Resilience intervention improves stress-related gene expression in adolescent and young adult HCT recipients.

BACKGROUND: Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes. OBJECTIVE: The objective of the current study was to explore the CTRA gene regulatory impact of the PRISM intervention among AYAs receiving HCT. We hypothesized that patients who received the intervention would have favorable gene expression signatures compared to those in the control arm. STUDY DESIGN: This was an ancillary study within a randomized trial testing the Promoting Resilience in Stress Management (PRISM) intervention on psychosocial outcomes among AYAs aged 12-24 years receiving HCT (NCT03640325). CTRA was quantified through genome-wide transcriptional profiles obtained from whole blood collected at baseline, 1-, and 3-months post HCT. Group differences in CTRA gene expression were estimated using mixed effect linear models. RESULTS: There were no baseline group differences in CTRA expression, but PRISM participants showed a greater decline in CTRA at 1 month compared to controls (ß -0.301 ± SE 0.114, p = 0.016), even when controlling for demographic (Group x Time interaction: F(2, 18) = 7.41, p = 0.004; ß -0.386 ± 0.127, p = 0.007) and clinical covariates (Group x Time interaction: F(2, 20) = 7.03, p = 0.005; ß -0.480 ± 0.144, p = 0.003). These differences were not detectable at 3 months (ß -0.147 ± SE 0.120, p=0.235). CONCLUSIONS: There was a change in stress-related gene expression among AYAs randomized to a psychosocial intervention. The stress-inflammation axis may be a targetable pathway in the AYA HCT population.

"It's what would work for her": An analysis of adaptations to the Individualized Positive Psychosocial Interaction program in US nursing homes.

BACKGROUND AND OBJECTIVES: The Individualized Positive Psychosocial Interaction (IPPI) Program is an adaptable, evidence-based intervention. IPPI trains nursing home care partners to engage residents living with moderate to severe dementia in preference-based, one-to-one interactions using emotion-focused communication. We sought to understand provider-driven adaptations made to the IPPI Program and whether the adaptations made were fidelity-consistent. RESEARCH DESIGN AND METHODS: Data were collected from n=78 interviews with n=23 nursing home provider champions who led a quality improvement project (QIP) to implement the IPPI with 3 to 5 residents per care community. Using content analysis, we report quantitative data on the adaptation characteristics according to the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) core modules and participant quotes to illustrate adaptations. RESULTS: Champions reported 34 adaptations, with an average of 2.6 adaptations per nursing home. The majority of IPPI adaptations pertained to implementation (65%; n=22), while 17% (n=6) were content and 17% (n=6) were context. Motivation for adaptations ranged from organizational (e.g., time constraints) to recipient (e.g., cognitive capacity). Most adaptations made to the IPPI protocol by care partners were fidelity-consistent (92%; n=33). DISCUSSION AND IMPLICATIONS: Care partners' adaptations to the IPPI made the intervention more resident-centric. Future healthcare intervention providers must consider the user perspective and encourage adaptations that further tailor to the user, as long as the adaptations are fidelity-consistent.

Task-specific relationships between error-related ERPs and behavior: Flanker, Stroop, and Go/Nogo tasks.

Performance monitoring has been widely studied during different forced-choice response tasks. Participants typically show longer response times (RTs) and increased accuracy following errors, but there are inconsistencies regarding the connection between error-related event-related brain potentials (ERPs) and behavior, such as RT and accuracy. The specific task in any given study could contribute to these inconsistencies, as different tasks may require distinct cognitive processes that impact ERP-behavior relationships. The present study sought to determine whether task moderates ERP-behavior relationships and whether these relationships are robustly observed when tasks and stimuli are treated as random effects. ERPs and behavioral indices (RTs and accuracy) recorded during flanker, Stroop, and Go/Nogo tasks from 180 people demonstrated a task-specific effect on ERP-behavior relationships, such that larger previous-trial error-related negativity (ERN) predicted longer RTs and greater likelihood of a correct response on subsequent trials during flanker and Stroop tasks but not during Go/Nogo task. Additionally, larger previous-trial error positivity (Pe) predicted faster RTs and smaller variances of RTs on subsequent trials for Stroop and Go/Nogo tasks but not for flanker task. When tasks and stimuli were treated as random effects, ERP-behavior relationships were not observed. These findings support the need to consider the task used for recording performance monitoring measures when interpreting results across studies.

Incidence of pregnancy related pulmonary embolism in Spain 2016-2021: an observational population-based retrospective study.

OBJECTIVE: This study aimed to estimate the overall and annual age-standardized incidence of pregnancy-related pulmonary embolism (PE) in Spain from 2016 to 2021, explore the distribution of PE events during pregnancy and the postpartum period, identify potential risk factors, and estimate mortality rates during hospital admission. METHODS: In a retrospective, observational, population-based study, data from the Spanish National Hospital Discharge Database were analyzed to identify women with hospital episodes of pregnancy-related-PE. The primary outcome was the overall and annual age-standardized incidence of pregnancy-related-PE, with secondary aims including the distribution of events during pregnancy and postpartum and the calculation of age-standardized mortality rates during admission. RESULTS: Among 2,178,805 births from 2016 to 2021, 522 women were diagnosed with pregnancy-related PE, yielding an overall age-standardized incidence of 2.83 cases per 10,000 births. A non-significant increasing trend was observed from 2.43 to 4.18 cases per 10,000 births (p = 0.06). Comorbidities were low, with a notable association between PE and SARS-CoV-2 infection during the last two years. The mortality rate among women with pregnancy-related PE was 2.8%, with a higher incidence of PE reported during the postpartum period. CONCLUSION: The incidence of pregnancy-related-PE in Spain exhibits a non-significant increasing trend, with a significant risk of mortality. The association with SARS-CoV-2 infection underscores the importance of vigilant monitoring and management of pregnant women, particularly during pandemics. This study contributes specific data on the incidence and characteristics of pregnancy-related-PE in Spain, emphasizing the need to consider PE in the differential diagnosis and management strategies for pregnant and postpartum women.

Promoting Resilience in Stress Management for Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes. Objective: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents. Design, Setting, and Participants: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November 30, 2022, at each of 2 children's hospitals, in Seattle, Washington, and Houston, Texas. Participants were ages 13 to 18 years with T1D for at least 12 months and elevated diabetes distress. Intervention: PRISM, a manualized, skills-based, individual intervention program that teaches stress management, goal setting, reframing, and meaning-making, facilitated by a coach and accompanied by a digital app, was delivered in three 30- to 60-minute sessions approximately 2 weeks apart. Main Outcomes and Measures: The 2 primary outcomes, diabetes distress and HbA1c levels, and 3 secondary outcomes, resilience, quality of life, and engagement in self-management behaviors, were assessed at baseline and 6 and 12 months after baseline. Linear mixed-effects regression models were used to evaluate associations between PRISM or usual care (UC) and these outcomes at both time points for the intention-to-treat population. Results: Among 172 adolescents (mean [SD] age, 15.7 [1.6] years), 96 were female (56%), and their baseline mean (SD) HbA1c level was 8.7% (2.0%). No differences were evident between PRISM and UC recipients in HbA1c levels (ß, -0.21 [95% CI, -0.65 to 0.22]; P = .33) or diabetes distress (ß, -2.71 [95% CI, -6.31 to 0.90]; P = .14) or any participant-reported outcome (eg, ß, 2.25 [95% CI, -0.30 to 4.80]; P = .08 for self-management behaviors) at 6 months. At 12 months, there was no statistically significant difference between arms in HbA1c levels (ß, -0.26 [95% CI, -0.72 to 0.19]; P = .25); however, PRISM recipients reported significantly greater amelioration of diabetes distress (ß, -4.59 [95% CI, -8.25 to -0.94]; P = .01) and improvement in self-management behaviors (ß, 3.4 [95% CI, 0.9 to 5.9]; P = .01) compared with UC recipients. Conclusions and Relevance: The findings in this randomized clinical trial of psychosocial and behavioral improvements associated with PRISM at 12 months illustrate the value of a strengths-based intervention. Integrating resilience skills-building with traditional diabetes care may be a promising approach for improving outcomes among adolescents with T1D and elevated diabetes distress. Trial Registration: ClinicalTrials.gov number: NCT03847194.

MicroBundlePillarTrack: A Python package for automated segmentation, tracking, and analysis of pillar deflection in cardiac microbundles.

Movies of human induced pluripotent stem cell (hiPSC)-derived engineered cardiac tissue (microbundles) contain abundant information about structural and functional maturity. However, extracting these data in a reproducible and high-throughput manner remains a major challenge. Furthermore, it is not straightforward to make direct quantitative comparisons across the multiple in vitro experimental platforms employed to fabricate these tissues. Here, we present "MicroBundlePillarTrack," an open-source optical flow-based package developed in Python to track the deflection of pillars in cardiac microbundles grown on experimental platforms with two different pillar designs ("Type 1" and "Type 2" design). Our software is able to automatically segment the pillars, track their displacements, and output time-dependent metrics for contractility analysis, including beating amplitude and rate, contractile force, and tissue stress. Because this software is fully automated, it will allow for both faster and more reproducible analyses of larger datasets and it will enable more reliable cross-platform comparisons as compared to existing approaches that require manual steps and are tailored to a specific experimental platform. To complement this open-source software, we share a dataset of 1,540 brightfield example movies on which we have tested our software. Through sharing this data and software, our goal is to directly enable quantitative comparisons across labs, and facilitate future collective progress via the biomedical engineering open-source data and software ecosystem.

MicroBundlePillarTrack: A Python package for automated segmentation, tracking, and analysis of pillar deflection in cardiac microbundles.

Movies of human induced pluripotent stem cell (hiPSC)-derived engineered cardiac tissue (microbundles) contain abundant information about structural and functional maturity. However, extracting these data in a reproducible and high-throughput manner remains a major challenge. Furthermore, it is not straightforward to make direct quantitative comparisons across the multiple in vitro experimental platforms employed to fabricate these tissues. Here, we present "MicroBundlePillarTrack," an open-source optical flow-based package developed in Python to track the deflection of pillars in cardiac microbundles grown on experimental platforms with two different pillar designs ("Type 1" and "Type 2" design). Our software is able to automatically segment the pillars, track their displacements, and output time-dependent metrics for contractility analysis, including beating amplitude and rate, contractile force, and tissue stress. Because this software is fully automated, it will allow for both faster and more reproducible analyses of larger datasets and it will enable more reliable cross-platform comparisons as compared to existing approaches that require manual steps and are tailored to a specific experimental platform. To complement this open-source software, we share a dataset of 1,540 brightfield example movies on which we have tested our software. Through sharing this data and software, our goal is to directly enable quantitative comparisons across labs, and facilitate future collective progress via the biomedical engineering open-source data and software ecosystem.

Quality of Care in the Last Two Years of Life for Children With Complex Chronic Conditions.

CONTEXT: Limited data exists about care received by children with complex chronic conditions (CCCs) in the final years of their disease and end-of-life (EOL). OBJECTIVE: To examine hospital performance on EOL quality measures and to describe healthcare services during the last two years of life for children with CCCs who died in-hospital. METHODS: Retrospective automated electronic health record review of children with ≥1 CCC ICD-10 diagnosis code, who died inpatient between October 2020 and March 2023 at a single quaternary U.S. children's hospital. Quality was assessed based on performance on 15 measures across five domains: healthcare utilization, interprofessional supports, medical intensity, symptom management, and communication. Quality EOL care and healthcare services in the last two years of life were determined overall by age group and per patient. Descriptive statistics were used to evaluate demographic differences by age. RESULTS: 266 children with CCCs died in the study timeframe; 45% were infants (n = 120), 52% (n = 137) were male, 42% (n = 113) were white, 64% (n = 170) were non-Hispanic, and 59% (n=156) had public insurance. Children had a median of three CCCs (IQR 2.4; range 1-8). On average, children met 69% (SD 13%) of EOL quality measures for which they were eligible. In the two years prior to death, 98% (n = 261) had an ICU admission, 75% (n = 200) had a procedure requiring sedation, and 29% (n = 79) had received cardiopulmonary resuscitation. 86% (n = 229) died in the ICU. CONCLUSION: In this study, children with CCCs met 69% of quality measures and received high-intensity healthcare in the last two years of life.

High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus.

Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (encoded by IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKε. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a regulatory pathway involving rs2297550, Ikaros, and IKKε implicated by human genetics in risk for SLE.

Management of paracondylar process fracture in three horses.

BACKGROUND: Fractures of the paracondylar process of the occipital bone may cause headshaking, neck pain and neurologic deficits. The condition is being recognised more frequently with increasing availability of computed tomography. However, to date only limited information is available as to presentation, treatment, surgical approach and outcome. OBJECTIVES: To describe the clinical signs, imaging findings, treatment, surgical approach and outcome in three horses diagnosed with paracondylar process fracture. STUDY DESIGN: Retrospective case series. METHODS: Clinical records and diagnostic images of affected cases were reviewed. RESULTS: Two cases had ventral nonunion fractures-one of these presented with neck pain, headshaking and behavioural changes, while in the other the fracture was a suspected incidental finding in a case of poor performance. A third case with a more dorsal fracture presented with acute facial nerve paralysis. Diagnosis was by computed tomography in all cases, although imaging of ventral fractures by radiography was found to be feasible. Where clinical signs could be associated confidently with the fracture, conservative management resulted in improvement but not complete resolution. Repeated recurrence of clinical signs after prolonged periods of remission necessitated surgical removal in one case, which was readily accomplished with the aid of ultrasound guidance, and led to rapid resolution of clinical signs without significant post-operative complications. The surgical approach is described. MAIN LIMITATIONS: Limited follow-up was available. CONCLUSIONS: Paracondylar process fracture should be considered as a differential diagnosis for headshaking, neck pain, poor performance and facial paresis, and is a justification for performing computed tomography in such cases. A multi-disciplinary approach is beneficial due to the potential for orthopaedic, neurologic, ophthalmologic and behavioural clinical signs, with additional need for expertise in diagnostic imaging and pain management. Surgical fragment removal should be considered for ventral fractures.

Effects of blood and root-dentin cleaning on the porosity and bond strength of a collagen bioceramic material.

To assess the effect of cleaning protocols on dentin contaminated with blood in reparative endodontic materials, bovine root samples were divided: no contamination (N); contamination (P); contamination and cleaning with saline (S), 2.5% NaOCl+saline (Na) or 2.5% NaOCl+17% EDTA+saline (NaE) and filled with: mineral trioxide aggregate (MTA), calcium-aluminate-cement (C), or C+collagen (Ccol) (n=13). The samples were evaluated for porosity, chemical composition, and bond strength. MTA porosity was lower than C (p=0.02) and higher than Ccol (p<0.001). P and NaE were similar (p=1.00), but higher than the other groups (p<0.001). MTA bond strength was similar to Ccol (p=0.777) and lower than C (p=0.028). P presented lower bond strength than the N (p<0.001); S and Na were similar to each other (p=0.969), but higher than P and lower than N (p<0.001). It was observed a predominance of mixed and cohesive failures. None of the samples showed Ca/P ratio values similar to human hydroxyapatite. This study showed that contamination with blood increased the materials porosity, but dentin cleaning with 2.5% NaOCl reduced this effect, and the collagen additive reduced the material porosity. Furthermore, blood contamination reduced the materials bond strength, and cleaning with saline or 2.5% NaOCl diminished this effect.

Health risk factors among adult individuals with and without diabetes in Brazil: Vigitel (2020-2023).

OBJECTIVE: This study aimed to analyze the risk factors associated with diabetes mellitus (DM) among Brazilian adults. STUDY DESIGN: Cross-sectional study. METHODS: Data of 75,860 Brazilian adults (≥18 years) were collected using the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey (Vigitel) (2020-2023). Variables assessed included self-reported medical diagnosis of DM, sociodemographic factors (sex, age, schooling, marital status) and DM risk factors (regular consumption of sweetened beverages (≥5 times/week), infrequent consumption of fruits and vegetables, and beans (<5 times/week), insufficient physical activity, prolonged screen time on cell phones, computers, tablets (CCT), and television (TV), smoking, heavy episodic drinking, excess weight, and obesity). Logistic regression models estimated crude and adjusted odds ratio (aOR) (adjusted for sociodemographic characteristics) for the association between the risk factors and the presence of DM. RESULTS: The overall prevalence of self-reported DM in the population was 9.2%. There was a lower chance of regular consumption of sweetened beverages (aOR 0.79; 95% CI: 0.65-0.97) and heavy episodic drinking (aOR 0.77; 95% CI: 0.65-0.93) and a greater chance of insufficient physical activity (aOR 1.40; 95% CI: 1.25-1.55), prolonged TV screen time (aOR 1.22; 95% CI: 1.09-1.36), excess weight (aOR 1.62; 95% CI: 1.44-1.82) and obesity (aOR 1.87; 95% CI: 1.67-2.10) among individuals with DM. CONCLUSION: There was a lower chance of regular consumption of sweetened beverages and heavy episodic drinking among individuals with DM and a greater chance of insufficient physical activity, prolonged TV screen time, excess weight, and obesity, among that.

Use of computational modeling to examine fingertip force production in children with hemiplegic cerebral palsy.

Most children with hemiplegic cerebral palsy (HCP), one of the most prevalent subtypes of cerebral palsy, struggle with grasping and manipulating objects. This impairment may arise from a diminished capacity to properly direct forces created with the finger pad due to aberrant force application. Children with HCP were asked to create maximal force with the index finger pad in the palmar (normal) direction with both the paretic and non-paretic hands. The resulting forces and finger postures were then applied to a computational musculoskeletal model of the hand to estimate the corresponding muscle activation patterns. Subjects tended to create greater shear force relative to normal force with the paretic hand (p < 0.05). The resultant force was directed 33.6°±10.8° away from the instructed palmar direction in the paretic hand, but only 8.0°±7.3° in the non-paretic hand. Additionally, participants created greater palmar force with the non-paretic hand than with the paretic hand (p < 0.05). These differences in force production are likely due to differences in muscle activation pattern, as our computational models showed differences in which muscles are active and their relative activations when recreating the measured force vectors for the two hands (p < 0.01). The models predicted reduced activation in the extrinsic and greater reductions in activation in the intrinsic finger muscles, potentially due to reduced voluntary activation or muscle atrophy. As the large shear forces could lead to objects slipping from grasp, muscle activation patterns may provide an important target for therapeutic treatment in children with HCP.

Clusters of resilience and vulnerability: executive functioning, coping and mental distress in patients with diffuse low-grade glioma.

PURPOSE: Diffuse low-grade gliomas (dLGG) often have a frontal location, which may negatively affect patients' executive functions (EF). Being diagnosed with dLGG and having to undergo intensive treatment can be emotionally stressful. The ability to cope with this stress in an adaptive, active and flexible way may be hampered by impaired EF. Consequently, patients may suffer from increased mental distress. The aim of the present study was to explore profiles of EF, coping and mental distress and identify characteristics of each profile. METHODS: 151 patients with dLGG were included. Latent profile analysis (LPA) was used to explore profiles. Additional demographical, tumor and radiological characteristics were included. RESULTS: Four clusters were found: 1) overall good functioning (25% of patients); 2) poor executive functioning, good psychosocial functioning (32%); 3) good executive functioning, poor psychosocial functioning (18%) and; 4) overall poor functioning (25%). Characteristics of the different clusters were lower educational level and more (micro)vascular brain damage (cluster 2), a younger age (cluster 3), and a larger tumor volume (cluster 4). EF was not a distinctive factor for coping, nor was it for mental distress. Maladaptive coping, however, did distinguish clusters with higher mental distress (cluster 3 and 4) from clusters with lower levels of mental distress (cluster 1 and 2). CONCLUSION: Four distinctive clusters with different levels of functioning and characteristics were identified. EF impairments did not hinder the use of active coping strategies. Moreover, maladaptive coping, but not EF impairment, was related to increased mental distress in patients with dLGG.

Direct measurement of repulsive and attractive pair potentials using pairs of optical traps.

We present a technique for measuring the interactions between pairs of colloidal particles in two optical traps. This method is particularly suitable for measuring strongly attractive potentials, an otherwise challenging task. The interaction energy is calculated from the distribution of inter-particle separations by accounting for the contribution from the optical traps with arbitrary trap profiles. The method is simple to implement and applicable to different types of pair potentials and optical trapping geometries. We apply the method to measure dipolar pair interactions in experiments with paramagnetic colloids in external magnetic fields. We obtain consistent and accurate results in all regimes, from strongly attractive to repulsive potentials. By means of computer simulations, we demonstrate that the proposed method can be successfully applied to systems with complex pair interactions characterized by multiple attractive and repulsive regimes, which are ubiquitous in soft and biological matter.

Improving Identification of Firearm Access in Children With Mental Health Complaints.

OBJECTIVE: To determine if electronic medical record (EMR) changes and implementation of a study on firearm storage practices changed identification of firearm exposure in children presenting to a pediatric emergency department (PED) with mental health complaints. We also sought to determine the accuracy of information collected on firearm storage practices. METHODS: Retrospective study of EMR documentation of firearm exposure in PED patients with mental health complaints from January 20, 2015 until November 20, 2017. EMR changes occurred on January 20, 2016 and the firearms study began on February 13, 2016. The primary outcome was documentation of firearm exposure. Secondary outcomes were documentation of unsafe firearm storage practices. We also examined differences between clinical and research documentation of unsafe firearm storage practices post-intervention. We compared groups using descriptive statistics and chi-squared tests. We used statistical process control to examine the relationship between interventions and changes in outcomes. RESULTS: 5582 encounters were examined. Identification of firearm exposure increased from 11 to 17% postintervention. Identification of unsafe storage practices increased from 1.9% to 4.4% across all encounters. Special cause variation in both metrics occurred concurrently with the interventions. Postintervention, unsafe firearms storage practices in firearm owning families were under-identified (39% identified as not triple-safe in clinical data vs 75% in research data). CONCLUSIONS: EMR changes and implementation of a firearms study improved identification of firearm exposure and unsafe storage practices in families of PED patients being evaluated for mental health complaints. However, unsafe storage practices continued to be under-identified in firearm-owning families.

The Susceptibility of Chickens to Zika Virus: A Comprehensive Study on Age-Dependent Infection Dynamics and Host Responses.

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology.

Quality of care and clinical inertia in the management of cardiovascular risk factors in patients with type 1 and type 2 diabetes: data from AMD annals.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

Equine grass sickness is associated with major abnormalities in the ultrastructure of skeletal neuromuscular junctions.

BACKGROUND: Equine grass sickness (EGS) is a frequently fatal multisystem neuropathy of equids. The aetiology is unknown; proposed causes include toxicoinfection with Clostridium botulinum and a mycotoxicosis. The effect of EGS on the organisation and structural integrity of the skeletal neuromuscular junction (NMJ), the target of botulinum neurotoxins (BoNTs), is unknown. OBJECTIVES: To compare the organisation and structural integrity of skeletal NMJs from EGS horses, control horses and one horse with a presumptive diagnosis of botulism. STUDY DESIGN: Blinded, retrospective case control. METHODS: NMJs in samples of diaphragm or intercostal muscle from six EGS horses, three control horses and one equine botulism case were compared using electron microscopy, morphometry and confocal light microscopy. RESULTS: A significantly higher percentage of EGS NMJs had abnormal morphology (EGS 72.2%, 95% CI 55.6-84.4; Controls 6.9%, 1.7-23.8; OR 35.1, 8.47-244.8; p < 0.001). EGS NMJs had a significantly lower mean volume fraction occupied by synaptic vesicles (SVs) (EGS 18.7%, 12.6-28.0; Controls 36.3%, 20.8-63.4; p = 0.024). EGS NMJs had evidence of accelerated SV exocytosis and SV depletion, accumulation of neurofilament-like material in terminal boutons and/or bouton degeneration. NMJs from the botulism horse had dense packing of SVs towards the presynaptic membrane active zone, consistent with BoNT intoxication, but had absence of the abnormalities identified in EGS NMJs. MAIN LIMITATIONS: Group sizes were limited by difficulties obtaining suitably processed samples. Ages of control and EGS horses differed. Botulism was diagnosed based on clinical and post mortem findings. CONCLUSIONS: EGS is associated with major changes in skeletal NMJ ultrastructure that are inconsistent with the effects of BoNTs. SV depletion may reflect increased exocytosis coupled with reduced repopulation of SVs via anterograde axonal transport and endocytosis, consistent with the action of an excitatory presynaptic toxin and/or neurotransmitter reuptake inhibitor. Skeletal NMJs represent a previously unrecognised target for the toxin that causes EGS.