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1.
Sex Health ; 212024 Jun.
Article in English | MEDLINE | ID: mdl-38935836

ABSTRACT

Background Gonorrhoea infections and antimicrobial resistance are rising in many countries, particularly among men who have sex with men, and an increasing proportion of infection is detected at extragenital sites. This study assessed trends in gonorrhoea diagnoses and antibiotic resistance at a sexual health service in New Zealand that followed national guidelines for specimen collection. Methods Routinely-collected data from Canterbury Health Laboratories of specimens taken at the Christchurch Sexual Health Service 2012-2022 were audited. Descriptive results included the number of patient testing events positive for gonorrhoea per year and site of infection (extragenital/urogenital). Annual test-positivity was calculated (number of positive patient testing events divided by total number of testing events) and the Cochran-Armitage Test for Trend was used to assess whether there was an association between test-positivity and year. Results Of 52,789 patient testing events, 1467 (2.8%) were positive for gonorrhoea (81% male). Half (49.3%) of people (57.9% of males, 12.2% of females) with a gonorrhoea infection had an extragenital infection in the absence of a urogenital infection. The number of extragenital infections increased at a faster rate than urogenital among males. Test-positivity increased from 1.3% in 2012 to 5.8% in 2022 (P Conclusions This study highlights the importance of extragenital sampling and maintaining bacterial culture methods for accurate diagnosis and treatment. The observation that gonorrhoea positivity rate and antimicrobial resistance rates are rising in New Zealand calls for urgent action.


Subject(s)
Gonorrhea , Humans , Gonorrhea/diagnosis , Gonorrhea/epidemiology , New Zealand/epidemiology , Male , Female , Neisseria gonorrhoeae/isolation & purification , Sexual Health/statistics & numerical data , Anti-Bacterial Agents/therapeutic use , Adult , Drug Resistance, Bacterial
2.
J Cell Sci ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38904097

ABSTRACT

PTPRK is a receptor tyrosine phosphatase linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell-cell contact. It regulates cell-cell adhesion, but is also reported to regulate numerous cancer-associated signalling pathways. However, its signalling mechanism remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.

3.
J Surg Res ; 299: 112-119, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749314

ABSTRACT

INTRODUCTION: Surgical cap attire plays an important role in creating a safe and sterile environment in procedural suites, thus the choice of reusable versus disposable caps has become an issue of much debate. Given the lack of evidence for differences in surgical site infection (SSI) risk between the two, selecting the cap option with a lower carbon footprint may reduce the environmental impact of surgical procedures. However, many institutions continue to recommend the use of disposable bouffant caps. METHODS: ISO-14044 guidelines were used to complete a process-based life cycle assessment to compare the environmental impact of disposable bouffant caps and reusable cotton caps, specifically focusing on CO2 equivalent (CO2e) emissions, water use and health impacts. RESULTS: Reusable cotton caps reduced CO2e emissions by 79% when compared to disposable bouffant caps (10 kg versus 49 kg CO2e) under the base model scenario with a similar reduction seen in disability-adjusted life years. However, cotton caps were found to be more water intensive than bouffant caps (67.56 L versus 12.66 L) with the majority of water use secondary to production or manufacturing. CONCLUSIONS: Reusable cotton caps have lower total lifetime CO2e emissions compared to disposable bouffant caps across multiple use scenarios. Given the lack of evidence suggesting a superior choice for surgical site infection prevention, guidelines should recommend reusable cotton caps to reduce the environmental impact of surgical procedures.


Subject(s)
Disposable Equipment , Equipment Reuse , Equipment Reuse/standards , Humans , Carbon Footprint , Cotton Fiber/analysis , Surgical Drapes , Surgical Wound Infection/prevention & control , Surgical Wound Infection/etiology
4.
Ecol Evol ; 14(5): e11432, 2024 May.
Article in English | MEDLINE | ID: mdl-38770127

ABSTRACT

Wombats are native herbivorous grazers that have adapted to Australia's low-quality forage. Studies on diet selection by bare-nosed wombats (Vombatus ursinus) are limited and are either observational or based on microhistological studies. The current study determined the diet of wombats through DNA metabarcoding across five study sites in New South Wales over a one-year period. Metabarcoding was chosen as it is non-invasive, less time consuming and more specific than traditional techniques. The list of 209 plant species identified as eaten by wombats in this study is much higher than previously reported, with grasses being the most common plant group identified in all samples. Most dietary items identified were introduced plant species. Seasonal differences in plants eaten occurred at four of the five study sites and may reflect dietary abundance and floristic composition at different times of year. Further studies are required to determine if the dietary items differ markedly across the entire range of wombats, and if nutrition influences dietary preferences.

5.
PLoS One ; 19(4): e0298808, 2024.
Article in English | MEDLINE | ID: mdl-38598488

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) presents at advanced stages and is refractory to most treatment modalities. Wnt signaling activation plays a critical role in proliferation and chemotherapeutic resistance. Minimal media conditions, growth factor dependency, and Wnt dependency were determined via Wnt inhibition for seven patient derived organoids (PDOs) derived from pancreatic tumor organoid libraries (PTOL). Organoids demonstrating response in vitro were assessed in vivo using patient-derived xenografts. Wnt (in)dependent gene signatures were identified for each organoid. Panc269 demonstrated a trend of reduced organoid growth when treated with ETC-159 in combination with paclitaxel or gemcitabine as compared with chemotherapy or ETC-159 alone. Panc320 demonstrated a more pronounced anti-proliferative effect in the combination of ETC-159 and paclitaxel but not with gemcitabine. Panc269 and Panc320 were implanted into nude mice and treated with ETC-159, paclitaxel, and gemcitabine as single agents and in combination. The combination of ETC-159 and paclitaxel demonstrated an anti-tumor effect greater than ETC-159 alone. Extent of combinatory treatment effect were observed to a lesser extent in the Panc320 xenograft. Wnt (in)dependent gene signatures of Panc269 and 320 were consistent with the phenotypes displayed. Gene expression of several key Wnt genes assessed via RT-PCR demonstrated notable fold change following treatment in vivo. Each pancreatic organoid demonstrated varied niche factor dependencies, providing an avenue for targeted therapy, supported through growth analysis following combinatory treatment of Wnt inhibitor and standard chemotherapy in vitro. The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Animals , Mice , Humans , Gemcitabine , Wnt Signaling Pathway , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Mice, Nude , Cell Proliferation , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Organoids/metabolism , Xenograft Model Antitumor Assays
6.
Vaccines (Basel) ; 12(4)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38675734

ABSTRACT

Efficacy data on two malaria vaccines, RTS,S and R21, targeting Plasmodium falciparum circumsporozoite protein (PfCSP), are encouraging. Efficacy may be improved by induction of additional antibodies to neutralizing epitopes outside of the central immunodominant repeat domain of PfCSP. We designed four rPfCSP-based vaccines in an effort to improve the diversity of the antibody response. We also evaluated P. falciparum merozoite surface protein 8 (PfMSP8) as a malaria-specific carrier protein as an alternative to hepatitis B surface antigen. We measured the magnitude, specificity, subclass, avidity, durability, and efficacy of vaccine-induced antibodies in outbred CD1 mice. In comparison to N-terminal- or C-terminal-focused constructs, immunization with near full-length vaccines, rPfCSP (#1) or the chimeric rPfCSP/8 (#2), markedly increased the breadth of B cell epitopes recognized covering the N-terminal domain, junctional region, and central repeat. Both rPfCSP (#1) and rPfCSP/8 (#2) also elicited a high proportion of antibodies to conformation-dependent epitopes in the C-terminus of PfCSP. Fusion of PfCSP to PfMSP8 shifted the specificity of the T cell response away from PfCSP toward PfMSP8 epitopes. Challenge studies with transgenic Plasmodium yoelii sporozoites expressing PfCSP demonstrated high and consistent sterile protection following rPfCSP/8 (#2) immunization. Of note, antibodies to conformational C-terminal epitopes were not required for protection. These results indicate that inclusion of the N-terminal domain of PfCSP can drive responses to protective, repeat, and non-repeat B cell epitopes and that PfMSP8 is an effective carrier for induction of high-titer, durable anti-PfCSP antibodies.

7.
Pediatr Surg Int ; 40(1): 77, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472473

ABSTRACT

Accurate measurement of pneumothorax (PTX) size is necessary to guide clinical decision making; however, there is no consensus as to which method should be used in pediatric patients. This systematic review seeks to identify and evaluate the methods used to measure PTX size with CXR in pediatric patients. A systematic review of the literature through 2021 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted using the following databases: Ovid/MEDLINE, Scopus, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar. Original research articles that included pediatric patients (< 18 years old) and outlined the PTX measurement method were included. 45 studies were identified and grouped by method (Kircher and Swartzel, Rhea, Light, Collins, Other) and societal guideline used. The most used method was Collins (n = 16; 35.6%). Only four (8.9%) studies compared validated methods. All found the Collins method to be accurate. Seven (15.6%) studies used a standard classification guideline and 3 (6.7%) compared guidelines and found significant disagreement between them. Pediatric-specific measurement guidelines for PTX are needed to establish consistency and uniformity in both research and clinical practice. Until there is a better method, the Collins method is preferred.


Subject(s)
Pneumothorax , Adolescent , Child , Humans , Clinical Decision-Making , Pneumothorax/therapy
8.
Eval Program Plann ; 103: 102407, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38367349

ABSTRACT

Implementing trauma-informed care in a special education environment serving youth from historically marginalized communities with high levels of exposure to potentially traumatic events (PTEs) requires a systematic tiered approach consistent with public health guidelines. Little is known about the implementation of this framework in special education settings where youth have significant emotional and behavioral difficulties. To address this need, a consultant-community partnership was forged between a hospital providing mental health services and a therapeutic day school that serves a special education cooperative. The current case study explores the design and implementation of a three-tiered model of trauma-informed care in a special education setting. This study will address the specific practices implemented at each tier, discuss successes and challenges, and summarize future directions for research, practice, and policy.


Subject(s)
Mental Health Services , Adolescent , Humans , Program Evaluation , Education, Special , Policy
9.
Sci Rep ; 14(1): 3694, 2024 02 14.
Article in English | MEDLINE | ID: mdl-38355954

ABSTRACT

Individual cancers are composed of heterogeneous tumor cells with distinct phenotypes and genotypes, with triple negative breast cancers (TNBC) demonstrating the most heterogeneity among breast cancer types. Variability in transcriptional phenotypes could meaningfully limit the efficacy of monotherapies and fuel drug resistance, although to an unknown extent. To determine if transcriptional differences between tumor cells lead to differential drug responses we performed single cell RNA-seq on cell line and PDX models of breast cancer revealing cell subpopulations in states associated with resistance to standard-of-care therapies. We found that TNBC models contained a subpopulation in an inflamed cellular state, often also present in human breast cancer samples. Inflamed cells display evidence of heightened cGAS/STING signaling which we demonstrate is sufficient to cause tumor cell resistance to chemotherapy. Accordingly, inflamed cells were enriched in human tumors taken after neoadjuvant chemotherapy and associated with early recurrence, highlighting the potential for diverse tumor cell states to promote drug resistance.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Cell Line, Tumor , Signal Transduction , Phenotype
10.
Front Psychol ; 15: 1232228, 2024.
Article in English | MEDLINE | ID: mdl-38344276

ABSTRACT

When deliberating, jurors may introduce misinformation that may influence other jurors' memory and decision-making. In two studies, we explored the impact of misinformation exposure during jury deliberation. Participants in both studies read a transcript of an alleged sexual assault. In Study 1 (N = 275), participants encountered either consistent pro-prosecution misinformation, consistent pro-defense misinformation, or contradictory misinformation (pro-prosecution and pro-defense). In Study 2 (N = 339), prior to encountering either pro-prosecution or pro-defense misinformation while reading a jury deliberation transcript, participants either received or did not receive a judicial instruction about misinformation exposure during deliberation. Participants in both studies completed legal decision-making variables (e.g., defendant guilt rating) before and after deliberation, and their memory was assessed for misinformation acceptance via recall and source memory tasks. In Study 1, misinformation type did not influence legal decision-making, but pro-prosecution misinformation was more likely to be misattributed as trial evidence than pro-defense or contradictory misinformation. In Study 2, pro-defense misinformation was more likely to be misattributed to the trial than pro-prosecution misinformation, and rape myths moderated this. Furthermore, exposure to pro-defense misinformation skewed legal decision-making towards the defense's case. However, the judicial instruction about misinformation exposure did not influence memory or decision-making. Together, these findings suggest that misinformation in jury deliberations may distort memory for trial evidence and bias decision-making, highlighting the need to develop effective safeguards for reducing the impact of misinformation in trial contexts.

11.
12.
Lancet Microbe ; 5(2): e151-e163, 2024 02.
Article in English | MEDLINE | ID: mdl-38219758

ABSTRACT

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance. FINDINGS: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved. INTERPRETATION: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions. FUNDING: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease.


Subject(s)
Daptomycin , Enterococcus faecium , Enterococcus faecium/genetics , Vancomycin/pharmacology , Linezolid , Tigecycline , Teicoplanin , Retrospective Studies , Anti-Bacterial Agents/pharmacology , Ampicillin/pharmacology , Drug Resistance, Microbial , Ciprofloxacin , Phenotype , Gentamicins , Streptomycin
13.
PLoS One ; 19(1): e0296489, 2024.
Article in English | MEDLINE | ID: mdl-38180989

ABSTRACT

Inattentional blindness refers to when people fail to notice obvious and unexpected events when their attention is elsewhere. Existing research suggests that inattentional blindness is a poorly understood concept that violates the beliefs that are commonly held by the public about vision and attention. Given that legal cases may involve individuals who may have experienced inattentional blindness, it is important to understand the beliefs legal populations and members of the community have about inattentional blindness, and their general familiarity and experience with the concept. Australian police officers (n = 94) and lawyers (n = 98), along with psychology students (n = 99) and community members (n = 100) completed a survey where they: a) stated whether an individual would have noticed an event in six legal vignettes, b) rated whether factors would make an individual more, less, or just as likely to notice an unexpected event, c) reported their familiarity with and personal experiences of inattentional blindness, and d) indicated whether they believed individuals could make themselves more likely to notice unexpected events. Respondents in all populations frequently responded "yes" to detecting the unexpected event in most legal vignettes. They also held misconceptions about some factors (expertise and threat) that would influence the noticing of unexpected events. Additionally, personal experiences with inattentional blindness were commonly reported. Finally, respondents provided strategies for what individuals can do to make themselves more likely to notice of unexpected events, despite a lack of evidence to support them. Overall, these findings provide direction for where education and training could be targeted to address misconceptions about inattentional blindness held by legal populations, which may lead to improved decision-making in legal settings.


Subject(s)
Blindness , Mental Disorders , Humans , Australia , Educational Status , Lawyers
14.
J Vitreoretin Dis ; 8(1): 75-81, 2024.
Article in English | MEDLINE | ID: mdl-38223773

ABSTRACT

Purpose: To determine the time-based incidence of total blindness after central retinal artery occlusion (CRAO) with secondary ocular neovascularization (ONV). Methods: In this retrospective cohort study, electronic records were queried using ICD-9 and ICD-10 codes to identify patients with secondary ONV post-CRAO. Patients with possible alternative ONV etiologies, previous panretinal photocoagulation (PRP), and/or previous antivascular endothelial growth factor (anti-VEGF) therapy were excluded. Clinical data included demographics, medical comorbidities, ONV manifestations, medical/surgical management, and best-corrected visual acuity (BCVA). Kaplan-Meier analysis was performed with total blindness (defined as a BCVA of no light perception) as the outcome of interest. Results: Of 345 eyes with CRAO, 34 met the inclusion criteria with a mean (±SD) follow-up of 22.0 ± 26.2 months. ONV management included PRP (70.6%), glaucoma drainage implant surgery or transscleral cyclophotocoagulation (32.4%), and intravitreal anti-VEGF therapy (mean 2.8 ± 5.6 injections per patient). The cumulative incidence of total blindness was 49.4% (95% confidence interval, 27.2%-71.6%) at 24 months, with 53.3% of cases occurring within 4 months of ONV onset. Conclusions: Post-CRAO ONV is associated with a high risk for progression from severe vision loss to total blindness. Neovascular glaucoma can present up to 4 months after CRAO, challenging the paradigm of "30-day-glaucoma." Routine gonioscopy should extend through this period, while glaucoma surgery can delay further vision loss. These findings can be used to counsel patients on the importance of follow-up adherence.

15.
Am J Obstet Gynecol ; 230(1): 95.e1-95.e10, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37429430

ABSTRACT

BACKGROUND: Maternal anticoagulation use may increase indeterminate result rates on cell-free DNA-based screening, but existing studies are confounded by inclusion of individuals with autoimmune disease, which alone is associated with indeterminate results. Changes in chromosome level Z-scores are proposed by others as a reason for indeterminate results, but the etiology of this is uncertain. OBJECTIVE: This study aimed to evaluate differences in fetal fraction, indeterminate result rate, and total cell-free DNA concentration in individuals on anticoagulation without autoimmune disease compared with controls undergoing noninvasive prenatal screening. Secondly, using a nested case-control design, we evaluated differences in fragment size, GC-content, and Z-scores to evaluate laboratory-level test characteristics. STUDY DESIGN: This was a retrospective single-institution study of pregnant individuals undergoing cell-free DNA-based noninvasive prenatal screening using low-pass whole-genome sequencing between 2017 and 2021. Individuals with autoimmune disease, suspected aneuploidy, and cases where fetal fraction was not reported were excluded. Anticoagulation included heparin-derived products (unfractionated heparin, low-molecular-weight heparin), clopidogrel, and fondaparinux, with a separate group for those on aspirin alone. An indeterminate result was defined as fetal fraction <4%. We evaluated the association between maternal anticoagulation or aspirin use, and fetal fraction, indeterminate results, and total cell-free DNA concentration using univariate and multivariate analyses, controlling for body mass index, gestational age at sample collection, and fetal sex. For the anticoagulation cohort, we compared laboratory-level test characteristics among cases (on anticoagulation) and a subset of controls. Lastly, we evaluated for differences in chromosome level Z-scores among those on anticoagulation with and without indeterminate results. RESULTS: A total of 1707 pregnant individuals met the inclusion criteria. Of those, 29 were on anticoagulation and 81 were on aspirin alone. For those on anticoagulation, the fetal fraction was significantly lower (9.3% vs 11.7%; P<.01), the indeterminate result rate was significantly higher (17.2% vs 2.7%; P<.001), and the total cell-free DNA concentration was significantly higher (218 pg/µL vs 83.7 pg/µL; P<.001). Among those on aspirin alone, the fetal fraction was lower (10.6% vs 11.8%; P=.04); however, there were no differences in the rate of indeterminate results (3.7% vs 2.7%; P=.57) or total cell-free DNA concentration (90.1 pg/µL vs 83.8 pg/µL; P=.31). After controlling for maternal body mass index, gestational age at sample collection, and fetal sex, anticoagulation was associated with an >8-fold increase in the likelihood of an indeterminate result (adjusted odds ratio, 8.7; 95% confidence interval, 3.1-24.9; P<.001), but not aspirin (adjusted odds ratio, 1.2; 95% confidence interval, 0.3-4.1; P=.8). Anticoagulation was not associated with appreciable differences in cell-free DNA fragment size or GC-content. Although differences in chromosome 13 Z-scores were observed, none were observed for chromosomes 18 or 21, and this difference did not contribute to the indeterminate result call. CONCLUSION: In the absence of autoimmune disease, anticoagulation use, but not aspirin, is associated with lower fetal fraction, higher total cell-free DNA concentration, and higher rates of indeterminate results. Anticoagulation use was not accompanied by differences in cell-free DNA fragment size or GC-content. Statistical differences in chromosome level Z-scores did not clinically affect aneuploidy detection. This suggests a likely dilutional effect by anticoagulation on cell-free DNA-based noninvasive prenatal screening assays contributing to low fetal fraction and indeterminate results, and not laboratory or sequencing-level changes.


Subject(s)
Autoimmune Diseases , Cell-Free Nucleic Acids , Pregnancy , Female , Humans , Prenatal Diagnosis/methods , Retrospective Studies , Heparin , Aneuploidy , Aspirin/therapeutic use , Anticoagulants/therapeutic use
16.
Article in English | MEDLINE | ID: mdl-38160526

ABSTRACT

Sarcoptic mange in wombats results from a skin infestation by Sarcoptes mites and if untreated, results in a slow and painful death. Moxidectin is a pesticide used to treat internal and external parasites in cattle, but has shown to effectively treat other animals, including wombats. Two methods were developed to analyse wombat plasma, and methods were also developed to analyse faeces and fur. Moxidectin-D3 was used as an internal standard and behaved almost identically to moxidectin, resulting in recoveries of 95-105 % across the three matrices, even when matrix interferences caused signal suppression as high 20 %, or when moxidectin loss was high. This was presumably due to the high binding efficiency of plasma for MOX and MOX-D3. Moxidectin limits of detection were 0.01 ng/mL in plasma, 0.3 ng/g dry weight equivalent for faeces and 0.5 ng/g for fur. This study also developed a method to isolate plasma macromolecules, allowing the extraction of bound moxidectin for quantitative purposes, with an LoQ of 0.05 ng/mL. This method was subsequently used to determine that moxidectin was 97-99.4 % bound to lipoproteins in wombat plasma and 98-99 % bound in sheep, cow and horse plasma. The method reported for plasma was quick, cheap, and conducive to large sample batches, while providing high sensitivity. While faecal samples required additional cleanup steps to reduce the matrix effect, co-extracted matrix components such as undigested chlorophyll continued to result in ionisation suppression in the MS/MS. The methods reported here were used to monitor moxidectin in wombats treated with a single pour-on treatment, and confirmed that the moxidectin concentration in wombat plasma had decreased by more than 90 % by 28 days after application, while providing protection against sarcoptic mites over the majority of their life cycle. Clearance of moxidectin occurred via faecal elimination over the four week period and while moxidectin accumulated on fur due to application as a pour-on, concentrations declined rapidly by the four week period as fur fell out and was replaced by fresh fur that did not contain moxidectin.


Subject(s)
Scabies , Tandem Mass Spectrometry , Female , Animals , Cattle , Sheep , Horses , Scabies/veterinary , Macrolides , Feces
17.
Explor Res Clin Soc Pharm ; 12: 100370, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38058359

ABSTRACT

Background: Evidence on the role of pharmacy teams in suicide prevention is growing. To support pharmacy teams, a video e-learning was produced by the Centre for Pharmacy Postgraduate Education (CPPE) involving an 'on-the-sofa' style group interview with people with personal and professional experience of suicide and suicide research. Objective: The objective was to measure any change in attitudes and preparedness for suicide prevention, following a video e-learning produced for pharmacy staff. Methods: People working in any sector of pharmacy in England and who accessed the training video were invited to complete a pre- and post- training questionnaire, between September 2019 and March 2021. Question types included demographics, experiences, attitudes as measured by the Attitudes to Suicide Prevention (ASP) scale, and preparedness. Descriptive statistics were used to summarize demographics and experience and paired t-tests were used to compare pre- and post- questionnaire responses. Results: Both questionnaires were completed by 147 people. Most worked in community pharmacy (88%) and were pharmacists (64%) or pharmacy technicians (20%). Attitudes to suicide prevention improved significantly (pre:31.20 (SD 6.04); post:28.40 (SD 6.50), p < 0.0001) after watching the video, as did self-reported preparedness. Conclusions: Pharmacy teams' self-reported attitudes and preparedness for suicide prevention improved after watching this suicide awareness video compared to baseline. Suicide awareness training tailored to pharmacy teams may be valuable, but the longitudinal impact of any suicide prevention training requires further exploration.

18.
Front Microbiol ; 14: 1231832, 2023.
Article in English | MEDLINE | ID: mdl-37680529

ABSTRACT

Grapevine trunk diseases (GTDs) are a substantial challenge to viticulture, especially with a lack of available control measures. The lack of approved fungicides necessitates the exploration of alternative controls. One promising approach is the investigation of disease escape plants, which remain healthy under high disease pressure, likely due to their microbiome function. This study explored the microbiome of grapevines with the disease escape phenotype. DNA metabarcoding of the ribosomal internal transcribed spacer 1 (ITS1) and 16S ribosomal RNA gene was applied to trunk tissues of GTD escape and adjacent diseased vines. Our findings showed that the GTD escape vines had a significantly different microbiome compared with diseased vines. The GTD escape vines consistently harbored a higher relative abundance of the bacterial taxa Pseudomonas and Hymenobacter. Among fungi, Aureobasidium and Rhodotorula were differentially associated with GTD escape vines, while the GTD pathogen, Eutypa, was associated with the diseased vines. This is the first report of the link between the GTD escape phenotype and the grapevine microbiome.

19.
BMC Health Serv Res ; 23(1): 1042, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773154

ABSTRACT

BACKGROUND: Population groups experience differential access to timely and high-quality mental healthcare. Despite efforts of recent UK policies to improve the accessibility of mental health services, there remains a lack of comprehensive understanding of inequalities in access to services needed to do this. This systematic mapping review aimed to address this gap by identifying which population groups continue to be poorly served by access to adult mental health services in the UK, how access has been measured, and what research methods have been applied. METHODS: Seven electronic databases were searched from January 2014 up to May 2022. Primary research studies of any design were included if they examined access to adult NHS mental health services in the UK by population groups at risk of experiencing inequalities. Study characteristics, measures of access, inequalities studied, and key findings were extracted. A best-fit framework approach was used, applying Levesque's Conceptual Framework for Healthcare Access to synthesise measures of access, and applying a template derived from Cochrane Progress-Plus and NHS Long Term Plan equality characteristics to synthesise key findings associated with inequalities. RESULTS: Of 1,929 publications retrieved, 152 studies of various types were included. The most frequently considered dimensions of inequality were gender, age, and ethnicity, whilst social capital, religion, and sexual orientation were least frequently considered. Most studies researched access by measuring "healthcare utilisation", followed by studies that measured "healthcare seeking". Key barriers to access were associated with individuals' "ability to seek" (e.g. stigma and discrimination) and "ability to reach" (e.g. availability of services). Almost half of the studies used routinely collected patient data, and only 16% of studies reported patient and public involvement. CONCLUSIONS: Little appears to have changed in the nature and extent of inequalities, suggesting that mental health services have not become more accessible. Actions to reduce inequalities should address barriers to population groups' abilities to seek and reach services such as stigma-reducing interventions, and re-designing services and pathways. Significant benefits exist in using routinely collected patient data, but its limitations should not be ignored. More theoretically informed research, using a holistic measurement of access, is needed in this area. REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/RQ5U7 .


Subject(s)
Mental Health Services , Humans , Male , Adult , Female , Ethnicity , Health Services Accessibility , Patient Acceptance of Health Care , United Kingdom
20.
Article in English | MEDLINE | ID: mdl-37646985

ABSTRACT

Early childhood is a heightened risk period for exposure to potentially traumatic events (PTEs) and a critical period for the development of foundational self-regulatory competencies that have potential cascading effects on future socioemotional functioning. This cross-sectional study examined associations between PTE exposure and socioemotional and adaptive functioning, and self-regulatory skills, in a community-based sample of 280 primarily Black and Latinx 3-5-year-olds. Results supported direct relations between PTE exposure and socioemotional and adaptive functioning. Attentional regulation was associated with PTEs and internalizing behaviors, externalizing behaviors, and adaptive behaviors. There was also a significant association of emotional regulation on the relationship between PTEs and internalizing and externalizing behaviors, but not adaptive functioning. Findings have implications for early intervention and educational and public policy, including the importance of scaffolding the development of self-regulatory skills among preschoolers with high PTE exposure.

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