Neurophysiologic Characteristics of the Anterior Nucleus of the Thalamus during Deep Brain Stimulation Surgery for Epilepsy.

INTRODUCTION: Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an increasingly promising treatment option for refractory epilepsy. Optimal therapeutic benefit has been associated with stimulation at the junction of ANT and the mammillothalamic tract (mtt), but electrophysiologic markers of this target are lacking. The present study examined microelectrode recordings (MER) during DBS to identify unique electrophysiologic characteristics of ANT and the ANT-mtt junction. METHODS: Ten patients with medically refractory epilepsy underwent MER during ANT-DBS implantation under general anesthesia. MER locations were determined based on coregistration of preoperative MRI, postoperative CT, and a stereotactic atlas of the thalamus (Morel atlas). Several neurophysiological parameters including single unit spiking rate, bursting properties, theta and alpha power and cerebrospinal fluid (CSF)-normalized root mean square (NRMS) of multiunit activity were characterized at recording depths and compared to anatomic boundaries. RESULTS: From sixteen hemispheres, 485 recordings locations were collected from a mean of 30.3 (15.64 ± 5.0 mm) recording spans. Three-hundred and ninety-four of these recording locations were utilized further for analysis of spiking and bursting rates, after excluding recordings that were more than 8 mm above the putative ventral ANT border. The ANT region exhibited discernible features including: (1) mean spiking rate (7.52 Hz ± 6.9 Hz; one-way analysis of variance test, p = 0.014 when compared to mediodorsal nucleus of the thalamus [MD], mtt, and CSF), (2) the presence of bursting activity with 40% of ANT locations (N = 59) exhibited bursting versus 24% the mtt (χ2; p < 0.001), and 32% in the MD (p = 0.38), (3) CSF-NRMS, a proxy for neuronal density, exhibited well demarcated changes near the entry and exit of ANT (linear regression, R = -0.33, p < 0.001). Finally, in the ANT, both theta (4-8 Hz) and alpha band power (9-12 Hz) were negatively correlated with distance to the ventral ANT border (linear regression, p < 0.001 for both). The proportion of recordings with spiking and bursting activity was consistently highest 0-2 mm above the ventral ANT border with the mtt. CONCLUSION: We observed several electrophysiological markers demarcating the ANT superior and inferior borders including multiple single cell and local field potential features. A local maximum in neural activity just above the ANT-mtt junction was consistent with the previously described optimal target for seizure reduction. These features may be useful for successful targeting of ANT-DBS for epilepsy.

Persistence of anxiety among Asian Americans: racial and ethnic heterogeneity in the longitudinal trends in mental well-being during the COVID-19 pandemic.

PURPOSE: To examine within-individual time trends in mental well-being and factors influencing heterogeneity of these trends. METHODS: Longitudinal telephone survey of adults over 3 waves from the New York City (NYC) Metropolitan area during the COVID-19 Pandemic. Participants reported depression using the Patient Health Questionnaire (PHQ)-8, anxiety using the Generalized Anxiety Disorder (GAD)-7, and past 30-day increases in tobacco or alcohol use at each wave. Adjusted mixed effects logistic regression models assessed time trends in mental well-being. RESULTS: There were 1227 respondents. Over 3 study waves, there were statistically significant decreasing time trends in the odds of each outcome (adjusted OR (95% CI) 0.47 (0.37, 0.60); p < 0.001 for depression; aOR (95% CI) 0.55 (0.45, 0.66); p < 0.001 for anxiety; aOR (95% CI) 0.50 (0.35, 0.71); p < 0.001 for past 30-day increased tobacco use; aOR (95% CI) 0.31 (0.24, 0.40); p < 0.001 for past 30-day increased alcohol use). Time trends for anxiety varied by race and ethnicity (p value for interaction = 0.05, 4 df); anxiety declined over time among white, Black, Hispanic, and Other race and ethnicity but not among Asian participants. CONCLUSIONS: In a demographically varied population from the NYC Metropolitan area, depression, anxiety and increased substance use were common during the first months of the pandemic, but decreased over the following year. While this was consistently the case across most demographic groups, the odds of anxiety among Asian participants did not decrease over time.

Axial Magnetic Resonance Angiography in Evaluating Revascularization after Indirect Bypass Surgery for Moyamoya Axial Magnetic Resonance Angiography after Indirect Bypass.

INTRODUCTION: At our institution, revascularization after indirect moyamoya surgery is routinely evaluated using magnetic resonance angiography (MRA) rather than catheter angiography. In this paper, we review how revascularization can be visualized on axial MRA and compare its visualization on MRA to that on catheter angiography. We also compare clinical outcomes of patients followed with routine postoperative MRA with outcomes of patients followed with routine catheter angiography. METHODS: We retrospectively reviewed the records of all patients treated at our institution who underwent unilateral encephaloduroarteriosynangiosis (EDAS) and/or pial synangiosis between the ages of 1 and 21 years and between December 31, 2003, and May 1, 2021. We included patients who underwent EDAS/pial synangiosis at other hospitals as long as they met all inclusion criteria. Inclusion criteria included having a preoperative MRA within 18 months of surgery and a postoperative MRA 3-30 months after surgery. Clinical outcomes included development of postoperative stroke and transient ischemic attacks (TIAs) and changes in symptoms (improved, unchanged, or worsened), including seizures, balance issues, and headaches. Clinical outcomes were compared between patients who had routine postoperative MRA only versus those who had routine postoperative angiograms, with or without routine MRA. For each surgery, we determined the ratios of the diameters and areas of the donor vessel and the contralateral corresponding vessel, as well as the relative signal intensities of these two vessels, on preoperative and 3- to 30-month postoperative MRA. We did the same for the middle meningeal artery (MMA) ipsilateral to the donor artery and the contralateral MMA. We assessed changes from pre- to post-operation in diameter ratios, area ratios, relative signal intensity, ivy sign, and in brain perfusion on arterial spin labeled (ASL) imaging. MRI and MRA measures of revascularization and flow were compared to Matsushima grades in patients who had postoperative catheter angiograms. RESULTS: Fifty-one operations for 42 unique patients were included. There were no significant differences in the rates of postoperative strokes, postoperative TIAs, changes in symptoms, or new symptoms after surgeries evaluated by routine postoperative MRA versus catheter angiogram (p = 0.282, 1, 0.664, and 0.727, respectively). There were significant associations between greater collateralization on postoperative MRA and greater median increases in preoperative-to-postoperative ratios of donor-vessel-over-contralateral-vessel diameter (p = 0.0461), ipsilateral-MMA-over-contralateral-MMA diameter (p = 0.0135), and the summed donor and ipsilateral MMA diameters over the summed contralateral vessel diameters (p < 0.001). The median increase in the ratio of the donor vessel and contralateral corresponding vessel diameters was significantly higher for Matsushima grade A versus B (p = 0.036). The median increase in the ratio of the sum of donor and ipsilateral MMA diameters over the sum of the contralateral vessel diameters was significantly higher for improved-versus-unchanged perfusion on ASL imaging (p = 0.0074). There was a nonsignificant association between greater postoperative collateralization on MRA and Matsushima grade (p = 0.1160). CONCLUSION: Cerebral revascularization after EDAS and pial synangiosis can be evaluated on axial MRA by comparing the diameter and/or signal intensity of the donor vessel and corresponding contralateral vessel, as well as the ipsilateral and contralateral MMA, on postoperative-versus-preoperative MRA. The use of routine postoperative MRA rather than catheter angiography does not appear to negatively affect outcomes.

Loss of NF1 in Drosophila Larvae Causes Tactile Hypersensitivity and Impaired Synaptic Transmission at the Neuromuscular Junction.

Autism spectrum disorder (ASD) is a neurodevelopmental condition in which the mechanisms underlying its core symptomatology are largely unknown. Studying animal models of monogenic syndromes associated with ASD, such as neurofibromatosis type 1 (NF1), can offer insights into its etiology. Here, we show that loss of function of the Drosophila NF1 ortholog results in tactile hypersensitivity following brief mechanical stimulation in the larva (mixed sexes), paralleling the sensory abnormalities observed in individuals with ASD. Mutant larvae also exhibit synaptic transmission deficits at the glutamatergic neuromuscular junction (NMJ), with increased spontaneous but reduced evoked release. While the latter is homeostatically compensated for by a postsynaptic increase in input resistance, the former is consistent with neuronal hyperexcitability. Indeed, diminished expression of NF1 specifically within central cholinergic neurons induces both excessive neuronal firing and tactile hypersensitivity, suggesting the two may be linked. Furthermore, both impaired synaptic transmission and behavioral deficits are fully rescued via knock-down of Ras proteins. These findings validate NF1 -/- Drosophila as a tractable model of ASD with the potential to elucidate important pathophysiological mechanisms.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) affects 1-2% of the overall population and can considerably impact an individual's quality of life. However, there are currently no treatments available for its core symptoms, largely because of a poor understanding of the underlying mechanisms involved. Examining how loss of function of the ASD-associated NF1 gene affects behavior and physiology in Drosophila may shed light on this. In this study, we identify a novel, ASD-relevant behavioral phenotype in NF1 -/- larvae, namely an enhanced response to mechanical stimulation, which is associated with Ras-dependent synaptic transmission deficits indicative of neuronal hyperexcitability. Such insights support the use of Drosophila neurofibromatosis type 1 (NF1) models in ASD research and may provide outputs for genetic or pharmacological screens in future studies.

Phosphorus fractions in leaves.

Leaf phosphorus (P) comprises four major fractions: inorganic phosphate (Pi ), nucleic acids, phospholipids, P-containing metabolites and a residual fraction. In this review paper, we investigated whether allocation of P fractions varies among groups of terrestrial vascular plants, and is indicative of a species' strategy to use P efficiently. We found that as leaf total P concentration increases, the Pi fraction increases the most, without a plateau, while other fractions plateau. Variability of the concentrations of leaf P fractions is greatest among families > species(family) > regions > plant life forms. The percentage of total P allocated to nucleic acid-P (20-35%) and lipid-P (14-34%) varies less among families/species. High photosynthetic P-use efficiency is associated with low concentrations of all P fractions, and preferential allocation of P to metabolite-P and mesophyll cells. Sequential resorption of P from senescing leaves starts with Pi , followed by metabolite-P, and then other organic P fractions. Allocation of P to leaf P fractions varies with season. Leaf phytate concentrations vary considerably among species, associated with variation in photosynthesis and defence. Plasticity of P allocation to its fractions is important for acclimation to low soil P availability, and species-specific P allocation is needed for co-occurrence with other species.

Differences in foliar phosphorus fractions, rather than in cell-specific phosphorus allocation, underlie contrasting photosynthetic phosphorus use efficiency among chickpea genotypes.

Although significant intraspecific variation in photosynthetic phosphorus (P) use efficiency (PPUE) has been shown in numerous species, we still know little about the biochemical basis for differences in PPUE among genotypes within a species. Here, we grew two high PPUE and two low PPUE chickpea (Cicer arietinum) genotypes with low P supply in a glasshouse to compare their photosynthesis-related traits, total foliar P concentration ([P]) and chemical P fractions (i.e. inorganic P (Pi), metabolite P, lipid P, nucleic acid P, and residual P). Foliar cell-specific nutrient concentrations including P were characterized using elemental X-ray microanalysis. Genotypes with high PPUE showed lower total foliar [P] without slower photosynthetic rates. No consistent differences in cellular [P] between the epidermis and mesophyll cells occurred across the four genotypes. In contrast, high PPUE was associated with lower allocation to Pi and metabolite P, with PPUE being negatively correlated with the percentage of these two fractions. Furthermore, a lower allocation to Pi and metabolite P was correlated with a greater allocation to nucleic acid P, but not to lipid P. Collectively, our results suggest that a different allocation to foliar P fractions, rather than preferential P allocation to specific leaf tissues, underlies the contrasting PPUE among chickpea genotypes.

Low-moderate dietary phytoestrogens transiently disrupt spermatogenesis and the seminal plasma proteome in the ram.

In brief: Dietary phytoestrogens disrupt a specific stage of ram spermatogenesis, causing subtle decreases in sperm quality by affecting the expression of pathways involved in the structural integrity of the spermatozoa. This paper demonstrates for the first time that ram reproduction is compromised by oestrogenic pasture, whilst also providing a longitudinal model for the impact of phytoestrogens on male fertility. Abstract: Compounds with oestrogen-like actions are now common in both the Western diet. The long-term impacts and underlying mechanisms by which oestrogenic compounds alter male reproduction, however, are unclear. To investigate this, we used a longitudinal sheep model examining the impact of oestrogenic pasture consumption on semen quality and production, testicular size, sexual behaviour and the seminal plasma proteome of Merino rams (n = 20), over a full spermatogenic cycle and in the subsequent breeding season. Throughout the study period, sexual behaviour, sperm production and motility were similar between the exposed and non-exposed rams (P > 0.05). However, between 5 and 8 weeks of exposure to dietary phytoestrogens, rams produced a higher percentage of spermatozoa with a specific malformation of the sperm midpiece and reduced DNA integrity, compared to non-exposed rams (P < 0.001). Investigation into the seminal plasma proteome revealed 93 differentially expressed proteins between phytoestrogen-exposed and control rams (P < 0.05). Exposure to phytoestrogens increased the expression of proteins involved in cellular structure development, actin cytoskeleton reorganisation, regulation of cell function and decreased expression in those related to catabolic processes. The greatest fold changes were in proteins involved in the assembly of the sperm flagella, removal of cytoplasm, spermatid development and maintenance of DNA integrity. After returning to non-oestrogenic pasture, no differences in any measure were observed between treatment groups during the subsequent breeding season. We conclude that dietary phytoestrogens can transiently disrupt specific stages of ram spermatogenesis, causing subtle decreases in sperm quality by affecting the expression of pathways involved in the structural integrity of the spermatozoa.

Enhanced nodulation and phosphorus acquisition from sparingly-soluble iron phosphate upon treatment with arbuscular mycorrhizal fungi in chickpea.

The coordination/trade-off among below-ground strategies for phosphorus (P) acquisition, including root morphology, carboxylate exudation and colonisation by arbuscular mycorrhizal fungi (AMF), is not well understood. This is the first study investigating the relationships between root nodulation, morphology, carboxylates and colonisation by an indigenous community of AMF under varying P levels and source. Two chickpea genotypes with contrasting amounts of rhizosheath carboxylates were grown in pots at six P levels (from 0 to 160 µg g-1 ) as KH2 PO4 (KP, highly soluble) or FePO4 (FeP, sparingly soluble), with or without AMF (±AMF) treatment. Under both FeP and KP, the presence of AMF inhibited shoot growth and shoot branching, decreased total root length and specific root length, increased mean root diameter and root tissue density and reduced carboxylates. However, the role of AMF in acquiring P differed between the two P sources, with the enhanced P acquisition under FeP while not under KP. Co-inoculation of AMF and rhizobia enhanced nodulation under FeP, but not under KP. Our results suggest that the effects of AMF on shoot branching were mediated by cytokinins as the reduced shoot branching in FeP40 and KP40 under +AMF relative to -AMF coincided with a decreased concentration of cytokinins in xylem sap for both genotypes.

Niche differentiation of Mucoromycotinian and Glomeromycotinian arbuscular mycorrhizal fungi along a 2-million-year soil chronosequence.

Current literature suggests ecological niche differentiation between co-occurring Mucoromycotinian arbuscular mycorrhizal fungi (M-AMF) and Glomeromycotinian AMF (G-AMF), but experimental evidence is limited. We investigated the influence of soil age, water availability (wet and dry), and plant species (native Microlaena stipoides and exotic Trifolium subterraneum) on anatomical root colonisation and DNA profiles of M-AMF and G-AMF under glasshouse conditions. We grew seedlings of each species in soils collected from the four stages of a soil chronosequence, where pH decreases from the youngest to oldest stages, and phosphorus (P) is low in the youngest and oldest, but high in the intermediate stages. We scored the percentage of root length colonised and used DNA metabarcoding to profile fungal richness and community composition associated with treatment combinations. Soil age, water availability, and plant species were important influencers of root colonisation, although no M-AMF were visible following staining of M. stipoides roots. Soil age and host plant influenced fungal richness and community composition. However, response to soil age, potential host species, and water availability differed between M-AMF and G-AMF. Root colonisation of T. subterraneum by M-AMF and G-AMF was inversely correlated with soil P level. Community composition of M-AMF and G-AMF was structured by soil age and, to a lesser extent, plant species. Richness of M-AMF and G-AMF was negatively, and positively, correlated with available P, respectively. These findings are experimental evidence of ecological niche differentiation of M-AMF and G-AMF and invite further exploration into interactive effects of abiotic and biotic factors on their communities along successional trajectories.

Use of the Posterior Auricular Artery for Indirect Bypass in Moyamoya: A Pediatric Case Series.

INTRODUCTION: Encephaloduroarteriosynangiosis (EDAS) for moyamoya is predominantly performed using a branch of the superficial temporal artery (STA) as the donor artery. At times, other branches of the external carotid artery are better suited for EDAS than is the STA. There is little information in the literature concerning using the posterior auricular artery (PAA) for EDAS in the pediatric age-group. In this case series, we review our experience using the PAA for EDAS in children and adolescents. CASE PRESENTATIONS: We describe the presentations, imaging, and outcomes of 3 patients in whom the PAA was used for EDAS, as well our surgical technique. There were no complications. All 3 patients were confirmed to have radiologic revascularization from their surgeries. All patients also had improvement of their preoperative symptoms, and no patient has had a stroke postoperatively. CONCLUSION: The PAA is a viable option for use as a donor artery in EDAS for the treatment of moyamoya in children and adolescents.

Fusion of Lateral Calvarial Sutures on Volume-Rendered Computed Tomography Reconstructions in Patients With Known Craniosynostosis.

INTRODUCTION: After treating a child with familial sagittal craniosynostosis, clinocephaly, and bilateral parietomastoid/posterior squamosal suture fusion, the authors wondered if major-suture synostosis and clinocephaly were associated with abnormal fusion of minor lateral calvarial sutures. METHODS: The authors reviewed all preoperative volume-rendered head computed tomography reconstructions performed for craniosynostosis at their institution from 2010 through 2014 and determined whether the sphenoparietal, squamosal, and parietomastoid sutures were open, partially fused, or fused. The authors determined whether any sutures were abnormally fused based upon a previous study from their center, in which abnormal fusion was defined as either 1 of 3 abnormal fusion patterns or abnormally-early fusion. The authors then determined the rate of abnormal fusion of these sutures and whether abnormal fusion was associated with (1) major-suture craniosynostosis, (2) type of craniosynostosis (sutures involved; single-suture versus multisuture; syndromic versus nonsyndromic), and (3) clinocephaly. RESULTS: In 97 included children, minor lateral sutures were abnormally fused in 8, or 8.2%, which was significantly higher than in children without craniosynostosis from our earlier study. Abnormal minor lateral suture fusion was not associated with the type of single-suture synostosis or with multisuture synostosis but was associated with syndromic synostosis. Four of 8 children with abnormal minor lateral suture fusion had multisuture synostosis and 6 had syndromic synostosis. Lateral sutures were abnormally fused in 1 of 4 subjects with clinocephaly, which was not significant. CONCLUSION: Abnormal minor lateral calvarial suture fusion is significantly associated with major-suture craniosynostosis, especially syndromic synostosis.

Shapes of subcortical structures in adolescents with and without familial history of substance use disorder.

It has been suggested that intergenerational transmission of risk for substance use disorder (SUD) manifests in the brain anatomy of substance naïve adolescents. While volume and shapes of subcortical structures (SSS) have been shown to be heritable, these structures, especially the pallidum, putamen, nucleus accumbens, and hippocampus, have also been associated with substance use disorders. However, it is not clear if those anatomical differences precede substance use or are the result of that use. Therefore, we examined if volume and SSS of adolescents with a family history (FH+) of SUD differed from adolescents without such a history (FH-). Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and volume/SSS. Using structural MRI and FSL software, we segmented subcortical structures and obtained indices of SSS and volumes of 64 FH+ and 58 FH- adolescents. We examined group differences in volume and SSS, and the correlations between volume/SSS and trait anxiety and impulsivity. FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of this structure did not differ between groups. Neither shape nor volume of the other subcortical structures differed between groups. In the FH+ adolescents, the left hippocampus shape was positively correlated with both trait anxiety and impulsivity, while in FH- adolescents a negative correlation pattern of SSS was seen in the hippocampus. SSS appears to capture local anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. Hippocampus shape also exhibits opposite patterns of correlation with anxiety and impulsivity scores across the FH+ and FH- adolescents. These novel findings may reveal neural correlates, not captured by traditional volumetric analysis, of familial transmission of increased vulnerability to SUD.

Agricultural land-use favours Mucoromycotinian, but not Glomeromycotinian, arbuscular mycorrhizal fungi across ten biomes.

Globally, agricultural land-use negatively affects soil biota that contribute to ecosystem functions such as nutrient cycling, yet arbuscular mycorrhizal fungi (AMF) are promoted as essential components of agroecosystems. Arbuscular mycorrhizal fungi include Glomeromycotinian AMF (G-AMF) and the arbuscule-producing fine root endophytes, recently re-classified into the Endogonales order within Mucoromycotina. The correct classification of Mucoromycotinian AMF (M-AMF) and the availability of new molecular tools can guide research to better the understanding of their diversity and ecology. To investigate the impact on G-AMF and M-AMF of agricultural land-use at a continental scale, we sampled DNA from paired farm and native sites across 10 Australian biomes. Glomeromycotinian AMF were present in both native and farm sites in all biomes. Putative M-AMF were favoured by farm sites, rare or absent in native sites, and almost entirely absent in tropical biomes. Temperature, rainfall, and soil pH were strong drivers of richness and community composition of both groups, and plant richness was an important mediator. Both fungal groups occupy different, but overlapping, ecological niches, with M-AMF thriving in temperate agricultural landscapes. Our findings invite exploration of the origin and spread of M-AMF and continued efforts to resolve the phylogeny of this newly reclassified group of AMF.

Evidence for Niche Differentiation in the Environmental Responses of Co-occurring Mucoromycotinian Fine Root Endophytes and Glomeromycotinian Arbuscular Mycorrhizal Fungi.

Fine root endophytes (FRE) were traditionally considered a morphotype of arbuscular mycorrhizal fungi (AMF), but recent genetic studies demonstrate that FRE belong within the subphylum Mucoromycotina, rather than in the subphylum Glomeromycotina with the AMF. These findings prompt enquiry into the fundamental ecology of FRE and AMF. We sampled FRE and AMF in roots of Trifolium subterraneum from 58 sites across temperate southern Australia. We investigated the environmental drivers of composition, richness, and root colonization of FRE and AMF by using structural equation modelling and canonical correspondence analyses. Root colonization by FRE increased with increasing temperature and rainfall but decreased with increasing phosphorus (P). Root colonization by AMF increased with increasing soil organic carbon but decreased with increasing P. Richness of FRE decreased with increasing temperature and soil pH. Richness of AMF increased with increasing temperature and rainfall but decreased with increasing soil aluminium (Al) and pH. Aluminium, soil pH, and rainfall were, in decreasing order, the strongest drivers of community composition of FRE; they were also important drivers of community composition of AMF, along with temperature, in decreasing order: rainfall, Al, temperature, and soil pH. Thus, FRE and AMF showed the same responses to some (e.g. soil P, soil pH) and different responses to other (e.g. temperature) key environmental factors. Overall, our data are evidence for niche differentiation among these co-occurring mycorrhizal associates.

Critical phosphorus requirements of Trifolium species: The importance of root morphology and root acclimation in response to phosphorus stress.

Differences in root morphology and acclimation to low-phosphorus (P) soil were examined among eight legume species from the Trifolium Section Tricocephalum to understand how these root attributes determine P acquisition. Ornithopus sativus was included as a highly P-efficient benchmark species. Plants were grown as microswards in pots with five rates of P supplied in a topsoil layer to mimic uneven P distribution within a field soil profile. Topsoil and subsoil roots were harvested separately to enable measurement of the nutrient-foraging responses. Critical P requirement (lowest P supply for maximum yield) varied over a threefold range, reflecting differences in root morphology and acclimation of nutrient-foraging roots to P stress. Among the species, there was a 3.2-fold range in root length density, a 1.7-fold range in specific root length, and a 2.1-fold range in root hair length. O. sativus had the lowest critical P requirement, displayed a high root length density, the highest specific root length, and the longest root hairs. Acquisition of P from P-deficient soil was facilitated by development of a large root hair cylinder (i.e. a large root-soil interface). This, in turn, was determined by the intrinsic root morphology attributes of each genotype, and the plasticity of its root morphology response to internal P stress. Root acclimation in low-P soil by all species was mostly associated with preferential allocation of mass to nutrient-foraging roots. Only O. sativus and four of the Trifolium species adjusted specific root length beneficially, and only O. sativus increased its root hair length in low-P soil.

Primary vaccination in foals: a comparison of the serological response to equine influenza and equine herpesvirus vaccines administered concurrently or 2 weeks apart.

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.

ESTABLISHING A QUALITY IMPROVEMENT CULTURE WITHIN A LARGE INTEGRATED MEDICAL-DENTAL HEALTH SYSTEM WITH A POPULATION BASED FOCUS.

OBJECTIVES: Quality improvement strategies have been an integral part of healthcare to attain improved care delivery and effective health outcomes. The dental quality initiative improvement (DQII) presented in this manuscript represents a case study of successful implementation of a quality improvement culture within a large integrated-medical-dental health system serving a largely rural population. METHODS: The key elements of DQII included steering committee establishment, definition or dental quality measures and development/implementation of a dental quality analytics dashboard (DQAD) that provides relevant data on dental quality measures. Qualitative metrics were applied to look at the improvement in performance for the various measures relative to quality benchmarks. RESULTS: DQII facilitated improved oversight of care continuity and provider performance surrounding quality measures at granular and/or institutional level. Improvement associated with care delivery performance relative to benchmarks was observed. CONCLUSIONS: DQII further advanced the quality improvement culture prevalent in our learning healthcare environment with its focus on value-based care delivery. DQII initiative and establishment of DQAD provided ability to track performance in operational care delivery for dental providers in a clinical setting in real time.

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline.

BACKGROUND: The alcohol cue reactivity paradigm is increasingly used to screen medications for the treatment of alcohol use disorder (AUD) and other substance use disorders. Yet, its prospective association with craving and naturalistic drinking outcomes in clinical trials remains unknown. This study embedded repeated human laboratory assessments of alcohol cue reactivity within the context of a randomized controlled trial to examine the effects of varenicline tartrate (Chantix® ), a partial agonist of α4ß2 nicotinic acetylcholine receptors, on alcohol craving among treatment-seeking heavy drinkers with AUD. Our main objectives were to test whether varenicline, as compared to placebo, blunts alcohol cue-elicited craving and test whether alcohol cue reactivity observed in the human laboratory predicts subsequent alcohol craving and use during the remainder of the trial. DESIGN AND METHODS: This double-blind, randomized, 2-site study compared the effects of varenicline (up to 2 mg/d) and placebo on responses to in vivo alcohol cue and affective picture cue exposure in the human laboratory. Forty-seven volunteers (18 females, 29 males), ages 23 to 67 years (M = 43.7, SD = 11.5), were recruited from the community via advertisements to participate in a clinical trial designed to study the effects of varenicline on alcohol use. Participants were randomized to either varenicline or placebo for 6 weeks. RESULTS: Varenicline did not attenuate cue-induced alcohol craving relative to placebo, but craving captured during the cue reactivity paradigm significantly predicted subsequent alcohol use in real-world settings during the clinical trial. Higher craving predicted heavier alcohol use. CONCLUSIONS: Our results are among the first to show alcohol cue-induced craving captured during a human laboratory paradigm predicts drinking outcomes in the context of a clinical trial.

Medication Development for Alcohol Use Disorder: A Focus on Clinical Studies.

Compared to other medical disorders, including other brain diseases, the number of medications approved for alcohol use disorder (AUD) is very small. Disulfiram, naltrexone (oral and long-acting), and acamprosate are approved by the US Food and Drug Administration (FDA) to treat patients with AUD. These medications are also approved in other countries, including in Europe, where the European Medicines Agency (EMA) also approved nalmefene for AUD. Furthermore, baclofen was recently approved for AUD in France. These approved medications have small effect sizes, which are probably the consequence of the fact that they only work for some patients, yet a personalized approach to match the right medication with the right patient is still in its infancy. Therefore, research is needed to expand the armamentarium of medications that clinicians can use to treat their patients, as well as to better develop personalized approaches. This book chapter reviews other medications, beyond those approved by the FDA, that have shown efficacy in clinical trials, as well as medications which are still in the early stages of evaluation in human studies.

Successful treatment of hemorrhagic brainstem cavernous malformation with hematoma evacuation and postoperative propranolol.

In this case, we describe an evident hemorrhagic brainstem cavernous malformation successfully treated with a planned sequence of surgical evacuation of the hematoma followed by postoperative propranolol therapy. In contrast to common practice, the cavernoma itself was not resected. A nearly 3-year-old male presented with altered mental status, gait disturbance, and facial palsy. CT and MRI demonstrated a large acute pontine hematoma. A large nearby vein suggested cavernous malformation. He was initially treated conservatively but a repeat CT scan demonstrated further expansion of hematoma and he was taken emergently to the OR. Due to the sensitive location of the hematoma in the pons, we planned to evacuate the hematoma without resecting any of the presumed cavernoma. Instead, we planned to treat the cavernoma with propranolol. Postoperatively, the patient's condition improved and was still improving at hospital discharge 2 weeks later. Six-month follow-up MRI showed no cavernoma with only hemosiderin at the site of the evacuated hematoma. This is the first reported case of a hemorrhagic brainstem cavernous malformation treated with a planned sequence of hematoma evacuation followed by propranolol without an attempt to resect the cavernoma.