bluuebunny/crossref_metadata_2025 huggingface dataset:
Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
Authors: Ehrlich Amy M. , Pacheco Alline R. , Henrick Bethany M. , Taft Diana , Xu Gege , Huda M. Nazmul , Mishchuk Darya , Goodson Michael L. , Slupsky Carolyn , Barile Daniela , Lebrilla Carlito B. , Stephensen Charles B. , Mills David A. , Raybould Helen E.
Published: November 2020

Background

Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host.

Results

In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2–related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors.

Conclusions

These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.
Emotion regulation through bifocal processing of fear inducing and disgust inducing stimuli
Authors: Wittfoth Dina , Pfeiffer Antonia , Bohne Michael , Lanfermann Heinrich , Wittfoth Matthias
Published: November 2020

Background

We present first-time evidence for the immediate neural and behavioral effects of bifocal emotional processing via visualized tapping for two different types of negative emotions (fear and disgust) in a sample of healthy participants.

Results

Independent of stimulus type, neural activation in the amygdala is increased during regulation, while activation in the ventral anterior cingulate cortex is decreased. Behavioral responses, as well as lateral and medial occipital regions and the dorsolateral prefrontal cortex show differential regulatory effects with respect to stimulus type.

Conclusions

Our findings suggest that emotion regulation through bifocal processing has a neural and behavioral signature that is distinct from previously investigated emotion regulation strategies. They support theoretical models of facilitated access to and processing of emotions during bifocal processing and suggest differential neural and behavioral effects for various types of negative emotions.
Occipital repetitive transcranial magnetic stimulation does not affect multifocal visual evoked potentials
Authors: Kolbe Robert , Aytulun Aykut , Müller Ann-Kristin , Ringelstein Marius , Aktas Orhan , Schnitzler Alfons , Hartung Hans-Peter , Groiss Stefan Jun , Albrecht Philipp
Published: November 2020

Background

To identify mechanisms of cortical plasticity of the visual cortex and to quantify their significance, sensitive parameters are warranted. In this context, multifocal visual evoked potentials (mfVEPs) can make a valuable contribution as they are not associated with cancellation artifacts and include also the peripheral visual field.

Objective

To investigate if occipital repetitive transcranial magnetic stimulation (rTMS) can induce mfVEP changes.

Methods

18 healthy participants were included in a single-blind crossover-study receiving sessions of excitatory, occipital 10 Hz rTMS and sham stimulation. MfVEP was performed before and after each rTMS session and changes in amplitude and latency between both sessions were compared using generalized estimation equation models.

Results

There was no significant difference in amplitude or latency between verum and sham group.

Conclusion

We conclude that occipital 10 Hz rTMS has no effect on mfVEP measures, which is in line with previous studies using full field VEP.
Population structure of Nepali spring wheat (Triticum aestivum L.) germplasm
Authors: Khadka Kamal , Torkamaneh Davoud , Kaviani Mina , Belzile Francois , Raizada Manish N. , Navabi Alireza
Published: November 2020

Background

Appropriate information about genetic diversity and population structure of germplasm improves the efficiency of plant breeding. The low productivity of Nepali bread wheat (Triticum aestivum L.) is a major concern particularly since Nepal is ranked the 4th most vulnerable nation globally to climate change. The genetic diversity and population structure of Nepali spring wheat have not been reported. This study aims to improve the exploitation of more diverse and under-utilized genetic resources to contribute to current and future breeding efforts for global food security.

Results

We used genotyping-by-sequencing (GBS) to characterize a panel of 318 spring wheat accessions from Nepal including 166 landraces, 115 CIMMYT advanced lines, and 34 Nepali released varieties. We identified 95 K high-quality SNPs. The greatest genetic diversity was observed among the landraces, followed by CIMMYT lines, and released varieties. Though we expected only 3 groupings corresponding to these 3 seed origins, the population structure revealed two large, distinct subpopulations along with two smaller and scattered subpopulations in between, with significant admixture. This result was confirmed by principal component analysis (PCA) and UPGMA distance-based clustering. The pattern of LD decay differed between subpopulations, ranging from 60 to 150 Kb. We discuss the possibility that germplasm explorations during the 1970s–1990s may have mistakenly collected exotic germplasm instead of local landraces and/or collected materials that had already cross-hybridized since exotic germplasm was introduced starting in the 1950s.

Conclusion

We suggest that only a subset of wheat “landraces” in Nepal are authentic which this study has identified. Targeting these authentic landraces may accelerate local breeding programs to improve the food security of this climate-vulnerable nation. Overall, this study provides a novel understanding of the genetic diversity of wheat in Nepal and this may contribute to global wheat breeding initiatives.
A full-length transcriptome and gene expression analysis reveal genes and molecular elements expressed during seed development in Gnetum luofuense
Authors: Deng Nan , Hou Chen , He Boxiang , Ma Fengfeng , Song Qingan , Shi Shengqing , Liu Caixia , Tian Yuxin
Published: November 2020

Background

Gnetumis an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening ofGnetumseeds. However, the molecular mechanisms related to this process remain unknown.

Results

We therefore assembled a full-length transcriptome from immature and matureG. luofuenseseeds using PacBio sequencing reads. We identified a total of 5726 novel genes, 9061 alternative splicing events, 3551 lncRNAs, 2160 transcription factors, and we found that 8512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7891 genes upregulated and 6432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening ofG. luofuense.

Conclusions

These findings provide a valuable molecular resource for understanding seed development of gymnosperms.
Comparison of analgesic efficacy between rectus sheath blockade, intrathecal morphine with bupivacaine, and intravenous patient-controlled analgesia in patients undergoing robot-assisted laparoscopic prostatectomy: a prospective, observational clinical study
Authors: Shim Jung-Woo , Cho Yun Jeong , Kim Minhee , Hong Sang Hyun , Moon Hyong Woo , Hong Sung Hoo , Chae Min Suk
Published: November 2020

Background

We explored the analgesic outcomes on postoperative day (POD) 1 in patients undergoing robot-assisted laparoscopic prostatectomy (RALP) who received intravenous patient-controlled analgesia (IV-PCA), rectus sheath bupivacaine block (RSB), or intrathecal morphine with bupivacaine block (ITMB).

Methods

This was a prospective, observational clinical trial. Patients were divided into three groups: IV-PCA (n = 30), RSB (n = 30), and ITMB (n = 30). Peak pain scores at rest and with coughing, cumulative IV-PCA drug consumption, the need for IV rescue opioids, and Quality of Recovery-15 (QoR-15) questionnaire scores collected on POD 1 were compared among the groups.

Results

The preoperative and intraoperative findings were comparable among the groups; the ITMB group required the least remifentanil of all groups. During POD 1, the ITMB group reported lower levels of pain at rest and with coughing, compared with the other two groups. During POD 1, incidences of severe pain at rest (10.0% vs. 23.3% vs. 40.0%) and with coughing (16.7% vs. 36.7% vs. 66.7%) were the lowest in the ITMB group compared with the RSB and IV-PCA groups, respectively. After adjustment for age, body mass index, diabetes mellitus, hypertension, and intraoperative remifentanil infusion, severe pain at rest was 0.167-fold less common in the ITMB group than in the IV-PCA group, while pain with coughing was 0.1-fold lower in the ITMB group and 0.306-fold lower in the RSB group, compared with the IV-PCA group. The ITMB group required lower cumulative IV-PCA drug infusions and less IV rescue opioids, while exhibiting a better QoR-15 global score, compared with the other two groups. Complications (nausea and pruritus) were significantly more common in the ITMB group than in the other two groups; however, we noted no ITMB- or RSB-related anesthetic complications (respiratory depression, post-dural headache, nerve injury, or puncture site hematoma or infection), and all patients were assessed as Clavien-Dindo grade I or II during the hospital stay.

Conclusion

Although ITMB induced complications of nausea and pruritus, this analgesic technique provided appropriate pain relief that enhanced patient perception related to early postoperative recovery.

Trial registration

Clinical Research Information Service, Republic of Korea, (approval number: KCT0005040) on May 20, 2020
Paraganglioma in the posterior mediastinum: a case report
Authors: Nam Jong-Ho , Park Jong-Seon , Choi Joon Hyuk
Published: November 2020

Background

Paragangliomas are tumors that arise from extra-adrenal chromaffin cells. Herein, we present a rare case of a functional paraganglioma in the posterior mediastinum.

Case presentation

A 36-year-old man presented with paroxysms of chest pain and headache. At presentation, the patient’s blood pressure was 190/120 mmHg. Chest computed tomography and magnetic resonance imaging revealed a left paravertebral mass in the posterior mediastinum. 123I-metaiodobenzylguanidine scanning revealed focally high tracer uptake in the left paravertebral area. The metanephrine level in the urine was elevated, confirming a rare, catecholamine-producing, functional paraganglioma in the posterior mediastinum. Before surgery, the patient was prepared by orally administering α- and β-adrenergic blockers. The mass was then resected via a lateral thoracotomy. The metanephrine level in urine was normal 24 h after surgery.

Conclusions

Paragangliomas in the posterior mediastinum are very rare, but more than half of all cases are functional. The associated symptoms are curable with complete resection, and long-term follow-up for recurrence is important.
Comparison of QT dispersion in patients with ST elevation acute myocardial infarction (STEMI) before and after treatment by streptokinase versus primary percutaneous coronary intervention (PCI)
Authors: Valizadeh Abbas , Soltanabadi Sahar , Koushafar Saeed , Rezaee Maryam , Jahankhah Reza
Published: November 2020

Background

QT dispersion (QTD) represents inhomogeneous ventricular repolarization such that an increased QTD may predispose the heart to malignant ventricular arrhythmias (VAs). This study was conducted to compare QTD in patients with ST-elevation myocardial infarction (STEMI) before and after treatment by streptokinase (SK) versus primary percutaneous coronary intervention (PCI).

Methods

The present case–control study was conducted on 185 STEMI patients who received SK (115 cases) or underwent primary PCI (70 cases). QTD and QT corrected dispersion before and 24 h after treatment. Likewise, they were also found to correct fatal arrhythmias (VT and VF) during the first 24 h after admission, and ejection fraction (EF) 24 h after treatment was evaluated.

Results

QTD decreased in the primary PCI group, though no significant difference was seen between the two studied groups (P > 0.05). A significant increase was detected in the EF mean values for the primary PCI-treated patients (P = 0.022). Moreover, there was a significant reduction in QTD of patients with fatal arrhythmias in the primary PCI group (P = 0.022).

Conclusion

An overall QTD reduction in the primary PCI group and a significant decrease in QTD of patients with fatal arrhythmias in the primary PCI group show that this treatment strategy is more efficient than thrombolytic therapy. As an important indicator of proper myocardial function, EF can independently predict improved myocardial function in the primary PCI group.
Right-sided infective endocarditis in association with a left-to-right shunt complicated by haemoptysis and acute renal failure: a case report
Authors: Hellwege Rubi Stephani , Gawaz Meinrad
Published: November 2020

Background

Infective endocarditis has a relevant clinical impact due to its high morbidity and mortality rates. Right-sided endocarditis has lower complication rates than left-sided endocarditis. Common complications are multiple septic pulmonary embolisms, haemoptysis, and acute renal failure. Risk factors associated with right-sided infective endocarditis are commonly related to intravenous drug abuse, central venous catheters, or infections due to implantable cardiac devices. However, patients with congenital ventricular septal defects might be at high risk of endocarditis and haemodynamic complications.

Case presentation

In the following, we present the case of a 23-year-old man without a previous intravenous drug history with tricuspid valve Staphylococcus aureus endocarditis complicated by acute renal failure and haemoptysis caused by multiple pulmonary emboli. In most cases, right-sided endocarditis is associated with several common risk factors, such as intravenous drug abuse, a central venous catheter, or infections due to implantable cardiac devices. In this case, we found a small perimembranous ventricular septal defect corresponding to a type 2 Gerbode defect. This finding raised the suspicion of a congenital ventricular septal defect complicated by a postendocarditis aneurysmal transformation.

Conclusions

Management of the complications of right-sided infective endocarditis requires a multidisciplinary approach. Echocardiographic approaches should include screening for ventricular septal defects in patients without common risk factors for tricuspid valve endocarditis. Patients with undiagnosed congenital ventricular septal defects are at high risk of infective endocarditis. Therefore, endocarditis prophylaxis after dental procedures and/or soft-tissue infections is highly recommended. An acquired ventricular septal defect is a very rare complication of infective endocarditis. Surgical management of small ventricular septal defects without haemodynamic significance is still controversial.
Investigation of the clinical significance and pathological features of lanthanum deposition in the gastric mucosa
Authors: Nishida Shinya , Ota Kazuhiro , Hattori Kimiaki , Iwatsubo Taro , Kawaguchi Shimpei , Kojima Yuichi , Takeuchi Toshihisa , Maeda Tamaki , Sakaguchi Masahiro , Higuchi Kazuhide
Published: November 2020

Background

There are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population.

Methods

We compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images.

Results

There was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180–3150 g] vs. 480 g [225–1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026).

Conclusions

We demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies.

Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393).
Physical therapy interventions for older people with vertigo, dizziness and balance disorders addressing mobility and participation: a systematic review
Authors: Regauer Verena , Seckler Eva , Müller Martin , Bauer Petra
Published: November 2020

Background

Vertigo, dizziness and balance disorders (VDB) are among the most relevant contributors to the burden of disability among older adults living in the community and associated with immobility, limitations of activities of daily living and decreased participation. The aim of this study was to identify the quality of evidence of physical therapy interventions that address mobility and participation in older patients with VDB and to characterize the used primary and secondary outcomes.

Methods

A systematic search via MEDLINE (PubMed), Cochrane Library, CINAHL, PEDro, forward citation tracing and hand search was conducted initially in 11/2017 and updated in 7/2019. We included individual and cluster-randomized controlled trials and trials with quasi-experimental design, published between 2007 and 2017/2019 and including individuals ≥65 years with VDB. Physical therapy and related interventions were reviewed with no restrictions to outcome measurement. Screening of titles, abstracts and full texts, data extraction and critical appraisal was conducted by two independent researchers. The included studies were heterogeneous in terms of interventions and outcome measures. Therefore, a narrative synthesis was conducted.

Results

A total of 20 randomized and 2 non-randomized controlled trials with 1876 patients met the inclusion criteria. The included studies were heterogeneous in terms of complexity of interventions, outcome measures and methodological quality. Vestibular rehabilitation (VR) was examined in twelve studies, computer-assisted VR (CAVR) in five, Tai Chi as VR (TCVR) in three, canal repositioning manoeuvres (CRM) in one and manual therapy (MT) in one study. Mixed effects were found regarding body structure/function and activities/participation. Quality of life and/or falls were assessed, with no differences between groups. VR is with moderate quality of evidence superior to usual care to improve balance, mobility and symptoms.

Conclusion

To treat older individuals with VDB, VR in any variation and in addition to CRMs seems to be effective. High-quality randomized trials need to be conducted to inform clinical decision making.

Trial registration

PROSPERO 2017 CRD42017080291.
Praziquantel treatment coverage among school age children against Schistosomiasis and associated factors in Ethiopia: a cross-sectional survey, 2019
Authors: Chisha Yilma , Zerdo Zerihun , Asnakew Mekuria , Churko Chuchu , Yihune Manaye , Teshome Abinet , Nigussu Nebiyu , Seife Fikire , Getachew Birhanu , Sileshi Markos
Published: November 2020

Background

World Health Organization estimated that 779 million people are at risk of getting schistosomiasis (SCH) and 240 million people were infected worldwide. SCH due to Schistosoma mansoni (S. mansoni) is a wide public health problem in Ethiopia. The aim of the survey was to quantify national and district disaggregated treatment coverage status for SCH and compare validated coverage with the one reported.

Methods

Community based cross-sectional survey was conducted in April 2019 among households with school age children (SAC) 5–14 years in seven purposively selected districts of the country. Segments to be surveyed were randomly selected and households to be interviewed from each segment were determined using systematic sampling technique. A total of 3378 households visited and 5679 SAC (5–14 years) were interviewed.

Results

Overall reported treatment coverage of Praziquantel (PZQ) against SCH was 4286 (75.5%). Males were 27% more likely to swallow the drug (AOR = 1.27; 95% CI: 1.09, 1.47) than females. SAC with age 10–14 years were 45% more likely to swallow the drug compared with their counter parts (5–9 years), (AOR =1.45; 95% CI: 1.25, 1.69). There is statistically significant association between PZQ swallowing status with school enrollment. (AOR = 20.90, 95% CI: 17.41, 25.08). Swallowing status of PZQ against SCH significantly higher for SAC treated in districts applied integrated treatment approach (87.5%) compared with SAC treated in vertical treatment approach (72.5%); P-value < 0.001. SACs were asked for reasons for not taking the drug and the main reported reason for not swallowing PZQ in the present study was none attending of the school.

Conclusions

Over all treatment coverage of PZQ against SCH in the present study was 75.5%. Although it is in accordance with WHO recommendation for Ethiopia, national programmatic improvements are necessary to achieve higher coverage in the future. To increase treatment coverage for PZQ against SCH in Ethiopia, school based training should target all schools. Moreover, mobilization, sensitization and implementation of the community wide treatment need to be improved.
The predicted impact of tuberculosis preventive therapy: the importance of disease progression assumptions
Authors: Sumner Tom , White Richard G.
Published: November 2020

Background

Following infection with Mycobacterium tuberculosis (M.tb), individuals may rapidly develop tuberculosis (TB) disease or enter a “latent” infection state with a low risk of progression to disease. Mathematical models use a variety of structures and parameterisations to represent this process. The effect of these different assumptions on the predicted impact of TB interventions has not been assessed.

Methods

We explored how the assumptions made about progression from infection to disease affect the predicted impact of TB preventive therapy. We compared the predictions using three commonly used model structures, and parameters derived from two different data sources.

Results

The predicted impact of preventive therapy depended on both the model structure and parameterisation. At a baseline annual TB incidence of 500/100,000, there was a greater than 2.5-fold difference in the predicted reduction in incidence due to preventive therapy (ranging from 6 to 16%), and the number needed to treat to avert one TB case varied between 67 and 157. The relative importance of structure and parameters depended on baseline TB incidence and assumptions about the efficacy of preventive therapy, with the choice of structure becoming more important at higher incidence.

Conclusions

The assumptions use to represent progression to disease in models are likely to influence the predicted impact of preventive therapy and other TB interventions. Modelling estimates of TB preventive therapy should consider routinely incorporating structural uncertainty, particularly in higher burden settings. Not doing so may lead to inaccurate and over confident conclusions, and sub-optimal evidence for decision making.
Knowledge of novel coronavirus disease (COVID-19) among dental surgeons of Nepal: a nationwide study
Authors: Sah Mukesh Kumar , Singh Abanish , Sangroula Raj Kumar
Published: November 2020

Background

COVID-19 is an emerging respiratory disease caused by a novel coronavirus. There is not much evidence assessing the knowledge of dental surgeons regarding COVID-19. This study was conducted to assess the knowledge of COVID-19 among dental surgeons of Nepal.

Methods

A web-based cross-sectional study was conducted among registered dental surgeons of Nepal. Ethical approval was obtained. Consent was taken, and knowledge on COVID-19 was assessed via a pre-tested structured questionnaire using Google form. The form was emailed to the participants. Descriptive analysis was performed using frequency, percentage, median and inter-quartile range. Man-Whitney test and Kruskal-Wallis tests were carried out to see the difference in knowledge score. P-value < 0.05 was considered statistically significant.

Results

Total 227 dental surgeons responded to the questionnaire (male: 46.4%; female: 53.7%). Almost two-third (65.2%) of the respondents were B.D.S. (Bachelor of Dental Surgery) graduates. Only 29.1% worked in the government hospitals. 17.6% were currently involved in COVID-19 management. Of the participants, 87.7% knew about the condition of the requirement of Personal Protective Equipment (PPE) but only 29.1% could correctly answer the framed question for PPE. The median knowledge score calculated was 14.0 (8.0–18.0). The bivariate analysis showed a statistically significant difference in knowledge score among the age group ≥30 years and < 30 years (p = 0.013); M.D.S. (Master of Dental Surgery) graduate and B.D.S. graduate (0.041); dental surgeons of government healthcare facilities and other healthcare facilities (p <  0.001); dental surgeons of COVID-19 centers and non-COVID-19 centers (0.002).

Conclusion

The dental surgeons of Nepal have a good knowledge of COVID-19, and they can be utilized for assisting in the management of COVID-19 cases in Nepal.
Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection
Authors:   for the H3Africa ACCME Research Group, Adebamowo Sally N. , Adeyemo Adebowale A. , Rotimi Charles N. , Olaniyan Olayinka , Offiong Richard , Adebamowo Clement A.
Published: November 2020

Background

Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.

Methods

Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes.

Results

The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10− 8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10− 6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10− 8), NR5A2 (OR: 3.65, p = 2.03 × 10− 7) and MIR365–2 (OR: 7.71, p = 2.63 × 10− 7) gene regions.

Conclusions

This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.
Mice lacking global Stap1 expression do not manifest hypercholesterolemia
Authors: Kanuri Babunageswararao , Fong Vincent , Haller April , Hui David Y. , Patel Shailendra B.
Published: November 2020

Background

Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1−/−) were characterized under standard chow and a 42% kcal western diet (WD).

Methods

Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons.

Results

Surprisingly, Stap1−/− mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1+/+ mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice.

Conclusion

These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.
Risk factors for severe acute kidney injury among patients with rhabdomyolysis
Authors: Yang Jia , Zhou Jiaojiao , Wang Xin , Wang Siwen , Tang Yi , Yang Lichuan
Published: November 2020

Background

Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis (RM). The aim of the present study was to assess patients at high risk for the occurrence of severe AKI defined as stage II or III of KDIGO classification and in-hospital mortality of AKI following RM.

Methods

We performed a retrospective study of patients with creatine kinase levels > 1000 U/L, who were admitted to the West China Hospital of Sichuan University between January 2011 and March 2019. The sociodemographic, clinical and laboratory data of these patients were obtained from an electronic medical records database, and univariate and multivariate regression analyses were subsequently conducted.

Results

For the 329 patients included in our study, the incidence of AKI was 61.4% and the proportion of stage I, stage II, stage III were 18.8, 14.9 and 66.3%, respectively. The overall mortality rate was 19.8%; furthermore, patients with AKI tended to have higher mortality rates than those without AKI (24.8% vs. 11.8%; P < 0.01). The clinical conditions most frequently associated with RM were trauma (28.3%), sepsis (14.6%), bee sting (12.8%), thoracic and abdominal surgery (11.2%) and exercise (7.0%). Furthermore, patients with RM resulting from sepsis, bee sting and acute alcoholism were more susceptible to severe AKI. The risk factors for the occurrence of stage II-III AKI among RM patients included hypertension (OR = 2.702), high levels of white blood cell count (OR = 1.054), increased triglycerides (OR = 1.260), low level of high-density lipoprotein cholesterol (OR = 0.318), elevated serum phosphorus (OR = 5.727), 500010,000 U/L (OR = 8.093). Age ≥ 60 years (OR = 2.946), sepsis (OR = 3.206) and elevated prothrombin time (OR = 1.079) were independent risk factors for in-hospital mortality in RM patients with AKI.

Conclusions

AKI is independently associated with mortality in patients with RM, and several risk factors were found to be associated with the occurrence of severe AKI and in-hospital mortality. These findings suggest that, to improve the quality of medical care, the early prevention of AKI should focus on high-risk patients and more effective management.
Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature
Authors: Zhou Qianyun , Zhang Yuanyuan , Zhou Guangping , Zhu Jihong
Published: November 2020

Background

TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed.

Case presentation

Both patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3 weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624 μmol/L), severe anemia (Hb: 41 g/L), and moderate thrombocytopenia (61 × 109/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied.

Conclusions

The diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.
Results-based financing to increase uptake of skilled delivery services in The Gambia: using the ‘three delays’ model to interpret midline evaluation findings
Authors:   The Project Implementation Committee (PIC), Ferguson Laura , Hasan Rifat , Boudreaux Chantelle , Thomas Hannah , Jallow Mariama , Fink Günther
Published: November 2020

Background

Delays in accessing skilled delivery services are a major contributor to high maternal mortality in resource-limited settings. In 2015, the government of The Gambia initiated a results-based financing intervention that sought to increase uptake of skilled delivery. We performed a midline evaluation to determine the impact of the intervention and explore causes of delays.

Methods

A mixed methods design was used to measure changes in uptake of skilled delivery and explore underlying reasons, with communities randomly assigned to four arms: (1) community-based intervention, (2) facility-based intervention, (3) community- and facility-based intervention, and (4) control. We obtained quantitative data from household surveys conducted at baseline (n = 1423) and midline (n = 1573). Qualitative data came from semi-structured interviews (baseline n = 20; midline n = 20) and focus group discussions (baseline n = 27; midline n = 39) with a range of stakeholders. Multivariable linear regression models were estimated using pooled data from baseline and midline. Qualitative data were recorded, transcribed, translated and thematically analyzed.

Results

No increase was found in uptake of skilled delivery services between baseline and midline. However, relative to the control group, significant increases in referral to health facilities for delivery were found in areas receiving the community-based intervention (beta = 0.078, p < 0.10) and areas receiving both the community-based and facility-based interventions (beta = 0.198, p < 0.05). There was also an increase in accompaniment to health facilities for delivery in areas receiving only community-based interventions (beta = 0.095, p < 0.05). Transportation to health facilities for delivery increased in areas with both interventions (beta = 0.102, p < 0.05). Qualitative data indicate that delays in the decision to seek institutional delivery usually occurred when women had limited knowledge of delivery indications. Delays in reaching a health facility typically occurred due to transportation-related challenges. Although health workers noted shortages in supplies and equipment, women reported being supported by staff and experiencing minimal delays in receiving skilled delivery care once at the facility.

Conclusions

Focusing efforts on informing the decision to seek care and overcoming transportation barriers can reduce delays in care-seeking among pregnant women and facilitate efforts to increase uptake of skilled delivery services through results-based financing mechanisms.
Community-based bilingual doulas for migrant women in labour and birth – findings from a Swedish register-based cohort study
Authors: Byrskog Ulrika , Small Rhonda , Schytt Erica
Published: November 2020

Background

Community-based bilingual doula (CBD) services have been established to respond to migrant women’s needs and reduce barriers to high quality maternity care. The aim of this study was to compare birth outcomes for migrant women who received CBD support in labour with birth outcomes for (1) migrant women who experienced usual care without CBD support, and (2) Swedish-born women giving birth during the same time period and at the same hospitals.

Methods

Register study based on data retrieved from a local CBD register in Gothenburg, the Swedish Medical Birth Register and Statistics Sweden. Birth outcomes for migrant women with CBD support were compared with those of migrant women without CBD support and with Swedish-born women. Associations were investigated using multivariable logistic regression, reported as odds ratios (aORs) with 95% confidence intervals (CI), adjusted for birth year, maternal age, marital status, hypertension, diabetes, BMI, disposable income and education.

Results

Migrant women with CBD support (n = 880) were more likely to have risk factors for adverse pregnancy outcomes than migrant women not receiving CBD support (n = 16,789) and the Swedish-born women (n = 129,706). In migrant women, CBD support was associated with less use of pain relief in nulliparous women (epidural aOR 0.64, CI 0.50–0.81; bath aOR 0.64, CI 0.42–0.98), and in parous women with increased odds of induction of labour (aOR 1.38, CI 1.08–1.76) and longer hospital stay after birth (aOR 1.19, CI 1.03–1.37). CBD support was not associated with non-instrumental births, perineal injury or low Apgar score. Compared with Swedish-born women, migrant women with CBD used less pain relief (nulliparous women: epidural aOR 0.50, CI 0.39–0.64; nitrous oxide aOR 0.71, CI 0.54–0.92; bath aOR 0.55, CI 0.36–0.85; parous women: nitrous oxide aOR 0.68, CI 0.54–0.84) and nulliparous women with CBD support had increased odds of emergency caesarean section (aOR 1.43, CI 1.05–1.94) and longer hospital stay after birth (aOR 1.31, CI 1.04–1.64).

Conclusions

CBD support appears to have potential to reduce analgesia use in migrant women with vulnerability to adverse outcomes. Further studies of effects of CBD support on mode of birth and other obstetric outcomes and women’s experiences and well-being are needed.
Impact of history of myomectomy on preterm birth risk in women with a leiomyomatous uterus: a propensity score analysis
Authors: Rault Emmanuel , Delorme Pierre , Goffinet François , Girault Aude
Published: November 2020

Background

To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy.

Methods

Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model.

Results

The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47–1.59]. These results were consistent for spontaneous preterm birth (OR 1.61; 95%CI [0.61–4.23]) and for the sensitivity analyses.

Conclusion

In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk.
Development of the Labor Pain Relief Attitude Questionnaire for pregnant women (LPRAQ-p)
Authors: Hulsbosch Lianne P , Nyklíček Ivan , Potharst Eva S , Boekhorst Myrthe GBM , Pop Victor JM
Published: November 2020

Background

Receiving epidural analgesia during labor can possibly have negative consequences for mother and child. Yet, the use of epidural analgesia rapidly increased in the Netherlands over the last decade. Since antenatal plans for labor pain relief have been related to epidural analgesia use during labor, the aim of the current study was to develop a Labor Pain Relief Attitude Questionnaire for pregnant women (LPRAQ-p).

Methods

Three focus group interviews were conducted with pregnant women, new mothers and caregivers and 13 candidate items were derived. Psychometric properties were tested with explorative factor analysis in sample I (N = 429) and a subsequent confirmatory factor analysis in a different sample II (N = 432).

Results

The explorative factor analysis suggested a two-factor seven-item solution: a ‘women’s perception’ and ‘social environment’ subscale. The confirmatory factor analysis confirmed an excellent six-item model fit with appropriate internal consistency. Higher scores on the six-item LPRAQ-p indicate greater willingness for request of pain relief medication during labor. Two-tailed t-tests showed that women with elevated levels of depression and pregnancy-specific distress symptoms, nulliparous women and multiparous women with complications during a previous delivery had greater willingness for request of pain relief medication during labor. Linear regression showed that the most important association with higher scores on the LPRAQ-p were high pregnancy-specific distress symptoms.

Conclusions

This study showed the LPRAQ-p to be a valid instrument to evaluate attitude towards labor pain relief in pregnant women. High scores on this questionnaire are associated with high levels of pregnancy-specific distress symptoms.
Factors influencing water immersion during labour: qualitative case studies of six maternity units in the United Kingdom
Authors: Milosevic Sarah , Channon Susan , Hughes Jacqueline , Hunter Billie , Nolan Mary , Milton Rebecca , Sanders Julia
Published: November 2020

Background

Water immersion during labour can provide benefits including reduced need for regional analgesia and a shorter labour. However, in the United Kingdom a minority of women use a pool for labour or birth, with pool use particularly uncommon in obstetric-led settings. Maternity unit culture has been identified as an important influence on pool use, but this and other possible factors have not been explored in-depth. Therefore, the aim of this study was to identify factors influencing pool use through qualitative case studies of three obstetric units and three midwifery units in the UK.

Methods

Case study units with a range of waterbirth rates and representing geographically diverse locations were selected. Data collection methods comprised semi-structured interviews, collation of service documentation and public-facing information, and observations of the unit environment. There were 111 interview participants, purposively sampled to include midwives, postnatal women, obstetricians, neonatologists, midwifery support workers and doulas. A framework approach was used to analyse all case study data.

Results

Obstetric unit culture was a key factor restricting pool use. We found substantial differences between obstetric and midwifery units in terms of equipment and resources, staff attitudes and confidence, senior staff support and women’s awareness of water immersion. Generic factors influencing use of pools across all units included limited access to waterbirth training, sociodemographic differences in desire for pool use and issues using waterproof fetal monitoring equipment.

Conclusions

Case study findings provide new insights into the influence of maternity unit culture on waterbirth rates. Access to pool use could be improved through midwives based in obstetric units having more experience of waterbirth, providing obstetricians and neonatologists with information on the practicalities of pool use and improving accessibility of antenatal information. In terms of resources, recommendations include increasing pool provision, ensuring birth room allocation maximises the use of unit resources, and providing pool room environments that are acceptable to midwives.