Modelling the role of enzymatic pathways in the metabolism of docosahexaenoic acid by monocytes and its association with osteoarthritic pain.

Chronic pain is a major cause of disability and suffering in osteoarthritis (OA) patients. Endogenous specialised pro-resolving molecules (SPMs) curtail pro-inflammatory responses. One of the SPM intermediate oxylipins, 17-hydroxydocasahexaenoic acid (17-HDHA, a metabolite of docosahexaenoic acid (DHA)), is significantly associated with OA pain. The aim of this multidisciplinary work is to develop a mathematical model to describe the contributions of enzymatic pathways (and the genes that encode them) to the metabolism of DHA by monocytes and to the levels of the down-stream metabolites, 17-HDHA and 14-hydroxydocasahexaenoic acid (14-HDHA), motivated by novel clinical data from a study involving 30 participants with OA. The data include measurements of oxylipin levels, mRNA levels, measures of OA severity and self-reported pain scores. We propose a system of ordinary differential equations to characterise associations between the different datasets, in order to determine the homeostatic concentrations of DHA, 17-HDHA and 14-HDHA, dependent upon the gene expression of the associated metabolic enzymes. Using parameter-fitting methods, local sensitivity and uncertainty analysis, the model is shown to fit well qualitatively to experimental data. The model suggests that up-regulation of some ALOX genes may lead to the down-regulation of 17-HDHA and that dosing with 17-HDHA increases the production of resolvins, which helps to down-regulate the inflammatory response. More generally, we explore the challenges and limitations of modelling real data, in particular individual variability, and also discuss the value of gathering additional experimental data motivated by the modelling insights.

Estimation of sensitivity and specificity of bulk tank milk PCR and 2 antibody ELISA tests for herd-level diagnosis of Mycoplasma bovis infection using Bayesian latent class analysis.

Mycoplasmosis (due to infection with Mycoplasma bovis) is a serious disease of beef and dairy cattle that can adversely impact health, welfare and productivity (Maunsell et al. (2011)). Mycoplasmosis can lead to a range of often severe, clinical presentations. Mycoplasma bovis (M. bovis) infection can present either clinically or subclinically, with the potential for recrudescence of shedding in association with stressful periods. Infection can be maintained within herds because of intermittent shedding (Calcutt et al., 2018, Hazelton et al., 2018). M. bovis is recognized as poorly responsive to treatment which represents a major challenge for control in infected herds. Given this, particular focus is needed on biosecurity measures to prevent introduction into uninfected herds in the first place. A robust and reliable laboratory test for surveillance is important both for herd-level prevention and control. The objective of this study was to estimate the sensitivity and specificity of 3 diagnostic tests (one PCR and 2 ELISA tests) on bulk tank milk, for the herd-level detection of M. bovis using Bayesian latent class analysis. In autumn 2018, bulk tank milk samples from 11,807 herds, covering the majority of the main dairy regions in Ireland had been submitted to the Department of Agriculture testing laboratory for routine surveillance were made available. A stratified random sample approach was used to select a cohort of herds for testing from this larger sample set. A final study population of 728 herds had bulk tank milk samples analyzed using a Bio-X ELISA (ELISA 1), an IDvet ELISA (ELISA 2) and a PCR test. A Bayesian latent class analysis (BLCA) was conducted to estimate the sensitivity (Se) and specificity (Sp) of the 3 diagnostic tests applied to bulk tank milk (BTM) for the detection of the herd-level infection. An overall LCA was conducted on all herds within a single population (a 3-test, 1-population model). The herds were also split into 2 populations based on herd size (small herds had < 82 cattle) (a 3-test, 2-population model) and separately into 3 regions in Ireland (Leinster, Munster and Connacht/Ulster) (a 3-test, 3-population model). The latent variable of interest was the herd-level M. bovis infection status. In total, 363/728 (50%) were large herds, 7 (1.0%) were positive on PCR, 88 (12%) positive on ELISA 1, and 406 (56%) positive on ELISA 2. Based on the 2-population model, the sensitivity (95% Bayesian credible interval (BCI) was 0.03 (0.02, 0.05), 0.22 (0.18, 0.27), 0.94 (0.88, 0.98) for PCR, ELISA 1 and ELISA 2 respectively. The specificity (95% BCI) was 0.99 (0.99, 1.0), 0.97 (0.95, 0.99), and 0.92 (0.86, 0.97) for PCR, ELISA 1 and ELISA 2 respectively. The herd-level true prevalence was estimated at 0.43 (BCI 0.35, 0.5) for smaller herds. The true prevalence was estimated at 0.62 (BCI 0.55, 0.69) for larger herds. The true prevalence was estimated at 0.56 (BCI 0.49, 0.463) in the 1-population model. For the 3-population model, the sensitivity (95% BCI) was 0.03 (0.02, 0.05), 0.24 (0.18, 0.29), 0.95 (0.9, 0.98) for PCR, ELISA 1 and ELISA 2 respectively. The specificity (95% BCI) was 0.99 (0.99, 1.0), 0.98 (0.96, 0.99), and 0.88 (0.79, 0.95) for PCR, ELISA 1 and ELISA 2 respectively. The herd-level true prevalence (95% BCI) was estimated at 0.65 (0.56, 0.73), 0.38 (0.28, 0.46) and 0.53 (0.4, 0.65) for population 1, 2, 3 respectively. Across all 3 models, the range in true prevalence was 38% to 65% of Irish dairy herds infected with M. bovis. The operating characteristics vary substantially between tests. The IDvet ELISA had a relatively high Se (the highest Se of the 3 tests studied) but it was estimated at 0.95 at its highest in 3-test, 3-population model. This test may be an appropriate test for herd-level screening or prevalence estimation within the context of the endemically infected Irish dairy cattle population. Further work is required to optimize this test and its interpretation when applied at herd-level to offset concerns related to the lower than optimal test Sp.

Pediatric non-galenic pial arteriovenous fistula's characteristics and outcomes: a systematic review.

INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.

Bovine Herpes Virus Type 1 (BoHV-1) seroprevalence, risk factor and Bovine Viral Diarrhoea (BVD) co-infection analysis from Ireland.

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged < 30 months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1130/5273; 95%CI: 20.32-22.53%). Univariable analysis suggested that BoHV-1 seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland declined in 2020 relative to 2018 (from 23.32 to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.

More May Not be Better: Enhanced Spacecraft Shielding May Exacerbate Cognitive Decrements by Increasing Pion Exposures during Deep Space Exploration.

The pervasiveness of deep space radiation remains a confounding factor for the transit of humans through our solar system. Spacecraft shielding both protects astronauts but also contributes to absorbed dose through galactic cosmic ray interactions that produce secondary particles. The resultant biological effects drop to a minimum for aluminum shielding around 20 g/cm2 but increase with additional shielding. The present work evaluates for the first time, the impact of secondary pions on central nervous system functionality. The fractional pion dose emanating from thicker shielded spacecraft regions could contribute up to 10% of the total absorbed radiation dose. New results from the Paul Scherrer Institute have revealed that low dose exposures to 150 MeV positive and negative pions, akin to a Mars mission, result in significant, long-lasting cognitive impairments. These surprising findings emphasize the need to carefully evaluate shielding configurations to optimize safe exposure limits for astronauts during deep space travel.

Autism intervention meta-analysis of early childhood studies (Project AIM): updated systematic review and secondary analysis.

OBJECTIVE: To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental outcomes. DESIGN: Updated systematic review and meta-analysis (autism intervention meta-analysis; Project AIM). DATA SOURCES: A search was conducted in November 2021 (updating a search done in November 2017) of the following databases and registers: Academic Search Complete, CINAHL Plus with full text, Education Source, Educational Administration Abstracts, ERIC, Medline, ProQuest Dissertations and Theses, PsycINFO, Psychology and Behavioral Sciences Collection, and SocINDEX with full text, Trials, and ClinicalTrials.gov. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any controlled group study testing the effects of any non-pharmacological intervention on any outcome in young autistic children younger than 8 years. REVIEW METHODS: Newly identified studies were integrated into the previous dataset and were coded for participant, intervention, and outcome characteristics. Interventions were categorized by type of approach (such as behavioral, developmental, naturalistic developmental behavioral intervention, and technology based), and outcomes were categorized by domain (such as social communication, adaptive behavior, play, and language). Risks of bias were evaluated following guidance from Cochrane. Effects were estimated for all intervention and outcome types with sufficient contributing data, stratified by risk of bias, using robust variance estimation to account for intercorrelation of effects within studies and subgroups. RESULTS: The search yielded 289 reports of 252 studies, representing 13 304 participants and effects for 3291 outcomes. When contributing effects were restricted to those from randomized controlled trials, significant summary effects were estimated for behavioral interventions on social emotional or challenging behavior outcomes (Hedges' g=0.58, 95% confidence interval 0.11 to 1.06; P=0.02), developmental interventions on social communication (0.28, 0.12 to 0.44; P=0.003); naturalistic developmental behavioral interventions on adaptive behavior (0.23, 0.02 to 0.43; P=0.03), language (0.16, 0.01 to 0.31; P=0.04), play (0.19, 0.02 to 0.36; P=0.03), social communication (0.35, 0.23 to 0.47; P<0.001), and measures of diagnostic characteristics of autism (0.38, 0.17 to 0.59; P=0.002); and technology based interventions on social communication (0.33, 0.02 to 0.64; P=0.04) and social emotional or challenging behavior outcomes (0.57, 0.04 to 1.09; P=0.04). When effects were further restricted to exclude caregiver or teacher report outcomes, significant effects were estimated only for developmental interventions on social communication (0.31, 0.13 to 0.49; P=0.003) and naturalistic developmental behavioral interventions on social communication (0.36, 0.23 to 0.49; P<0.001) and measures of diagnostic characteristics of autism (0.44, 0.20 to 0.68; P=0.002). When effects were then restricted to exclude those at high risk of detection bias, only one significant summary effect was estimated-naturalistic developmental behavioral interventions on measures of diagnostic characteristics of autism (0.30, 0.03 to 0.57; P=0.03). Adverse events were poorly monitored, but possibly common. CONCLUSION: The available evidence on interventions to support young autistic children has approximately doubled in four years. Some evidence from randomized controlled trials shows that behavioral interventions improve caregiver perception of challenging behavior and child social emotional functioning, and that technology based interventions support proximal improvements in specific social communication and social emotional skills. Evidence also shows that developmental interventions improve social communication in interactions with caregivers, and naturalistic developmental behavioral interventions improve core challenges associated with autism, particularly difficulties with social communication. However, potential benefits of these interventions cannot be weighed against the potential for adverse effects owing to inadequate monitoring and reporting.

Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium.

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Uncovering the Protective Neurologic Mechanisms of Hypofractionated FLASH Radiotherapy.

Implementation of ultra-high dose-rate FLASH radiotherapy (FLASH-RT) is rapidly gaining traction as a unique cancer treatment modality able to dramatically minimize normal tissue toxicity while maintaining antitumor efficacy compared with standard-of-care radiotherapy at conventional dose rate (CONV-RT). The resultant improvements in the therapeutic index have sparked intense investigations in pursuit of the underlying mechanisms. As a preamble to clinical translation, we exposed non-tumor-bearing male and female mice to hypofractionated (3 × 10 Gy) whole brain FLASH- and CONV-RT to evaluate differential neurologic responses using a comprehensive panel of functional and molecular outcomes over a 6-month follow-up. In each instance, extensive and rigorous behavioral testing showed FLASH-RT to preserve cognitive indices of learning and memory that corresponded to a similar protection of synaptic plasticity as measured by long-term potentiation (LTP). These beneficial functional outcomes were not found after CONV-RT and were linked to a preservation of synaptic integrity at the molecular (synaptophysin) level and to reductions in neuroinflammation (CD68+ microglia) throughout specific brain regions known to be engaged by our selected cognitive tasks (hippocampus, medial prefrontal cortex). Ultrastructural changes in presynaptic/postsynaptic bouton (Bassoon/Homer-1 puncta) within these same regions of the brain were not found to differ in response to dose rate. With this clinically relevant dosing regimen, we provide a mechanistic blueprint from synapse to cognition detailing how FLASH-RT reduces normal tissue complications in the irradiated brain. Significance: Functional preservation of cognition and LTP after hypofractionated FLASH-RT are linked to a protection of synaptic integrity and a reduction in neuroinflammation over protracted after irradiation times.

Legal Minors Who Inject: Differences in Socio-Demographics and Treatment Needs Compared to Adults in a Swedish National Sample of People with Injecting Drug Use.

BACKGROUND: Injection drug use among legal minors is under-researched. Although the population may be small in absolute terms, treatment needs may be greater than for those who began injecting as adults. Such knowledge may help tailor services more effectively. Previous research tends to use selective samples or focuses solely on medical indicators. The present study uses a larger sample drawn from national register data in Sweden over a 9-year period (2013-2021) to analyze differences in medical and social treatment needs between people who began injecting as legal minors and their older counterparts. METHOD: Data on first-time visitors to needle and syringe programmes (n = 8225, mean age 37.6, 26% women) were used. Historical socio-demographics and presenting treatment needs were compared between those with a debut injecting age under 18, and those who began injecting as adults. RESULTS: The prevalence of injecting before 18 years was 29%. This group had more negative social circumstances, such as leaving school early, worse health, and greater service consumption, compared to those who began injecting as adults. In particular, they had been subjected to a greater level of control measures, such as arrest and compulsory care. CONCLUSIONS: The present study shows that there are important health and social differences between those who inject prior to 18 and those who begin injecting as adults. This raises important questions for both child protection services and harm reduction approaches for legal minors who inject, who still qualify as 'children' in a legal and policy sense.

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-site Integrative Data Analysis by the Autism Sensory Research Consortium.

Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. Methods Leveraging a combined sample of 3,868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses unambiguously supported the validity of a supra-modal HYPER construct (ω H = .800), whereas a coherent supra-modal HYPO construct was not supported (ω H = .611), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ω H = .799; 4/7 modalities). Within each sensory construct, modality-specific subscales demonstrated substantial added value beyond the supra-modal score. Meta-analytic correlations varied by construct, although sensory features tended to correlate most strongly with other domains of core autism features and co-occurring psychiatric symptoms. Certain subconstructs within the HYPO and SEEK domains were also associated with lower adaptive behavior scores. Limitations: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to parent-report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. Conclusion Psychometric issues may limit the degree to which some measures of supra-modal HYPO/SEEK can be interpreted. Depending on the research question at hand, modality-specific response pattern scores may represent a valid alternative method of characterizing sensory reactivity in autism.

Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy.

BACKGROUND: Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes. METHODS: Cohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment. Animals were sacrificed 6 months post-irradiation and tissues were analyzed for neurological and cerebrovascular decrements. RESULTS: The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neurocognitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin), and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and the preservation of the cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels. CONCLUSIONS: Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlights its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefits of FLASH-RT that extend from synapse to cognition and the microvasculature.

Exploring plant volatile-mediated interactions between native and introduced plants and insects.

In invasion scenarios, native and introduced species co-occur creating new interactions and modifying existing ones. Many plant-plant and plant-insect interactions are mediated by volatile organic compounds (VOCs), however, these have seldom been studied in an invasion context. To fill this knowledge gap, we explored some interactions mediated by VOCs between native and introduced plants and insects in a New Zealand system. We investigated whether a native plant, Leptospermum scoparium (manuka), changes its volatile profile when grown adjacent to two European introduced plants, Calluna vulgaris (heather) and Cytisus scoparius (Scotch broom), in a semi-field trial using potted plants without above- or below-ground physical contact. We also investigated the influence of plant cues on the host-searching behaviour of two beetles, the native Pyronota festiva (manuka beetle), and the introduced biocontrol agent Lochmaea suturalis (heather beetle), by offering them their host-plant and non-host volatiles versus clean air, and their combination in a Y-tube olfactometer. As a follow-up, we performed preference/feeding tests in Petri dishes with fresh plant material. Results of the semi-field experiment show a significant reduction in green leaf volatiles, sesquiterpenes and total volatile emissions by manuka plants neighbouring heather. In the Y-tube assays, the native beetle P. festiva performed poorly in discriminating between host and non-host plants based on plant volatile cues only. However, it performed relatively well in the Petri dish tests, where other cues (i.e., visual, gustatory or tactile) were present. In contrast, the introduced beetle L. suturalis showed high host-specificity in both Y-tube and Petri dish assays. This study illustrates the importance of VOCs in mediating interactions between introduced and native species, suggesting that invasive plants can disrupt native plants' communication and affect the host-searching behaviour of native insects. It also reinforces the relevance of regular host testing on introduced weed biocontrol agents to avoid unwanted host shifts or host-range expansion.

Radiology of Intra-Aortic Balloon Pump Catheters.

Radiographs play an important role in ascertaining appropriate placement of the intra-aortic balloon pump catheter. This imaging essay highlights correct and incorrect positioning of these catheters, with emphasis on the variability of radiopaque markers used with different catheter models and on axillary versus femoral catheter placement routes. Keywords: Conventional Radiography, CT, Percutaneous, Cardiac, Vascular, Aorta, Anatomy, Cardiac Assist Devices, Catheters © RSNA, 2022.

"It's always hard being a mom, but the pandemic has made everything harder": A qualitative exploration of the experiences of perinatal women during the COVID-19 pandemic.

BACKGROUND: Understanding the psychosocial impacts of the COVID-19 pandemic in vulnerable groups, such as pregnant and parenting women, is a critical research and clinical imperative. Although many survey-based perinatal health studies have contributed important information about mental health, few have given full voice about the experiences of pregnant and postpartum women during the prolonged worldwide pandemic using a qualitative approach. OBJECTIVE: The purpose of this study is to explore the lived experience of pregnant and postpartum women in the United States during the ongoing COVID-19 pandemic. DESIGN: Qualitative phenomenological study. SETTING: This study was conducted in the community, by recruiting women throughout the U.S. PARTICIPANTS: Fifty-four pregnant and postpartum women participated in qualitative interviews. METHODS: Data from one-on-one semi-structured interviews were analyzed using a team-based phenomenological qualitative approach. RESULTS: Two key themes were apparent: the pandemic has shined a light on the many typical struggles of motherhood; and, there is a lack of consistent, community-based or healthcare system resources available to address the complex needs of pregnant and postpartum women, both in general and during the pandemic. CONCLUSIONS: Going forward, as the world continues to deal with the current pandemic and possible future global health crises, health care systems and providers are encouraged to consider the suggestions provided by these participants: talk early and often to women about mental health; help pregnant and postpartum women create and institute a personal plan for early support of their mental health needs and create an easily accessible mental health network; conceptualize practice methods that enhance coping and resilience; practice in community-based and interdisciplinary teams (e.g., midwives, doulas, perinatal social workers/ psychotherapists) to ensure continuity of care and to foster relationships between providers and pregnant/ postpartum women; and consider learning from other countries' successful perinatal healthcare practices. REGISTRATION: Number (& date of first recruitment): not applicable. TWEETABLE ABSTRACT: Pregnant and postpartum women insist that mental health care must be overhauled, stating the pandemic has highlighted inherent cracks in the system.

Seroprevalence of Mycoplasma bovis in bulk milk samples in Irish dairy herds and risk factors associated with herd seropositive status.

Mycoplasma bovis is a serious disease of cattle worldwide; mastitis, pneumonia, and arthritis are particularly important clinical presentations in dairy herds. Mycoplasma bovis was first identified in Ireland in 1994, and the reporting of Mycoplasma-associated disease has substantially increased over the last 5 years. Despite the presumed endemic nature of M. bovis in Ireland, there is a paucity of data on the prevalence of infection, and the effect of this disease on the dairy industry. The aim of this observational study was to estimate apparent herd prevalence for M. bovis in Irish dairy herds using routinely collected bulk milk surveillance samples and to assess risk factors for herd seropositivity. In autumn 2018, 1,500 herds out of the 16,858 herds that submitted bulk tank milk (BTM) samples to the Department of Agriculture testing laboratory for routine surveillance were randomly selected for further testing. A final data set of 1,313 sampled herds with a BTM ELISA result were used for the analysis. Testing was conducted using an indirect ELISA kit (ID Screen Mycoplasma bovis). Herd-level risk factors were used as explanatory variables to determine potential risk factors associated with positive herd status (reflecting past or current exposure to M. bovis). A total of 588 of the 1,313 BTM samples were positive to M. bovis, providing an apparent herd prevalence of 0.45 (95% CI: 0.42, 0.47) in Irish dairy herds in autumn 2018. Multivariable analysis was conducted using logistic regression. The final model identified herd size, the number of neighboring farms, in-degree and county as statistically significant risk factors for herd BTM seropositivity to M. bovis. The results suggest a high apparent herd prevalence of seropositivity to M. bovis, and evidence that M. bovis infection is now endemic in the Irish dairy sector. In addition, risk factors identified are closely aligned to what we would expect of an infectious disease. Awareness raising and education about this important disease is warranted given the widespread nature of exposure and likely infection in Irish herds. Further work on the validation of diagnostic tests for herd-level diagnosis should be undertaken as a matter of priority.

Postoperative surgical site infection rate in patients with diabetes following Mohs micrographic surgery: a retrospective analysis.

BACKGROUND: Incidence of surgical site infection (SSI) following Mohs micrographic surgery (MMS) amongst patients with diabetes is largely unknown. OBJECTIVE: Evaluate diabetes as a potential SSI risk factor in MMS by comparing SSI incidence in a cohort of patients with and without diabetes. METHODS: A 5-year retrospective review to determine SSI rate in patients with diabetes compared to patients without diabetes. SSI incidence in patients with diabetes was further compared by A1c, and the impact of antibiotics on SSI rate was also examined. RESULTS: Overall rate of SSI was 1.47% (53/3597 cases). SSI rate amongst patients with diabetes was 1.95% (14/719 cases) compared to 1.35% (39/2878 cases) in patients without diabetes, with a non-significant odds ratio for SSI of 1.45 (95% CI = 0.78-2.68, P = 0.241). Multivariable logistic regression analysis revealed no difference in SSI. Stratification of diabetic patients by A1c into ≥7.0 and <7.0 compared to patients without diabetes yielded no statistically significant difference in SSI amongst all groups (P = 0.815). Whether an antibiotic was prescribed did not significantly impact SSI rate between groups. CONCLUSION: No significant difference in postoperative SSI was found in patients with diabetes compared to patients without diabetes following MMS regardless of degree of glycaemic control.

Exposure to environmentally relevant concentrations of ambient fine particulate matter (PM2.5) depletes the ovarian follicle reserve and causes sex-dependent cardiovascular changes in apolipoprotein E null mice.

BACKGROUND: Fine particulate matter (PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. However, effects of exposure to PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. Further, we hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of PM2.5 in females. RESULTS: Hyperlipidemic apolipoprotein E (Apoe) null ovary-intact or ovariectomized female mice and testis-intact male mice were exposed to concentrated ambient PM2.5 or filtered air for 12 weeks, 5 days/week for 4 h/day using a versatile aerosol concentration enrichment system. Primordial, primary, and secondary ovarian follicle numbers were decreased by 45%, 40%, and 17%, respectively, in PM2.5-exposed ovary-intact mice compared to controls (P < 0.05). The percentage of primary follicles with granulosa cells positive for the mitosis marker Ki67 was increased in the ovaries from PM2.5-exposed females versus controls (P < 0.05), consistent with increased recruitment of primordial follicles into the growing pool. Exposure to PM2.5 increased the percentages of primary and secondary follicles with DNA damage, assessed by γH2AX immunostaining (P < 0.05). Exposure to PM2.5 increased the percentages of apoptotic antral follicles, determined by TUNEL and activated caspase 3 immunostaining (P < 0.05). Removal of the ovaries and PM2.5-exposure exacerbated the atherosclerotic effects of hyperlipidemia in females (P < 0.05). While there were statistically significant changes in blood pressure and heart rate variability in PM2.5-compared to Air-exposed gonad-intact males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods. CONCLUSIONS: These results demonstrate that subchronic PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles. Further, PM2.5 exposure and removal of the ovaries each increase atherosclerosis progression in Apoe-/- females. Premature loss of ovarian function is associated with increased risk of osteoporosis, cardiovascular disease and Alzheimer's disease in women. Our results thus support possible links between PM2.5 exposure and other adverse health outcomes in women.

Breaking barriers: Neurodegenerative repercussions of radiotherapy induced damage on the blood-brain and blood-tumor barrier.

Exposure to radiation during the treatment of CNS tumors leads to detrimental damage of the blood brain barrier (BBB) in normal tissue. Effects are characterized by leakage of the vasculature which exposes the brain to a host of neurotoxic agents potentially leading to white matter necrosis, parenchymal calcification, and an increased chance of stroke. Vasculature of the blood tumor barrier (BTB) is irregular leading to poorly perfused and hypoxic tissue throughout the tumor that becomes resistant to radiation. While current clinical applications of cranial radiotherapy use dose fractionation to reduce normal tissue damage, these treatments still cause significant alterations to the cells that make up the neurovascular unit of the BBB and BTB. Damage to the vasculature manifests as reduction in tight junction proteins, alterations to membrane transporters, impaired cell signaling, apoptosis, and cellular senescence. While radiotherapy treatments are detrimental to normal tissue, adapting combined strategies with radiation targeted to damage the BTB could aid in drug delivery. Understanding differences between the BBB and the BTB may provide valuable insight allowing clinicians to improve treatment outcomes. Leveraging this information should allow advances in the development of therapeutic modalities that will protect the normal tissue while simultaneously improving CNS tumor treatments.

Population structure, intergroup interaction, and human contact govern infectious disease impacts in mountain gorilla populations.

Infectious zoonotic diseases are a threat to wildlife conservation and global health. They are especially a concern for wild apes, which are vulnerable to many human infectious diseases. As ecotourism, deforestation, and great ape field research increase, the threat of human-sourced infections to wild populations becomes more substantial and could result in devastating population declines. The endangered mountain gorillas (Gorilla beringei beringei) of the Virunga Massif in east-central Africa suffer periodic disease outbreaks and are exposed to infections from human-sourced pathogens. It is important to understand the possible risks of disease introduction and spread in this population and how human contact may facilitate disease transmission. Here we present and evaluate an individual-based, stochastic, discrete-time disease transmission model to predict epidemic outcomes and better understand health risks to the Virunga mountain gorilla population. To model disease transmission we have derived estimates for gorilla contact, interaction, and migration rates. The model shows that the social structure of gorilla populations plays a profound role in governing disease impacts with subdivided populations experiencing less than 25% of the outbreak levels of a single homogeneous population. It predicts that gorilla group dispersal and limited group interactions are strong factors in preventing widespread population-level outbreaks of infectious disease after such diseases have been introduced into the population. However, even a moderate amount of human contact increases disease spread and can lead to population-level outbreaks.

Dos and don'ts for mHealth-based clinical support among clinicians in South Africa: Results from a 1-day workshop.

Digital technologies continue to penetrate the South African (SA) healthcare sector at an increasing rate. Clinician-to-clinician diagnostic and management assistance through mHealth is expanding rapidly, reducing professional isolation and unnecessary referrals, and promoting better patient outcomes and more equitable healthcare systems. However, the widespread uptake of mHealth use raises ethical concerns around patient autonomy and safety, and guidance for healthcare workers around the ethical use of mHealth is needed. This article presents the results of a multi-stakeholder workshop at which the 'dos and don'ts' pertaining to mHealth ethics in the SA context were formulated and aligned to seven basic recommendations derived from the literature and previous multi-stakeholder, multi-country meetings.