bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes and outcomes measurements used in intervention studies of pelvic girdle pain and lumbopelvic pain: a systematic review
Authors: Wuytack Francesca , O’Donovan Maggie
Published: November 2019

Background

Pelvic girdle pain is a common problem during pregnancy and postpartum with significant personal and societal impact and costs. Studies examining the effectiveness of interventions for pelvic girdle pain measure different outcomes, making it difficult to pool data in meta-analysis in a meaningful and interpretable way to increase the certainty of effect measures. A consensus-based core outcome set for pelvic girdle pain can address this issue. As a first step in developing a core outcome set, it is essential to systematically examine the outcomes measured in existing studies.

Objective

The objective of this systematic review was to identify, examine and compare what outcomes are measured and reported, and how outcomes are measured, in intervention studies and systematic reviews of interventions for pelvic girdle pain and for lumbopelvic pain (which includes pelvic girdle pain).

Methods

We searched PubMed, Cochrane Library, PEDro and Embase from inception to the 11th May 2018. Two reviewers independently selected studies by title/abstract and by full text screening. Disagreement was resolved through discussion. Outcomes reported and their outcome measurement instruments were extracted and recorded by two reviewers independently. We assessed the quality of reporting with two independent reviewers. The outcomes were grouped into core domains using the OMERACT filter 2.0 framework.

Results

A total of 107 studies were included, including 33 studies on pelvic girdle pain and 74 studies on lumbopelvic pain. Forty-six outcomes were reported across all studies, with the highest amount (26/46) in the ‘life impact’ domain. ‘Pain’ was the most commonly reported outcome in both pelvic girdle pain and lumbopelvic pain studies. Studies used different instruments to measure the same outcomes, particularly for the outcomes pain, function, disability and quality of life.

Conclusions

A wide variety of outcomes and outcome measurements are used in studies on pelvic girdle pain and lumbopelvic pain. The findings of this review will be included in a Delphi survey to reach consensus on a pelvic girdle pain - core outcome set. This core outcome set will allow for more effective comparison between future studies on pelvic girdle pain, allowing for more effective translation of findings to clinical practice.
Clinical, genetic, and molecular characterization of hyperphosphatasia with mental retardation: a case report and literature review
Authors: Abi Farraj Layal , Khatoun Wassim Daoud , Abou Chebel Naji , Wakim Victor , Dawali Katia , Ghassibe-Sabbagh Michella
Published: November 2019

Background

Hyperphosphatasia with mental retardation syndrome (HPMRS) is a recessive disorder characterized by high blood levels of alkaline phosphatase together with typical dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and developmental delay. Genes involved in the glycosylphosphatidylinositol pathway and known to be mutated in HPMRS have never been characterized in the Lebanese population.

Case presentation

Herein, we describe a pair of monozygotic twins presenting with severe intellectual disability, distinct facial dysmorphism, developmental delay, and increased alkaline phosphatase level. Two individuals underwent whole exome sequencing followed by Sanger sequencing to confirm the co-segregation of the mutation in the consanguineous family. A biallelic loss of function mutation inPGAP3was detected. Both patients were homozygous for the c.203delC (p.C68LfsX88) mutation and the parents were carriers confirming the founder effect of the mutation. High ALP serum levels confirmed the molecular diagnosis.

Conclusion

Our findings have illustrated the genomic profile ofPGAP3-related HPMRS which is essential for targeted molecular and genetic testing. Moreover, we found previously unreported clinical findings such as hypodontia and skin hyperpigmentation. These features, together with the novel mutation expand the phenotypic and genotypic spectrum of this rare recessive disorder.
A bacterial assay for rapid screening of IAA catabolic enzymes
Authors: Brunoni Federica , Collani Silvio , Šimura Jan , Schmid Markus , Bellini Catherine , Ljung Karin
Published: November 2019

Background

Plants rely on concentration gradients of the native auxin, indole-3-acetic acid (IAA), to modulate plant growth and development. Both metabolic and transport processes participate in the dynamic regulation of IAA homeostasis. Free IAA levels can be reduced by inactivation mechanisms, such as conjugation and degradation. IAA can be conjugated via ester linkage to glucose, or via amide linkage to amino acids, and degraded via oxidation. Members of the UDP glucosyl transferase (UGT) family catalyze the conversion of IAA to indole-3-acetyl-1-glucosyl ester (IAGlc); by contrast, IAA is irreversibly converted to indole-3-acetyl-l-aspartic acid (IAAsp) and indole-3-acetyl glutamic acid (IAGlu) by Group II of the GRETCHEN HAGEN3 (GH3) family of acyl amido synthetases. Dioxygenase for auxin oxidation (DAO) irreversibly oxidizes IAA to oxindole-3-acetic acid (oxIAA) and, in turn, oxIAA can be further glucosylated to oxindole-3-acetyl-1-glucosyl ester (oxIAGlc) by UGTs. These metabolic pathways have been identified based on mutant analyses, in vitro activity measurements, and in planta feeding assays. In vitro assays for studying protein activity are based on producing Arabidopsis enzymes in a recombinant form in bacteria or yeast followed by recombinant protein purification. However, the need to extract and purify the recombinant proteins represents a major obstacle when performing in vitro assays.

Results

In this work we report a rapid, reproducible and cheap method to screen the enzymatic activity of recombinant proteins that are known to inactivate IAA. The enzymatic reactions are carried out directly in bacteria that produce the recombinant protein. The enzymatic products can be measured by direct injection of a small supernatant fraction from the bacterial culture on ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UHPLC–ESI-MS/MS). Experimental procedures were optimized for testing the activity of different classes of IAA-modifying enzymes without the need to purify recombinant protein.

Conclusions

This new method represents an alternative to existing in vitro assays. It can be applied to the analysis of IAA metabolites that are produced upon supplementation of substrate to engineered bacterial cultures and can be used for a rapid screening of orthologous candidate genes from non-model species.
ADC correlation with Sirtuin1 to assess early chemoradiotherapy response of locally advanced esophageal carcinoma patients
Authors: Chen Ying , Xie Tieming , Ye Zhimin , Wang Fangzheng , Long Dan , Jiang Mingxiang , Fang Jun , Lin Qingren , Li Kai , Wang Zhun , Fu Zhenfu
Published: November 2019

Aims

To determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT).

Methods

A total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1~2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and ΔADC, ADCratio were calculated. Pearson’s correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman’s rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT.

Results

The findings of this study showed different correlations between ADC values and the levels of SIRT1 (ΔADC: r = − 0.943, P = 0.002; ADCratio: r = − 0.911, P = 0.000; intra-ADC: r = − 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between ΔADC and early response to treatment (ρ = 0.615, P = 0.023), and multivariable logistic regression revealed that ΔADC was significantly associated with short-term response of CRT in esophageal carcinoma patients.

Conclusions

In summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.
Thoracoscopic partial lung resection following pneumonectomy: a report of three cases
Authors: Goto Hidenori , Mun Mingyon , Mori Shohei , Samejima Joji , Matsuura Yosuke , Nakao Masayuki , Uehara Hirohumi , Nakagawa Ken , Okumura Sakae
Published: November 2019

Background

The prognosis of patients who undergo unilateral pneumonectomy and subsequently develop a contralateral pulmonary tumor can be improved by tumor resection. Thus, surgery is a treatment option if the patient’s pulmonary function and performance status are satisfactory. To date, there have been only few cases reporting thoracoscopic lung resection for pulmonary tumor after contralateral pneumonectomy because of the difficulty in respiratory management during surgery. Thoracoscopic surgery requires the maintenance of the operative field to allow the lung to collapse, and in partial lung resection we need to identify tumor localization. The identification of a tumor lesion just inferior to the pleura is easy; however, the identification of a tumor lesion in the deep parts is difficult. The tumor in the deep part of the lung segments can be easily located if the tumor-affected lobe is allowed to completely collapse. Therefore, ventilation technique should be modified according to the tumor localization.

Case presentation

Here, we report three cases of thoracoscopic partial lung resections for pulmonary tumors that developed after contralateral pneumonectomy. Intermittent manual ventilation using a tracheal tube was performed in two cases with a lesion just inferior of the pleura. The tumors in both patients were resected using automatic suturing devices while arresting manual ventilation. The affected lobe was allowed to collapse using a bronchial blocker in one of the cases with a lesion in the deep part. Furthermore, she had contralateral pneumothorax with bullae on the right upper and lower lobes of the lung. The tumor in the deep part of the lung segment and ruptured bullae were easily located and resected using automatic suturing devices. The hemodynamic status of the patients was stable, and the intra- and postoperative courses were uneventful.

Conclusions

Our cases demonstrate that thoracoscopic lung resection after contralateral pneumonectomy can be performed if intermittent manual ventilation is utilized when the tumor is located just inferior to the pleura and if selective double ventilation using an intrabronchial blocker is utilized when the tumor is located in the deep part.
Peripheral nerve injury-induced alterations in VTA neuron firing properties
Authors: Huang Shuo , Borgland Stephanie L. , Zamponi Gerald W.
Published: November 2019

The ventral tegmental area (VTA) is one of the main brain regions harboring dopaminergic (DA) neurons, and plays important roles in reinforcement and motivation. Recent studies have indicated that DA neurons not only respond to rewarding stimuli, but also to noxious stimuli. Furthermore, VTA DA neurons undergo plasticity during chronic pain. Lateral and medial VTA neurons project to different brain areas, and have been characterized via their distinct electrophysiological properties. In this study, we characterized electrophysiological properties of lateral and medial VTA DA neurons using DAT-cre reporter mice, and examined their plasticity during neuropathic pain states. We observed various DA subpopulations in both the lateral and medial VTA, as defined by action potential firing patterns, independently of synaptic inputs. Our results demonstrated that lateral and medial VTA DA neurons undergo differential plasticity after peripheral nerve injury that leads to neuropathic pain. However, these changes only reside in specific DA subpopulations. This study suggests that lateral and medial VTA DA neurons are differentially affected during neuropathic pain conditions, and emphasizes the importance of subpopulation specificity when targeting VTA DA neurons for treatment of neuropathic pain.
Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma
Authors: Liu Ziyu , Lin Yan , Zhang Jinyan , Zhang Yumei , Li Yongqiang , Liu Zhihui , Li Qian , Luo Ming , Liang Rong , Ye Jiazhou
Published: November 2019

Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.
Interleukin-8 promotes integrin β3 upregulation and cell invasion through PI3K/Akt pathway in hepatocellular carcinoma
Authors: Sun Fengkai , Wang Jianping , Sun Qi , Li Fanni , Gao Hengjun , Xu Lin , Zhang Jiao , Sun Xiaoyan , Tian Yanan , Zhao Qiujie , Shen Huimin , Zhang Kai , Liu Jun
Published: November 2019

Background

Interleukin-8 (IL-8) plays a vital role in the invasion and metastasis of hepatocellular carcinoma (HCC), and is closely associated with poor prognosis of HCC patients. Integrin αvβ3, a member of the integrin family, has been reported to be overexpressed in cancer tissues and mediate the invasion and metastasis of HCC cells. However, the relationship between IL-8 and integrin αvβ3 in HCC and the underlying mechanism of IL-8 and integrin αvβ3 in the invasion of HCC remains unclear.

Methods

The expression of IL-8, integrin αv and integrin β3 in HCC cells and tissues was detected by quantitative real-time PCR, Western blot and immunohistochemistry. Transwell assay and Western blot was used to detect the invasiveness, the expression of integrin β3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8.

Results

IL-8, integrin αv and integrin β3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin β3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin β3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin β3 expression was significantly inhibited by transfection with CXCR1 siRNA or CXCR2 siRNA. When we stimulated HCC cells with exogenous IL-8, cell invasion and the levels of integrin β3, p-PI3K, and p-Akt increased, which could be effectively reversed by adding PI3K inhibitor LY294002.

Conclusions

Our results suggest that IL-8 promotes integrin β3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin β3 axis may serve as a potential treatment target for patients with HCC.
Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives – a review
Authors: Gupta Sudeep , Nag Shona , Aggarwal Shyam , Rauthan Amit , Warrier Narayanankutty
Published: November 2019

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.
Application of NICE or SNC guidelines may reduce the need for computerized tomographies in patients with mild traumatic brain injury: a retrospective chart review and theoretical application of five guidelines
Authors: Svensson Sebastian , Vedin Tomas , Clausen Linus , Larsson Per-Anders , Edelhamre Marcus
Published: November 2019

Background

Traumatic brain injuries continue to be a significant cause of mortality and morbidity worldwide. Most traumatic brain injuries are classified as mild, with a low but not negligible risk of intracranial hemorrhage. To help physicians decide which patients might benefit from a computerized tomography (CT) of the head to rule out intracranial hemorrhage, several clinical decision rules have been developed and proven effective in reducing the amount of negative CTs, but they have not been compared against one another in the same cohort as to which one demonstrates the best performance.

Methods

This study involved a retrospective review of the medical records of patients seeking care between January 1 and December 31, 2017 at Helsingborg Hospital, Sweden after head trauma. The Canadian CT Head Rule (CCHR), the New Orleans Criteria (NOC), the National Emergency X-Radiography Utilization Study II (NEXUS II), the National Institute of Health and Care Excellence (NICE) guideline and the Scandinavian Neurotrauma Committee (SNC) guideline were analyzed. A theoretical model for each guideline was constructed and applied to the cohort to yield a theoretical CT-rate for each guideline. Performance parameters were calculated and compared.

Results

One thousand three hundred fifty-three patients were included; 825 (61%) CTs were performed, and 70 (5.2%) cases of intracranial hemorrhage were found. The CCHR and the NOC were applicable to a minority of the patients, while the NEXUS II, the NICE, and the SNC guidelines were applicable to the entire cohort. A theoretical application of the NICE and the SNC guidelines would have reduced the number of CT scans by 17 and 9% (P = < 0.0001), respectively, without missing patients with intracranial hemorrhages requiring neurosurgical intervention.

Conclusion

A broad application of either NICE or the SNC guidelines could potentially reduce the number of CT scans in patients suffering from mTBI in a Scandinavian setting, while the other guidelines seemed to increase the CT frequency. The sensitivity for intracranial hemorrhage was lower than in previous studies for all guidelines, but no fatality or need for neurosurgical intervention was missed by any guideline when they were applicable.
The Danish prehospital emergency healthcare system and research possibilities
Authors: Lindskou Tim Alex , Mikkelsen Søren , Christensen Erika Frischknecht , Hansen Poul Anders , Jørgensen Gitte , Hendriksen Ole Mazur , Kirkegaard Hans , Berlac Peter Anthony , Søvsø Morten Breinholt
Published: November 2019

The emergency medical healthcare system outside hospital varies greatly across the globe - even within the western world. Within the last ten years, the demand for emergency medical service systems has increased, and the Danish emergency medical service system has undergone major changes.

Therefore, we aimed to provide an updated description of the current Danish prehospital medical healthcare system.

Since 2007, Denmark has been divided into five regions each responsible for health services, including the prehospital services. Each region may contract their own ambulance service providers. The Danish emergency medical services in general include ambulances, rapid response vehicles, mobile emergency care units and helicopter emergency medical services. All calls to the national emergency number, 1-1-2, are answered by the police, or the Copenhagen fire brigade, and since 2011 forwarded to an Emergency Medical Coordination Centre when the call relates to medical issues. At the Emergency Medical Coordination Centre, healthcare personnel assess the situation guided by the Danish Index for Emergency Care and determine the level of urgency of the situation, while technical personnel dispatch the appropriate medical emergency vehicles. In Denmark, all healthcare services, including emergency medical services are publicly funded and free of charge. In addition to emergency calls, other medical services are available for less urgent health problems around the clock. Prehospital personnel have since 2015 utilized a nationwide electronic prehospital medical record. The use of this prehospital medical record combined with Denmark’s extensive registries, linkable by the unique civil registration number, enables new and unique possibilities to do high quality prehospital research, with complete patient follow-up.
A new therapy in Epstein-Barr virus-associated lymphoproliferative disease: a case report and a revision of the literature
Authors: Xu Lingling , Ba Hongjun , Lin Hongrong , Zhong Liangying , Li Suping , Tang Wen , Ke Zhiyong , Ye Ziyin
Published: November 2019

Background

Systemic chronic active Epstein-Barr virus infection is an extremely rare childhood disease. Since chronic active Epstein-Barr virus infection can trigger the onset of Epstein-Barr virus-associated lymphoproliferative disease. The clinical manifestations of the disease vary according to the site of involvement; therefore, management may be challenging. Currently, there are no standardized guidelines for treating Chronic active Epstein-Barr virus infection effectively.

Case presentation

We report a case of chronic active Epstein-Barr virus infection in a 5-year-old Chinese boy with intestinal, vascular, and neurological involvement. At age of 2 years and 7 months old, he had hepatomegaly and been diagnosed with Epstein-Barr virus infection. After treatment, he showed some clinical improvement. At age of 3 years and 3 months old, he presented with recurrent fever and diarrhea. Then he received methylprednisolone for 1 year and his symptoms ameliorated. At the age of 5 years, his symptoms recurred and had gastrointestinal hemorrhage and developed polyuria, frequent convulsions and hyponatremia. He was transferred to our hospital for further management. He was unconscious on admission and was diagnosised Epstein-Barr virus-lymphoproliferative disorder, based on the results in situ hybridization of EBV-encoded miRNA in sigmoid colon. Three-dimensional CT angiography demonstrated an aneurysm in the right internal carotid artery. Abdominal CT showed dilatation of vessels in part of the intestinal wall. He was also diagnosised Epstein-Barr virus encephalitis based on the elevated Epstein-Barr virus antibody titers and presence of Epstein-Barr virus DNA in the Cerebrospinal Fluid.

A repeated duodenal artery embolization and symptomatic therapy could not control the hemorrhage after admission. He subsequently received treatment with ganciclovir, glucocorticoid, thalidomide, and propranolol. Hemorrhage was controlled in 5 days; his symptoms improved. The fever did not recur and the CSF pressure was also normalized. A follow-up CT at 3 months after admission showed regression of the aneurysm in the right internal carotid artery and the vascular lesion in the duodenum.

Discussion and conclusions

A new treatment protocol including thalidomide and propranolol resulted in a marked improvement in his clinical symptoms, and shows promise as a novel and effective therapeutic approach for Chronic active Epstein-Barr virus infection-associated lymphoproliferative disorder.
Scrub typhus ecology: a systematic review of Orientia in vectors and hosts
Authors: Elliott Ivo , Pearson Isabelle , Dahal Prabin , Thomas Nigel V. , Roberts Tamalee , Newton Paul N.
Published: November 2019

Scrub typhus, caused byOrientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites (‘chiggers’) and 83,000 vertebrates. The proportion ofO. tsutsugamushipositivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of humanOrientiasp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.
Development of a recombinase polymerase amplification (RPA) fluorescence assay for the detection of Schistosoma haematobium
Authors: Rostron Penelope , Pennance Tom , Bakar Faki , Rollinson David , Knopp Stefanie , Allan Fiona , Kabole Fatma , Ali Said M. , Ame Shaali M. , Webster Bonnie L.
Published: November 2019

Background

Accurate diagnosis of urogenital schistosomiasis is vital for surveillance and control programmes. While a number of diagnostic techniques are available there is a need for simple, rapid and highly sensitive point-of-need (PON) tests in areas where infection prevalence and intensity are low. Recombinase Polymerase Amplification (RPA) is a sensitive isothermal molecular diagnostic technology that is rapid, portable and has been used at the PON for several pathogens.

Results

A real time fluorescence RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic repeat region was developed and was able to detect 1 fg of S. haematobium gDNA. Results were obtained within 10 minutes using a small portable battery powered tube scanner device that incubated reactions at 40 °C, whilst detecting DNA amplification and fluorescence over time. The assay’s performance was evaluated using 20 urine samples, with varying S. haematobium egg counts, from school children from Pemba Island, Zanzibar Archipelago, Tanzania. Prior to RPA analysis, samples were prepared using a quick crude field DNA extraction method, the Speed Extract Kit (Qiagen, Manchester, UK). Positive assay results were obtained from urine samples with egg counts of 1–926 eggs/10 ml, except for two samples, which had inconclusive results. These two samples had egg counts of two and three eggs/10 ml of urine.

Conclusions

The RT-ShDra1-RPA assay proved robust for S. haematobium gDNA detection and was able to amplify and detect S. haematobium DNA in urine samples from infected patients. The assay’s speed and portability, together with the use of crude sample preparation methods, could advance the rapid molecular diagnosis of urogenital schistosomiasis at the PON within endemic countries.
Efficacy of a moxidectin/imidacloprid spot-on formulation (Advocate®) for the treatment of Troglostrongylus brevior in naturally infected cats in a field study in Greece
Authors: Diakou Anastasia , Morelli Simone , Dimzas Dimitris , Di Cesare Angela , Capelli Gioia , Parrinello Chiara , Pollmeier Matthias , Schaper Roland , Traversa Donato
Published: November 2019

Background

Troglostrongylus brevior is a lungworm of wild felids that recently has been recognized as agent of severe respiratory disease in domestic cats in Mediterranean and Balkan countries. Nevertheless, the information on treatment options for feline troglostrongylosis is still poor. The aim of this pilot field trial was to evaluate the efficacy of the spot-on formulation containing 1% w/v moxidectin and 10% w/v imidacloprid (Advocate® spot-on solution for cats, Bayer Animal Health GmbH) in the treatment of T. brevior infection in naturally infected cats in Greece.

Methods

The trial was a negative control, multicentre, clinical efficacy study conducted according to the standards of Good Scientific Practice (GSP). Sixteen cats in two study sites, naturally infected with T. brevior, were allocated to an untreated control group (G1, n = 8) or a treatment group (G2, n = 8), according to a randomization list. Animals assigned to G2 were treated with Advocate® for cats on days 0 and 28 at the recommended dose rate and animals assigned to G1 received a rescue treatment with the same product on days 56 and 84. Efficacy was assessed on days 28 and 56 in G2 and on days 84 and 112 in G1 by faecal larval counts. The primary efficacy criterion was the absence of T. brevior first-stage larvae (L1) following treatment. Other efficacy parameters were the quantitative comparison of L1 presence before (baseline) and after one or two treatments in both groups.

Results

All G2 cats were negative for T. brevior L1 at the first post-treatment evaluation (100% efficacy) while G1 cats were persistently shedding L1. The difference of the mean number of L1 per gram between G2 and G1 was statistically significant (P < 0.001). All G1 cats were negative (100% efficacy) for T. brevior L1 at the first post-rescue-treatment evaluation. Therefore, treatment efficacy at study completion was 100% in both groups in terms of stopping the L1 shedding in the faeces of the animals. No adverse effects were observed during the study.

Conclusions

These results indicate that Advocate® spot-on solution for cats represents an option for treating cats naturally infected with T. brevior.
The life-cycle of the avian haemosporidian parasite Haemoproteus majoris, with emphasis on the exoerythrocytic and sporogonic development
Authors: Ilgūnas Mikas , Romeiro Fernandes Chagas Carolina , Bukauskaitė Dovilė , Bernotienė Rasa , Iezhova Tatjana , Valkiūnas Gediminas
Published: November 2019

Background

Haemoproteus parasites (Haemosporida, Haemoproteidae) are cosmopolitan in birds and recent molecular studies indicate enormous genetic diversity of these pathogens, which cause diseases in non-adapted avian hosts. However, life-cycles remain unknown for the majority of Haemoproteus species. Information on their exoerythrocytic development is particularly fragmental and controversial. This study aimed to gain new knowledge on life-cycle of the widespread blood parasite Haemoproteus majoris.

Methods

Turdus pilaris and Parus major naturally infected with lineages hPHYBOR04 and hPARUS1 of H. majoris, respectively, were wild-caught and the parasites were identified using microscopic examination of gametocytes and PCR-based testing. Bayesian phylogeny was used to determine relationships between H. majoris lineages. Exoerythrocytic stages (megalomeronts) were reported using histological examination and laser microdissection was applied to isolate single megalomeronts for genetic analysis. Culicoides impunctatus biting midges were experimentally exposed in order to follow sporogonic development of the lineage hPHYBOR04.

Results

Gametocytes of the lineage hPHYBOR04 are indistinguishable from those of the widespread lineage hPARUS1 of H. majoris, indicating that both of these lineages belong to the H. majoris group. Phylogenetic analysis supported this conclusion. Sporogony of the lineage hPHYBOR04 was completed in C. impunctatus biting midges. Morphologically similar megalomeronts were reported in internal organs of both avian hosts. These were big roundish bodies (up to 360 μm in diameter) surrounded by a thick capsule-like wall and containing irregularly shaped cytomeres, in which numerous merozoites developed. DNA sequences obtained from single isolated megalomeronts confirmed the identification of H. majoris.

Conclusions

Phylogenetic analysis identified a group of closely related H. majoris lineages, two of which are characterized not only by morphologically identical blood stages, but also complete sporogonic development in C. impunctatus and development of morphologically similar megalomeronts. It is probable that other lineages belonging to the same group would bear the same characters and phylogenies based on partial cytb gene could be used to predict life-cycle features in avian haemoproteids including vector identity and patterns of exoerythrocytic merogony. This study reports morphologically unique megalomeronts in naturally infected birds and calls for research on exoerythrocytic development of haemoproteids to better understand pathologies caused in avian hosts.
Strongyloidiasis in northern Vietnam: epidemiology, clinical characteristics and molecular diagnosis of the causal agent
Authors: Van De Nguyen , Minh Pham Ngoc , Van Duyet Le , Mas-Coma Santiago
Published: November 2019

Background

Strongyloidiasis is a health problem in Vietnam, but appropriate information is still limited. The aim of this study was to determine the prevalence, geographical distribution, epidemiological aspects, symptoms and other health indicators of Strongyloides stercoralis infections in patients from 27 provinces of northern Vietnam attending the Hanoi Medical University Hospital during 2016 and 2017.

Methods

Blood samples of 2000 patients were analyzed for S. stercoralis infection with an IgG ELISA test. Seroprevalence was analyzed by gender, age group, locality of origin (rural or urban areas) and symptoms. Stools from the seropositive patients were examined for the detection of worms which were subsequently used for species identification by morphology and rDNA ITS1 sequencing.

Results

A seroprevalence of 20% was detected, showing an increasing prevalence from young to older age groups but without significant gender difference. Seroprevalence was higher in rural areas than in urban areas, both in general and individually in all provinces without exception, and lower in the mountainous areas than in the large valley lowlands. The follow-up of the 400 patients showed eosinophilia in 100% of cases, diarrhoea in 64.5%, digestion difficulties in 58.0%, stomachache in 45.5%, stomach and duodenal ulcers in 44.5%, itching in 28.0% and fever in 9.5%. The prevalence of symptoms and signs were also higher in older age groups than in younger age groups. Worms were detected in stools of 10.5% of the patients. Sequencing of a 501-bp nuclear ribosomal DNA ITS1 fragment allowed for the verification of infection by Strongyloides stercoralis.

Conclusions

To our knowledge, this study is the largest survey of human strongyloidiasis in Vietnam so far and the first molecular identification of this nematode species in this country. Long-term chronicity may probably be usual in infected subjects, mainly in the older age groups.
Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels or predict imminent progression to symptomatic disease
Authors: Hafiz Waleed , Nori Rawad , Bregasi Ariana , Noamani Babak , Bonilla Dennisse , Lisnevskaia Larissa , Silverman Earl , Bookman Arthur A. M. , Johnson Sindhu R. , Landolt-Marticorena Carolina , Wither Joan
Published: November 2019

Background

Fatigue is a common symptom of systemic autoimmune rheumatic disease (SARD). Patients with SARD have a protracted pre-clinical phase during which progressive immunologic derangements occur culminating in disease. In this study, we sought to determine when fatigue develops and whether its presence correlates with inflammatory factors or predicts disease progression.

Methods

Anti-nuclear antibody (ANA)-negative healthy controls (HCs) and ANA-positive participants with no criteria, at least one clinical criteria (undifferentiated connective tissue disease, UCTD), or meeting SARD classification criteria were recruited. Fatigue was assessed using a modified version of the FACIT-F questionnaire and the presence of fibromyalgia determined using a questionnaire based on the modified 2010 ACR criteria. Peripheral blood expression of five IFN-induced genes was quantified by NanoString and the levels of IL-1β, IL-6, or TNF-α by ELISA.

Results

Fatigue was as prevalent and severe in individuals lacking SARD criteria as it was in UCTD and SARD. Overall, ~ 1/3 of ANA+ subjects met fibromyalgia criteria, with no differences between sub-groups. Although fatigue was more severe in these individuals, those lacking fibromyalgia remained significantly more fatigued than ANA− HC. However, even in these subjects, fatigue correlated with the widespread pain index and symptom severity scores on the fibromyalgia questionnaire. Fatigue was not associated with elevated cytokine levels in any of the ANA+ sub-groups and did not predict imminent disease progression.

Conclusions

Fatigue is common in ANA+ individuals lacking sufficient criteria for a SARD diagnosis, correlates with fibromyalgia-related symptoms, and is not associated with inflammation or predictive of disease progression.
Hypervirulent clade 2, ribotype 019/sequence type 67 Clostridioides difficile strain from Japan
Authors: Saito Ryoichi , Usui Yukino , Ayibieke Alafate , Nakajima Jun , Prah Isaac , Sonobe Kazunari , Aiso Yoshibumi , Ito Shiori , Itsui Yasuhiro , Hadano Yoshiro , Nukui Yoko , Koike Ryuji , Tohda Shuji
Published: November 2019

Background

Clostridioides difficile ribotype (RT) 019/sequence type (ST) 67 strains belong to a hypervirulent lineage closely related to RT027/ST1; however, limited data are available for hypervirulent clade 2 lineages in Japan. Herein, we report the draft genome of a C. difficile strain B18-123 belonging to clade 2, RT019/ST67 for the first time in Japan.

Results

The pathogenicity locus carried by B18-123 (19.6 kb) showed higher homology (97.29% nucleotide identity) with strain R20291 (RT027/ST1) than the reference strain 630 (RT012/ST54), and B18-123 harbored 8-nucleotide substitutions in tcdC. However, it did not contain an 18-base pair (bp) deletion or a single-bp deletion at position 117 in tcdC, which was identified in the previous strain R20291. A cytotoxicity assay revealed similar cytotoxicity levels between strains B18-123 and ATCC BAA-1870 (RT027/ST1). The B18-123 strain was found to be susceptible to metronidazole and vancomycin.

Conclusion

Our findings contribute to the further understanding of the characteristics of hypervirulent clade 2 including RT019/ST67 lineages.
Differential expression of CCR2 and CX3CR1 on CD16+ monocyte subsets is associated with asthma severity
Authors: Al-Rashoudi Reem , Moir Gillian , Al-Hajjaj Mohamed S. , Al-Alwan Monther M. , Wilson Heather M. , Crane Isabel J.
Published: November 2019

Background

Monocytes play an important role in immune and inflammatory diseases and monocyte subsets are predictors of disease in certain conditions. Expression of the chemokine receptors, CCR2 and CX3CR1 on monocyte subsets relates to their function and can be used in their characterization. Our objective was to determine whether CD14, CD16, CCR2 and CX3CR1 on monocyte subsets are potential indicators of asthma severity.

Methods

Blood samples were collected from Saudi Arabian patients with asthma and normal healthy individuals. Six-color flow-cytometry phenotypic analysis was used to identify human blood monocyte subsets, based on their expression of CD14 and CD16 following CD45 gating. Expression of CCR2 and CX3CR1 was analysed on classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) subsets and correlated with disease severity.

Results

We demonstrated a significant increase in percentage of total CD45-positive monocytes in the blood of patients with severe asthma, but the proportion of the individual monocyte subsets was not significantly changed when patients with mild, moderate and severe asthma were compared with healthy individuals. CD16 expression (mean fluorescence intensity, MFI) was decreased on intermediate and non-classical subsets in patients with severe asthma compared to healthy controls. CX3CR1 expression was also lower, with a lower percentage of cells expressing CX3CR1 in the non-classical CD14+CD16++ subset in all patients with asthma and this was inversely related to the percentage of cells expressing CCR2.

Conclusions

CCR2 expression on monocytes indicated a tendency toward more phagocytic monocytes in patients with asthma. The differential expression of CD16, CX3CR1 and CCR2 on monocyte subsets in peripheral blood indicates modulation of the inflammatory response and suggests a role for monocytes in asthma pathogenesis.
Eucalyptus oil poisoning: two case reports
Authors: Ittyachen Abraham M. , George Georgie Rajan , Radhakrishnan Meera , Joy Yetin
Published: November 2019

Background

Eucalyptus oil poisoning is rare in adults but is not that uncommon in children. The common side effects in children include depression in the level of consciousness, ataxia, seizures, and vomiting. Unlike in children, seizures are unusual in adult patients with eucalyptus oil poisoning. We report the cases of two patients with eucalyptus oil poisoning, both adults who unintentionally took eucalyptus oil and presented to the emergency room of our institution with seizures.

Case presentation

Two adult Indian men who unintentionally consumed eucalyptus oil presented to the emergency room of our institution with seizures. In both patients, arterial blood gas analysis showed the presence of severe metabolic acidosis. Both the patients were managed in the intensive care unit and received standard supportive care. Metabolic acidosis was corrected with intravenous bicarbonate infusion. They were successfully discharged on the fourth day.

Conclusions

All physicians should be aware of the toxic effects of eucalyptus oil, which is used often in daily life in India. Supportive care in an intensive care unit, including rapid correction of metabolic acidosis and adequate maintenance of hemodynamic parameters, will lead to a rapid recovery. Warning labels should be made mandatory on all products that contain eucalyptus oil.
Comparative analysis of cellular expression pattern of schizophrenia risk genes in human versus mouse cortex
Authors: Zhang Hai-Long , Long Jia-Wen , Han Wei , Wang Jiuzhou , Song Weichen , Lin Guan Ning , Yin Dong-Min
Published: November 2019

Background

Schizophrenia is a common psychiatric disease with high hereditary. The identification of schizophrenia risk genes (SRG) has shed light on its pathophysiological mechanisms. Mouse genetic models have been widely used to study the function of SRG in the brain with a cell type specific fashion. However, whether the cellular expression pattern of SRG is conserved between human and mouse brain is not thoroughly studied.

Results

We analyzed the single-cell transcription of 180 SRG from human and mouse primary visual cortex (V1). We compared the percentage of glutamatergic, GABAergic and non-neuronal cells that express each SRG between mouse and human V1 cortex. Thirty percent (54/180) of SRG had significantly different expression rate in glutamatergic neurons between mouse and human V1 cortex. By contrast, only 5.6% (10/180) of SRG showed significantly different expression in GABAergic neurons, which is similar with the ratio of SRG (15/180) with species difference in total cell populations. Strikingly, the percentage of non-neuronal cells expressing all SRG are indistinguishable between human and mouse V1 cortex. We further analyzed the biological significance of differentially expressed SRG by gene ontology. The species-different SRG in glutamatergic neurons are highly expressed in dendrite and axon. They are enriched in the biological process of response to stimulus. However, the differentially expressed SRG in GABAergic neurons are enriched in the regulation of organelle organization.

Conclusion

GABAergic neurons are more conserved in the expression of SRG than glutamatergic neurons while the non-neuronal cells show the species conservation for the expression of all SRG. It should be cautious to use mouse models to study those SRG which show different cellular expression pattern between human and mouse cortex.