Safety and Acceptability of Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data From Individual Patients.

BACKGROUND & AIMS: Diagnosis and surveillance of Barrett's esophagus (BE) and eosinophilic esophagitis (EoE) have become emerging public health issues. Cytosponge is a novel, minimally invasive esophageal cell collection device. We aimed to assess the data on safety and acceptability of this device. METHODS: We performed a patient-level review of 5 prospective trials assessing Cytosponge performance in patients with reflux disease, BE and EoE in primary and secondary care. Acceptability of Cytosponge and subsequent endoscopy were recorded with visual analogue scale (VAS), wherein 0 and 10 denoted lowest and highest acceptability. Median VAS scores were compared using a Mann-Whitney test. The number of attempts, failures in swallowing the device and occurrence of adverse events were analyzed. Risk factors for failure in swallowing were analyzed using a multivariate regression model. RESULTS: In total, 2672 Cytosponge procedures were performed, in 2418 individuals from 2008 through 2017. There were 2 adverse events related to the device: a minor pharyngeal bleed and a case of detachment (<1:2000). The median acceptability score for the Cytosponge was 6.0 (interquartile range [IQR], 5.0-8.0), which was higher than the score for endoscopy without sedation (median 5.0; IQR, 3.0-7.0; P < .001) and lower than the score for endoscopy with sedation (median 8.0; IQR, 5.0-9.0; P < .001). Nearly all patients (91.1%) successfully swallowed the Cytosponge, most on the first attempt (90.1%). Failure to swallow the device was more likely to occur in secondary care (odds ratio, 5.13; 95% CI, 1.48-17.79; P < .01). CONCLUSIONS: The Cytosponge test is a safe procedure with good acceptability ratings in a variety of health care settings

Genera of phytopathogenic fungi: GOPHY 1

Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 genera of phytopathogenic fungi: Bipolaris, Boeremia, Calonectria, Ceratocystis, Cladosporium, Colletotrichum, Coniella, Curvularia, Monilinia, Neofabraea, Neofusicoccum, Pilidium, Pleiochaeta, Plenodomus, Protostegia, Pseudopyricularia, Puccinia, Saccharata, Thyrostroma, Venturia and Wilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, nine new combinations, and four typifications of older names

Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance

Purpose Studies previously implicated PRRX1 in craniofacial development, including demonstration of murine Prrx1 expression in the pre-osteogenic cells of the cranial sutures. We investigated the role of heterozygous missense and loss-of-function variants in PRRX1 associated with craniosynostosis. Methods Trio-based genome, exome or targeted sequencing were used to screen PRRX1 in patients with craniosynostosis; immunofluorescence analyses were used to assess nuclear localization of wild-type and mutant proteins. Results Genome sequencing identified 2 of 9 sporadically affected individuals with syndromic/multisuture craniosynostosis who were heterozygous for rare/undescribed variants in PRRX1. Exome or targeted sequencing of PRRX1 revealed a further 9/1449 patients with craniosynostosis harboring deletions or rare heterozygous variants within the homeodomain. By collaboration, seven additional individuals (four families) were identified with putatively pathogenic PRRX1 variants. Immunofluorescence analyses showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localization. Of patients with variants considered likely pathogenic, bicoronal or other multi-suture synostosis was present in 11/17 (65% of the cases). Pathogenic variants were inherited from unaffected relatives in many instances, yielding a 12.5% penetrance estimate for craniosynostosis. Conclusion This work supports a key role for PRRX1 in cranial suture development and shows that haploinsufficiency of PRRX1 is a relatively frequent cause of craniosynostosis

Globalization intentions in tension: The case of Singapore

10.1177/0020872810371202International Social Work535671-68

The effects of ocular magnification on Spectralis spectral domain optical coherence tomography scan length

Purpose The purpose of this study was to assess the effects of incorporating individual ocular biometry measures of corneal curvature, refractive error, and axial length on scan length obtained using Spectralis spectral domain optical coherence tomography (SD-OCT). Methods Two SD-OCT scans were acquired for 50 eyes of 50 healthy participants, first using the Spectralis default keratometry (K) setting followed by incorporating individual mean-K values. Resulting scan lengths were compared to predicted scan lengths produced by image simulation software, based on individual ocular biometry measures including axial length. Results Axial length varied from 21.41 to 29.04 mm. Spectralis SD-OCT scan lengths obtained with default-K ranged from 5.7 to 7.3 mm, and with mean-K from 5.6 to 7.6 mm. We report a stronger correlation of simulated scan lengths incorporating the subject’s mean-K value (ρ = 0.926, P < 0.0005) compared to Spectralis default settings (ρ = 0.663, P < 0.0005). Conclusions Ocular magnification appears to be better accounted for when individual mean-K values are incorporated into Spectralis SD-OCT scan acquisition versus using the device’s default-K setting. This must be considered when taking area measurements and lateral measurements parallel to the retinal surface

A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

Background: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. Methods: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. Findings: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. Interpretation: Taken together, the COVID-19 NAb-testTM device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care

Pesticide residues with hazard classifications relevant to non-target species including humans are omnipresent in the environment and farmer residences

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring “no data available” situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical