Late solitary bone metastasis of a primary pulmonary synovial sarcoma with SYT-SSX1 translocation type: case report with a long follow-up

Primary synovial sarcoma outside its classical presentation in para-articular soft tissue of young patients is rare but regularly reported. One of the rarest primary locations is the lung. We describe a 73-year-old female patient who presented with a solitary malignant bone tumor 8years after the resection of a lung neoplasm. The bone tumor was classified as an osteosarcoma and the lung tumor as an atypical carcinoid tumor at their first respective diagnostic work-ups. The resection of the affected humerus with allograft and endoprosthesis implantation followed. Reevaluation of the tumor samples at the time of the local recurrence of the bone tumor 6years following the initial symptoms of the bone tumor lead to the reclassification of both specimens as synovial sarcomas. Both neoplasms contained the SYT-SSX1 type of the diagnostic translocation t(X;18) as detected by the reverse-transcription polymerase chain reaction analysis. The patient died 14years after the resection of the primary synovial sarcoma of the lung and 6years following the occurrence of the bone metastasis. This prolonged clinical course is uncommon for the SYT-SSX1 translocation, which, in other locations, is usually associated with an unfavorable prognosi

Inventory and changes of rock glacier creep speeds in Ile Alatau and Kungöy Ala-Too, northern Tien Shan, since the 1950s

This research has been supported by the European Research Council (ICEMASS (grant no. 320816)) and the European Space Agency (grant nos. 40001161196/15/I-NB, 4000123681/18/I-NB, 4000109873/14/I-NB, 4000127593/19/I-NS, and 4000127656/19/NL/FF/gp). This work was funded by the ESA projects GlobPermafrost (40001161196/15/I-NB), Permafrost_CCI (4000123681/18/I-NB), and Glaciers_CCI (4000109873/14/I-NB, 4000127593/19/I-NS) and the ESA EarthExplorer10 Mission Advisory Group (4000127656/19/NL/FF/gp) as well as by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant agreement no. 320816.Spatio-temporal patterns related to the viscous creep in perennially frozen sediments of rock glaciers in cold mountains have rarely been studied outside the densely populated European Alps. This study investigates the spatial and temporal variability of rock glacier movement in the Ile Alatau and Kungöy Ala-Too mountain ranges, northern Tien Shan, a region with particularly large and fast rock glaciers. Over the study region of more than 3000 km2, an inventory of slope movements was constructed using a large number of radar interferograms and high-resolution optical imagery. The inventory includes more than 900 landforms, of which around 550 were interpreted as rock glaciers. Out of the active rock glaciers inventoried, 45 are characterized by a rate of motion exceeding 100 cm/a. From these fast rock glaciers we selected six (Gorodetzky, Morenny, Archaly, Ordzhonikidze, Karakoram, and Kugalan Tash) and studied them in more detail using offset tracking between repeat aerial images and historical and modern high-resolution optical satellite data. Two of these rock glaciers showed a steady increase in decadal surface velocities from the 1950s onwards, with speeds being roughly 2 to 4 times higher in recent years compared to the 1950s and 1960s. Three rock glaciers showed similar accelerations over the last 1 to 2 decades but also phases of increased speeds in the 1960s. This development indicates a possible significant increase in current sediment and ice fluxes through rock glaciers and implies that their material transport in the region might gain geomorphodynamic importance relative to material transport by glaciers, assuming the latter decreases together with the regional glacier shrinkage. The study demonstrates how air and satellite image archives are exploited to construct one of the longest decennial times series of rock glacier speeds currently available. Our results are in line with findings from Europe about rock glacier speeds increasing with atmospheric warming and underline local variability of such an overall response.Publisher PDFPeer reviewe

Digital multiplex ligation assay for highly multiplexed screening of β-lactamase-encoding genes in bacterial isolates

Increasing incidence of antibiotic resistance in clinical and environmental settings calls for increased scalability in their surveillance. Current screening technologies are limited by the number of samples and genes that can easily be screened. We demonstrate here digital multiplex ligation assay (dMLA) as a low-cost targeted genomic detection workflow capable of highly-parallel screening of bacterial isolates for multiple target gene regions simultaneously. Here, dMLA is used for simultaneous detection of 1187 β-lactamase-encoding genes, including extended spectrum β-lactamase (ESBL) genes, in 74 bacterial isolates. We demonstrate dMLA as a light-weight and cost-efficient workflow which provides a highly scalable tool for antimicrobial resistance surveillance and is also adaptable to genetic screening applications beyond antibiotic resistance

Glucocorticoid hypersensitivity as a rare but potentially fatal side effect of paediatric asthma treatment: a case report

<p>Abstract</p> <p>Introduction</p> <p>Immediate-type hypersensitivity to glucocorticosteroids is rare but well known among allergists. Surprisingly, very few reports of glucocorticosteroid hypersensitivity in children exist although glucocorticosteroid treatment is particularly common in this age group.</p> <p>Case presentation</p> <p>We report the case of a 2-year-old boy who developed generalized urticaria, facial angio-oedema, nausea and severe dyspnoea after intravenous application of prednisolone-21-hydrogen succinate. Skin prick testing with prednisolone-21-hydrogen succinate elicited a positive result; no reactions were observed to prednisone, betamethasone or dexamethasone. While fluorescence enzyme immunoassay analysis revealed no specific IgE antibodies against prednisolone-21-hydrogen succinate, CD63-based basophil activation testing with the culprit drug prednisolone-21-hydrogen succinate was positive. In contrast, additional incubation of basophils with prednisone, betamethasone and dexamethasone did not elicit any significant response. Hence, we performed an oral provocation test with betamethasone and a titrated intravenous dexamethasone challenge. As both drugs were tolerated without any complications they were recommended for future treatment.</p> <p>Conclusion</p> <p>In a child with confirmed immediate-type hypersensitivity to glucocorticosteroids, it is still not possible to predict which glucocorticosteroid might be tolerated by solely relying on clinical history or results of skin and <it>in vitro </it>testing. Therefore, incremental glucocorticosteroid challenges under standardized clinical conditions remain necessary in order to facilitate a patient-tailored emergency treatment and to avoid severe reactions to glucocorticosteroids in these patients.</p

Health risks for sanitation service workers along a container-based urine collection system and resource recovery value chain

Container-based sanitation (CBS) within a comprehensive service system value chain offers a low-cost sanitation option with potential for revenue generation but may increase microbial health risks to sanitation service workers. This study assessed occupational exposure to rotavirus and Shigella spp. during CBS urine collection and subsequent struvite fertilizer production in eThekwini, South Africa. Primary data included high resolution sequences of hand-object contacts from annotated video and measurement of fecal contamination from urine and surfaces likely to be contacted. A stochastic model incorporated chronological surface contacts, pathogen concentrations in urine, and literature data on transfer efficiencies of pathogens to model pathogen concentrations on hands and risk of infection from hand-to-mouth contacts. The probability of infection was highest from exposure to rotavirus during urine collection (∼10; -1; ) and struvite production (∼10; -2; ), though risks from Shigella spp. during urine collection (∼10; -3; ) and struvite production (∼10; -4; ) were non-negligible. Notably, risk of infection was higher during urine collection than during struvite production due to contact with contaminated urine transport containers. In the scale-up of CBS, disinfection of urine transport containers is expected to reduce pathogen transmission. Exposure data from this study can be used to evaluate the effectiveness of measures to protect sanitation service workers

Comparison of alterations of chromosome 17 in carcinoma of the ovary and of the breast

 Breast and ovarian carcinomas share a region of allelic loss on chromosome 17q25, suggesting that these tumours may arise by similar molecular pathways. We analysed paraffin-embedded tissues from 84 sporadic ovarian carcinomas and 42 sporadic infiltrating ductal carcinomas of the breast for abnormalities on chromosome 17. Loss of heterozygosity (LOH) of at least one informative marker on 17q was identified in 49 of 82 (60%) ovarian carcinomas, as against only 6 of 40 (15%) informative breast carcinomas ( P <0.0001). In ovarian carcinoma, LOH was most commonly observed for GH on 17q23 (56%), and was also frequently observed at 17q21 (46%). In contrast, LOH of D17S1330/CTT16 on 17q25 was observed in only 19% of ovarian tumours. LOH in breast carcinomas was most frequently observed at 17q21 (16%), less frequently at 17q23 (7%) and not identified at all at 17q25 in any breast cancers. Immunohistochemical analysis demonstrated overexpression of the p53 gene product in 38 of 84 (45%) ovarian carcinomas, as against 10 of 42 (24%) breast carcinomas ( P =0.0195). p53 immunoreactivity was significantly associated with LOH in ovarian and breast cancers. Immunohistochemical expression of HER2/ neu was observed in 6 of 84 (7%) ovarian and 3 of 42 (7%) breast carcinomas. There was no relationship between HER2/ neu immunoreactivity and LOH. Although sporadic carcinomas of breast and ovary share some regions of allelic loss on chromosome 17q, differences in other alterations on this chromosome suggest divergent pathways of tumour development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42250/1/428-434-6-517_94340517.pd

Inferring transmission fitness advantage of SARS-CoV-2 variants of concern from wastewater samples using digital PCR, Switzerland, December 2020 through March 2021

BackgroundThroughout the COVID-19 pandemic, SARS-CoV-2 genetic variants of concern (VOCs) have repeatedly and independently arisen. VOCs are characterised by increased transmissibility, increased virulence or reduced neutralisation by antibodies obtained from prior infection or vaccination. Tracking the introduction and transmission of VOCs relies on sequencing, typically whole genome sequencing of clinical samples. Wastewater surveillance is increasingly used to track the introduction and spread of SARS-CoV-2 variants through sequencing approaches.AimHere, we adapt and apply a rapid, high-throughput method for detection and quantification of the relative frequency of two deletions characteristic of the Alpha, Beta, and Gamma VOCs in wastewater.MethodsWe developed drop-off RT-dPCR assays and an associated statistical approach implemented in the R package WWdPCR to analyse temporal dynamics of SARS-CoV-2 signature mutations (spike Δ69-70 and ORF1a Δ3675-3677) in wastewater and quantify transmission fitness advantage of the Alpha VOC.ResultsBased on analysis of Zurich wastewater samples, the estimated transmission fitness advantage of SARS-CoV-2 Alpha based on the spike Δ69-70 was 0.34 (95% confidence interval (CI): 0.30-0.39) and based on ORF1a Δ3675-3677 was 0.53 (95% CI: 0.49-0.57), aligning with the transmission fitness advantage of Alpha estimated by clinical sample sequencing in the surrounding canton of 0.49 (95% CI: 0.38-0.61).ConclusionDigital PCR assays targeting signature mutations in wastewater offer near real-time monitoring of SARS-CoV-2 VOCs and potentially earlier detection and inference on transmission fitness advantage than clinical sequencing. Keywords: B.1.1.7; SARS-CoV-2; digital PCR; drop-off assays; transmission fitness

Digital multiplex ligation assay for highly multiplexed screening of beta-lactamase-encoding genes in bacterial isolates

Increasing incidence of antibiotic resistance in clinical and environmental settings calls for increased scalability in their surveillance. Current screening technologies are limited by the number of samples and genes that can easily be screened. We demonstrate here digital multiplex ligation assay (dMLA) as a low-cost targeted genomic detection workflow capable of highly-parallel screening of bacterial isolates for multiple target gene regions simultaneously. Here, dMLA is used for simultaneous detection of 1187 beta-lactamase-encoding genes, including extended spectrum beta-lactamase (ESBL) genes, in 74 bacterial isolates. We demonstrate dMLA as a light-weight and cost-efficient workflow which provides a highly scalable tool for antimicrobial resistance surveillance and is also adaptable to genetic screening applications beyond antibiotic resistance.Tamminen et al. develop a digital multiplex ligation assay (dMLA) that enables the detection of bacterial isolates using probe hybridization and ligation-based assays with next-generation sequencing. Their method can be applied in high-throughput and affordable screening for antibiotic resistance

Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection