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1.
J Hosp Infect ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782054

ABSTRACT

BACKGROUND: Intravenous (IV) antibiotic use in secondary care in England is widespread. Timely appropriate intravenous to oral switch (IVOS) has the potential to deliver significant clinical and operational benefits. To date, antimicrobial stewardship (AMS) efforts around IVOS have not focused on the nursing staff who administer antibiotics, which represents a significant gap in AMS programmes. AIMS: To determine the involvement of bedside nurses in acute trusts in the Midlands region of England in IVOS in their organisations and describe their views regarding how to improve IVOS. METHODS: An anonymous self-administered mixed-methods online survey was developed and distributed to nursing staff in acute trusts via antimicrobial stewardship networks between March and May 2023. Quantitative data was analysed to describe participant demographics and behaviours, whereas barriers and enablers to IVOS were explored through thematic content analysis of responses to open-ended questions. FINDINGS: 545 nursing staff responded to the survey. The majority (65.3%) routinely suggested IVOS to clinicians, despite only 50.6% being aware of local IVOS policies. One third (34.7%) did not suggest IVOS, relying on doctors, believing their patients needed IV treatment, or lacked knowledge and skills to request IVOS. Content analysis of suggestions for improving the rate of IVOS proposed three major themes (People, Process, System) and identified that education and training, improved confidence and interprofessional relationships, and prompts were important drivers. CONCLUSIONS: Nursing staff suggest IVOS to other clinicians, but more education and resources are needed to enable and empower them in this role.

4.
Sci Total Environ ; 901: 165862, 2023 Nov 25.
Article in English | MEDLINE | ID: mdl-37541500

ABSTRACT

Acanthamoeba is an opportunistic free-living heterotrophic protist that is the most predominant amoeba in diverse ecological habitats. Acanthamoeba causes amoebic keratitis (AK), a painful and potentially blinding corneal infection. Major risk factors for AK have been linked to non-optimal contact lens hygiene practices and Acanthamoeba contamination of domestic and recreational water. This study investigated the incidence and seasonal variation of Acanthamoeba spp. within coastal lagoons located on the eastern coast of Australia and then examined the association between Acanthamoeba and water abiotic factors and bacterial species within the water. Water samples were collected from four intermittently closed and open lagoons (ICOLLs) (Wamberal, Terrigal, Avoca and Cockrone) every month between August 2019 to July 2020 except March and April. qPCR was used to target the Acanthamoeba 18S rRNA gene, validated by Sanger sequencing. Water abiotic factors were measured in situ using a multiprobe metre and 16S rRNA sequencing (V3-V4) was performed to characterise bacterial community composition. Network analysis was used to gauge putative associations between Acanthamoeba incidence and bacterial amplicon sequence variants (ASVs). Among 206 water samples analysed, 79 (38.3%) were Acanthamoeba positive and Acanthamoeba level was significantly higher in summer compared with winter, spring, or autumn (p = 0.008). More than 50% (23/45) water samples of Terrigal were positive for Acanthamoeba which is a highly urbanised area with extensive recreational activities while about 32% (16/49) samples were positive from Cockrone that is the least impacted lagoon by urban development. All sequenced strains belonged to the pathogenic genotype T4 clade except two which were of genotype clades T2 and T5. Water turbidity, temperature, intl1 gene concentration, and dissolved O2 were significantly associated with Acanthamoeba incidence (p < 0.05). The ASVs level of cyanobacteria, Pseudomonas spp., Candidatus spp., and marine bacteria of the Actinobacteria phylum and Acanthamoeba 18S rRNA genes were positively correlated (Pearson's r ≥ 0.14). The presence of Acanthamoeba spp. in all lagoons, except Wamberal, was associated with significant differences in the composition of bacterial communities (beta diversity). The results of this study suggest that coastal lagoons, particularly those in urbanised regions with extensive water recreational activities, may pose an elevated risk to human health due to the relatively high incidence of pathogenic Acanthamoeba in the summer. These findings underscore the importance of educating the public about the rare yet devastating impact of AK on vision and quality of life, highlighting the need for collaborative efforts between public health officials and educators to promote awareness and preventive measures, especially focusing lagoons residents and travellers.

5.
Emerg Infect Dis ; 29(5): 929-936, 2023 05.
Article in English | MEDLINE | ID: mdl-36972709

ABSTRACT

To compare SARS-CoV-2 antibody seroprevalence among children with seropositive confirmed COVID-19 case counts (case ascertainment by molecular amplification) in Colorado, USA, we conducted a cross-sectional serosurvey during May-July 2021. For a convenience sample of 829 Colorado children, SARS-CoV-2 seroprevalence was 36.7%, compared with prevalence of 6.5% according to individually matched COVID-19 test results reported to public health. Compared with non-Hispanic White children, seroprevalence was higher among Hispanic, non-Hispanic Black, and non-Hispanic other race children, and case ascertainment was significantly lower among Hispanic and non-Hispanic Black children. This serosurvey accurately estimated SARS-CoV-2 prevalence among children compared with confirmed COVID-19 case counts and revealed substantial racial/ethnic disparities in infections and case ascertainment. Continued efforts to address racial and ethnic differences in disease burden and to overcome potential barriers to case ascertainment, including access to testing, may help mitigate these ongoing disparities.


Subject(s)
COVID-19 , Humans , Child , COVID-19/epidemiology , SARS-CoV-2 , Colorado/epidemiology , Seroepidemiologic Studies , Cross-Sectional Studies
6.
Nat Biotechnol ; 41(10): 1457-1464, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36747096

ABSTRACT

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine.

7.
PLoS One ; 18(1): e0280865, 2023.
Article in English | MEDLINE | ID: mdl-36706131

ABSTRACT

Multiple approaches can be used to communicate public health messages through mass media. It is unclear which approaches are superior for meeting the needs of the general community along with vulnerable population subgroups. To compare different public health strategy communication approaches for influencing the COVID-safe behavioural intentions of both community and vulnerable population subgroups. This study will conduct three concurrent 'helix' randomised controlled trials with Latin square sequencing and factorial intervention allocation to assess the effectiveness of different communication strategies amongst the Australian general community and six subgroups that are considered vulnerable to contracting, transmitting or experiencing severe consequences of COVID-19 infection. Communication approaches being compared include: the format of communication (written versus video), who is providing information (general practitioner, politician, community-representative), what is said and how it is delivered (direct information provision versus conversational approach) and the visual content of video messaging (animation versus 'talking head'). Recruited participants will be randomly allocated to receive a specific combination of health messaging strategies using six different COVID-19 context areas. Outcomes will be assessed in a survey using behaviour intention questions, and questions surrounding level of agreement with feeling represented in the health messaging strategy. These trials will use a unique research approach to provide an experimental evidence base to help guide development of impactful and inclusive COVID-19 and related public health messaging. All three trials are registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Trial 1: Update and impact of Government recommendations about COVID-19 (coronavirus)-Stage 3, Trial 1, vulnerable subgroup populations (ACTRN12622000606785). Trial 2: Update and impact of Government recommendations about COVID-19 (coronavirus)-Stage 3, Trial 2, community group (ACTRN12622000605796). Trial 3: Update and impact of Government recommendations about COVID-19 (coronavirus)-Stage 3, Trial 3, What communication strategy is most effective for both vulnerable and community group populations? (ACTRN12622000617763).


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Australia/epidemiology , Communication , Surveys and Questionnaires , Randomized Controlled Trials as Topic
8.
Bioinformatics ; 39(1)2023 01 01.
Article in English | MEDLINE | ID: mdl-36484688

ABSTRACT

MOTIVATION: Over 300 000 protein-protein interaction (PPI) pairs have been identified in the human proteome and targeting these is fast becoming the next frontier in drug design. Predicting PPI sites, however, is a challenging task that traditionally requires computationally expensive and time-consuming docking simulations. A major weakness of modern protein docking algorithms is the inability to account for protein flexibility, which ultimately leads to relatively poor results. RESULTS: Here, we propose DockNet, an efficient Siamese graph-based neural network method which predicts contact residues between two interacting proteins. Unlike other methods that only utilize a protein's surface or treat the protein structure as a rigid body, DockNet incorporates the entire protein structure and places no limits on protein flexibility during an interaction. Predictions are modeled at the residue level, based on a diverse set of input node features including residue type, surface accessibility, residue depth, secondary structure, pharmacophore and torsional angles. DockNet is comparable to current state-of-the-art methods, achieving an area under the curve (AUC) value of up to 0.84 on an independent test set (DB5), can be applied to a variety of different protein structures and can be utilized in situations where accurate unbound protein structures cannot be obtained. AVAILABILITY AND IMPLEMENTATION: DockNet is available at https://github.com/npwilliams09/docknet and an easy-to-use webserver at https://biosig.lab.uq.edu.au/docknet. All other data underlying this article are available in the article and in its online supplementary material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Algorithms , Neural Networks, Computer , Humans , Proteome , Pharmacophore , Area Under Curve , Computational Biology
9.
Ann Otol Rhinol Laryngol ; 132(10): 1233-1248, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36582148

ABSTRACT

OBJECTIVES: Endovascular embolization has emerged as an effective treatment for intractable epistaxis. This systematic review and meta-analysis aimed to calculate the rates of success, rebleeds, and complications and to identify the etiologies and complications of patients who undergo endovascular embolization. METHODS: This systematic review and meta-analysis was conducted per the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were extracted from Scopus, PubMed, Web of Science, and Cochrane Central and were filtered by a systematic review process using Rayyan software. A random-effects model was used to quantify the rates success, rebleeds, and complications. RESULTS: Forty-two studies were included, totaling 1660 patients. The pooled success rate was 89% (95% confidence interval [CI] 86%-92%) and the pooled rebleed rate was 19% (95% CI 16%-22%). The pooled minor complication rate was 18% (95% CI 11%-27%). The most common major complication was soft tissue necrosis followed by stroke. The most common minor complication was facial pain. No minor complications were reported to be permanent. Of the patients who failed initial embolization, 42% underwent repeat embolization and 34% underwent surgical arterial ligation. CONCLUSIONS: Endovascular embolization is an effective treatment for intractable epistaxis. The decision to perform embolization should be carefully weighed given the rare but significant major complications.


Subject(s)
Embolization, Therapeutic , Epistaxis , Humans , Epistaxis/etiology , Epistaxis/therapy , Treatment Outcome , Embolization, Therapeutic/adverse effects , Ligation/adverse effects
10.
Environ Res ; 219: 115144, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36584839

ABSTRACT

Marine water temperatures are increasing globally, with eastern Australian estuaries warming faster than predicted. There is growing evidence that this rapid warming of coastal waters is increasing the abundance and virulence of pathogenic members of the Vibrionaceae, posing a significant health risk to both humans and aquatic organisms. Fish disease, notably outbreaks of emerging pathogens in response to environmental perturbations such as heatwaves, have been recognised in aquaculture settings. Considerably less is known about how rising sea surface temperatures will impact the microbiology of wild fish populations, particularly those within estuarine systems that are more vulnerable to warming. We used a combination of Vibrio-specific quantitative PCR and amplicon sequencing of the 16S rRNA and hsp60 genes to examine seawater and fish (Pelates sexlineatus) gut microbial communities across a quasi-natural experimental system, where thermal pollution from coal-fired power stations creates a temperature gradient of up to 6 °C, compatible with future predicted temperature increases. At the warmest site, fish hindgut microbial communities were in a state of dysbiosis characterised by shifts in beta diversity and a proliferation (71.5% relative abundance) of the potential fish pathogen Photobacterium damselae subsp. damselae. Comparable patterns were not identified in the surrounding seawater, indicating opportunistic proliferation within estuarine fish guts under thermal stress. A subsequent evaluation of predicted future warming-related risk due to pathogenic Vibrionaceae in temperate estuarine fish demonstrated that warming is likely to drive opportunistic pathogen increases in the upper latitudinal range of this estuarine fish, potentially impacting adaptations to future warming. These findings represent a breakthrough in our understanding of the dynamics of emerging pathogens in populations of wild aquatic organisms within environments likely to experience rapid warming under future climate change.


Subject(s)
Vibrionaceae , Animals , Humans , Aquatic Organisms , Australia , Dysbiosis/veterinary , Estuaries , Fishes , RNA, Ribosomal, 16S/genetics , Temperature , Vibrionaceae/genetics , Water , Intestines
11.
Environ Pollut ; 314: 120222, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36150623

ABSTRACT

Estuaries are critical habitats subject to a range of stressors requiring effective management. Microbes are gaining recognition as effective environmental indicators, however, the response of host associated communities to stressors remains poorly understood. We examined microbial communities from seawater, sediments and the estuarine fish Pelates sexlineatus, in Australia's largest urbanised estuary, and hypothesised that anthropogenic contamination would be reflected in the microbiology of these sample types. The human faecal markers Lachno3 and HF183 were not detected, indicating negligible influence of sewage, but a gradient in copy numbers of the class 1 integron (intI-1), which is often used as a marker for anthropogenic contamination, was observed in sediments and positively correlated with metal concentrations. While seawater communities were not strongly driven by metal contamination, shifts in the diversity and composition of the fish gut microbiome were observed, with statistical links to levels of metal contamination (F2, 21 = 1.536, p < 0.01). Within the fish gut microbiome, we further report increased relative abundance of amplicon sequence variants (ASVs; single inferred DNA sequences obtained in sequencing) identified as metal resistant and potentially pathogenic genera, as well as those that may have roles in inflammation. These results demonstrate that microbial communities from distinct habitats within estuarine systems have unique response to stressors, and alterations of the fish gut microbiome may have implications for the adaptation of estuarine fish to legacy metal contamination.


Subject(s)
Estuaries , Gastrointestinal Microbiome , Animals , Humans , Environmental Monitoring/methods , Sewage , Metals/toxicity , Metals/analysis , Fishes
12.
Front Public Health ; 10: 912188, 2022.
Article in English | MEDLINE | ID: mdl-35910912

ABSTRACT

Methods of communications and the nature of messaging are critically important in influencing public behavior. The COVID-19 pandemic has resulted in major disruptions to all aspects of life globally and has triggered multiple approaches of health messaging to the general public to communicate COVID-19 preventative measures. This study aimed to identify: (1) differences between age groups in the main avenues used by people to obtain COVID-19 related information; and (2) whether age and information sources were associated with correct interpretation of government messaging relating to how people understand or interpret the terms "self-isolation" and "social distancing." An online survey was conducted in 2020. Participants were aged over 18 years and grouped into age group decades. Differences in sources of COVID-19 information were compared visually between age groups. Logistic regression was used to determine whether age and each of the various methods of communication of COVID-19 information were independently associated with correct response to the self-isolation, or the social distancing statements. There were 3,300 survey respondents 85% female; age sub-groups: 18-29 (7.4%); 30-39 (10.6%); 40-49 (17.6%); 50-59 (22.9%); 60-69 (25.9%); 70-79 (13.9%); and 80+ (1.7%). People accessed public health messaging information from a wide variety of sources that changed as they aged (e.g., older people were more likely to be exposed to COVID-19 information via television news programs and less likely via social media platforms). Age was frequently associated with whether the message key terms were interpreted correctly or incorrectly, but in some cases, it promoted more correct responses whereas in others, fewer correct responses. There was no difference between being exposed to COVID-19 information via mainstream media, compared with social media, or compared with Government sources of information, in terms of whether COVID-19 messages were interpreted correctly. In order to improve future public health messaging, there is a need for multiple avenues of communication to meet the needs and preferences across and within age groups. Further investigation is warranted into the clarity of the content and method of delivery of public health messages, to ensure optimal understanding of public health messages by vulnerable populations and across the community.


Subject(s)
COVID-19 , Social Media , Adult , Aged , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Physical Distancing , SARS-CoV-2
13.
Am J Otolaryngol ; 43(5): 103582, 2022.
Article in English | MEDLINE | ID: mdl-35988367

ABSTRACT

PURPOSE: To determine if tranexamic acid (TXA) reduces the need for operative re-cauterization in the setting of a post-tonsillectomy hemorrhage (PTH). METHODS: A retrospective chart review was performed on 1428 adult and pediatric patients who underwent tonsillectomy over a two-year period at a tertiary care hospital with continuous otolaryngologic coverage. Collected data of PTH patients included age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, length of stay (LOS), the requirement of a blood transfusion, day of PTH, TXA usage and route, complications from TXA administration, and TXA failure requiring operative intervention. RESULTS: The incidence of pediatric PTH during the study period was 5.7 %. Twenty-seven out of fifty-five PTH patients received topical, nebulized, or intravenous TXA. No adverse effects were noted with TXA administration. TXA usage provided resolution of the PTH in 77.8 % of patients. No significant differences were found in age, gender, BMI, LOS, ASA classification, rate of blood transfusion, or TXA treatment modality between the patients that received TXA and those that did not. CONCLUSIONS: Treatment of PTH with TXA appears to reduce the need for operative control of PTH. In the setting of reducing operative risk, improving health care utilization, or in a setting without immediate otolaryngologic provider coverage, the role of TXA is promising. Further larger clinical or multi-institution studies are needed to determine the efficacy of TXA, its route of administration, and its optimal dosage. LEVEL OF EVIDENCE: Level 4, Retrospective cohort study.


Subject(s)
Antifibrinolytic Agents , Tonsillectomy , Tranexamic Acid , Adult , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/therapeutic use , Blood Loss, Surgical , Child , Humans , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/prevention & control , Retrospective Studies , Tonsillectomy/adverse effects , Tranexamic Acid/adverse effects , Tranexamic Acid/therapeutic use
14.
Water Res ; 218: 118534, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35537251

ABSTRACT

Urbanised beaches are regularly impacted by faecal pollution, but management actions to resolve the causes of contamination are often obfuscated by the inability of standard Faecal Indicator Bacteria (FIB) analyses to discriminate sources of faecal material or detect other microbial hazards, including antibiotic resistance genes (ARGs). We aimed to determine the causes, spatial extent, and point sources of faecal contamination within Rose Bay, a highly urbanised beach within Sydney, Australia's largest city, using molecular microbiological approaches. Sampling was performed across a network of transects originating at 9 stormwater drains located on Rose Bay beach over the course of a significant (67.5 mm) rainfall event, whereby samples were taken 6 days prior to any rain, on the day of initial rainfall (3.8 mm), three days later after 43 mm of rain and then four days after any rain. Quantitative PCR (qPCR) was used to target marker genes from bacteria (i.e., Lachnospiraceae and Bacteroides) that have been demonstrated to be specific to human faeces (sewage), along with gene sequences from Heliobacter and Bacteriodes that are specific to bird and dog faeces respectively, and ARGs (sulI, tetA, qnrS, dfrA1 and vanB). 16S rRNA gene amplicon sequencing was also used to discriminate microbial signatures of faecal contamination. Prior to the rain event, low FIB levels (mean: 2.4 CFU/100 ml) were accompanied by generally low levels of the human and animal faecal markers, with the exception of one transect, potentially indicative of a dry weather sewage leak. Following 43 mm of rain, levels of both human faecal markers increased significantly in stormwater drain and seawater samples, with highest levels of these markers pinpointing several stormwater drains as sources of sewage contamination. During this time, sewage contamination was observed up to 1000 m from shore and was significantly and positively correlated with often highly elevated levels of the ARGs dfrA1, qnrS, sulI and vanB. Significantly elevated levels of the dog faecal marker in stormwater drains at this time also indicated that rainfall led to increased input of dog faecal material from the surrounding catchment. Using 16S rRNA gene amplicon sequencing, several indicator taxa for stormwater contamination such as Arcobacter spp. and Comamonadaceae spp. were identified and the Bayesian SourceTracker tool was used to model the relative impact of specific stormwater drains on the surrounding environment, revealing a heterogeneous contribution of discrete stormwater drains during different periods of the rainfall event, with the microbial signature of one particular drain contributing up to 50% of bacterial community in the seawater directly adjacent. By applying a suite of molecular microbiological approaches, we have precisely pinpointed the causes and point-sources of faecal contamination and other associated microbiological hazards (e.g., ARGs) at an urbanised beach, which has helped to identify the most suitable locations for targeted management of water quality at the beach.


Subject(s)
Sewage , Water Microbiology , Animals , Bacteria/genetics , Bayes Theorem , Dogs , Environmental Monitoring , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Sewage/microbiology , Water Pollution/analysis , Water Quality
15.
Environ Pollut ; 307: 119456, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35561796

ABSTRACT

Anthropogenic waste streams can be major sources of antibiotic resistant microbes within the environment, creating a potential risk to public health. We examined patterns in the occurrence of a suite of antibiotic resistance genes (ARGs) and their links to enteric bacteria at a popular swimming beach in Australia that experiences intermittent contamination by sewage, with potential points of input including stormwater drains and a coastal lagoon. Samples were collected throughout a significant rainfall event (40.8 mm over 3 days) and analysed using both qPCR and 16S rRNA amplicon sequencing. Before the rainfall event, low levels of faecal indicator bacteria and a microbial source tracking human faeces (sewage) marker (Lachno3) were observed. These levels increased over 10x following rainfall. Within lagoon, drain and seawater samples, levels of the ARGs sulI, dfrA1 and qnrS increased by between 1 and 2 orders of magnitude after 20.4 mm of rain, while levels of tetA increased by an order of magnitude after a total of 40.8 mm. After 40.8 mm of rain sulI, tetA and qnrS could be detected 300 m offshore with levels remaining high five days after the rain event. Highest levels of sewage markers and ARGs were observed adjacent to the lagoon (when opened) and in-front of the stormwater drains, pinpointing these as the points of ARG input. Significant positive correlations were observed between all ARGs, and a suite of Amplicon Sequence Variants that were identified as stormwater drain indicator taxa using 16S rRNA amplicon sequencing data. Of note, some stormwater drain indicator taxa, which exhibited correlations to ARG abundance, included the human pathogens Arcobacter butzleri and Bacteroides fragilis. Given that previous research has linked high levels of ARGs in recreationally used environments to antimicrobial resistant pathogen infections, the observed patterns indicate a potentially elevated human health risk at a popular swimming beach following significant rainfall events.


Subject(s)
Anti-Bacterial Agents , Sewage , Australia , Drug Resistance, Microbial/genetics , Environmental Monitoring , Genes, Bacterial , Humans , RNA, Ribosomal, 16S/genetics , Seawater , Sewage/microbiology
16.
Nat Methods ; 19(5): 554-559, 2022 05.
Article in English | MEDLINE | ID: mdl-35501386

ABSTRACT

DNA-based points accumulation for imaging in nanoscale topography (DNA-PAINT) is a powerful super-resolution microscopy method that can acquire high-fidelity images at nanometer resolution. It suffers, however, from high background and slow imaging speed, both of which can be attributed to the presence of unbound fluorophores in solution. Here we present two-color fluorogenic DNA-PAINT, which uses improved imager probe and docking strand designs to solve these problems. These self-quenching single-stranded DNA probes are conjugated with a fluorophore and quencher at the terminals, which permits an increase in fluorescence by up to 57-fold upon binding and unquenching. In addition, the engineering of base pair mismatches between the fluorogenic imager probes and docking strands allowed us to achieve both high fluorogenicity and the fast binding kinetics required for fast imaging. We demonstrate a 26-fold increase in imaging speed over regular DNA-PAINT and show that our new implementation enables three-dimensional super-resolution DNA-PAINT imaging without optical sectioning.


Subject(s)
DNA , Fluorescent Dyes , Microscopy, Fluorescence/methods
17.
J Pediatr Hematol Oncol ; 44(8): 486-488, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35426856

ABSTRACT

Ewing sarcoma is an EWS-ETS family member-driven malignancy that most commonly arises from bone. Cutaneous Ewing sarcoma is a rare variant which harbors an EWS-ETS family fusion but demonstrates an immunohistochemical staining pattern distinct from classic Ewing tumors. EWSR1 fluorescence in situ hybridization testing interpretation can be challenging in the setting of cutaneous Ewing sarcoma, making an integrated histologic and sequencing approach key for an accurate diagnosis. Here, we report a pediatric patient with a history of neuroblastoma treated with surgery only that developed a cutaneous nodule and was diagnosed with cutaneous Ewing sarcoma as a second primary cancer.


Subject(s)
Bone Neoplasms , Neoplasms, Second Primary , Sarcoma, Ewing , Humans , Child , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/genetics , In Situ Hybridization, Fluorescence , Oncogene Proteins, Fusion/genetics , RNA-Binding Protein EWS/genetics , Family , Bone Neoplasms/diagnosis , Bone Neoplasms/genetics , Bone Neoplasms/pathology
18.
Development ; 149(1)2022 01 01.
Article in English | MEDLINE | ID: mdl-34878097

ABSTRACT

Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation is incompletely understood. Set2, which deposits H3K36me3 modifications, is required for GSC differentiation during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (Msl3) and histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate GSC differentiation in female Drosophila. Msl3, acting independently of the rest of the male-specific lethal complex, promotes transcription of genes, including a germline-enriched ribosomal protein S19 paralog RpS19b. RpS19b upregulation is required for translation of RNA-binding Fox protein 1 (Rbfox1), a known meiotic cell cycle entry factor. Thus, Msl3 regulates GSC differentiation by modulating translation of a key factor that promotes transition to an oocyte fate.


Subject(s)
Drosophila Proteins/metabolism , Nuclear Proteins/metabolism , Oogenesis , Oogonia/metabolism , Transcription Factors/metabolism , Animals , Drosophila Proteins/genetics , Drosophila melanogaster , Female , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Meiosis , Nuclear Proteins/genetics , Oogonia/cytology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Transcription Factors/genetics
19.
Am J Clin Pathol ; 157(6): 858-862, 2022 06 07.
Article in English | MEDLINE | ID: mdl-34871340

ABSTRACT

OBJECTIVES: We investigate the number of autopsy reports that did or did not document the presence or absence of the gallbladder or appendix or document abdominal scars in patients following cholecystectomy or appendectomy. We also report gallbladder and appendix pathology at autopsy. METHODS: Autopsy reports from patients 18 years or older autopsied at a community teaching hospital between January 1, 2009, and December 31, 2018 were reviewed. Nonabdominal autopsies were excluded. Histopathologic examination of the gallbladder and appendix was only performed if gross pathology was seen. RESULTS: Of the 385 autopsies studied, 48 (12.5%) had cholecystectomies, of which 6 (12.5%) did not document abdominal scars. Sixty-two (16.1%) had appendectomies, of which 12 (19.4%) did not document abdominal scars. The presence or absence of the gallbladder and appendix was not documented in 6 (1.6%) and 16 (4.2%) of reports, respectively. Pathology was seen in 87 (25.8%) gallbladders and 4 (1.2%) appendixes. CONCLUSIONS: Absence of the gallbladder or appendix is a relatively common autopsy finding. Auditing autopsy reports for documentation of their presence or absence, along with associated abdominal scars, are potential quality assurance indicators of autopsy reports. Documentation of these elements could be improved by changing the autopsy template or using synoptic reporting.


Subject(s)
Appendix , Appendectomy , Appendix/pathology , Appendix/surgery , Autopsy , Cicatrix/pathology , Gallbladder/pathology , Humans
20.
Ecol Evol ; 11(11): 7069-7079, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34141276

ABSTRACT

Mutual reinforcement between abiotic and biotic factors can drive small populations into a catastrophic downward spiral to extinction-a process known as the "extinction vortex." However, empirical studies investigating extinction dynamics in relation to species' traits have been lacking.We assembled a database of 35 vertebrate populations monitored to extirpation over a period of at least ten years, represented by 32 different species, including 25 birds, five mammals, and two reptiles. We supplemented these population time series with species-specific mean adult body size to investigate whether this key intrinsic trait affects the dynamics of populations declining toward extinction.We performed three analyses to quantify the effects of adult body size on three characteristics of population dynamics: time to extinction, population growth rate, and residual variability in population growth rate.Our results provide support for the existence of extinction vortex dynamics in extirpated populations. We show that populations typically decline nonlinearly to extinction, while both the rate of population decline and variability in population growth rate increase as extinction is approached. Our results also suggest that smaller-bodied species are particularly prone to the extinction vortex, with larger increases in rates of population decline and population growth rate variability when compared to larger-bodied species.Our results reaffirm and extend our understanding of extinction dynamics in real-life extirpated populations. In particular, we suggest that smaller-bodied species may be at greater risk of rapid collapse to extinction than larger-bodied species, and thus, management of smaller-bodied species should focus on maintaining higher population abundances as a priority.

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