home visits.

Discussion

Primary outcomes of this study will be the effect of the intervention on maternal psychological state, and infant growth. Other outcomes will include the effect of the intervention on milk production, infant behaviours, and the microbiome composition in breastmilk and maternal and infant’s gut. Results of this study will provide greater understanding about maternal-infant factors which influence the success of breastfeeding, and which may then be useful targets for future interventions.

Trial registration

ClinicalTrials.gov identifier: NCT03674632. Registered 14 September 2018.