Phenology and habitat associations of the invasive Asian longhorned tick from Ohio, USA.

Geographically expanding and invading ticks are a global concern. The Asian longhorned tick (ALT, Haemaphysalis longicornis) was introduced to the mid-Atlantic US between 2010 and 2017 and recently invaded Ohio, an inland state. To date, ALTs in the US have been associated with livestock exsanguination and transmission of the agent of bovine theileriosis. To inform management, studies describing tick ecology and epidemiology of associated disease agents are critical. In this study, we described phenology, habitat and host associations, and tested for agents of medical and veterinary concern at the site of the first known established ALT population in Ohio, where pesticide treatment was applied in early fall 2021. In spring-fall 2022, we sampled wildlife (small mammals) and collected ticks from forest, edge, and grassland habitats. We also opportunistically sampled harvested white-tailed deer at nearby processing stations and fresh wildlife carcasses found near roads. Field-collected ALTs were tested for five agents using real-time PCR. We found that ALT nymphs emerged in June, followed by adults, and concluded with larvae in the fall. ALTs were detected in all habitats but not in wildlife. We also found a 4.88% (2/41) prevalence of Anaplasma phagocytophilum across ALT adults and nymphs. Host and habitat associations were similar to other studies in the eastern United States, but two potential differences in phenology were identified. Whether ALTs will acquire more endemic disease agents requires further investigations. Our findings provide the first evidence regarding ALT life history from the Midwest region of the United States and can inform exposure risk and guide integrated management.

Learning of clinical pharmacology by future prescribers in Bologna: Teachers' and students' reflections on the way forward.

AIMS: In this reflection paper, the authors, based on their experience as teachers and students of the courses of Pharmacology at the University of Bologna, reflect on their specific roles towards innovation in the teaching of Clinical Pharmacology. METHODS: Strengths, weaknesses and challenges are presented as identified during the teaching and learning experience in the currently evolving medical degree programmes of the University in light of current trends in medical education. RESULTS: Keeping in mind the identified challenges together with the features proposed for the model prescriber (knowledgeable, contemporary, communicative and safe), we indicate some ways to improve the students' experience and make sure they develop up-to-date skills in Clinical Pharmacology taking advantage of recent ongoing collaborations at European level. International collaboration is indeed necessary to adequately address the current challenges of teaching clinical pharmacology. CONCLUSION: Our shared conclusion is that empowering students with a scientifically sound method to retrieve relevant information and developing their skills to communicate in an interprofessional and, wherever possible, international environment is the key to prepare future prescribers and, ultimately, to improve patient safety.

Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging.

OBJECTIVE: Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity. METHODS: Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool. RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone. CONCLUSIONS: The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.

Transorbital sonography in idiopathic intracranial hypertension: Single-center study, systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) provides a noninvasive tool to detect intracranial pressure by assessing optic nerve sheath diameter (ONSD) and optic disc elevation (ODE). The utility of TOS in the diagnosis of idiopathic intracranial hypertension (IIH) has been increasingly recognized. METHODS: A single-center case-control study sought to compare TOS-acquired ONSD and ODE among IIH-cases versus patients with other neurological diseases (controls). Furthermore, a systematic review and meta-analysis was conducted to present pooled mean differences and diagnostic measures of ONSD and ODE between IIH-cases and controls. RESULTS: In the single-center study, consisting of 31 IIH-cases and 34 sex- and age-matched controls, ONSD values were higher among IIH-cases than controls (p<.001), while ODE was more prevalent in cases (65% vs. 15%; p<.001). The receiver-operating characteristic (ROC)-curve analysis revealed that the optimal cutoff value of ONSD for predicting IIH was 5.15 mm, with an area under the curve (AUC) of 0.914 (95% confidence interval [CI]: 0.861-0.967) and sensitivity and specificity values of 85% and 90%, respectively. In a meta-analysis of 14 included studies with 415 IIH-cases, ONSD and ODE values were higher in IIH-cases than controls (mean difference in ONSD 1.20 mm; 95% CI: 0.96-1.44 mm and in ODE 0.3 mm; 95% CI: 0.33-0.67 mm). With regard to ONSD, pooled sensitivity, specificity, and diagnostic odds ratio were calculated at 85.5% (95% CI: 77.9-90.8%), 90.7% (95% CI: 84.6-94.5%), and 57.394 (95% CI: 24.597-133.924), respectively. The AUC in summary ROC-curve analysis was 0.878 (95% CI: 0.858-0.899) with an optimal cutoff point of 5.0 mm. CONCLUSIONS: TOS has a high diagnostic utility for the noninvasive diagnosis of IIH and may deserve wider implementation in everyday clinical practice.

Describing the experience of livestock producers from Ohio, USA with ticks and associated diseases.

BACKGROUND: As tick ranges expand across North America, the risk of tick bites and tick-borne diseases (TBDs, i.e. diseases or syndromes associated with ticks) rises for humans and animals, making prevention critical. Several U.S. studies have examined knowledge, attitudes, and practices regarding ticks and TBDs for various cohorts of people. However, among occupational groups with high exposure risk from ticks and TBDs are livestock producers, of which we know little about. To help address this gap, an electronic questionnaire was distributed to livestock producers in Ohio, U.S, a state with a robust agricultural sector. METHODS: We generated descriptive statistics and conducted a multiple correspondence analysis followed by hierarchical clustering on principal components to identify producers with similar response profiles. RESULTS: Responses from 57 producers showed that most (52.6%) think the American dog tick (Dermacentor variabilis) is found in Ohio but are unsure about other species. Although several TBDs are present in Ohio, most (> 50%) producers were unsure or unaware of their presence. Interestingly, most (54.4%) thought ticks pose major health risks for their livestock but fewer (49.1%) thought the same for humans. Regardless, most producers did employ at least one prevention method for themselves (96.5%) and their animals (82.5%). Cluster analysis (n = 48) identified three groups: the largest (n = 21) was considered "aware and cautious" consisting primarily of farm owners. The others generally practiced less prevention and consisted primarily of farm employees. CONCLUSIONS: Our findings indicate that producers in Ohio practice prevention for themselves and their livestock, but demonstrate gaps in knowledge (e.g., TBD occurrence) and attitudes (e.g., health risks) that could be addressed via educational formats we found producers preferred (e.g., extension materials), to encourage informed prevention. This is especially important for farm employees that may practice less prevention because of lower awareness. Our study can guide others in regions faced with similar tick and TBD risks to protect occupational and livestock health.

Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis.

INTRODUCTION: Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention. METHODS: We conducted a systematic review and meta-analysis including all available randomized controlled clinical trials (RCTs) that investigated the efficacy and safety of factor XIa inhibitors versus controls in primary or secondary stroke prevention. The primary efficacy and safety outcomes of interest were symptomatic ischemic stroke (IS) and the composite of major bleeding and clinically relevant non-major bleeding. RESULTS: Four phase II dose-finding RCTs were included, comprising a total of 4732 patients treated with factor XIa inhibitors versus 1798 controls. Treatment with factor XIa inhibitors did not reduce the risk of IS compared to controls (RR: 0.89; 95% CI: 0.67-1.17). The composite of symptomatic IS and covert infarcts on brain MRI (RR: 1.01; 95% CI: 0.87-1.18), the composite of symptomatic IS and transient ischemic attack (TIA; RR: 0.78; 95% CI: 0.61-1.01), and the composite of major adverse cardiovascular events (RR: 1.07; 95% CI: 0.87-1.31) did not differ between the treatment groups. Treatment with factor XIa inhibitors did not increase the risk of the composite of major bleeding and clinically relevant non-major bleeding (RR: 1.19; 95% CI: 0.65-2.16), major bleeding alone (RR: 1.19; 95% CI: 0.64-2.22), intracranial bleeding (RR: 0.91; 95% CI: 0.26-3.19) or all-cause mortality (RR: 1.21; 95% CI: 0.77-1.90). CONCLUSION: This meta-analysis provides reassuring evidence regarding the safety of factor XIa inhibitors. These findings, coupled with potential signals of efficacy in reducing IS (and TIA), underscore the importance of ongoing phase III RCTs for providing definitive data regarding the effect of factor XIa inhibition on stroke prevention.

An established population of Asian longhorned ticks (Acari: Ixodidae) in Ohio, USA.

We describe the first known established Asian longhorned tick (ALT) (Acari: Ixodidae: Haemaphysalis longicornis Neumann) population in Ohio, USA. In mid-summer 2021, we collected ALTs from an infested pasture in response to an alert that grazing cattle had been infested with ticks, and 3 of them had died. No ALTs were reported following pesticide treatment of the pasture in fall 2021. In the laboratory, we identified 9,287 ticks to species, representing all 3 life stages, as ALTs and tested 100 of the adult females for infectious agents relevant to human and animal health, including Theileria orientalis, a cattle disease agent. Eight field-collected ticks were positive for Anaplasma phagocytophilum (n = 100, 8%); no other infectious agents were detected. Active environmental surveillance showed the return of ALTs in June 2022 despite the tick control efforts in 2021. As ALTs continue to expand their range in the United States, active and passive surveillance studies will be needed to characterize their evolving role in human and animal health.

A survey of knowledge, attitudes, and practices of veterinary professionals regarding ticks and tick-borne diseases: Insights from Ohio, USA.

Globally, ticks are becoming more problematic as agricultural pests and vectors of tick-borne diseases (TBDs), many of which are shared between animals and people. Veterinary professionals, including veterinarians and non-veterinarians, are considered a vulnerable group through occupational exposure. To inform educational interventions at the intrapersonal level, a common approach is to first assess knowledge, attitudes, and practices (KAP) of target populations. Thus, our objective was to assess KAP of veterinary professionals in Ohio, a state faced with expanding and invading ticks of medical and veterinary concern. Using a convenience sample, we surveyed 178 veterinary professionals across Ohio with an electronic questionnaire that covered knowledge, attitudes, practices, exposures, demography, education, and surveillance regarding ticks and TBDs. We found that veterinary professionals had cautionary attitudes towards ticks and TBDs and practiced prevention for themselves and their patients, even when tick exposures were infrequently reported. However, veterinary professionals significantly lacked in knowledge regarding tick biology and local TBD epidemiology. Furthermore, we found that knowledge regarding tick biology and attitudes towards ticks and TBDs did not associate with practices. Instead, we found that veterinarian status and routine tick checks of patients were associated with frequent discussions of tick prevention with clients. Our findings emphasize that most tick exposures of veterinary professionals are occupational, and thus prevention should start at the workplace. Cultivating knowledge of veterinary professionals regarding tick biology and local TBD epidemiology may lead to greater motivation and confidence with identifying ticks and testing for TBDs, which may also increase the diagnostic capacity of veterinary professionals for tick and TBD surveillance. Because veterinary professionals typically interact with both animals and their owners, improving their KAP regarding ticks and TBDs, can in turn promote animal, human, and environmental health within a "One Health" context.

Endovascular Treatment for Acute Basilar Artery Occlusion: A Fragility Index Meta-Analysis.

INTRODUCTION: High-quality evidence regarding the use of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) has been provided by recently completed randomized controlled clinical trials (RCTs). METHODS: We conducted a systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of EVT in addition to best medical treatment (BMT) versus BMT alone for BAO. The random-effects model was used, while the fragility index (FI) was calculated for dichotomous outcomes of interest. RESULTS: Four RCTs were included comprising a total of 988 patients with acute BAO (mean age: 65.6 years, 70% men, median NIHSS: 24, 39% pretreatment with intravenous thrombolysis). EVT was related to higher likelihood of good functional outcome (RR: 1.54; 95% CI: 1.16-2.05; I2 = 60%), functional independence (RR: 1.83; 95% CI: 1.08-3.08; I2 = 79%) and reduced disability at 3 months (adjusted common OR: 1.96; 95% CI: 1.26-3.05; I2 = 59%) compared to BMT alone. Despite that EVT was associated with a higher risk for symptomatic intracranial hemorrhage (RR: 7.78; 95% CI: 2.36-25.61; I2 = 0%) and any intracranial hemorrhage (RR: 2.85; 95% CI: 1.50-5.44; I2 = 16%), mortality at 3 months was lower among patients that received EVT plus BMT versus BMT alone (RR: 0.76; 95% CI: 0.65-0.89; I2 = 0%). However, sufficient robustness was not evident in any of the reported associations (FI < 10) including the overall effect regarding the primary outcome. The former associations were predominantly driven by RCTs with recruitment limited in China. CONCLUSIONS: EVT combined with BMT is associated with a higher likelihood of achieving good functional outcomes and a lower risk of death at 3 months compared to BMT alone, despite the higher risk of sICH. An individual-patient data meta-analysis is warranted to uncover and adjust for potential sources of heterogeneity and to provide further insight.

Molecular prevalence of Anaplasma marginale and associated risk factors in beef cattle herds from Ohio: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of Anaplasma marginale, the causative agent of bovine anaplasmosis, in beef herds from Ohio; evaluate farm identity and animal age as risk factors; and examine serologic cross-reactivity with Anaplasma phagocytophilum, an emerging disease agent. ANIMALS: 4 beef cattle herds (n = 327) sampled between December 2020 and December 2021. PROCEDURES: To address the broader investigation of characterizing Anaplasma spp and genotypes in Ohio, herds with a history of clinical anaplasmosis were targeted. Blood was screened for antibodies to Anaplasma spp using a competitive enzyme-linked immunosorbent assay with seropositive samples tested for A marginale using real-time PCR. If negative, samples were also tested for A phagocytophilum. RESULTS: We estimated a statewide molecular prevalence of 38.53% (95% CI, 33.26% to 43.81%), with some farms exhibiting higher prevalence than others (19.40% to 56.86%). Accounting for farm identity, the odds of an animal becoming infected increased by 1.41 (95% CI, 1.28 to 1.58) for every year in age. Forty-four animals tested seropositive but PCR negative for A marginale. Out of these, 2 tested positive for A phagocytophilum. CLINICAL RELEVANCE: Our study was the first to report prevalence estimates for bovine anaplasmosis in Ohio. Although prevalence was higher than other states, this is most likely due to our sampling approach. Our results suggested that older animals are more likely to be infected with A marginale, and when animals are instead infected with A phagocytophilum, serology alone can be misleading wherever the 2 species co-occur. Our study can guide wider epidemiological studies for informing management in Ohio.

Physiological links with behavior and fitness: The acute adrenocortical response predicts trappability but not survival in male and female deermice.

The "Cort-Fitness" hypothesis predicts a negative relationship between baseline glucocorticoids (GCs) and fitness, although evidence for this hypothesis remains mixed. Such ambiguity could partially exist because blood GCs, typically used in field studies, can fluctuate too rapidly to measure accurately, while the relationship between GCs and trappability is often neglected. Here, by addressing these factors, we examined relationships between GC measures and survival of North American deermice (Peromyscus maniculatus; hereafter deermice) as a model system. To do this, we used more stable GC measures, including the integrated measures of baseline and stress response fecal corticosterone metabolites (FCMs), and downstream measures of neutrophil/lymphocyte ratio (N/L ratio), and body condition score (BCS), to characterize their relationships with survival and trappability. Over two years, deermice were live-trapped monthly, evaluated for BCS, and sampled for feces and blood. Stress response FCMs were evaluated only at first capture. Mark-recapture models, with GC measures as predictors of either survival or trappability, were compared to identify top models. We found that stress response FCMs negatively predicted trappability, and weaker evidence that BCS positively predicted survival. Although the latter provides some support for the "Cort-Fitness" hypothesis, there was no support when using integrated measures. Instead, our findings suggest that deermice with a lower adrenocortical response (i.e. stress response FCMs) were more likely to be captured. Therefore, GC-trappability relationships must be investigated in field studies to avoid linking the wrong GC profile to fitness, and physiological measures other than blood GCs may be useful for detecting GC-fitness patterns.

Evaluating the cerebrospinal fluid tap test with the Hellström iNPH scale for patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: The cerebrospinal fluid tap test (CSF TT) is used for selecting shunt surgery candidates among patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to evaluate the predictive value of the CSF TT, by using the Hellström iNPH scale for shunted iNPH patients with a standardized method. METHODS: One hundred and sixteen shunt-operated iNPH patients were retrospectively included in this study. The gait and balance domains in the iNPH scale were used as outcome measures for the CSF TT and the total iNPH scale score as the postoperative outcome. A positive response to CSF TT was defined as a change of ≥ 5 points in the gait domain and ≥ 16 points in the balance domain. Differences between CSF TT responders and non-responders, sensitivity, specificity, positive and negative predictive values, accuracy, and correlations between changes from baseline to post CSF TT and from baseline to the postoperative follow-up, were calculated. RESULTS: In the CSF TT there were 63.8% responders in the gait domain and correspondingly 44.3% in the balance domain. CSF TT responders had a significantly better postoperative outcome in the total scale score (gait P ≤ 0.001, balance P ≤ 0.012) and gait CSF TT responders improved more in gait (P ≤ 0.001) and balance CSF TT responders in balance (P ≤ 0.001). No differences between CSF TT gait or balance responders could be found in neuropsychological or urinary continence assessments postoperatively. The sensitivity and specificity of the CSF TT and the outcome of the total iNPH scale score postoperatively were 68.1% and 52.0% for gait and 47.8% and 68.0% for balance, respectively. CONCLUSIONS: The CSF TT, with the Hellström iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive.

Optical Coherence Tomography Revealing Ganglion Cell Loss in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Although there may theoretically be a disturbance in the eye or the visual pathways due to abnormal cerebrospinal fluid (CSF) dynamics in idiopathic normal pressure hydrocephalus (iNPH), it has not been studied systemically. Optical coherence tomography (OCT) is a noninvasive, reproducible procedure for quantitative and qualitative analysis of retinal morphology. METHODS: OCT was used to study the eye fundus before and after a CSF tap test in patients with iNPH compared with healthy individuals (HIs). Twelve patients with iNPH (6 females and 6 males) with a median age of 76 years (64-84 years) and 21 HIs (11 females and 10 males) with a median age of 73 years (64-79 years) were included. The patients underwent neurological, cognitive, and physiotherapeutic evaluation. Brain magnetic resonance imaging, CSF tap test via lumbar puncture, and subsequently CSF analysis were performed. OCT was performed before and after CSF removal. HIs underwent OCT once. RESULTS: The patients had significantly reduced retinal ganglion cell layer thickness 71 µm (56-81 µm) compared with the HIs, 79.5 µm (72-90 µm) (P = 0.001), but no significant changes were observed before or after the CSF tap test. All patients improved in motor function in a 10-m walk test after the CSF tap test. The median CSF pressure was 15 and 1 cm H2O, respectively, before and after lumbar puncture with removal of median 43.5 mL CSF. CONCLUSIONS: This pilot study shows OCT findings that differ from HIs and implies a rational for becoming a valuable tool in the diagnosis of iNPH. Further studies are warranted to elucidate the pathology of the retina in iNPH.

Relationships among host microbiota, parasite resistance or tolerance, and host fitness.

Article impact statement: Parasite-induced shifts in host microbiota that lead to parasite resistance or tolerance may have unintended consequences for host fitness.

Publisher Correction: Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Imaging Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Assessment of the Stress Response in North American Deermice: Laboratory and Field Validation of Two Enzyme Immunoassays for Fecal Corticosterone Metabolites.

Stress physiology is commonly employed in studies of wildlife ecology and conservation. Accordingly, we need robust and suitable methods to measure stress physiology in the field. Fecal cortisol/corticosterone metabolites (FCMs) are now increasingly being used to non-invasively evaluate adrenocortical activity; a measure of stress physiology. However, immunoassays that measure FCMs must be appropriately validated prior to their use and factors that can influence FCMs, such as trap-induced stress, must be considered. Deermice (Peromyscus maniculatus) are widely used in scientific studies so that developing methods that appropriately measure their adrenocortical activity is critical. In the laboratory, we tested the suitability of two enzyme immunoassays (EIAs; a corticosterone EIA, and a group-specific 5α-pregnane-3ß,11ß,21-triol-20-one EIA) in deermice by challenging individuals with dexamethasone and adrenocorticotropic hormone (ACTH). We found that dexamethasone suppressed FCM levels within ~10 h post injection whereas ACTH increased FCM levels within ~2 h post injection. In the field, we found that FCM levels generally increased with more time in trap confinement when using both EIAs. Although we acknowledge low sample sizes (N = 4), our results validated the two EIAs for use with FCMs from deermice.