First report of Bretziella fagacearum infecting chestnut in Michigan.

In the summer of 2021, a 20-year-old 'Colossal' (Castanea sativa × C. crenata hybrid) tree in a commercial chestnut orchard in northwest Michigan suddenly declined. Until 2023, an additional 26 adjacent trees declined, suggesting the occurrence of root-graft transmission of the pathogen. The initial wilting of leaves progressed to complete tree death in about 10 days. Symptoms included wilting, and bronzing, followed by tanning starting at leaf apex and margins, with significant defoliation. Sometimes black-to-brown streaks of discoloration appear in the sapwood, with no signs of mycelial mat production on dead trees. Branches from symptomatic trees in two different areas of the orchard were submitted to Plant and Pest Diagnostics at Michigan State University. Bretziella fagacearum (Bretz) Z.W. de Beer, Marinc., T.A. Duong & M.J. Wingf. was detected in both samples using nested PCR (Wu et al. 2011) and qPCR (Bourgault et al. 2022). The products of the nested PCR were sequenced (GenBank accession nos. OR522695-OR522696) and BLASTn search results showed 100% identity to an ex-type strain of B. fagacearum (MH865866). Surface-sterilized discolored sapwood chips were plated on acidified potato dextrose agar (aPDA). Bretziella fagacearum was consistently recovered; colony and endoconidia morphology aligned with the description of the pathogen (De Beer et al. 2017). A pure culture (BF277) was obtained for inoculation experiments. To confirm pathogenicity, 10 'Colossal' chestnut seedlings (average stem diameter of 9 mm) were inoculated in the greenhouse with a 14-day old culture of BF277. Using a conical drill bit, two 0.4 mm diameter holes were drilled, one was 5 cm above the soil line at a 45° angle and the other was on the opposite side of the stem at least 10 cm above the soil line. A 50-µl conidial suspension (1 × 107 conidia per ml) was applied and the holes were sealed with Parafilm. Five 'Colossal' seedlings were inoculated with sterile water. Leaf epinasty with bent petioles was observed 14 days later. Leaf wilting and necrosis similar to natural infection in the orchard were observed at 24 and 34 days after inoculation, respectively. Water-inoculated control plants showed no symptoms. Bretziella fagacearum was reisolated from symptomatic plants by surface sterilizing leaf petioles with 75% ethanol (30 s), followed by 10% (v/v) bleach (1 min), and two rinses with sterile deionized water (>1 min). Petiole pieces (~1 cm) were plated on aPDA. The pathogen was reisolated from six symptomatic plants and detected using qPCR in the remaining four seedlings. Bretziella fagacearum was not detected in control plants. The identity of the recovered fungus was confirmed following the amplification of the internal transcribed spacer (ITS) from extracted genomic DNA, as described in Chahal et al. 2022. The resulting PCR product was sequenced and assembled into a consensus sequence using Geneious Prime. The consensus sequence (accession no. OR515809) revealed 100% identity to the ex-type of B. fagacearum (KU042044). This is the first record of B. fagacearum infecting chestnut trees in Michigan. Previously, B. fagacearum has been reported infecting Chinese chestnut (C. mollissima) in Missouri (Bretz and Long, 1950). Oak wilt is widely distributed in Michigan and is the predominant disease afflicting red oaks in the Midwestern U.S. Consequently, constant vigilance and monitoring are essential in chestnut orchards to promptly detect and effectively manage potential infections.

A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb E3 ligases.

Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.

First Report of Colletotrichum fioriniae Infecting Hop (Humulus lupulus) in Michigan.

In July of 2020, a hop (Humulus lupulus L.) grower in Berrien County, Michigan submitted 'Chinook' leaf samples to MSU Plant & Pest Diagnostics. The leaves were covered in small, tan colored lesions, with a small chlorotic halo with an approximate diameter of 5 mm. The grower reported that foliar lesions were in the lower 2 m of the fully developed hop canopy. Disease incidence and severity were estimated at approximately 20% and 5 to 10%, respectively. After incubation at 100% relative humidity, acervuli with orange spore masses and a few setae were present. A pure culture was obtained from these sporulating lesions using water agar. The isolate was hyphal tipped onto potato dextrose agar (PDA) and stored in a glycerol-salt solution at -80o C (isolate CL001) (Miles et al. 2011). On PDA, cultures displayed gray growth on the top of the colony and a red color on the underside of the Petri dish. After 14 days, acervuli with no setae appeared exuding orange conidial masses on the surface of the culture. Conidia were hyaline, aseptate, smooth-walled and rounded at the ends and measured on average 15.89 µm (13.81 to 16.91 µm) × 7.26 (6.82 to 8.41 µm) (n = 20). The color and size of the conidia matched other descriptions of C. acutatum sensu lato (Damm et al. 2012). Four loci (ITS/515 bp - OQ026167, GAPDH/238 bp - OQ230832, CHS1/228 bp -OQ230830, and TUB2/491 bp - OQ230831) were amplified from isolate CL001 (using the primers ITS1/ITS4, GDF1/GDR1, CSH-79f/CHS-354R, and T1/Bt-2b, respectively) and had 100% pairwise identity with C. fioriniae 125396 (JQ948299, JQ948629, JQ948960, JQ949950, respectively, Damm et al. 2012). The GAPDH, CSH1, and TUB2 sequences from isolate CL001 were trimmed, concatenated and aligned with 31 different members of Colletotrichum acutatum sensu lato and C. gloesporioides 356878 (Damm et al. 2012; Kennedy et al. 2022). The alignment was then used to produce a maximum likehood phylogenetic tree using Geneious Prime (Biomatters Ltd.) with the PHYML add on using the HKY + G model (G = 0.34) (Guindon et al. 2010). Isolate CL001 had the closest similarity to C. fioriniae with a bootstrap value of 100. Pathogenicity tests were performed on 2 month-old 'Chinook' hop plants. Twelve plants were inoculated with 50 ml of a conidial suspension (7.95 x 106 conidia/ml) of isolate CL001 (n = 6) or water (n = 6) using a spray bottle until runoff. Inoculated plants were sealed in clear plastic bags and grown in a greenhouse at 21o C with a photoperiod of 14 h. After 7 days, lesions appeared on the hop plants inoculated with CL001, but no symptoms appeared on the water inoculated hop plants. Lesions with a chlorotic halo were observed but they were smaller than field lesions and no setae were present (approx. 1 mm in diam.). Leaves were surface sterilized (0.3% sodium hypochlorite solution for 15 s and then rinsed three times) and the leading margin of the lesions or healthy tissue (water control) were placed on 1% ampicillin amended PDA. Fungal isolates on PDA morphologically matched C. fioriniae were recovered from all CL001-inoculated plants. No C. fioriniae isolates were recovered from the water-inoculated plants. Based on conidial morphology, the four loci, and the phylogenetic tree, isolate CL001 was identified as C. fioriniae. This is the first report of Colletotrichum fioriniae (syn = Glomerella acutata var. fioriniae Marcelino & Gouli) infecting common hop and further investigation is needed to determine if management is needed for this pathogen.

Cold urticaria in a pediatric cohort: Clinical characteristics, management, and natural history.

BACKGROUND: Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU). METHODS: We prospectively enrolled children with coldU from 2013-2021 in a cohort study at the Montreal Children's Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution. RESULTS: Fifty-two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second-generation H1-antihistamines (sgAHs). Well-controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR) = 0.69 [95%CI: 0.53, 0.92]). Elevated eosinophils were associated with cold-induced anaphylaxis (coldA; aOR = 1.38 [95%CI: 1.04, 1.83]), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient-years, which was lower than that of CSU (adjusted hazard ratio = 0.43 [95%CI: 0.21, 0.89], p < 10-2 ). CONCLUSION: Pediatric coldU bears a substantial risk of anaphylaxis and a low-resolution rate. Absolute eosinophil count and co-existing CSU may be useful predictive factors.

Physician's perspective regarding asthma guided self-management: directives or guidance?

INTRODUCTION: Asthma guided self-management enhances patients' control of their condition under the guidance of the treating physician. The aim of the present study was to understand how physicians perceive, endorse, uptake, and support asthma guided self-management. METHODS: We conducted a secondary supplementary analysis of data originally collected as part of a multicenter collective case study in which physicians treating patients with asthma were interviewed. Using reflective thematic analysis, we aimed to explore physicians' understanding of guided asthma self-management as related to four ideas, namely: (a) understanding of the disease management and treatment goals; (b) defining medical frame and guidance; (c) describing the importance of patient-physician relationship; and (d) implementing asthma guided self-management. RESULTS: Evidence indicates that physicians perceived optimal guided self-management as related to patients' adherence to physician's instructions and recommendations, supported by the adjustment of prescribed pharmaceutical therapy contingent upon patient's symptoms. Some physicians also perceived behavior change and environmental control along with the medical recommendations. While physicians' perception of asthma and its treatment were aligned with the recommended guidelines-i.e., patient-centered care approach based on guided self-management, the actual guidance offered to patients remained primarily directive and paternalistic. Non-pharmacological approaches, such as exercise, smoking cessation, patient self-monitoring, and self-management supported by education and written self-management plans, were given little consideration in the context of the recommended treatment plan.

First report of Neofusicoccum ribis causing stem blight and dieback of blueberry (Vaccinium corymbosum) in Michigan.

In July 2020, a 3-year-old 'Envoy' northern highbush blueberry bush (Vaccinium corymbosum L.) from a commercial farm in Van Buren County, Michigan was submitted to the Plant & Pest Diagnostics laboratory at Michigan State University. Field disease assessments across the 2-acre planting were an incidence of 2-5% and a severity of 50-100%. Symptoms included red shoot flagging and dead shoots retaining dry leaves, shoots with light green leaves and necrotic margins, and brown-black cankers at the base of the symptomatic shoots. Shoot sections displaying wood discoloration were surface disinfested by dipping in 95% ethanol and flame sterilized. The internal discolored tissues (0.5 cm2) were plated onto 1% ampicillin and streptomycin, quarter-strength potato dextrose agar (PDA) and incubated at room temperature until fungal colonies were observed. A fungus with rapid growth, developing white and then dark gray mycelium, resembling species in the family Botryosphaeriaceae was isolated and subcultured. After DNA extraction and amplification, sequences of three loci were obtained: the internal transcribed spacer (ITS) region, ß-tubulin (Bt), and elongation factor 1-α (EF1) using primer pairs ITS1/ITS4, Bt2a/Bt2b, and EF1-728/EF1-986R, respectively (Slippers et al. 2004). The sequences showed 100% identity with Genbank numbers KF766205 (ITS region, 562 bp - OP588109), MT592721 (Bt, 436 bp - OP585548), and MT592229 (EF1, 306 bp - OP585547) of N. ribis (Slippers et al. 2013, Zhang et al. 2021). Sequences were identified using PopSet 1995604550 (Zhang et al. 2021). Pathogenicity was tested on 2-year-old 'Blueray' blueberries. Five plants, 3 shoots per plant (n = 15) were surface-sterilized with a 3% bleach solution by rinsing, wounded with razor blades using a scratching method in 'X' patterns across the length of the wound, and then inoculated using mycelium plugs (5 mm) from 7-day old cultures grown on full-strength PDA. Plugs were crushed and spread onto the wound and the wound was wrapped with parafilm. Control plant shoots (n = 9) were mock inoculated using sterile PDA plugs. Plants were maintained in the greenhouse at 23°C under a 14-hour photoperiod and imaged at 0-, 7-, and 12-days post inoculation (dpi). Symptoms began developing within 7 dpi. At 12 dpi, 9 of 15 inoculated shoots began displaying leaf necrosis and deep red or brown stem discoloration 6 cm above and below the wound, while controls remained healthy. Fungi morphologically identical to the original isolate were reisolated from sections taken from 2.5, 6.3, and 7 cm above and below the inoculation site. Species identity was confirmed by sequencing as described above. Neofusicoccum species are widespread and commonly associated with canker and dieback symptoms of blueberries (Flor et al. 2022). To our knowledge, this is the first report of stem blight and dieback caused by N. ribis in Michigan blueberry production. The species N. parvum and N. ribis have been reported on southern highbush blueberries in California (Koike et al. 2014) and Florida (Wright and Harmon 2010), but neither has been reported on blueberry in Michigan. Accurate diagnoses of Botryosphaeria fungal species in blueberries is critical for effective disease control and yield loss reduction.

Clinical Characteristics, Management, and Natural History of Chronic Inducible Urticaria in a Pediatric Cohort.

BACKGROUND: Some forms of chronic urticaria (CU) can be specifically attributed to a response to a definite trigger, referred to as chronic inducible urticaria (CIndU). We aimed to assess the demographics, clinical characteristics, comorbidities, natural history, and management of pediatric patients with CIndU. METHODS: Over a 6-year period, children presenting to the allergy clinic at the Montreal Children's Hospital (MCH) with CIndU were prospectively recruited. CU was defined as the presence of wheals and/or angioedema, occurring for at least 6 weeks. A standardized diagnostic test was used to establish the presence of a specific form of urticaria. Resolution was defined as the absence of hives for 1 year without treatment. RESULTS: Sixty-four patients presented with CIndU, of which 51.6% were male, with a median age of 12.5 (interquartile range 7.3, 15.9) years. Cold CU and cholinergic CU were the most common subtypes (60.3 and 41.3%, respectively). Basophil counts were undetectable in 48.4% of the cases, and C-reactive protein levels were elevated in 7.8% of patients. Of all cases, 71.4% were controlled with second-generation antihistamines. The resolution rate was of 45.3% (95% confidence interval 33.1-57.5%), based on per-protocol population within the 6-year course of the study. Resolution was more likely in patients who presented with well-controlled urticaria control test scores and elevated CD63 counts and in those suffering from thyroid comorbidity. CONCLUSION: The natural history of CIndU resolution in pediatric patients was relatively low and was associated with elevated CD63 levels, as well as thyroid comorbidity.

Reduced Microstructural Lateralization in Males with Chronic Schizophrenia: A Diffusional Kurtosis Imaging Study.

Decreased brain lateralization is considered a trait marker of schizophrenia. Whereas reductions in both functional and macrostructural gray matter laterality in schizophrenia are well established, the investigation of gray matter microstructural lateralization has so far been limited to a small number of ex vivo studies, which limits the understanding of neurobiological substrates involved and development of adequate treatments. The aim of the current study was to assess in vivo gray matter microstructure lateralization patterns in schizophrenia by employing the diffusion kurtosis imaging (DKI)-derived mean kurtosis (MK) metric. MK was calculated for 18 right-handed males with chronic schizophrenia and 19 age-matched healthy control participants in 46 bilateral gray matter regions of interest (ROI). Microstructural laterality indexes (µLIs) were calculated for each subject and ROI, and group comparisons were conducted across regions. The relationship between µLI values and performance on the Wisconsin Card Sorting Test (WCST) was also evaluated. We found that compared with healthy controls, males with chronic schizophrenia had significantly decreased µLI across cortical and subcortical gray matter regions, which was correlated with poorer performance on the WCST. Our results suggest the ability of DKI-derived MK to capture gray matter microstructural lateralization pathology in vivo.

Validation of a Novel Electronic Health Record Patient Portal Advance Care Planning Delivery System.

BACKGROUND: Advance care planning allows patients to articulate their future care preferences should they no longer be able to make decisions on their own. Early advance care planning in outpatient settings provides benefits such as less aggressive care and fewer hospitalizations, yet it is underutilized due to barriers such as provider time constraints and communication complexity. Novel methods, such as patient portals, provide a unique opportunity to conduct advance care planning previsit planning for outpatient care. This follow-up to our pilot study aimed to conduct pragmatic testing of a novel electronic health record-tethered framework and its effects on advance care planning delivery in a real-world primary care setting. OBJECTIVE: Our intervention tested a previsit advance care planning workflow centered around a framework sent via secure electronic health record-linked patient portal in a real-world clinical setting. The primary objective of this study was to determine its impact on frequency and quality of advance care planning documentation. METHODS: We conducted a pragmatic trial including 2 sister clinical sites, one site implementing the intervention and the other continuing standard care. A total of 419 patients aged between 50 and 93 years with active portal accounts received intervention (n=200) or standard care (n=219). Chart review analyzed the presence of advance care planning and its quality and was graded with previously established scoring criteria based on advance care planning best practice guidelines from multiple nations. RESULTS: A total of 19.5% (39/200) of patients who received previsit planning responded to the framework. We found that the intervention site had statistically significant improvement in new advance care planning documentation rates (P<.01) and quality (P<.01) among all eligible patients. Advance care planning documentation rates increased by 105% (19/39 to 39/39) and quality improved among all patients who engaged in the previsit planning framework (n=39). Among eligible patients aged between 50 and 60 years at the intervention site, advance care planning documentation rates increased by 37% (27/96 to 37/96). Advance care planning documentation rates increased 34% among high users (27/67 to 36/67). CONCLUSIONS: Advance care planning previsit planning using a secure electronic health record-supported patient portal framework yielded improvement in the presence of advance care planning documentation, with highest improvement in active patient portal users and patients aged between 50 and 60 years. Targeted previsit patient portal advance care planning delivery in these populations can potentially improve the quality of care in these populations.

Constrained by our connections: white matter's key role in interindividual variability in visual working memory capacity.

Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (f(axon)), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in f(axon) within a widely distributed network of white matter tracts. Increased f(axon) associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition.

Implementing the Better Starts For All Pilot Mobile and Telehealth Intervention in Ohio Appalachia: Improving Access to Maternal Healthcare.

INTRODUCTION: Women in Ohio Appalachia experience greater maternal health disparities relative to the general U.S. population, resulting in poorer health outcomes. This paper describes the Ohio Better Starts for All (BSFA) program that provides mobile maternal health services in rural Ohio. METHODS: This three-year intervention was delivered through a community-clinical partnership in Ohio Appalachia. The program's preliminary evaluation and opportunities were informed by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. RESULTS: Over six months, 86 patients were referred to the BSFA program, 54 (62.8 %) were seen by the maternal care team, and 14 out of 19 scheduled clinic days were held. Five clinics were canceled due to inclement weather, mobile unit breakdown, or provider COVID-19 infection. DISCUSSION: Maternal care providers must provide equitable care to patients, with particular attention to those who face substantial challenges accessing obstetric services. The BSFA program offers one promising solution to help women overcome barriers to accessing care.

A Portfolio Coach-Informed Professional Development Framework.

INTRODUCTION: A majority of US medical schools have incorporated faculty coach-supported educational portfolios into the curriculum. Existing research describes coach professional development, competencies, and program perceptions. However, limited research exists on how programs address coach professional development needs. Our sequential objectives were to (1) explore faculty coach professional development experiences within medical student coaching programs and (2) develop a preliminary framework for medical faculty coach professional development. METHODS: Faculty portfolio coaches who completed 4 years of a longitudinal coaching program were recruited to complete a semi-structured exit interview. Interviews were transcribed using detailed transcription. Two analysts inductively generated a codebook of parent and child codes to identify themes. They compared themes to the professional development model proposed by O'Sullivan and Irby. RESULTS: Of the 25 eligible coaches, 15 completed the interview. Our team organized themes into two broad domains paralleling the established model: program-specific professional development and career-relevant professional development. Four program-specific professional development themes emerged: doing; modeling; relating; and hosting. Three career-relevant professional development themes emerged: advancement; meaning; and understanding. We then applied themes within each domain to propose strategies to optimize coach professional development and develop a framework modeled after O'Sullivan and Irby. DISCUSSION: To our knowledge, we propose the first portfolio coach-informed framework for professional development. Our work builds on established standards, expert opinion, and research responsible for portfolio coach professional development and competencies. Allied health institutions with portfolio coaching programs can apply the framework for professional development innovation.

Default-mode network disruption in mild traumatic brain injury.

PURPOSE: To investigate the integrity of the default-mode network (DMN) by using independent component analysis (ICA) methods in patients shortly after mild traumatic brain injury (MTBI) and healthy control subjects, and to correlate DMN connectivity changes with neurocognitive tests and clinical symptoms. MATERIALS AND METHODS: This study was approved by the institutional review board and complied with HIPAA regulations. Twenty-three patients with MTBI who had posttraumatic symptoms shortly after injury (<2 months) and 18 age-matched healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging was performed at 3 T to characterize the DMN by using ICA methods, including a single-participant ICA on the basis of a comprehensive template from core seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) nodes. ICA z images of DMN components were compared between the two groups and correlated with neurocognitive tests and clinical performance in patients by using Pearson and Spearman rank correlation. RESULTS: When compared with the control subjects, there was significantly reduced connectivity in the PCC and parietal regions and increased frontal connectivity around the MPFC in patients with MTBI (P < .01). These frontoposterior opposing changes within the DMN were significantly correlated (r = -0.44, P = .03). The reduced posterior connectivity correlated positively with neurocognitive dysfunction (eg, cognitive flexibility), while the increased frontal connectivity correlated negatively with posttraumatic symptoms (ie, depression, anxiety, fatigue, and postconcussion syndrome). CONCLUSION: These results showed abnormal DMN connectivity patterns in patients with MTBI, which may provide insight into how neuronal communication and information integration are disrupted among DMN key structures after mild head injury.

Reference values for respiratory sinusoidal oscillometry in children aged 3 to 17 years.

BACKGROUND: New oscillometry devices allowing quantification of respiratory function using tidal breathing are commercially available, but reference equations are lacking for the multiethnic Canadian pediatric population. METHODS: We conducted a prospective cross-sectional study of healthy children carefully selected for absence of asthma, atopy, tobacco smoke, obesity, prematurity, and recent respiratory infection. Triplicate measures were obtained of respiratory system resistance (Rrs) and reactance (Xrs), area under the reactance curve (AX) and resonant frequency (Fres) on four signals, whose testing order was randomized: two signals on the Resmon Pro Full (8 Hz and 5-11-19 Hz) and two signals on the tremoflo C-100 (5-37 Hz and 7-41 Hz). Feasibility was defined as the ability to obtain valid reproducible results. Prediction equations and 95% confidence intervals were derived for whole- and within-breath Rrs and Xrs and for AX and Fres, using linear regression or Generalized Additive Models for Location, Scale and Shape. RESULTS: Of 306 children randomized, valid and reproducible results on ≥1 signal were obtained in 299 (98%) multiethnic (69% Caucasians: 8% Black: 23% Others) children aged 3-17 years, 91-189 cm tall. Standing height was the strongest predictor with no significant effect of sex, age, body mass index or ethnicity. Significant within-patient differences were observed between Resmon Pro and tremoflo C-100 measurements, justifying the derivation of device-specific reference equations. CONCLUSION: Valid reproducible oscillometry measurements are highly feasible in children aged 3 years and older. Device-specific reference equations, valid for our multiethnic population, are derived.

Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury.

PURPOSE: To explore the neural correlates of the thalamus by using resting-state functional magnetic resonance (MR) imaging and to investigate whether thalamic resting-state networks (RSNs) are disrupted in patients with mild traumatic brain injury (MTBI). MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from 24 patients with MTBI and 17 healthy control subjects. The patients had varying degrees of symptoms, with a mean disease duration of 22 days. The resting-state functional MR imaging data were analyzed by using a standard seed-based whole-brain correlation method to characterize thalamic RSNs. Student t tests were used to perform comparisons. The association between thalamic RSNs and performance on neuropsychologic and neurobehavioral measures was also investigated in patients with MTBI by using Spearman rank correlation. RESULTS: A normal pattern of thalamic RSNs was demonstrated in healthy subjects. This pattern was characterized as representing relatively symmetric and restrictive functional thalamocortical connectivity, suggesting an inhibitory property of the thalamic neurons during the resting state. This pattern was disrupted, with significantly increased thalamic RSNs (P ≤ .005) and decreased symmetry (P = .03) in patients with MTBI compared with healthy control subjects. Increased functional thalamocortical redistributive connectivity was correlated with diminished neurocognitive functions and clinical symptoms in patients with MTBI. CONCLUSION: These findings of abnormal thalamic RSNs lend further support to the presumed subtle thalamic injury in patients with MTBI. Resting-state functional MR imaging can be used as an additional imaging modality for detection of thalamocortical connectivity abnormalities and for better understanding of the complex persistent postconcussive syndrome.

Community Use of Epinephrine for the Treatment of Anaphylaxis: A Review and Meta-Analysis.

BACKGROUND: Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre-hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines. OBJECTIVES: A search was conducted on PubMed and Embase in April 2020. Our systematic review focused on 4 domains: (1) epinephrine use in the pre-hospital setting; (2) barriers to epinephrine use in the pre-hospital setting; (3) cost evaluation and cost-effectiveness of epinephrine use; and (4) programs and strategies to improve epinephrine use during anaphylaxis. METHODS: Two meta-analyses with logit transformation were conducted to: (1) calculate the pooled estimate of the rate of epinephrine use in the pre-hospital setting among cases of anaphylaxis and (2) calculate the pooled estimate of the rate of biphasic reactions among all cases of anaphylaxis. RESULTS: Epinephrine use in the pre-hospital setting was significantly higher for children compared with adults (20.98% [95% confidence interval (CI): 16.38%, 26.46%] vs 7.17% [95% CI: 2.71%, 17.63%], respectively, P = .0027). The pooled estimate of biphasic reactions among all anaphylaxis cases was 3.92% (95% CI: 2.88%, 5.32%). Our main findings indicate that pre-hospital use of epinephrine in anaphylaxis remains suboptimal. Major barriers to the use of epinephrine were identified as low prescription rates of epinephrine autoinjectors and lack of stock epinephrine in schools, which was determined to be cost-effective. Finally, in reviewing programs and strategies, numerous studies have engineered effective methods to promote adequate and timely use of epinephrine. CONCLUSION: The main findings of our study demonstrated that across the globe, prompt epinephrine use in cases of anaphylaxis remains suboptimal. For practical recommendations, we would suggest considering stock epinephrine in schools and food courts to increase the use of epinephrine in the community. We recommend use of pamphlets in public areas (ie, malls, food courts, etc.) to assist in recognizing anaphylaxis and after that with prompt epinephrine administration, to avoid the rare risk of fatality in anaphylaxis cases.

Diffusion kurtosis imaging of gray matter in young adults with autism spectrum disorder.

Prior ex vivo histological postmortem studies of autism spectrum disorder (ASD) have shown gray matter microstructural abnormalities, however, in vivo examination of gray matter microstructure in ASD has remained scarce due to the relative lack of non-invasive methods to assess it. The aim of this work was to evaluate the feasibility of employing diffusional kurtosis imaging (DKI) to describe gray matter abnormalities in ASD in vivo. DKI data were examined for 16 male participants with a diagnosis of ASD and IQ>80 and 17 age- and IQ-matched male typically developing (TD) young adults 18-25 years old. Mean (MK), axial (AK), radial (RK) kurtosis and mean diffusivity (MD) metrics were calculated for lobar and sub-lobar regions of interest. Significantly decreased MK, RK, and MD were found in ASD compared to TD participants in the frontal and temporal lobes and several sub-lobar regions previously associated with ASD pathology. In ASD participants, decreased kurtosis in gray matter ROIs correlated with increased repetitive and restricted behaviors and poor social interaction symptoms. Decreased kurtosis in ASD may reflect a pathology associated with a less restrictive microstructural environment such as decreased neuronal density and size, atypically sized cortical columns, or limited dendritic arborizations.

Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T.

OBJECTIVE: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes. MATERIALS AND METHODS: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia. RESULTS: The mean regional CBF was significantly lower in patients with MTBI (45.9 +/- 9.8 ml/100 g min(-1)) as compared to normal controls (57.1 +/- 8.1 ml/100 g min(-1); p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients. CONCLUSIONS: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease.