Suicide by Ethyl Methacrylate Ingestion.

ABSTRACT: This case report characterizes a unique way in which suicide was accomplished through ingestion of chemicals typically used to create acrylic fingernails that resulted in death. Ethyl methacrylate and acrylic powder are commonly combined to form acrylic nails in nail salons. The process of applying acrylic nails utilizes each substance by mixing both before it typically solidifies within seconds of combining the two compounds. Ingestion of these compounds has not been previously described within the medical literature. The decedent was a nail technician at a local salon. He was found unresponsive in his yard which led to a 911 call. At the scene, a mostly empty 16-oz bottle of ethyl methacrylate, a chemical used at the salon where he worked, was found. At autopsy, the decedent's body had a strong chemical odor consistent with odors present at nail salons. Significant gastrointestinal tract damage was seen including discoloration within the esophagus, and the stomach contained a molded, hardened nail compound. The cause of death was ruled as complications of nail acrylic powder and liquid ethyl methacrylate ingestion. This case shows the unusual findings seen at autopsy from a decedent who committed suicide by ingestion of ethyl methacrylate with acrylic powder.

Pre-Injury Statin Exposure is Associated With Improved Outcomes in Injured Patients That Receive Whole Blood.

Introduction: Whole blood (WB) is associated with improved mortality while lowering blood product utilization. Furthermore, statin medications are associated with favorable outcomes in traumatic brain injury and risk reduction of venous thromboembolism. However, the use of statin medications has not been evaluated in those receiving WB. The objective of this study is to determine the effects of pre-injury statin exposure on patients receiving WB.Methods: Patients that underwent WB first resuscitation and received pre-injury statins were compared to those that did not receive pre-injury statins. Demographics as well as complication rates, blood product transfusion volumes, and mortality were evaluated. Univariate and multivariable analyses were used to determine independent predictors of mortality.Results: In the study period, 785 patients received WB as part of their resuscitation. One hundred and thirty five patients (17.3%) took statin medications prior to injury. Patients that were exposed to a pre-injury statin had a lower mortality rate than those that were not exposed (21.5% vs 32.5%, P = .01). After adjusting for imbalances, age, ISS, Glasgow Coma Scale, admission systolic blood pressures, and pre-injury statin use were independent predictors of mortality following multiple logistic regression. When evaluating outcomes based on statin intensity, the use of high-intensity statins was associated with lower mortality (OR: .37, 95% CI: .13-.93), whereas moderate and low-intensity statins were not.Conclusion: In patients resuscitated with WB, pre-injury statins use was associated with improved outcomes. Specifically, patients that received high-intensity pre-injury statins appeared to be the population that benefited.

Histological staining alters circular dichroism SHG measurements of collagen.

Circular dichroism second harmonic generation microscopy (CDSHG) is a powerful imaging technique, which allows three-dimensional visualization of collagen fibril orientation in tissues. However, recent publications have obtained contradictory results on whether CDSHG can be used to reveal the relative out-of-plane polarity of collagen fibrils. Here we compare CDSHG images of unstained tendon and tendon which has been stained with hematoxylin and eosin. We find significant differences in the CDSHG between these two conditions, which explain the recent contradictory results within the literature.

Developing Oak Buds Produce Volatile Emissions in Response to Herbivory by Freshly Hatched Caterpillars.

Plant responses to damage by insectivorous herbivores are well-documented in mature leaves. The resulting herbivore-induced plant volatiles (HIPVs) protect the plant by attracting carnivorous arthropods and even some insectivorous vertebrates, to parasitize or consume the plant invaders. However, very little is known about plant production of HIPVs in developing buds, particularly when herbivorous insects are too small to be considered a prey item. It is additionally unclear whether plants respond differently to generalist and specialist chewing insects that overlap in distribution. Therefore, we compared HIPV production of Downy oak (Quercus pubescens Willd.) buds infested with freshly hatched caterpillars of Tortrix viridana (specialist) and Operophtera brumata (generalist), against uninfested buds. Of the compounds identified in both years of the experiment, we found that (Z)-hex-3-enyl acetate, (E)-ß-ocimene, acetophenone, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), methyl salicylate, α-copaene, α-humulene, (E)-caryophyllene, and (E,E)-α-farnesene appeared to be higher in infested buds compared to controls. We found no difference in HIPV production between the specialist and the generalist herbivores. Production of HIPVs was also associated with leaf damage, with higher HIPV production in more severely attacked buds. Thus, our study shows that oak trees already start responding to insect herbivory before leaves are developed, by producing compounds similar to those found in damaged mature leaves. Future work should focus on how Downy oak may benefit from initiating alarm cues at a time when carnivorous arthropods and insectivorous vertebrates are unable to use herbivorous insects as host or food.

Proximal humeral fractures with vascular compromise.

Aims: Vascular compromise due to arterial injury is a rare but serious complication of a proximal humeral fracture. The aims of this study were to report its incidence in a large urban population, and to identify clinical and radiological factors which are associated with this complication. We also evaluated the results of the use of our protocol for the management of these injuries. Methods: A total of 3,497 adult patients with a proximal humeral fracture were managed between January 2015 and December 2022 in a single tertiary trauma centre. Their mean age was 66.7 years (18 to 103) and 2,510 (72%) were female. We compared the demographic data, clinical features, and configuration of those whose fracture was complicated by vascular compromise with those of the remaining patients. The incidence of vascular compromise was calculated from national population data, and predictive factors for its occurrence were investigated using univariate analysis. Results: A total of 18 patients (0.5%) had a proximal humeral fracture and clinical evidence of vascular compromise, giving an annual incidence of 0.29 per 100,000 of the population. Their mean age was 68.7 years (45 to 92) and ten (56%) were female. Evidence of a mixed pattern neurological deficit (brachial plexus palsy) (odds ratio (OR) 380.6 (95% CI 85.9 to 1,685.8); p < 0.001), complete separation of the proximal shaft from the humeral head with medial displacement (OR 39.5 (95% CI 14.0 to 111.8); p < 0.001), and a fracture-dislocation (OR 5.0 (95% CI 1.6 to 15.3); p = 0.015) were all associated with an increased risk of associated vascular compromise. A policy of reduction and fixation of the fracture prior to vascular surgical intervention had favourable outcomes without vascular sequelae. Conclusion: The classic signs of distal ischaemia are often absent in patients with proximal injuries to major vessels. We were able to identify specific clinical and radiological 'red flags' which, particularly when present in combination, should increase the suspicion of a fracture with an associated vascular injury, and facilitate early diagnosis and appropriate combined orthopaedic and vascular intervention.

Investigating quantitative histological characteristics in renal pathology using HistoLens.

HistoLens is an open-source graphical user interface developed using MATLAB AppDesigner for visual and quantitative analysis of histological datasets. HistoLens enables users to interrogate sets of digitally annotated whole slide images to efficiently characterize histological differences between disease and experimental groups. Users can dynamically visualize the distribution of 448 hand-engineered features quantifying color, texture, morphology, and distribution across microanatomic sub-compartments. Additionally, users can map differentially detected image features within the images by highlighting affected regions. We demonstrate the utility of HistoLens to identify hand-engineered features that correlate with pathognomonic renal glomerular characteristics distinguishing diabetic nephropathy and amyloid nephropathy from the histologically unremarkable glomeruli in minimal change disease. Additionally, we examine the use of HistoLens for glomerular feature discovery in the Tg26 mouse model of HIV-associated nephropathy. We identify numerous quantitative glomerular features distinguishing Tg26 transgenic mice from wild-type mice, corresponding to a progressive renal disease phenotype. Thus, we demonstrate an off-the-shelf and ready-to-use toolkit for quantitative renal pathology applications.

They all rock: A systematic comparison of conformational movements in LeuT-fold transporters.

Many membrane transporters share the LeuT fold-two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters, the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets.

Assessment of Adolescents in Child-to-Parent Violence: Invariance, Prevalence, and Reasons.

Child-to-parent violence is a form of family violence where the children are the aggressors. OBJECTIVE: This study first aimed to analyze the psychometric validity of the Child-to-Parent Violence Questionnaire (CPV-Q) among Ecuadorian adolescents. Second, the measurement invariance across the children's sex was examined. Finally, the prevalence of child-to-parent violence (CPV) was also determined. METHODS: A total of 2084 adolescents aged 12 to 18 years participated in this study. The participants were residents of two provinces in southern Ecuador. A higher percentage of participants were women. They lived mostly with their father and mother. The married marital status of the parents was the most frequently reported. Most of the fathers and mothers of the participants completed primary education. The sampling design was probabilistic, with proportional allocation by age and quotas according to the number of inhabitants per province. The sample size was determined by using a finite population formula. All the participants were randomly selected. The CPV-Q was used to assess child-to-parent violence. The items were adapted linguistically and tailored to the Ecuadorian context. RESULTS: The questionnaire demonstrated excellent model fit and adequate reliability. Full measurement invariance was held for all scales except for the reasons subscale pertaining to fathers. Statistically significant differences were observed with respect to the sex of the aggressor, with control/domain behaviors toward both parents and psychological violence toward the mother being more frequent among daughters than sons. Similarly, reactive reasons were more frequent among daughters than sons. CONCLUSION: This study provides significant psychometric evidence on the CPV-Q in Ecuadorian adolescents along with data on the prevalence of violence against parents.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19.

Objective: The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on self-reported alterations in taste and/or smell function. Methods: Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019 (post-COVID-19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure-self-reported total recovery of chemosensory symptoms-was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc). Results: The median time between COVID-19 symptom onset and the interviews was 81 days (interquartile range: 60-104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery. Those who took oral zinc were less likely to improve. Conclusions: No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

The Pressure Reactivity Index as a Measure for Cerebrovascular Autoregulation: Validation in a Porcine Cranial Window Model.

BACKGROUND AND OBJECTIVES: Pressure reactivity index (PRx) has been proposed as a metric associated with cerebrovascular autoregulatory (CA) function and has been thoroughly investigated in clinical research. In this study, PRx is validated in a porcine cranial window model, developed to visualize pial arteriolar autoregulation and its limits. METHODS: We measured arterial blood pressure, intracranial pressure, pial arteriolar diameter, and red blood cell (RBC) velocity in a closed cranial window piglet model during gradual balloon catheter-induced arterial hypotension (n = 10) or hypertension (n = 10). CA limits were derived through piecewise linear regression of calculated RBC flux vs cerebral perfusion pressure (CPP), leading for each arteriole to 1 lower limit of autoregulation (LLA) and 2 upper limits of autoregulation (ULA1 and ULA2). Autoregulation limits were compared with PRx thresholds, and receiver operating curve analysis was performed with and without CPP binning. A linear mixed effects model of PRx was performed. RESULTS: Receiver operating curve analysis indicated an area under the curve (AUC) for LLA prediction by a PRx of 0.65 (95% CI: 0.64-0.67) and 0.77 (95% CI: 0.69-0.86) without and with CPP binning, respectively. The AUC for ULA1 prediction by PRx was 0.69 (95% CI: 0.68-0.69) without and 0.75 (95% CI: 0.68-0.82) with binning. The AUC for ULA2 prediction was 0.55 (95% CI: 0.55-0.58) without and 0.63 (95% CI 0.53-0.72) with binning. The sensitivity and specificity of binned PRx were 65%/90% for LLA, 69%/71% for ULA1, and 59%/74% for ULA2, showing wide interindividual variability. In the linear mixed effects model, pial arteriolar diameter changes were significantly associated with PRx changes (P = .002), whereas RBC velocity (P = .28) and RBC flux (P = .24) were not. CONCLUSION: We conclude that PRx is predominantly determined by pial arteriolar diameter changes and moderately predicts CA limits. Performance to detect the CA limits varied highly on an individual level. Active therapeutic strategies based on PRx and the associated correlation metrics should incorporate these limitations.

Signatures of wave erosion in Titan's coasts.

The shorelines of Titan's hydrocarbon seas trace flooded erosional landforms such as river valleys; however, it is unclear whether coastal erosion has subsequently altered these shorelines. Spacecraft observations and theoretical models suggest that wind may cause waves to form on Titan's seas, potentially driving coastal erosion, but the observational evidence of waves is indirect, and the processes affecting shoreline evolution on Titan remain unknown. No widely accepted framework exists for using shoreline morphology to quantitatively discern coastal erosion mechanisms, even on Earth, where the dominant mechanisms are known. We combine landscape evolution models with measurements of shoreline shape on Earth to characterize how different coastal erosion mechanisms affect shoreline morphology. Applying this framework to Titan, we find that the shorelines of Titan's seas are most consistent with flooded landscapes that subsequently have been eroded by waves, rather than a uniform erosional process or no coastal erosion, particularly if wave growth saturates at fetch lengths of tens of kilometers.

A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (INaR) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, INaR is thought to drive high rates of repetitive neuronal firing. However, INaR is often studied in combination with the persistent or noninactivating portion of sodium currents (INaP). We used dynamic clamp to test how INaR and INaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned INaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold INaP is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed INaP and INaR can be inversely scaled by adjusting occupancy in the slow-inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune INaP and Purkinje neuron repetitive firing rates.

Achieving an Optimal Outcome After Stage 1 Palliation for Hypoplastic Left Heart Syndrome and Variants: Frequency, Associated Factors, and Subsequent Outcomes.

BACKGROUND: We sought to measure frequency of achieving an optimal outcome after stage 1 palliation (S1P) for hypoplastic left heart syndrome and variants, determine factors associated with optimal outcomes, and compare outcomes after stage 2 palliation (S2P) using the National Pediatric Cardiology Quality Improvement Collaborative database (2008-2016). METHODS AND RESULTS: This is a retrospective cohort study with optimal outcome defined a priori as meeting all of the following: (1) discharge after S1P in <19 days (top quartile), (2) no red flag or major event readmissions before S2P, and (3) performing S2P between 90 and 240 days of age. Optimal outcome was achieved in 256 of 2182 patients (11.7%). Frequency varied among centers from 0% to 25%. Factors independently associated with an optimal outcome after S1P were higher gestational age (odds ratio [OR], 1.1 per week [95% CI, 1.0-1.2]; P=0.02); absence of a genetic syndrome (OR, 2.5 [95% CI, 1.2-5]; P=0.02); not requiring a post-S1P catheterization (OR, 2.7 [95% CI, 1.5-4.8]; P=0.01), intervention (OR, 1.5 [95% CI, 1.1-2]; P=0.006), or a procedure (OR, 4.5 [95% CI, 2.8-7.1]; P<0.001) before discharge; and not having a post-S1P complication (OR, 2.7 [95% CI, 1.9-3.7]; P<0.001). Those with an optimal outcome after S1P had improved S2P outcomes including shorter length of stay, less ventilator days, shorter bypass time, and fewer postoperative complications. CONCLUSIONS: Identifying patients at lowest risk for poor outcomes during the home interstage period could shift necessary resources to those at higher risk, alter S2P postoperative expectations, and improve quality of life for families at lower risk.

Study of the Structure of Hyperbranched Polyglycerol Coatings and Their Antibiofouling and Antithrombotic Applications.

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation.

Assessing the locomotor demands of international men's and women's rugby sevens match-play according to passage of play.

This study aimed to evaluate the effect of discrete passages of play on locomotor demands of international men's and women's rugby sevens matches and their relationship with winning or losing. Thirteen men's and thirteen women's international rugby sevens players wore 10 Hz Global Positioning Systems during twelve Tokyo Olympic games matches (966 observations; 507 for men, 459 for women). Discrete ball-in-play periods were categorised as: 'Single-phase defence', 'single-phase attack', 'multi-phase defence', 'multi-phase attack', 'multi-phase defence to attack', or 'multi-phase attack to defence'. Relative total distance, alongside high-speed (>5.0 m∙s-1), acceleration (>3 m∙s-2), and deceleration (>3 m∙s-2) distances were recorded for each passage. Separately for men and women, linear mixed models examined the effect of passage type and match outcome (win or loss) on locomotor demands, whilst controlling for opposition ranking. In men, relative total distance ranged from 137 m∙min-1 to 174 m∙min-1 for 'multi-phase defence to attack' and 'multi-phase attack', respectively. In women, 'multi-phase attack' elicited the lowest relative total distance (118 m∙min-1), whereas the greatest values (186 m∙min-1) were recorded for 'single-phase defence'. For men, there were significant interactions between match outcome and passage type for relative total (p<0.001) and high-speed (p = 0.006) distance. During 'multi-phase attack', relative total distance was greater for wins versus losses (174 vs 138 m.min-1, p = 0.024). However, for 'single-phase defence', relative total distance was lower for wins (128 vs 164 m.min-1, p<0.001). For women, there were significant interactions between match outcome and passage type for relative total (p = 0.036), high-speed (p = 0.003), and deceleration (p = 0.015) distances. Locomotor responses were influenced by passage type and match result for men and women. Knowing the demands of each passage type may inform training drills targeted at developing match-play-specific physical, technical, and tactical adaptations. Understanding how passages differ between matches won and lost could also inform team technical/tactical preparation including selection.

Collaboration matters: A randomized controlled trial of patient-clinician collaboration in suicide risk assessment and intervention.

BACKGROUND: Clinician collaboration can help high-risk individuals to manage their suicidal crises. However, limited research has directly examined how higher patient-clinician collaboration during assessment and intervention can effectively reduce suicidal ideation. This novel randomized clinical trial compared a high vs. low level of patient-clinician collaboration by pairing commonly used assessment (Structured Interview vs. Narrative Assessment) and intervention approaches (Safety Planning Intervention vs. Crisis Response Planning). We hypothesized that the interventions involving higher (than lower) patient-clinician collaboration during assessment (Narrative Assessment) or intervention (Crisis Response Planning) would lead to larger reductions in suicidal ideation. METHODS: Eighty-two participants with a history of suicide ideation and/or attempts were randomly assigned to one of the four interventions varying in patient-clinician collaboration. After attrition, sixty-six participants completed the study. Suicidal ideation via ecological momentary assessment was measured 14 days before and 14 days after treatment. RESULTS: Although the severity of suicidal ideation decreased in all groups, the two groups that included highly collaborative assessment had larger pre-post reductions in suicidal ideation (Narrative Assessment+Safety Plan; dwithin = 0.26, and Narrative Assessment+Crisis Response Plan; dwithin = 0.19) than the groups that included a checklist-based assessment (Structured Interview). LIMITATIONS: Longer follow-up periods with a larger sample would have provided an understanding of the durability of intervention effects. CONCLUSION: Results suggest that the inclusion of higher patient-clinician collaboration techniques during suicide risk assessment can effectively reduce suicidal thoughts. Thus, clinician-led collaborative risk assessment approaches can enhance the effects of safety planning-type interventions among patients with elevated risk for suicide versus checklist-based assessment approaches.

High temperatures reduce growth, infection, and transmission of a naturally occurring fungal plant pathogen.

Climate change is rapidly altering the distribution of suitable habitats for many species as well as their pathogenic microbes. For many pathogens, including vector-borne diseases of humans and agricultural pathogens, climate change is expected to increase transmission and lead to pathogen range expansions. However, if pathogens have a lower heat tolerance than their host, increased warming could generate so-called thermal refugia for hosts. Predicting the outcomes of warming on disease transmission requires detailed knowledge of the thermal tolerances of both the host and the pathogen. Such thermal tolerance studies are generally lacking for fungal pathogens of wild plant populations, despite the fact that plants form the base of all terrestrial communities. Here, we quantified three aspects of the thermal tolerance (growth, infection, and propagule production) of the naturally occurring fungal pathogen Microbotryum lychnidis-dioicae, which causes a sterilizing anther-smut disease on the herbaceous plant Silene latifolia. We also quantified two aspects of host thermal tolerance: seedling survival and flowering rate. We found that temperatures >30°C reduced the ability of anther-smut spores to germinate, grow, and conjugate in vitro. In addition, we found that high temperatures (30°C) during or shortly after the time of inoculation strongly reduced the likelihood of infection in seedlings. Finally, we found that high summer temperatures in the field temporarily cured infected plants, likely reducing transmission. Notably, high temperatures did not reduce survival or flowering of the host plants. Taken together, our results show that the fungus is considerably more sensitive to high temperatures than its host plant. A warming climate could therefore result in reduced disease spread or even local pathogen extirpation, leading to thermal refugia for the host.

Genomic analysis of Helicobacter pylori in Australia: Antimicrobial resistance, phylogenetic patterns, and virulence factors.

BACKGROUND AND AIM: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally, but little is known about contemporary resistance patterns, virulence factors, and phylogenetic patterns of isolates within Australia. We aimed to characterize antimicrobial resistance and genetic mutations associated with adverse clinical outcomes. METHODS: Whole genome sequencing, culturing, and antibiotic sensitivity data for refractory H. pylori isolates at Australian centers were collected between 2013 and 2022. Phylogenetic origins, antibiotic resistance mutations, and virulence factors were examined with phenotypic resistance profiles. RESULTS: One hundred thirty-five isolates underwent culture, with 109 of these undergoing whole genome sequencing. Forty-three isolates were isolated from patients in South Australia and 66 from Western Australia. Isolates originated primarily from hpEurope (59.6%), hpEastAsia (25.7%), and hpNEAfrica (6.4%). Antimicrobial resistance to clarithromycin was seen in 85% of isolates, metronidazole in 52%, levofloxacin in 18%, rifampicin in 14%, and amoxicillin in 9%. Most isolates (59%) were multi-drug resistant. Resistance concordance between genetically determined resistance and phenotypic resistance was 92% for clarithromycin and 94% for levofloxacin. Analysis of virulence factors demonstrated cag pathogenicity island (cagPAI) in 67% of isolates and cagA in 61%, correlating with isolate genetic origin. The most virulent s1m1 vacuolating cytotoxin A genotype was present in 26% of isolates. CONCLUSION: Refractory H. pylori isolates in Australia emanate from multiple global origins. Strong concordance between genetic and phenotypic antibiotic resistance profiles raises the possibility of utilizing genetic profiling in clinical practice. The dynamic landscape of H. pylori in Australia warrants the establishment of a national database to monitor H. pylori resistance and evolving virulence.

Development of a comprehensive cardiovascular disease genetic risk assessment test.

Background: Despite monogenic and polygenic contributions to cardiovascular disease (CVD), genetic testing is not widely adopted, and current tests are limited by the breadth of surveyed conditions and interpretation burden. Methods: We developed a comprehensive clinical genome CVD test with semi-automated interpretation. Monogenic conditions and risk alleles were selected based on the strength of disease association and evidence for increased disease risk, respectively. Non-CVD secondary findings genes, pharmacogenomic (PGx) variants and CVD polygenic risk scores (PRS) were assessed for inclusion. Test performance was modeled using 2,594 genomes from the 1000 Genomes Project, and further investigated in 20 previously tested individuals. Results: The CVD genome test is composed of a panel of 215 CVD gene-disease pairs, 35 non-CVD secondary findings genes, 4 risk alleles or genotypes, 10 PGx genes and a PRS for coronary artery disease. Modeling of test performance using samples from the 1000 Genomes Project revealed ~6% of individuals with a monogenic finding in a CVD-associated gene, 6% with a risk allele finding, ~1% with a non-CVD secondary finding, and 93% with CVD-associated PGx variants. Assessment of blinded clinical samples showed complete concordance with prior testing. An average of 4 variants were reviewed per case, with interpretation and reporting time ranging from 9-96 min. Conclusions: A genome sequencing based CVD genetic risk assessment can provide comprehensive genetic disease and genetic risk information to patients with CVD. The semi-automated and limited interpretation burden suggest that this testing approach could be scaled to support population-level initiatives.