bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic yield and safety of transbronchial cryobiopsy in sarcoidosis
Authors: Jacob Maria , Bastos Hélder Novais , Mota Patrícia Caetano , Melo Natália , Cunha Rui , Pereira José Miguel , Guimarães Susana , Souto Moura Conceição , Morais António
Published: October 2019

Introduction

Transbronchial lung cryobiopsy (TBLC) is an endoscopic technique proven to be useful in diagnostic approach to interstitial lung disease (ILD), but its role in sarcoidosis is not fully established. The aim of the present study was to assess the diagnostic yield of TBLC in sarcoidosis and its safety profile.

Methods

Retrospective analysis of patients, evaluated in a tertiary hospital ILD outpatient clinic, who underwent TBLC in the diagnostic work-up. TBLC was performed in accordance with the 2018 expert statement from the Cryobiopsy Working Group.

Results

32 patients were included (mean±sdage 47.7±12.6 years, 59.4% male) and divided into three groups: highly likely sarcoidosis (n=21), possible sarcoidosis (n=6) and unlikely sarcoidosis (n=5). A mean of 2.8±0.8 TBLCs were performed. The definitive diagnosis was established by TBLC in 20 out of 27 patients with suspected sarcoidosis. Two patients were diagnosed with sarcoidosis by other methods performed afterwards. TBLC leaded to other diagnosis as well, such as fungal infection (n=1), hypersensitivity pneumonitis (n=1) and silicosis (n=3), making the diagnostic yield for suspected sarcoidosis of TBLC of 92.6%. TBLC was also able to show compatible histological features in five patients whom sarcoidosis was not previously considered. The complications reported overall were pneumothorax in five (15.6%) patients and moderate bleeding in one (3.1%) case.

Conclusion

In this cohort, TBLC was a safe, reliable and useful procedure in sarcoidosis diagnosis. These results suggest that TBLC can be used successfully in those cases where a definitive diagnosis could not be reached with the usual and less-invasive diagnostic tools.
Radiosensitizing Effect of Gadolinium Oxide Nanocrystals in NSCLC Cells Under Carbon Ion Irradiation
Authors: Li Feifei , Li Zihou , Jin Xiaodong , Liu Yan , Li Ping , Shen Zheyu , Wu Aiguo , Zheng Xiaogang , Chen Weiqiang , Li Qiang
Published: October 2019

Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC.

Graphical Abstract
PlantSimLab - a modeling and simulation web tool for plant biologists
Authors: Ha S. , Dimitrova E. , Hoops S. , Altarawy D. , Ansariola M. , Deb D. , Glazebrook J. , Hillmer R. , Shahin H. , Katagiri F. , McDowell J. , Megraw M. , Setubal J. , Tyler B. M. , Laubenbacher R.
Published: October 2019

Background

At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists.

Results

This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers.

Conclusions

Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.
A framework for TRIM21-mediated protein depletion in early mouse embryos: recapitulation of Tead4 null phenotype over three days
Authors: Israel Steffen , Casser Ellen , Drexler Hannes C.A. , Fuellen Georg , Boiani Michele
Published: October 2019

Background

While DNA and RNA methods are routine to disrupt the expression of specific genes, complete understanding of developmental processes requires also protein methods, because: oocytes and early embryos accumulate proteins and these are not directly affected by DNA and RNA methods. When proteins in the oocyte encounter a specific antibody and theTRIpartiteMotiv-containing21(TRIM21) ubiquitin-protein ligase, they can be committed to degradation in the proteasome, producing a transient functional knock-out that reveals the role of the protein. However, there are doubts about whether this targeted proteolysis could be successfully used to study mammalian development, because duration of the transient effect is unknown, and also because amounts of reagents delivered must be adequate in relation to the amount of target protein, which is unknown, too.

Results

We show that the mouse egg contains up to 1E-02 picomoles/protein, as estimated by mass spectrometry using the intensity-based absolute quantification (iBAQ) algorithm. However, the egg can only accommodate ≈1E-04 picomoles of antibody or TRIM21 without incurring toxic effects. Within this framework, we demonstrate that TRIM21-mediated protein depletion efficiently disrupts the embryonic process of trophectoderm formation, which critically depends on theTEA domain family member 4(Tead4) gene. TEAD4 depletion starting at the 1-cell stage lasts for 3 days prior to a return of gene and protein expression to baseline. This time period is long enough to result in a phenotype entirely consistent with that of the published null mutation and RNA interference studies: significant underexpression of trophectodermal genesCdx2andGata3and strongly impaired ability of embryos to cavitate and implant in the uterus. Omics data are available via ProteomeXchange (PXD012613) and GEO (GSE124844).

Conclusions

TRIM21-mediated protein depletion can be an effective means to disrupt gene function in mouse development, provided the target gene is chosen carefully and the method is tuned accurately. The knowledge gathered in this study provides the basic know-how (prerequisites, requirements, limitations) to expedite the protein depletion of other genes besidesTead4.
Immune cell infiltration characteristics and related core genes in lupus nephritis: results from bioinformatic analysis
Authors: Cao Yiling , Tang Weihao , Tang Wanxin
Published: October 2019

Background

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. In the present study, we used CIBERSORT and gene set enrichment analysis (GSEA) of gene expression profiles to identify immune cell infiltration characteristics and related core genes in LN.

Results

Datasets from the Gene Expression Omnibus, GSE32591 and GSE113342, were downloaded for further analysis. The GSE32591 dataset, which included 32 LN glomerular biopsy tissues and 14 glomerular tissues from living donors, was analyzed by CIBERSORT. Different immune cell types in LN were analyzed by the Limma software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on GSEA were performed by clusterProfiler software. Lists of core genes were derived from Spearman correlation between the most significant GO term and differentially expressed immune cell gene from CIBERSORT. GSE113342 was employed to validate the association between selected core genes and clinical manifestation. Five types of immune cells revealed important associations with LN, and monocytes emerged as having the most prominent differences. GO and KEGG analyses indicated that immune response pathways are significantly enriched in LN. The Spearman correlation indicated that 15 genes, including FCER1G, CLEC7A, MARCO, CLEC7A, PSMB9, and PSMB8, were closely related to clinical features.

Conclusions

This study is the first to identify immune cell infiltration with microarray data of glomeruli in LN by using CIBERSORT analysis and provides novel evidence and clues for further research of the molecular mechanisms of LN.
Altered activity in the nucleus raphe magnus underlies cortical hyperexcitability and facilitates trigeminal nociception in a rat model of medication overuse headache
Authors: Potewiratnanond Prangtip , le Grand Supang Maneesri , Srikiatkhachorn Anan , Supronsinchai Weera
Published: October 2019

Background

The pathogenesis of medication overuse headache (MOH) involves hyperexcitability of cortical and trigeminal neurons. Derangement of the brainstem modulating system, especially raphe nuclei may contribute to this hyperexcitability. The present study aimed to investigate the involvement of the nucleus raphe magnus (NRM) in the development of cortical and trigeminal hyperexcitability in a rat model of MOH.

Results

Chronic treatment with acetaminophen increased the frequency of cortical spreading depression (CSD) and the number of c-Fos-immunoreactive (Fos-IR) neurons in the trigeminal nucleus caudalis (TNC). In the control group, muscimol microinjected into the NRM increased significantly the frequency of CSD-evoked direct current shift and Fos-IR neurons in the TNC. This facilitating effect was not found in rats with chronic acetaminophen exposure. In a model of migraine induced by intravenous systemic infusion of nitroglycerin (NTG), rats with chronic exposure to acetaminophen exhibited significantly more frequent neuronal firing in the TNC and greater Fos-IR than those without the acetaminophen treatment. Muscimol microinjection increased neuronal firing in the TNC in control rats, but not in acetaminophen-treated rats. The number of Fos-IR cells in TNC was not changed significantly.

Conclusion

Chronic exposure to acetaminophen alters the function of the NRM contributing to cortical hyperexcitability and facilitating trigeminal nociception.
Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation
Authors: Hesselkilde Eva Zander , Carstensen Helena , Flethøj Mette , Fenner Merle , Kruse Ditte Dybvald , Sattler Stefan M. , Tfelt-Hansen Jacob , Pehrson Steen , Braunstein Thomas Hartig , Carlson Jonas , Platonov Pyotr G. , Jespersen Thomas , Buhl Rikke
Published: October 2019

Background

Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model.

Method

Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups.

Results

AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed.

Conclusion

Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma
Authors: Takaya Hiroaki , Namisaki Tadashi , Kitade Mitsuteru , Kaji Kosuke , Nakanishi Keisuke , Tsuji Yuki , Shimozato Naotaka , Moriya Kei , Seki Kenichiro , Sawada Yasuhiko , Saikawa Soichiro , Sato Shinya , Kawaratani Hideto , Akahane Takemi , Noguchi Ryuichi , Matsumoto Masanori , Yoshiji Hitoshi
Published: October 2019

Background

To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis.

Methods

Serum levels of alpha-fetoprotein, des-γ-carboxy prothrombin,Lens culinarisagglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis.

Results

The von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 andp < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels.

Conclusions

The von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.
The clinical presentation of Legionella arthritis reveals the mode of infection and the bacterial species: case report and literature review
Authors: Ibranosyan Marine , Beraud Laetitia , Lemaire Hélène , Ranc Anne-Gaëlle , Ginevra Christophe , Jarraud Sophie , Descours Ghislaine
Published: October 2019

Background

While Legionella is a common cause of pneumonia, extrapulmonary infections like arthritis are scarce. Here, we describe a case of monoarthritis due to Legionella bozemanii, with no history of pneumonia. We provide a literature review of the 9 previously published Legionella arthritis and highlight a dichotomous epidemiology suggesting different physiopathological pathways leading to joint infection.

Case presentation

A 56-year old woman under immunosuppressive treatment by oral and intra-articular corticosteroids, methotrexate, and tocilizumab for an anti-synthetase syndrome was hospitalized for worsening pain and swelling of the left wrist for 3 days. Clinical examination showed left wrist synovitis and no fever. The arthritis occurred a few days after an accidental fall on wet asphalt responsible for a cutaneous wound followed by a corticosteroid intra-articular injection. Due to both the negativity of conventional culture of articular fluid and suspicion of infection, 16S rRNA and specific PCRs were performed leading to the identification of L. bozemanii. Legionella-specific culture of the articular fluid was performed retrospectively and isolated L. bozemanii. The empiric antibiotic therapy was switched for oral levofloxacin and rifampin and the patient recovered after a 12-week treatment.

Conclusion

We report a case of L. bozemanii monoarthritis in an immunosuppressed woman, following a fall on wet asphalt and intra-articular corticosteroid injection. The review of the literature found that the clinical presentation reveals the mode of infection and the bacterial species. Monoarthritis more likely occurred after inoculation in patients under immunosuppressive therapy and were associated with non-Legionella pneumophila serogroup 1 (Lp1) strains that predominate in the environment. Polyarthritis were more likely secondary legionellosis localizations after blood spread of Lp1, the most frequently found in pneumonia. In both settings, 16S rRNA and Legionella-specific PCR were key factors for the diagnosis.
A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis
Authors: O’Connor Ciara , Collins Aedin , Twomey Eilish , Hensey Conor , Caird John , Gavin Patrick J.
Published: October 2019

Background

Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.

Case presentation

We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation.

Conclusions

Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.
Continuous hemodiafiltration as a rescue therapy for patients with cardiopulmonary failure caused by enterovirus-71: a retrospective observational study in a PICU
Authors: Wang Chunxia , Cui Yun , Zhu Yan , Wang Fei , Rong Qunfang , Zhang Yucai
Published: October 2019

Background

Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU).

Methods

A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed.

Results

Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] μg/L/h, P = 0.029),

Conclusions

CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.
Survival analysis of patients with tuberculosis in Erbil, Iraqi Kurdistan region
Authors: Balaky Salah Tofik Jalal , Mawlood Ahang Hasan , Shabila Nazar P.
Published: October 2019

Background

Tuberculosis is an important health concern in Iraq, but limited research has examined the quality of tuberculosis care and the survival of the patients. This study aimed to assess the 12-month survival of tuberculosis patients and evaluate the effect of the associated risk factors on patients’ survival.

Methods

We reviewed the records of 728 patients with tuberculosis who were registered and treated at the Chest and Respiratory Disease Center in Erbil, Iraqi Kurdistan Region, from January 2012 to December 2017. Demographic data, the site of the disease, and treatment outcomes were retrieved from patients’ records. Data analysis included the use of the Kaplan–Meier method and the log-rank test to calculate the estimates of the survival and assess the differences in the survival among the patients. The Cox regression model was used for univariate and multivariate analysis.

Results

The mean period of the follow-up of the patients was 7.6 months. Of 728 patients with tuberculosis, 50 (6.9%) had died. The 12-month survival rate of our study was 93.1%. A statistically significant difference was detected in the survival curves of different age groups (P < 0.001) and the site of the disease (P = 0.012). In multivariate analysis, lower survival rates were only observed among patients aged ≥65 years (hazard ratio = 9.36, 95% CI 2.14–40.95) and patients with extrapulmonary disease (hazard ratio = 2.61, 95% CI 1.30–5.27).

Conclusion

The 12-month survival rate of tuberculosis patients managed at the Chest and Respiratory Disease Center in Erbil was similar to the international rates. The high rates of extrapulmonary tuberculosis and the low survival rate necessitate further studies and action with a possible revision to the tuberculosis management strategy.
Methodology for sampling women at high maternal risk in administrative data
Authors: Vanderlaan Jennifer , Dunlop Anne , Rochat Roger , Williams Bryan , Shapiro Susan E.
Published: October 2019

Background

In population level studies, the conventional practice of categorizing women into low and high maternal risk samples relies upon ascertaining the presence of various comorbid conditions in administrative data. Two problems with the conventional method include variability in the recommended comorbidities to consider and inability to distinguish between maternal and fetal risks. High maternal risk sample selection may be improved by using the Obstetric Comorbidity Index (OCI), a system of risk scoring based on weighting comorbidities associated with maternal end organ damage. The purpose of this study was to compare the net benefit of using OCI risk scoring vs the conventional risk identification method to identify a sample of women at high maternal risk in administrative data.

Methods

This was a net benefit analysis using linked delivery hospitalization discharge and vital records data for women experiencing singleton births in Georgia from 2008 to 2012. We compared the value identifying a sample of women at high maternal risk using the OCI score to the conventional method of dichotomous identification of any comorbidities. Value was measured by the ability to select a sample of women designated as high maternal risk who experienced severe maternal morbidity or mortality.

Results

The high maternal risk sample created with the OCI had a small but positive net benefit (+ 0.6), while the conventionally derived sample had a negative net benefit indicating the sample selection performed worse than identifying no woman as high maternal risk.

Conclusions

The OCI can be used to select women at high maternal risk in administrative data. The OCI provides a consistent method of identification for women at risk of maternal morbidity and mortality and avoids confounding all obstetric risk factors with specific maternal risk factors. Using the OCI may help reduce misclassification as high maternal risk and improve the consistency in identifying women at high maternal risk in administrative data.
High starchy food intake may increase the risk of adverse pregnancy outcomes: a nested case-control study in the Shaanxi province of Northwestern China
Authors: Huang Liyan , Shang Li , Yang Wenfang , Li Danyang , Qi Cuifang , Xin Juan , Wang Shanshan , Yang Liren , Zeng Lingxia , Chung Mei Chun
Published: October 2019

Background

There was a wider disparity in the diet characterization among most studies on diet and pregnancy outcomes in different countries, and the research in northern China is limited. Therefore, the purpose of the present study that was conducted in northwest China was to understand the dietary characteristics of periconceptional women and to explore the relationship between and specific dietary patterns with adverse pregnancy outcomes.

Methods

A nested case-control study was conducted from October 2017 to November 2018 in Shaanxi, China. Based on a prospective cohort of 368 women who were pregnant or prepared for pregnancy, 63 participants who developed the outcomes of gestational hypertension, gestational diabetes, preterm birth, low birth weight, and birth defects were included in the case group. A total of 237 healthy pregnant women were included during the same period in the control group. Dietary intake was assessed using a validated food frequency questionnaire for the three months before pregnancy and the first trimester. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Dietary patterns were derived using factor analysis. Stratified analysis was performed on the overall, single and multiple adverse pregnancy outcomes categories. Adjustment was made for sociodemographic characteristics and nutritional supplement status.

Results

Six major dietary patterns were identified. The ‘starchy’ dietary pattern, composed of high intake in noodle and flour products and/or rice and its products, was associated with the odds of developing of adverse pregnancy outcomes (OR: 2.324, 95% CI: 1.293–4.178). This risk remained significant following adjustment for potential confounders of maternal demographic characteristics and nutritional status (aOR: 2.337, 95% CI:1.253–4.331). Strong association were found during the first trimester of pregnancy, but showed no association during the three months before pregnancy (aOR:1.473, 95% CI: 0.682–3.234).

Conclusions

High starchy food intake was associated with adverse pregnancy outcomes, particularly during the first trimester of pregnancy. Health education focusing on periconceptional dietary patterns could be a practical strategy for preventing adverse pregnancy outcomes.
Management of acutely decompensated chronic thromboembolic pulmonary hypertension in late pregnancy: a case report
Authors: Valko Luca , Csosza Gyorgyi , Merei Akos , Muhl Diana , Faludi Reka , Karlocai Kristof , Lorx Andras , Gal Janos
Published: October 2019

Background

Pregnancy in patients with pulmonary hypertension is associated with increased risk of maternal and fetal death. Physiological changes during pregnancy, labor and the postpartum period may all lead to acute decompensation of chronic right heart failure with rapid progression to circulatory collapse. As such, guidelines discourage planned pregnancies in women suffering from pulmonary hypertension. There are, however, rare cases of pulmonary hypertension which have previously been undiagnosed and only become apparent during late stage pregnancy. These individuals require close monitoring and multidisciplinary management.

Case presentation

We describe the case of a 34-year-old female who presented with acute decompensation of previously undiagnosed pulmonary hypertension during the 30th week of her second pregnancy. Echocardiography and CT scan confirmed severe pulmonary hypertension and right heart failure with no new thromboembolic component. Following stabilization of cardiorespiratory parameters with high FiO2 noninvasive ventilation, intravenous epoprostenol and levosimendan treatment, Cesarean section was performed under epidural anesthesia. Close monitoring was continued in the postoperative period and cardiovascular parameters were managed with ongoing inotropic and escalating vasodilator therapy. The findings were consistent with chronic thromboembolic pulmonary hypertension. Persistent hypoxia was found to be a result of right bronchial obstruction caused by blood clots, which resolved with bronchoscopic intervention. Ongoing postpartum management resulted in improved cardiovascular parameters and oxygenation. Epoprostenol treatment was successfully converted to subcutaneous treprostinil therapy and the patient was discharged home to care for her healthy baby girl. Optimal timing of pulmonary endarterectomy will be chosen based upon functional status and patient preference.

Conclusions

The case described is the first published report of previously undiagnosed pulmonary hypertension presenting with acute right heart failure in late pregnancy successfully managed by pharmacological therapy, noninvasive ventilation and a Cesarean performed under epidural anesthesia. The case illustrates that despite the challenges, acutely discovered right heart failure can be successfully managed with a comprehensive multidisciplinary treatment plan.
Midwives’ perceptions of being ‘with woman’: a phenomenological study
Authors: Bradfield Zoe , Hauck Yvonne , Duggan Ravani , Kelly Michelle
Published: October 2019

Background

Being ‘with woman’ is a central construct of the midwifery profession however, minimal research has been undertaken to explore the phenomenon from the perspective of midwives. The aim of this study was to describe Western Australian midwives’ perceptions of the phenomenon of being ‘with woman’ during the intrapartum period.

Methods

Descriptive phenomenology was selected as the methodology for this study. Thirty one midwives working across a variety of care models participated in individual interviews. Giorgi’s four stage phenomenological approach was employed to analyse data.

Results

Three themes were extracted 1) Essential to professional identity; 2) Partnership with women; and 3) Woman-Centred Practice. Midwives described the importance of being ‘with woman’ to the work and identification of midwifery practice. Developing a connection with the woman and providing woman-centred care inclusive of the woman’s support people was highlighted.

Conclusions

For the first time, we are able to offer evidence of how midwives understand and perceive the phenomenon of being ‘with woman’ which has theoretical and practical utility. Findings from this study provide evidence that supports expert commentary and confirms that midwives conceptualise the phenomenon of being ‘with woman’ as essential to the identity and practice of the profession. Some previously identified ‘good midwifery practices’ were revealed as practical manifestations of the phenomenon. This new knowledge facilitates clarity and provides evidence to support statements of professional identity, which is useful for the development of educational curricula as well as supporting graduate and professional midwives. The findings emphasise the importance of the development of language around this important philosophical construct which permeates midwifery practice, enhances professional agency and supports the continued emphasis of being ‘with woman’ with new understanding of its applied practices in a variety of care models.
Efficacy and safety of HER2 inhibitors in combination with or without pertuzumab for HER2-positive breast cancer: a systematic review and meta-analysis
Authors: Chen Shanshan , Liang Yu , Feng Zhangying , Wang Mingxia
Published: October 2019

Background

Although the dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab and docetaxel, has shown promising results in HER2+ breast cancer patients, whether the dose, efficacy and safety of this treatment differs from those of other pertuzumab-based dual anti-HER2 therapies remain controversial. This systematic review evaluates the efficacy and safety of H (trastuzumab or trastuzumab emtansine ± chemotherapy) + P (pertuzumab) compared with those of H in HER2+ breast cancer patients.

Methods

A comprehensive search was performed to identify eligible studies comparing the efficacy and safety of H + P versus H. The pathologic complete response (pCR), median progression-free survival (PFS) and overall survival (OS) were the primary outcomes, and safety was the secondary outcome. A subgroup analysis of pCR according to hormone receptor (HR) status was performed. All analyses were conducted using STATA 11.0.

Results

Twenty-six studies (9872 patients) were identified. In the neoadjuvant setting, H + P significantly improved the pCR [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.08–1.63;p = 0.006]. In the metastatic setting, H + P significantly improved PFS [hazard ratios (HRs) = 0.75; 95% CI, 0.68–0.84;p < 0.001]. There was a trend towards better OS but that it did not reach statistical significance (HRs = 0.81; 95% CI, 0.64–1.03;p = 0.082). A subgroup analysis revealed that the HER2+/HR- patients who received H + P showed the highest increase in the pCR. Rash, diarrhea, epistaxis, mucosal inflammation, and anemia were significantly more frequently observed with H + P than with H, whereas myalgia was less frequent (OR = 0.91; 95% CI, 0.82–1.01;p = 0.072), and no significant difference in cardiac toxicity was observed between these therapies (OR = 1.26; 95% CI, 0.81–1.95;P = 0.309).

Conclusions

Our study confirms that H + P is superior to H in the (neo)adjuvant treatment of HER2+ breast cancer, and increase the risk of acceptable and tolerable toxicity (rash, diarrhea, epistaxis, mucosal inflammation, and anemia).

Trial registration

A systematic review protocol was registered with PROSPERO (identification number:CRD42018110415).
TMPRSS2-ERG fusions confer efficacy of enzalutamide in an in vivo bone tumor growth model
Authors: Semaan Louie , Mander Navneet , Cher Michael L. , Chinni Sreenivasa R.
Published: October 2019

Background

Castrate Resistant Prostate Cancer (CRPC) is an advanced disease resistant to systemic traditional medical or surgical castration, and resistance is primarily attributed to reactivation of AR through multiple mechanisms. TMPRSS2-ERG fusions have been shown to regulate AR signaling, interfere with pro-differentiation functions, and mediate oncogenic signaling. We have recently shown that ERG regulates intra-tumoral androgen synthesis and thereby facilitates AR function in prostate cancer cells. We hypothesize that enzalutamide treatment will be more effective in cells/tumors with TMPRSS2-ERG translocations because these tumors have increased AR signaling.

Methods

ERG knockdown was performed with VCaP cells using lentiviral infections to generate VCaP ERGshRNA cells and control VCaP scr cells with scrambled shRNA. Cell-growth analysis was performed to determine the effect of enzalutamide. Reverse transcription, quantitative real-time PCR (RT-qPCR) was used to determine the expression of AR responsive genes. Luciferase tagged VCaP scr and shRNA infected cells were used in an intra-tibial animal model for bone tumor growth analysis and enzalutamide treatment used to inhibit AR signaling in bone tumors. Western blotting analyzed VCaP bone tumor samples for ERG, AR, AKR1C3 and HSD3B1 and HSD3B2 expression.

Results

Enzalutamide inhibited the growth of VCaP scr cells more effectively than shERG cells. Analysis of AR responsive genes shows that Enzalutamide treatment at 5 micromolar concentration inhibited by 85–90% in VCaP Scr cells whereas these genes were inhibited to a lesser extent in VCaP shERG cells. Enzalutamide treatment resulted in severe growth inhibition in VCaP scr shRNA cells compared to VCaP shERG cells. In bone tumor growth experiment, VCaP ERG shRNA cells grew at slower than VCaP scr shRNA cells. Androgen biosynthetic enzyme expression is lower VCaP shERG bone tumors compared to VCaP scr shRNA bone tumors and enzalutamide inhibited the enzyme expression in both types of tumors.

Conclusions

These data suggest that ERG transcription factor regulates androgen biosynthetic enzyme expression that enzalutamide treatment is more effective against VCaP bone tumors with an intact ERG expression, and that knocking down ERG in VCaP cells leads to a lesser response to enzalutamide therapy. Thus, ERG expression status in tumors could help stratify patients for enzalutamide therapy.
Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls: study protocol of a cluster-randomised controlled trial in western Kenya
Authors: Zulaika Garazi , Kwaro Daniel , Nyothach Elizabeth , Wang Duolao , Zielinski-Gutierrez Emily , Mason Linda , Eleveld Alie , Chen Tao , Kerubo Emily , van Eijk Annemieke , Pace Cheryl , Obor David , Juma Jane , Oyaro Boaz , Niessen Louis , Bigogo Godfrey , Ngere Isaac , Henry Carl , Majiwa Maxwell , Onyango Clayton O. , ter Kuile Feiko O. , Phillips-Howard Penelope A.
Published: October 2019

Background

Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls’ health, school equity, and life-chances.

Methods

Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls’ assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout.

Discussion

If proved safe and effective, the interventions offer a potential contribution toward girls’ schooling, health, and equity in low- and middle-income countries.

Trial registration

ClinicalTrials.gov NCT03051789, 15th February 2017.
A cross-sectional study investigating lifestyle and weight perception of undergraduate students in southern Italy
Authors: Gallè Francesca , Sabella Elita Anna , Da Molin Giovanna , Liguori Giorgio , Montagna Maria Teresa , Orsi Giovanni Battista , Valerio Giuliana , Napoli Christian
Published: October 2019

Background

The aim of the study was to explore lifestyle of undergraduate students in southern Italy and to investigate their determinants.

Methods

An anonymous, web-based questionnaire investigating weight and its perception, smoking and alcohol use, achievement of recommended levels of physical activity and time spent daily in screen-based sedentary behaviors was administered to students attending two universities in southern Italy. Age, gender, city, type of degree course attended, occupational status and residential status were considered as possible demographic determinants.

Results

The majority of the participants reported a normal weight (71.2%), were non-smokers (66.6%), occasional alcohol consumers (60.5%) and insufficiently active (62.6%), with a reported mean screen time exceeding 2 h per day. Gender, city, type of degree course and occupational status were found to be associated with lifestyle by regression analysis. Normal weight, overweight and obese students were generally properly aware of their weight condition; however, weight misperceptions were registered among normal and underweight undergraduates.

Conclusions

This study highlighted some critical issues regarding lifestyles of university students that suggest the need for health promotion interventions targeted mainly on physical activity.
Smoking beliefs across genders, a comparative analysis of seven European countries
Authors: Grard Adeline , Schreuders Michael , Alves Joana , Kinnunen Jaana M. , Richter Matthias , Federico Bruno , Kunst Anton , Clancy Luke , Lorant Vincent
Published: October 2019

Background

Most European countries have seen a decrease in the prevalence of adolescent smoking. This decrease has, however, been patterned by gender. Girls’ smoking rates have now overtaken boys’ in many European countries. The two genders may not, however, share the same smoking beliefs and this could explain differences between the genders in smoking prevalence. We describe gender differences in smoking beliefs and investigate variations between countries, along with their gender context.

Methods

In 2016, we conducted the SILNE R study (Smoking Inequalities Learning from Natural Experiments – Renew) in 55 schools located in seven European countries: Belgium, Italy, The Netherlands, Portugal, Finland, Ireland, and Germany. We surveyed 12,979 students aged 14–16 years (50% were girls). We classified smoking beliefs into four categories: positive individual, positive social, negative individual, and negative social beliefs. We expected girls to score higher on the last three of those categories and we hypothesized that countries with a more gender-equal culture would have less gender difference in beliefs about smoking.

Results

One out of two smoking beliefs differed significantly between genders. Negative social beliefs were more common in girls, while beliefs about the dating-related aspects of smoking were more common in boys. We identified Germany and Belgium as the only countries with no gender differences in any of the belief scales. No correlation was found, however, between these scales and the Gender Inequality Index.

Conclusions

In some countries, gender-specific interventions might be implemented; however, two opposing strategies might be used, depending on whether such programs are aimed at boys or girls.
What has changed HIV and syphilis infection among men who have sex with men (MSM) in Southwest China: a comparison of prevalence and behavioural characteristics (2013–2017)
Authors: Zhang Yangchang , Wu Guohui , Lu Rongrong , Xia Wanyuan , Hu Ling , Xiong Yang , Xie Junhao , Yu Qiuhua , Ye Mengliang
Published: October 2019

Background

Chongqing reportedly has a large MSM population and a high STI prevalence in previous studies. However, most studies are attributed to independent cross-sectional studies, few studies have investigated trends in the prevalence of syphilis and HIV, as well as behavioural characteristics among MSM using serial surveillance surveys.

Methods

Data were collected in Chongqing through face-to-face questionnaire interview and laboratory testing in Chongqing. The respondents were recruited among MSM by snowball sampling from May 2013 to December 2017. The self-report questionnaire primarily included socio-demographics, HIV knowledge, and HIV-related behaviour characteristics over the year. Blood specimens were tested to diagnose HIV and syphilis infection by Chongqing CDC. Cochran-Armitage trend test and multivariate logistic regression were conducted to compare the changes in STI prevalence and independent behavioural factors among MSM.

Results

There were 6568 eligible participants (98.4%). The overall HIV prevalence was 20.5% among MSM in Chongqing, with a decrease from 23.0% in 2013 to 19.2% in 2017. The overall syphilis prevalence was 5.8%, with an increase from 3.2% in 2013 to 6.7% in 2017. The proportion of consistent condom use (CCU) during anal intercourse (46.3 to 57.7%,P<0.001),CCU with regular male partners(47.7 to 59.7%,P<0.001), CCU with casual male partners (51.5 to 62.3%,P<0.001) and drug use during anal intercourse (0.3 to 1.4%,P<0.05) were increasing. By contrast, a significant decrease was reported in the percentage of MSM with more than two regular male partners (66.0 to 21.4%,P<0.001) and more than two casual male partners (38.3 to 20.7%,P<0.001). A significant difference was observed in syphilis infection, testing for HIV antibodies and drug use during anal intercourse in the past years between the HIV-positive and HIV-negative respondents.

Conclusion

A decreasing trend of HIV prevalence was showed during among MSM from 2013 to 2017 in Chongqing. While gradual reduction of high-risk behaviors along with HIV prevalence supported development of STI counselling and testing, increasing syphilis infection and drug use during anal intercourse warrants further understanding.