bluuebunny/crossref_metadata_2025 huggingface dataset:
Damage initiation and fracture analysis of honeycomb core single cantilever beam sandwich specimens
Authors: Saseendran Vishnu , Varatharaj Pirashandan , Perera Shenal , Seneviratne Waruna
Published: April 2020

Fracture testing and analysis of aerospace grade honeycomb core sandwich constructions using a single cantilever beam test methodology is presented here. Influence of various parameters such as facesheet thickness, core density, honeycomb cell-size, and core thickness were studied. A Winkler-based foundation model was used to calculate compliance and energy-release rate, and further compare with finite element model and experiments. A cohesive zone model was developed to predict the disbond initiation and simulate the interface crack propagation in the single cantilever beam sandwich specimen. The mode I interface fracture toughness obtained from the translating base single cantilever beam setup was provided as input in this cohesive zone model. It is shown that the presented cohesive zone approach is robust, and is able to capture the debonding phenomenon for majority of the honeycomb core specimens.
Initial experience in self-monitoring of intraocular pressure
Authors: McGarva Emily , Farr Jane , Dabasia Priya , Lawrenson John G , Murdoch Ian E
Published: April 2020

Background/aims

Diurnal variation in intraocular pressure (IOP) is a routine assessment in glaucoma management. Providing patients the opportunity to perform self-tonometry might empower them and free hospital resource. We previously demonstrated that 74% of patients can use the Icare® HOME tonometer. This study further explores Icare® HOME patient self-monitoring.

Methods

Patients were trained by standard protocol to use the Icare® HOME rebound tonometer. Patient self-tonometry was compared to Goldmann applanation tonometry (GAT) over one clinical day. Following this, each patient was instructed to undertake further data collection that evening and over the subsequent two days.

Results

Eighteen patients (35 eyes) participated. Good agreement was demonstrated between GAT and Icare® HOME for IOPs up to 15 mm Hg. Above this IOP the Icare® tended to over-read, largely explained by 2 patients with corneal thickness >600 um. The mean peak IOP during ‘clinic hours’ phasing was 16.7 mm Hg and 18.5 mm Hg (p = 0.24) over three days. An average range of 5.0, 7.0 and 9.8 mm Hg was shown during single day clinic, single day home and three day home phasing respectively (p =<0.001). The range of IOP was lower in eyes with prior trabeculectomy (6.1 mm Hg vs 12.2 mm Hg). All patients undertook one reading in the early morning at home with an average of 4.8 readings during, and 3.1 readings after office hours.

Conclusions

This small study shows that self-tonometry is feasible. The findings from home phasing demonstrated higher peak and trough IOPs, providing additional clinical information. Home phasing is a viable alternative. The cost-effectiveness of this approach has yet to be addressed.
Rescue of migrated Woven Endobridge devices using a stent-retriever-technique in a porcine model
Authors: Simgen Andreas , Yilmaz Umut , Dietrich Philipp , Tomori Toshiki , Mühl-Benninghaus Ruben , Laschke Matthias W , Menger Michael D , Reith Wolfgang , Kettner Michael
Published: April 2020

Purpose

The Woven Endobridge device (WEB) has become widely applied for the treatment of intracranial aneurysms. Complications are rare, however, especially dislocations and migrations can potentially increase poor clinical outcome. The aim of this study was to assess the feasibility and effectiveness of rescuing migrated Woven Endobridges using different stent retrievers.

Methods

In a porcine model, Woven Endobridges of different sizes (SLS 4, SLS 7, SL 5 × 3, SL 4 × 3) were placed into the axillary arteries. By means of two different stent retrievers (Solitaire Platinum and 3D Revascularization Device), a total of 20 rescue maneuvers were performed. For this purpose, the retrievers were deployed distally of the migrated Woven Endobridges. After retracting the stent retrievers partially, the Woven Endobridges were trapped within the microcatheter. Rescue rates, time, attempts and complications were assessed.

Results

Successful rescue of the migrated Woven Endobridges was observed in all cases (100%). Rescue was slightly faster (177.8 ± 72.8 s vs. 223.4 ± 104.1 s) with fewer attempts (1.5 ± 0.8 vs. 1.8 ± 0.9) when using the 3D Revascularization Device compared to the Solitaire Platinum. However, there were no significant differences (p = 0.327; p = 0.554). Migration of the Woven Endobridges during rescue was seen with both stent retrievers in a comparable frequency (p = 0.642). Further complications, such as entrapment of the stent-retriever–WovenEndobridge-complex at the intermediate catheter, vasospasm, perforation or dissection, were not observed.

Conclusions

Rescue of migrated Woven Endobridges using stent retrievers is a feasible and effective method. Rescue rates, times and attempts with the Solitaire Platinum and 3D Revascularization Device are comparable with each other.
Efficacy of combination therapy with dexmedetomidine for benzodiazepines-induced disinhibition during endoscopic retrograde cholangiopancreatography
Authors: Ikeda Yuki , Yoshida Makoto , Ishikawa Kazuma , Kubo Tomohiro , Murase Kazuyuki , Takada Kohichi , Miyanishi Koji , Kobune Masayoshi , Kato Junji
Published: April 2020

Background:

Benzodiazepines (BZDs) and analgesics are widely used for conscious sedation during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic procedures are sometimes discontinued because of BZD-induced disinhibitory reactions such as excessive movement. We evaluated the usefulness of dexmedetomidine (DEX) for BZD-induced disinhibition in ERCP.

Methods:

Between February 2018 and August 2019, 22 patients who underwent EUS or ERCP were enrolled. All patients showed BZD-induced excessive movement at the first examination (BZD group) and received DEX at the second examination (DEX group). The initial DEX dose was 6 μg/kg/h for a 10-min loading, followed by 0.4 μg/kg/h during the procedure. BZDs and analgesics were administered before scope insertion. An additional sedative was administered to achieve a Ramsay sedation scale (RSS) of 4–5. Sedative effect, procedure completion rate, and changes in circulatory and respiratory dynamics were evaluated.

Results:

Mean RSS scores were significantly higher ( p < 0.001) in the DEX (5.1 ± 0.5) compared with the BZD (4.0 ± 0.5) group. The movement score ( p < 0.001) and number of additional sedatives required ( p < 0.01) were lower in the DEX group. The procedure completion rate was significantly higher in the DEX (95.5%) compared with the BZD group (63.6%; p < 0.05). Significant differences in the frequency of hypotension ( p = 1.00), bradycardia ( p = 0.22), and respiratory depression ( p = 0.68) were not noted between groups.

Conclusions:

The addition of DEX to BZD therapy yielded better sedative efficacy, lower excessive movement, a reduction in BZDs used, and a higher procedure complete rate. DEX may be used as an alternative method for BZD-induced inhibition during ERCP.
Comparison Among Garlic, Berberine, Resveratrol, Hibiscus sabdariffa, Genus Zizyphus, Hesperidin, Red Beetroot, Catha edulis, Portulaca oleracea, and Mulberry Leaves in the Treatment of Hypertension and Type 2 DM: A Comprehensive Review
Authors: Amin Amira R. , Kassab Rami B. , Abdel Moneim Ahmed E. , Amin Hatem K.
Published: April 2020

Diabetes mellitus (DM) and hypertension are 2 of the most prevalent diseases with poor impact on health status worldwide. In most cases, they coexist with other metabolic disorders as well as cardiac, micro- and macrovascular complications. Many plants are known for their hypotensive, cardioprotective, and/or antidiabetic activities. Their active ingredients either identified and isolated or still utilized as herbal preparations of certain plant parts. The use of medicinal plants comprises the main basis for most of the traditional medicine (TM) systems and procedures. As conventional medicines seem insufficient to control such progressive diseases, herbal agents from TM could be used as adjuvant with good impact on disease control and progression as well as other concomitant health conditions. The aim of this study is to compare the efficacy of 10 different herbal medicines of botanical origin or herbal preparations in the management of hypertension and its cardiovascular complications and type 2 DM along with various coexisting health disorders. These herbal medicines are garlic, berberine, resveratrol, Hibiscus sabdariffa, Zizyphus ( oxyphylla, mucronate, jujube, rugosa), hesperidin, red beetroot, Catha edulis, mulberry leaves, and Portulaca oleracea.
Greater burden of risk factors and less effect of cardiac rehabilitation in elderly with low educational attainment: The Eu-CaRE study
Authors: Kjesbu Ingunn E , Mikkelsen Nicolai , Sibilitz Kirstine L , Wilhelm Matthias , Pena-Gil Carlos , González-Salvado Violeta , Iliou Marie Christine , Zeymer Uwe , Meindersma Esther P , Ardissino Diego , van der Velde Astrid E , Van ‘t Hof Arnoud W J , de Kluiver Ed P , Prescott Eva
Published: April 2020

Aims

Socioeconomic status is a strong predictor of cardiovascular health. The aim of this study was to describe the immediate and long-term effects of cardiac rehabilitation (CR) across socioeconomic strata in elderly cardiac patients in Europe.

Methods and results

The observational EU-CaRE study is a prospective study with eight CR sites in seven European countries. Patients ≥65 years with coronary heart disease or heart valve surgery participating in CR were consecutively included. Data were obtained at baseline, end of CR and at one-year follow up. Educational level as a marker for socioeconomic status was divided into basic, intermediate and high. The primary endpoint was exercise capacity (peak oxygen consumption (VO2peak)). Secondary endpoints were cardiovascular risk factors, medical treatment and scores for depression, anxiety and quality of life (QoL). A total of 1626 patients were included; 28% had basic, 48% intermediate and 24% high education. A total of 1515 and 1448 patients were available for follow-up analyses at end of CR and one-year, respectively. Patients with basic education were older and more often female. At baseline we found a socioeconomic gradient in VO2peak, lifestyle-related cardiovascular risk factors, anxiety, depression and QoL. The socioeconomic gap in VO2peak increased following CR (p for interaction <0.001). The socioeconomic gap in secondary outcomes was unaffected by CR. The use of evidence-based medication was good in all socioeconomic groups.

Conclusions

We found a strong socioeconomic gradient in VO2peak and cardiovascular risk factors that was unaffected or worsened after CR. To address inequity in cardiovascular health, the individual adaption of CR according to socioeconomic needs should be considered.
Case Series of Bedside Renal Cell Carcinoma Detected by Point-of-Care Ultrasound in the Ambulatory Setting
Authors: Setia Gayatri , Kedan Ilan
Published: April 2020

Background: Kidney and renal pelvic cancer was the sixth most common cancer in men and 10th most common in women in the United States in 2018. Renal cell carcinoma (RCC), accounts for 86% of malignancies of the kidney. RCC patients are often asymptomatic; up to 25-30% have metastases at diagnosis. Few present with the triad of gross hematuria, flank pain, and abdominal mass. In RCC patients, 36% had 2 symptoms of the triad, and 60% had gross hematuria as 1 symptom. Point-of-care ultrasound (POCUS) offers a way to identify clinically meaningful anatomic abnormalities. This case series presents 3 patients in whom routine POCUS examination performed in an outpatient cardiology clinic found asymptomatic renal masses, resulting in surgical resection and cure of early-stage RCCs. Case Presentation: Patient 1: 54-year-old female with hypertension (HTN). Two solid masses were identified with POCUS in the right kidney. Patient 2: 63-year-old male with coronary artery disease (CAD) and HTN was seen at an 8-month follow-up visit. A 6-cm mass was identified in the left kidney. Patient 3: 69-year-old male with CAD, HTN, and smoking history seen at 5-month follow-up visit. A 3-cm mass in the right kidney was identified. Conclusions: Incorporating POCUS into the routine physical examination in the ambulatory care setting may improve rates of detection and increase the pretest probability of identifying renal pathology with formal imaging studies. With minimal clinician training, earlier and increased detection of asymptomatic RCC may result in improved patient survival.
Risk of Deep Vein Thrombosis After Acute Achilles Tendon Rupture: A Secondary Analysis of a Randomized Controlled Trial Comparing Early Controlled Motion of the Ankle Versus Immobilization
Authors: Barfod Kristoffer Weisskirchner , Nielsen Emil Graakjær , Olsen Beth Hærsted , Vinicoff Pablo Gustavo , Troelsen Anders , Holmich Per
Published: April 2020

Background:

Immobilization of the ankle joint has been suggested as a key element in the pathogenesis leading to deep vein thrombosis (DVT).

Purpose:

To investigate whether early controlled ankle motion (ECM) could reduce the incidence of DVT compared with immobilization (IM) in the treatment of acute Achilles tendon rupture.

Study Design:

Randomized controlled trial; Level of evidence, 2.

Methods:

Patients aged 18 to 70 years were eligible for inclusion, and treatment was nonoperative. The ECM group performed movements of the ankle 5 times a day from weeks 3 to 8 after rupture. The control group was immobilized for 8 weeks. The outcome measure was DVT diagnosed with color Doppler ultrasound for above- and below-knee DVT at 2 and 8 weeks. The Achilles tendon Total Rupture Score, the heel-rise work test, and the Copenhagen Achilles ultrasonographic Length Measurement were performed at 4-, 6-, and 12-month follow-up.

Results:

A total of 189 patients were assessed for eligibility from February 2014 to December 2016. Of these, 130 were randomized: 68 patients were allocated to the ECM group and 62 to the IM group. All patients participated in follow-up at 8 weeks assessing for DVT. In total, 62 (47.7%) patients were diagnosed with DVT: 33 of 68 (48.5%) in the ECM group and 28 of 61 (46.8%) in the IM group ( P = .84). DVT did not affect treatment outcomes at 4, 6, and 12 months. D-dimer had low sensitivity (71%) for detecting DVT.

Conclusion:

We found that 1 in 2 patients presented with DVT in nonoperative treatment of acute Achilles tendon rupture. The ECM protocol revealed no benefit versus IM in reducing the incidence of DVT. DVT did not influence functional and patient-reported outcomes the first year after rupture. D-dimer seems an inappropriate test for detection of DVT in patients with acute Achilles tendon rupture.

Registration:

NCT02015364 ( ClinicalTrials.gov identifier).
CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia
Authors: Schmoellerl Johannes , Barbosa Inês Amorim Monteiro , Eder Thomas , Brandstoetter Tania , Schmidt Luisa , Maurer Barbara , Troester Selina , Pham Ha Thi Thanh , Sagarajit Mohanty , Ebner Jessica , Manhart Gabriele , Aslan Ezgi , Terlecki-Zaniewicz Stefan , Van der Veen Christa , Hoermann Gregor , Duployez Nicolas , Petit Arnaud , Lapillonne Helene , Puissant Alexandre , Itzykson Raphael , Moriggl Richard , Heuser Michael , Meisel Roland , Valent Peter , Sexl Veronika , Zuber Johannes , Grebien Florian
Published: April 2020

Fusion proteins involving Nucleoporin 98 (NUP98) are recurrently found in acute myeloid leukemia (AML) and are associated with poor prognosis. Lack of mechanistic insight into NUP98-fusion–dependent oncogenic transformation has so far precluded the development of rational targeted therapies. We reasoned that different NUP98-fusion proteins deregulate a common set of transcriptional targets that might be exploitable for therapy. To decipher transcriptional programs controlled by diverse NUP98-fusion proteins, we developed mouse models for regulatable expression of NUP98/NSD1, NUP98/JARID1A, and NUP98/DDX10. By integrating chromatin occupancy profiles of NUP98-fusion proteins with transcriptome profiling upon acute fusion protein inactivation in vivo, we defined the core set of direct transcriptional targets of NUP98-fusion proteins. Among those, CDK6 was highly expressed in murine and human AML samples. Loss of CDK6 severely attenuated NUP98-fusion–driven leukemogenesis, and NUP98-fusion AML was sensitive to pharmacologic CDK6 inhibition in vitro and in vivo. These findings identify CDK6 as a conserved, critical direct target of NUP98-fusion proteins, proposing CDK4/CDK6 inhibitors as a new rational treatment option for AML patients with NUP98-fusions.
Puccinia triticina pathotypes THTT and THTS display complex transcript profiles on wheat cultivar Thatcher
Authors: Wei Jie , Cui Liping , Zhang Na , Du Dongdong , Meng Qingfang , Yan Hongfei , Liu Daqun , Yang Wenxiang
Published: April 2020

Background

Wheat leaf rust is an important disease worldwide. Understanding the pathogenic molecular mechanism of Puccinia triticina Eriks. (Pt) and the inconstant toxic region is critical for managing the disease. The present study aimed to analyze the pathogenic divergence between Pt isolates.

Results

Total RNA was extracted from the wheat cultivar Thatcher infected by two Pt isolates, Tc361_1 (THTT) and Tc284_2 (THTS), at 144 h post inoculation (hpi). The mRNA was then sequenced, and a total of 2784 differentially expressed genes (DEGs) were detected. Forty-five genes were specifically expressed in THTT; these genes included transcription initiation factors and genes with transmembrane transporter activity and other genes. Twenty-six genes were specifically expressed in THTS, including genes with GTPase activity, ABC transporters and other genes. Fifty-four differentially expressed candidate effectors were screened from the two isolates. Two candidate effectors were chosen and validated on tobacco, and the results showed that they could inhibit necrosis induced by BAX. qRT-PCR of 12 significant DEGs was carried out to validate that the results are similar to those of RNA-seq at 144 hpi, to show the expression levels of these DEGs in the early stage and to elucidate the differences in expression between the two Pt pathotypes.

Conclusion

The results obtained in this study showed that although the two pathotypes of THTT and THTS contribute similar virulence to wheat, there are a large number of genes participate in the interaction with the susceptible wheat cultivar Thatcher, and revealed the pathogenicity of rust is very complicated.
Genome-wide analysis of Jatropha curcas MADS-box gene family and functional characterization of the JcMADS40 gene in transgenic rice
Authors: Tang Yuehui , Wang Jian , Bao Xinxin , Wu Qian , Yang Tongwen , Li Han , Wang Wenxia , Zhang Yizhen , Bai Nannan , Guan Yaxin , Dai Jiaxi , Xie Yanjie , Li Shen , Huo Rui , Cheng Wei
Published: April 2020

Background

Physic nut (Jatropha curcas), an inedible oilseed plant, is among the most promising alternative energy sources because of its high oil content, rapid growth and extensive adaptability. Proteins encoded by MADS-box family genes are important transcription factors participated in regulating plant growth, seed development and responses to abiotic stress. However, there has been no in-depth research on the MADS-box genes and their roles in physic nut.

Results

In our study, 63 MADS-box genes (JcMADSs) were identified in the physic nut genome, and classed into five groups (MIKCC, Mα, Mβ, Mγ, MIKC*) according to phylogenetic comparison with Arabidopsis homologs. Expression profile analysis based on RNA-seq suggested that many JcMADS genes had the strongest expression in seeds, and seven of them responded in leaves to at least one abiotic stressor (drought and/or salinity) at one or more time points. Transient expression analysis and a transactivation assay indicated that JcMADS40 is a nucleus-localized transcriptional activator. Plants overexpressing JcMADS40 did not show altered plant growth, but the overexpressing plants did exhibit reductions in grain size, grain length, grain width, 1000-seed weight and yield per plant. Further data on the reduced grain size in JcMADS40-overexpressing plants supported the putative role of JcMADS genes in seed development.

Conclusions

This study will be useful in order to further understand the process of MADS-box genes involved in regulating growth and development in addition to their functions in abiotic stress resistance, and will eventually provide a theoretical basis for the functional investigation and the exploitation of candidate genes for the molecular improvement of physic nut.
AsHSP26.8a, a creeping bentgrass small heat shock protein integrates different signaling pathways to modulate plant abiotic stress response
Authors: Sun Xinbo , Zhu Junfei , Li Xin , Li Zhigang , Han Liebao , Luo Hong
Published: April 2020

Background

Small heat shock proteins (sHSPs) are critical for plant response to biotic and abiotic stresses, especially heat stress. They have also been implicated in various aspects of plant development. However, the acting mechanisms of the sHSPs in plants, especially in perennial grass species, remain largely elusive.

Results

In this study,AsHSP26.8a, a novel chloroplast-localized sHSP gene from creeping bentgrass (Agrostis stoloniferaL.) was cloned and its role in plant response to environmental stress was studied.AsHSP26.8aencodes a protein of 26.8 kDa. Its expression was strongly induced in both leaf and root tissues by heat stress. TransgenicArabidopsisplants overexpressing AsHSP26.8a displayed reduced tolerance to heat stress. Furthermore, overexpression of AsHSP26.8a resulted in hypersensitivity to hormone ABA and salinity stress. Global gene expression analysis revealed AsHSP26.8a-modulated expression of heat-shock transcription factor gene, and the involvement of AsHSP26.8a in ABA-dependent and -independent as well as other stress signaling pathways.

Conclusions

Our results suggest that AsHSP26.8a may negatively regulate plant response to various abiotic stresses through modulating ABA and other stress signaling pathways.
The role of late reperfusion in ST-segment elevation myocardial infarction: a real-world retrospective cohort study
Authors: Guo Qixin , Huang Jinyu , Shen Yong , Tong Guoxin , Li Hong , Meng Shasha
Published: April 2020

Background

Early reperfusion of the coronary artery has become the first choice for patients with ST-segment elevation myocardial infarction (STEMI). How to deal with patients who miss the time window for early reperfusion is still controversial. Based on real-world data, this study was conducted to explore whether percutaneous coronary intervention (PCI) has an advantage over standard drug therapy in patients who miss the optimal treatment window.

Methods

Consecutive patients who were diagnosed with STEMI and met the inclusion criteria between 2009 and 2018 in our center were retrospectively included in this cohort study. The primary endpoint events were major adverse cardiac events (MACEs), including heart failure, sudden cardiac death, malignant arrhythmia, thrombi and bleeding events during the period of admission. Secondary endpoint events were components of MACEs. At the same time, we also evaluated angina pectoris at admission and discharge through Canadian Cardiovascular Society (CCS) grading.

Results

This study enrolled 417 STEMI patients and divided them into four groups (PCI < 3 days, 14.87%; 3 days<PCI < 7 days, 21.104%; PCI > 7 days, 34.29%; MED, 29.74%). During the period of admission, MACEs occurred in 52 cases. The incidence of MACEs was 11.29, 7.95, 4.20 and 25.81% in the four respective groups (p < 0.0001). The MED group had higher rates of MACEs (OR = 3.074; 95% CI 0.1.116–8.469, p = 0.03) and cardiac death (OR = 3.027; 95% CI 1.121–8.169, p = 0.029) compared to the PCI group. Although both treatments were effective in improving CCS grade at discharge, the PCI group improved more significantly (p < 0.0001).

Conclusions

In the real world, delayed PCI can be more effective in patients with angina symptoms at discharge and reduce the incidence of MACEs and cardiac death during hospitalization. The timing of intervention was independent of the occurrence of MACEs during hospitalization and of improvement in symptoms.
Implications of sex offender classification on reporting demographic characteristics, health, and criminal careers: results from an Australian jurisdiction
Authors: Gullotta Mathew , Greenberg David , Adily Armita , Cale Jesse , Butler Tony G.
Published: April 2020

Background

Cross-sectional and retrospective offence data are often used to classify sex offenders in epidemiological and survey research, but little empirical evidence exists regarding the practical implications of this for applied research. This study describes the classification of sex offenders from a cohort of prisoners recruited as part of an Australian inmate health survey and the implications for reporting results.

Methods

Data-linkage was used to join the New South Wales (NSW) Inmate Health Surveys to the states re-offending database to identify men with histories of sexual offending. Sex offenders were classified into men who sexually offended against children only (ChildSOs), against adults only (AdultSOs), and men who sexually offended against both children and adults (Age-PolySOs).

Results

Using historical offending data rather than the current offence information only, an additional 35.4% of men with histories of sexual offences were identified. Differences were found between the three sex offender subgroups in terms of demographic characteristics, health, and criminal careers. Age-PolySOs reported higher educational attainment, were less likely to report being self-employed, single marital status, and having children. Half the ChildSOs self-reported a mental health issue and half of the ChildSOs and Age-PolySOs reported four or more chronic health conditions. Age-PolySOs were older than the other sex offender groups when committing their first non-sexual, non-violent crime (M = 43.2 years, SD = 13.8); violent crime (M = 39.5 years, SD = 11.1); and sexual crime (M = 47.8 years, SD = 11.2). Age-PolySOs also committed more sexual offences (M = 5.91, SD = 11.2) compared to those who only offended against one victim age group.

Conclusion

These findings suggested that historical offending records should be used to more accurately identify sex offender subgroups and that differences in demographic, health, and criminal careers exist for the different sex offender subgroups.
Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema
Authors: Loo Evelyn Xiu Ling , Zain Amanda , Yap Gaik Chin , Purbojati Rikky W. , Drautz-Moses Daniela I. , Koh Yan Qing , Chong Yap Seng , Tan Kok Hian , Gluckman Peter D. , Yap Fabian , Eriksson Johan Gunnar , Tham Elizabeth , Shek Lynette Pei-chi , Kjelleberg Staffan , Schuster Stephan C. , Banerjee Ritu , Lee Bee Wah
Published: April 2020

Background

While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producingEnterobacteriaceaein Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producingE. coliandK. pneumoniaein the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants.

Methods

We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics.

Results

The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistantEscherichia coliandKlebsiella pneumoniaewere detected in 4 (5.3%) and 32 (42.7%) of subjects respectively.

Conclusion

In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.
Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study
Authors: Diallo Alhassane , Diallo Boubacar Djelo , Camara Lansana Mady , Kounoudji Lucrèce Ahouéfa Nadège , Bah Boubacar , N’Zabintawali Fulgence , Carlos-Bolumbu Miguel , Diallo Mamadou Hassimiou , Sow Oumou Younoussa
Published: April 2020

Background

Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes.

Methods

We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories.

Results

Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3–8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218).

Conclusion

Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.
The first study of successful pregnancies in Chinese patients with Phenylketonuria
Authors: Wang Lin , Ye Fang , Zou Hui , Wang Kundi , Chen Zhihua , Hui Qin , Han Bingjuan , He Chun , Li Xiaowen , Shen Ming
Published: April 2020

Background

Since the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU).

Method

Married patients with PKU from 2012 to 2017 were enrolled to receive prenatal counseling and regular health assessments. Study-related assessments included the timing of Phe-restricted diets, maternal weight gain, gestational age, pregnancy complications, and blood Phe concentrations (both pre-conception and during pregnancy), obstetrical data, and offspring outcomes(e.g. anthropomorphic measurements and developmental quotients [DQs]).

Results

A total of six offspring were successfully delivered. The mean ± SD (range) age of the mother at delivery was 26.3 ± 4.7 (range: 21.1–32.5) years. The mean duration of Phe control before pregnancy was 5.5 ± 1.3(range: 3.1–6.5) months. During pregnancy, the proportion of blood Phe concentrations within the clinically-recommended target range (120–360 μmol/L) ranged from 63.2–83.5%. Low birth weight (< 2500 g) offspring occurred in two women who experienced suboptimal metabolic control. In addition, offspring DQ was related to the proportion of blood Phe levels per trimester that were within the recommended range (r = 0.886,p = 0.016).

Conclusion

This is the first report of women in China with PKU who successfully gave birth to clinically healthy babies. Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride (6R-BH4) may be an option to improve the management of blood Phe levels.
Cytokine-induced killer cell/dendritic cell combined with cytokine-induced killer cell immunotherapy for treating advanced gastrointestinal cancer
Authors: Du Hansong , Yang Jia , Zhang Ying
Published: April 2020

Background

This study aimed to investigate the efficacy and safety of cytokine-induced killer (CIK)/dendritic cell combined with CIK (DC–CIK) cell therapy in advanced gastrointestinal cancer (GIC).

Methods

The PubMed, Cochrane library, and Embase were searched to conduct a meta-analysis of clinical controlled trials to evaluate the efficacy and safety of CIK/DC–CIK cell therapy in advanced GIC. The pooled risk ratios (RRs) or weighted mean difference (WMD) with 95% confidence intervals (95% CIs) were calculated.

Results

A total of nine studies with 1113 patients were identified. The overall survival (RR = 1.84, 95% CI = 1.41–2.40,Pheterogeneity = 0.654,I2 = 0%), progression-free survival (RR = 1.99, 95% CI = 1.52–2.60,Pheterogeneity = 0.727,I2 = 0%), and quality of life (WMD = 16.09, 95% CI = 1.66–30.52,Pheterogeneity < 0.001,I2 = 98.8%) were significantly improved in patients who received chemotherapy combined with CIK/DC–CIK cells, and no severe adverse events were reported.

Conclusion

This meta-analysis suggested that the combination of CIK/DC–CIK immunotherapy and chemotherapy was safe and applicable for patients with advanced GIC. It is a feasible choice to prolong survival and improve quality of life.
Clinical utility of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab: a single-center retrospective study
Authors: Kitagawa Yusuke , Osumi Hiroki , Shinozaki Eiji , Ota Yumiko , Nakayama Izuma , Suzuki Takeshi , Wakatsuki Takeru , Ogura Mariko , Ooki Akira , Takahari Daisuke , Suenaga Mitsukuni , Chin Keisho , Yamaguchi Kensei
Published: April 2020

Background

This study aimed to evaluate the efficacy and the safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev) in clinical practice.

Methods

We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF as preventing or treating grade 3 or 4 neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0.

Results

A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients, and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or 4 neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.8%), no dose adjustment was required.

Conclusions

PEG-G-CSF is useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.
Anti-HER2 induced myeloid cell alterations correspond with increasing vascular maturation in a murine model of HER2+ breast cancer
Authors: Bloom Meghan J. , Jarrett Angela M. , Triplett Todd A. , Syed Anum K. , Davis Tessa , Yankeelov Thomas E. , Sorace Anna G.
Published: April 2020

Background

Therapy targeted to the human epidermal growth factor receptor type 2 (HER2) is used in combination with cytotoxic therapy in treatment of HER2+ breast cancer. Trastuzumab, a monoclonal antibody that targets HER2, has been shown pre-clinically to induce vascular changes that can increase delivery of chemotherapy. To quantify the role of immune modulation in treatment-induced vascular changes, this study identifies temporal changes in myeloid cell infiltration with corresponding vascular alterations in a preclinical model of HER2+ breast cancer following trastuzumab treatment.

Methods

HER2+ tumor-bearing mice (N = 46) were treated with trastuzumab or saline. After extraction, half of each tumor was analyzed by immunophenotyping using flow cytometry. The other half was quantified by immunohistochemistry to characterize macrophage infiltration (F4/80), vascularity (CD31 and α-SMA), proliferation (Ki67) and cellularity (H&E). Additional mice (N = 10) were used to quantify differences in tumor cytokines between control and treated groups.

Results

Immunophenotyping showed an increase in macrophage infiltration 24 h after trastuzumab treatment (P ≤ 0.05). With continued trastuzumab treatment, the M1 macrophage population increased (P = 0.02). Increases in vessel maturation index (i.e., the ratio of α-SMA to CD31) positively correlated with increases in tumor infiltrating M1 macrophages (R = 0.33, P = 0.04). Decreases in VEGF-A and increases in inflammatory cytokines (TNF-α, IL-1β, CCL21, CCL7, and CXCL10) were observed with continued trastuzumab treatment (P ≤ 0.05).

Conclusions

Preliminary results from this study in a murine model of HER2+ breast cancer show correlations between immune modulation and vascular changes, and reveals the potential for anti-HER2 therapy to reprogram immunosuppressive components of the tumor microenvironment. The quantification of immune modulation in HER2+ breast cancer, as well as the mechanistic insight of vascular alterations after anti-HER2 treatment, represent novel contributions and warrant further assessment for potential clinical translation.
Multilevel analysis of factors that influence overweight in children: research in schools enrolled in northern Brazil School Health Program
Authors: Andrade de Medeiros Moreira Renata , Ricardo Moreira Tiago , Dias da Costa Glauce , Vidigal Castro Luiza Carla , Minardi Mitre Cotta Rosângela
Published: April 2020

Background

The study evaluates children in schools that participate in the School Health Program in the Northern region of Brazil with the objective of assessing whether their schools interfered in the development of overweight/obesity and how individual and school environment variables behave according to contextual analysis.

Methods

The analyses were carried out with 1036 children from 25 municipal public schools in Northern Brazil that participated in the School Health Program. We evaluated both individual characteristics and scholar environment through univariate and multivariate logistic regressions to identify which of these factors were related to overweight/obesity as well as the effect of varying such associations.

Results

The considered individuals had an median age of 8 years, being 54.9% female and 27.8% presenting overweight/obesity. In multivariate logistic regression, the overweight/obesity variance in schools was 0.386 (individual variables) and 0.102 (individual and school variables), explaining 23.7% of the variation, reduction of ICC and MOR. The Akaike Information Criterion between the models was reduced and the likelihood ratio indicated better adequacy of the latter model. The investigated children had a greater chance of developing overweight/obesity when they performed 2+ sedentary activities/day, depending on school location as well as whether or not candies were sold in the school surroundings. On the other hand, a lower chance of developing overweight/obesity was identified in children that ate 5+ meals/day and practiced dance at school.

Conclusion

We observed that the variables inherent to both individuals and schools favored the development of overweight/obesity in children. It is relevant that scholar curriculums incorporate healthy eating interventions and encourage body practices associated with policies that restrain the sale of ultra-processed food in schools as well as the development of intersectoral actions between education and health to control childhood obesity.
Associations of health literacy with socioeconomic position, health risk behavior, and health status: a large national population-based survey among Danish adults
Authors: Svendsen Majbritt Tang , Bak Carsten Kronborg , Sørensen Kristine , Pelikan Jürgen , Riddersholm Signe Juul , Skals Regitze Kuhr , Mortensen Rikke Nørmark , Maindal Helle Terkildsen , Bøggild Henrik , Nielsen Gitte , Torp-Pedersen Christian
Published: April 2020

Background

Health literacy concerns the ability of citizens to meet the complex demands of health in modern society. Data on the distribution of health literacy in general populations and how health literacy impacts health behavior and general health remains scarce. The present study aims to investigate the prevalence of health literacy levels and associations of health literacy with socioeconomic position, health risk behavior, and health status at a population level.

Methods

A nationwide cross-sectional survey linked to administrative registry data was applied to a randomly selected sample of 15,728 Danish individuals aged ≥25 years. By the short form HLS-EU-Q16 health literacy was measured for the domains of healthcare, disease prevention, and health promotion. Adjusted multinomial logistic regression analyses were used to estimate associations of health literacy with demographic and socioeconomic characteristics, health risk behavior (physical activity, smoking, alcohol consumption, body weight), and health status (sickness benefits, self-assessed health).

Results

Overall, 9007 (57.3%) individuals responded to the survey. Nearly 4 in 10 respondents faced difficulties in accessing, understanding, appraising, and applying health information. Notably, 8.18% presented with inadequate health literacy and 30.94% with problematic health literacy. Adjusted for potential confounders, regression analyses showed that males, younger individuals, immigrants, individuals with basic education or income below the national average, and individuals receiving social benefits had substantially higher odds of inadequate health literacy. Among health behavior factors (smoking, high alcohol consumption, and inactivity), only physical behavior [sedentary: OR: 2.31 (95% CI: 1.81; 2.95)] was associated with inadequate health literacy in the adjusted models. The long-term health risk indicator body-weight showed that individuals with obesity [OR: 1.78 (95% CI: 1.39; 2.28)] had significantly higher odds of lower health literacy scores. Poor self-assessed health [OR: 4.03 (95% CI: 3.26; 5.00)] and payments of sickness absence compensation benefits [OR: 1.74 (95% CI: 1.35; 2.23)] were associated with lower health literacy scores.

Conclusions

Despite a relatively highly educated population, the prevalence of inadequate health literacy is high. Inadequate health literacy is strongly associated with a low socioeconomic position, poor health status, inactivity, and overweight, but to a lesser extent with health behavior factors such as smoking and high alcohol consumption.
Cervical cancer screening program based on primary DNA-HPV testing in a Brazilian city: a cost-effectiveness study protocol
Authors: Teixeira Julio Cesar , Vale Diama Bhadra , Bragança Joana Froes , Campos Cirbia Silva , Discacciati Michelle Garcia , Zeferino Luiz Carlos
Published: April 2020

Background

The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses.

Methods

The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011–2016).

Discussion

The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.