Genome-Wide Association Study to Identify Possible Candidate Genes of Snap Bean Leaf and Pod Color.

Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral nutrition because every nutrient deficiency and many diseases produce symptoms that affect color. In order to identify significant loci related to both leaf and pod color in a snap bean (Phaseolus vulgaris L.) diversity panel, a genome-wide association study (GWAS) was carried out. Leaf color in one and pod traits in multiple environments were characterized using a colorimeter. L*a*b* color data were recorded and used to calculate chroma (C*) and hue angle (H°). Leaves were evaluated at three positions (lower, middle, and upper) in the canopy and both pod exterior and interior colors were obtained. GWAS was conducted using two reference genomes that represent the Andean (G19833) and Middle American (5-593) domestication centers. Narrow sense heritabilities were calculated using the mixed linear model (MLM) method in genome association and prediction integrated tool (GAPIT), and significant single nucleotide polymorphisms (SNPs) for each color parameter were obtained using the Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) GWAS model with two principal components (PCAs). In comparison to pod color traits, narrow sense heritabilities of leaf traits were low and similar for both reference genomes. Generally, narrow sense heritability for all traits was highest in the lower, followed by middle, and then upper leaf positions. Heritability for both pod interior and exterior color traits was higher using the G19833 reference genome compared to 5-593 when evaluated by year and means across years. Forty-five significant SNPs associated with leaf traits and 872 associated with pods, totaling 917 significant SNPs were identified. Only one SNP was found in common for both leaf and pod traits on Pv03 in the 5-593 reference genome. One-hundred thirteen significant SNPs, 30 in leaves and 83 in pods had phenotypic variation explained (PVE) of 10% or greater. Fourteen SNPs (four from G19833 and ten from 5-593) with ≥10 PVE%, large SNP effect, and largest p-value for L* and H° pod exterior was identified on Pv01, Pv02, Pv03, and Pv08. More SNPs were associated with pod traits than with leaf traits. The pod interior did not exhibit colors produced by anthocyanins or flavonols which allowed the differentiation of potential candidate genes associated with chloroplast and photosynthetic activity compared to the pod exterior where candidate genes related to both flavonoids and photosynthesis affected color. Several SNPs were associated with known qualitative genes including the wax pod locus (y), persistent color (pc), purple pods (V), and two genes expressed in seeds but not previously reported to affect other plant tissues (B and J). An evaluation of significant SNPs within annotated genes found a number, within a 200 kb window, involved in both flavonoid and photosynthetic biosynthetic pathways.

Influence of organic plant breeding on the rhizosphere microbiome of common bean (Phaseolus vulgaris L.).

Introduction: We now recognize that plant genotype affects the assembly of its microbiome, which in turn, affects essential plant functions. The production system for crop plants also influences the microbiome composition, and as a result, we would expect to find differences between conventional and organic production systems. Plant genotypes selected in an organic regime may host different microbiome assemblages than those selected in conventional environments. We aimed to address these questions using recombinant inbred populations of snap bean that differed in breeding history. Methods: Rhizosphere microbiomes of conventional and organic common beans (Phaseolus vulgaris L.) were characterized within a long-term organic research site. The fungal and bacterial communities were distinguished using pooled replications of 16S and ITS amplicon sequences, which originated from rhizosphere samples collected between flowering and pod set. Results: Bacterial communities significantly varied between organic and conventional breeding histories, while fungal communities varied between breeding histories and parentage. Within the organically-bred populations, a higher abundance of a plant-growth-promoting bacteria, Arthrobacter pokkalii, was identified. Conventionally-bred beans hosted a higher abundance of nitrogen-fixing bacteria that normally do not form functional nodules with common beans. Fungal communities in the organically derived beans included more arbuscular mycorrhizae, as well as several plant pathogens. Discussion: The results confirm that the breeding environment of crops can significantly alter the microbiome community composition of progeny. Characterizing changes in microbiome communities and the plant genes instrumental to these changes will provide essential information about how future breeding efforts may pursue microbiome manipulation.

Advancing primary care: Doctoral program for physician associates and nurse practitioners.

The United States faces an impending crisis in primary care physician shortages, while Physician Associates (PAs) and Nurse Practitioners (NPs) are poised to help bridge the gap. This manuscript explores a groundbreaking solution: introducing a clinical doctorate program tailored to PAs and NPs, designed to equip them with the knowledge and skills to assume leadership roles in primary care. Unlike traditional medical education, this innovative approach allows these professionals to continue their clinical practice while advancing their education, addressing the workforce shortage and the need for advanced leadership within the primary care landscape. This comprehensive curriculum includes intensive didactic coursework, residency-like training, credentialing examinations, and research opportunities, positioning PAs and NPs as critical contributors to the future of primary care. By recognizing their untapped potential and investing in their advanced education, we can elevate the quality and accessibility of primary care, ensuring that healthcare delivery reaches new heights.

An older adult advantage in autobiographical recall.

This pre-registered online study aimed to measure the effect of environmental support on age-differences in autobiographical memory alongside memory for images. Young and older adults reported autobiographical memories about which they regularly thought (high environmental support through practice) or that were experimentally cued to be mundane (low environmental support). The support manipulation was also applied to descriptions of images that were produced whilst images remained on screen (high support) or produced from memory (low support). In line with existing theory, support disproportionately benefitted older adults in the quantity of information produced. However, analysis of the autobiographical descriptions showed no age deficit in reporting episodic detail, in contrast to much of the existing literature. A second group of young and older adults also evaluated the descriptions produced, and older adults' descriptions were consistently rated as higher quality than young adults' descriptions across several dimensions, such as vividness and clarity. An unplanned meta-analysis was conducted to assess if a publication bias existed in the literature favoring the reporting of age-deficits in producing episodic detail in autobiographical memory: there was no evidence for a bias and the modal result of age deficits was generally supported. A key distinction is that the current study was conducted online - evidence is presented to argue that older adults may perform better at autobiographical memory tasks outside the lab.

Genome-Wide Association Study (GWAS) of White Mold Resistance in Snap Bean.

White mold can result in snap bean yield losses of 90 to 100% when field conditions favor the pathogen. A genome-wide association study (GWAS) was conducted to detect loci significantly associated with white mold resistance in a panel of snap bean (Phaseolus vulgaris L.) cultivars. Two populations of snap bean were used in this study. The first population was the BeanCAP (Coordinated Agriculture Project) Snap Bean Diversity Panel (SBDP) (n = 136), and the second population was the Snap Bean Association Panel (SnAP) (n = 378). SBDP was evaluated for white mold reaction in the field in 2012 and 2013, and SnAP was screened in a greenhouse only using the seedling straw test in 2016. Two reference genomes representing the Andean and Middle American centers of domestication were utilized to align the genotyping-by-sequencing (GBS) data. A GWAS was performed using FarmCPU with one principal component after comparing five models. Thirty-four single-nucleotide polymorphisms (SNPs) significantly associated with white mold resistance were detected. Eleven significant SNPs were identified by the seedling straw test, and 23 significant SNPs were identified by field data. Fifteen SNPs were identified within a 100 kb window containing pentatricopeptide repeat (PPR)-encoding genes, and eleven were close to leucine-rich repeat (LRR)-encoding genes, suggesting that these two classes are of outsized importance for snap bean resistance to white mold.

Loss of pod strings in common bean is associated with gene duplication, retrotransposon insertion and overexpression of PvIND.

Fruit development has been central in the evolution and domestication of flowering plants. In common bean (Phaseolus vulgaris), the principal global grain legume staple, two main production categories are distinguished by fibre deposition in pods: dry beans, with fibrous, stringy pods; and stringless snap/green beans, with reduced fibre deposition, which frequently revert to the ancestral stringy state. Here, we identify genetic and developmental patterns associated with pod fibre deposition. Transcriptional, anatomical, epigenetic and genetic regulation of pod strings were explored through RNA-seq, RT-qPCR, fluorescence microscopy, bisulfite sequencing and whole-genome sequencing. Overexpression of the INDEHISCENT ('PvIND') orthologue was observed in stringless types compared with isogenic stringy lines, associated with overspecification of weak dehiscence-zone cells throughout the pod vascular sheath. No differences in DNA methylation were correlated with this phenotype. Nonstringy varieties showed a tandemly direct duplicated PvIND and a Ty1-copia retrotransposon inserted between the two repeats. These sequence features are lost during pod reversion and are predictive of pod phenotype in diverse materials, supporting their role in PvIND overexpression and reversible string phenotype. Our results give insight into reversible gain-of-function mutations and possible genetic solutions to the reversion problem, of considerable economic value for green bean production.

Iconography of Beans and Related Legumes Following the Columbian Exchange.

Common bean (Phaseolus vulgaris L.), maize, and squash were described by explorers as early as 1492. The illustration of common bean recognized as the first in Europe is in Fuchs' Di Historias Stirpium, published in 1542 and a half-century after beans were observed in the Caribbean. Besides herbals and herbarium specimens, the sources of information on the introduction of New World crops are paintings and illustrations. Two early sources of images of maize and squash are the Grandes Heures d'Anne de Bretagne and the Loggia di Amore e Psiche in the Villa Farnesina, Rome. The former was illustrated between 1507 and 1508 and has an image identified as the common bean. The Villa Farnesina Loggia was decorated in 1515-1518, with festoons containing three instances of bean pods. Our first objective was to evaluate these images to determine whether they represented depictions of common bean earlier than the illustration by Fuchs. Neither image appears to be a common bean based on a combination of botanical characters and size. Folio 194 of the Grandes Heures d'Anne de Bretagne is most likely a Vigna species in the Ceratotropis subgenus. In the Loggia, one set of pods appears to be a species in the Mimosoideae subfamily and the second and third sets of pods most closely resemble Canavalia gladiata. Neither image likely represents common beans and are probably Old-World species. Secondly, illustrations of common beans from ten early herbals were analyzed for traits that are characteristic of the centers of domestication and races of common beans. Our objective was to characterize the diversity observed among herbals and determine whether beans from both centers of domestication were present. We potentially identified both Middle American, race Mesoamerica and Andean, race Nueva Granada types. We posit that both Middle American and Andean types were in the Caribbean at the time of the Columbian exchange and that beans from both centers were informally introduced into Europe early on. This review of 16th-century manuscripts and illustrations has provided some answers to the questions of what and when common beans reached Europe and provide new hypotheses for researchers studying the origins, diversity, and distribution of this crop.

Dysphagia after Stroke: An Unmet Antibiotic Stewardship Opportunity.

The goal of antibiotic stewardship is to improve antibiotic use, often by reducing unnecessary treatment. Bedside dysphagia screening tools help identify patients at high risk of aspiration following stroke. Presence of dysphagia does not indicate a need for antibiotic treatment. Therefore, this retrospective, cohort study was developed to evaluate the association of dysphagia and antibiotic prescribing following stroke. There were 117 patients included. Patients were placed into 2 cohorts based on the results of the dysphagia screening, with 55 patients positive for dysphagia and 62 patients negative for dysphagia. Patients with dysphagia tended to be older, had higher National Institutes of Health stroke scores, and lower renal function. Patients with dysphagia were prescribed more empiric antibiotics than those without dysphagia (18.2% vs. 3.2%, p = 0.01). This resulted in 53 antibiotic days of therapy in the dysphagia cohort compared to 19 antibiotic days of therapy in the no dysphagia cohort (p = 0.1). No patients later developed pneumonia and only one patient was started antibiotics after 48 h. Two cases of Clostridioides difficile were reported. Both patients were in the dysphagia cohort and received antibiotics. Multivariable logistic regression demonstrated that positive chest x-ray findings and failed dysphagia screen were independent conditions associated with initiating antibiotics. These findings indicate that antibiotic use was higher in patients following stroke with a positive dysphagia screen. Close monitoring of stroke patients, particularly when positive for dysphagia, might be an under-recognized antibiotic stewardship opportunity.

Baseline Knowledge Attitudes Satisfaction and Aspirations With Advance Care Planning: A Cross-Sectional Study.

BACKGROUND: Studies have consistently demonstrated low rates of adoption of Advance Care Planning in the community. METHODS: We studied Medicare enrollees age 65 and over and non-Medicare patients using a cross-sectional survey undertaken in February and March 2019 using questionnaires completed by out-patients attending a teaching hospital clinic in East Tennessee USA. We evaluated patient knowledge, attitudes, satisfaction and aspirations towards Advance Care Planning. RESULTS: 141 properly completed questionnaires were used. All Medicare enrollees were aware of Advanced Care Planning compared to 43% in the non-Medicare group. 70% of the Medicare enrollees and 94% of non-Medicare group were not ready to complete a written Advanced Care Plan. Of the respondents, 46% had appointed spouses, 24% adult children, 11% siblings, 10% parents, 3.6% friends and 1.2% aunts as their surrogate medical decision makers. 41% agreed that they were satisfied with their current advance care planning arrangements. This research identified that individual's knowledge, attitudes and aspirations influenced the adoption of Advance Care. CONCLUSIONS: Patients have adopted the Advance Care Plan concept but have modified it to reduce their concerns by using family and loved ones to convey their wishes instead of filling the required legal documents. Clinicians could improve this informal system and increase the observability of the treatment choices including the use of video and web-based tools.

Boosting the diagnostic power of amyloid-ß PET using a data-driven spatially informed classifier for decision support.

BACKGROUND: Amyloid-ß (Aß) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aß deposition is a necessary cause or response to the cellular pathology of Alzheimer's disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal. We present a data-driven, spatially informed classifier to boost the diagnostic power of amyloid PET in AD. METHODS: Voxel-wise k-means clustering of amyloid-positive voxels was performed; clusters were mapped to brain anatomy and tested for their associations by diagnostic category and disease severity with 758 amyloid PET scans from volunteers in the AD continuum from the Alzheimer's Disease Neuroimaging Initiative (ADNI). A machine learning approach based on this spatially constrained model using an optimised quadratic support vector machine was developed for automatic classification of scans for AD vs non-AD pathology. RESULTS: This classifier boosted the accuracy of classification of AD scans to 81% using the amyloid PET alone with an area under the curve (AUC) of 0.91 compared to other spatial methods. This increased sensitivity to detect AD by 15% and the AUC by 9% compared to the use of a composite region of interest SUVr. CONCLUSIONS: The diagnostic classification accuracy of amyloid PET was improved using an automated data-driven spatial classifier. Our classifier highlights the importance of considering the spatial variation in Aß PET signal for optimal interpretation of scans. The algorithm now is available to be evaluated prospectively as a tool for automated clinical decision support in research settings.

Associated SNPs, Heritabilities, Trait Correlations, and Genomic Breeding Values for Resistance in Snap Beans (Phaseolus vulgaris L.) to Root Rot Caused by Fusarium solani (Mart.) f. sp. phaseoli (Burkholder).

Root rot is a major constraint to snap bean (Phaseolus vulgaris) production in the United States and around the world. Genetic resistance is needed to effectively control root rot disease because cultural control methods are ineffective, and the pathogen will be present at the end of one season of production on previously clean land. A diversity panel of 149 snap bean pure lines was evaluated for resistance to Fusarium root rot in Oregon. Morphological traits potentially associated with root rot resistance, such as aboveground biomass, adventitious roots, taproot diameter, basal root diameter, deepest root angle, shallowest root angle, root angle average, root angle difference, and root angle geometric mean were evaluated and correlated to disease severity. A genome wide association study (GWAS) using the Fixed and random model Circulating Probability Unification (FarmCPU) statistical method, identified five associated single nucleotide polymorphisms (SNPs) for disease severity and two SNPs for biomass. The SNPs were found on Pv03, Pv07, Pv08, Pv10, and Pv11. One candidate gene for disease reaction near a SNP on Pv03 codes for a peroxidase, and two candidates associated with biomass SNPs were a 2-alkenal reductase gene cluster on Pv10 and a Pentatricopeptide repeat domain on Pv11. Bean lines utilized in the study were ranked by genomic estimated breeding values (GEBV) for disease severity, biomass, and the root architecture traits, and the observed and predicted values had high to moderate correlations. Cross validation of genomic predictions showed slightly lower correlational accuracy. Bean lines with the highest GEBV were among the most resistant, but did not necessarily rank at the very top numerically. This study provides information on the relationship of root architecture traits to root rot disease reaction. Snap bean lines with genetic merit for genomic selection were identified and may be utilized in future breeding efforts.

A natively flexible 32-bit Arm microprocessor.

Nearly 50 years ago, Intel created the world's first commercially produced microprocessor-the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 µm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. 2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention-that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects.

Αlpha 5 subunit-containing GABAA receptors in temporal lobe epilepsy with normal MRI.

GABAA receptors containing the α5 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of α5-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that α5 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared α5 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI ('MRI-negative') and healthy controls, and interrogated the relationship between α5 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median ± interquartile age 49 ± 13 years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40 ± 8) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. 'Bandpass' exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [V F; dominated by signal from α1 (α2, α3)-containing receptors] and the slow component (V S; dominated by signal from α5-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of V F and V S measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher V S in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cortex) and the insulae, in addition to increases of ∼24% and ∼26% in the ipsilateral and contralateral hippocampal areas (P < 0.004). This was associated with reduced V F:V S ratios within the same areas (P < 0.009). Comparisons of V S for each individual with epilepsy versus controls did not consistently lateralize the epileptogenic lobe. Memory scores were significantly lower in the epilepsy group than in controls (mean ± standard deviation -0.4 ± 1.0 versus 0.7 ± 0.3; P = 0.02). In individuals with epilepsy, hippocampal V S did not correlate with memory performance on the Adult Memory and Information Processing Battery. They had reduced V F in the hippocampal area, which was significant ipsilaterally (P = 0.03), as expected from [11C]flumazenil studies. We found increased tonic inhibitory neurotransmission in our cohort of MRI-negative temporal lobe epilepsy who also had co-morbid memory impairments. Our findings are consistent with a subunit shift from α1/2/3 to α5 in MRI-negative temporal lobe epilepsy.

Oral vancomycin prophylaxis for the prevention of Clostridium difficile infection: A systematic review and meta-analysis.

OBJECTIVE: Recently, oral vancomycin prophylaxis (OVP) has been suggested for the prevention of Clostridium difficile infection (CDI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of this approach. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a computerized search of MEDLINE, EMBASE, and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for eligibility. Relevant data were extracted and analyzed. Publication bias was assessed using the Egger test. RESULTS: Ultimately, 8 retrospective studies and 1 prospective study examining 2174 patients, published between 2016 and 2019 were included in the review. OVP was associated with decreased CDI (odds ratio, 0.263; 95% confidence interval, 0.13-0.52) with considerable heterogeneity (I2 = 61%). Meta-regression showed that total daily dose of OVP correlated with CDI, explaining 100% of heterogeneity between studies. Furthermore, 3 studies evaluated the risk of vancomycin-resistant enterococci (VRE) infection after OVP and found no significant increase. CONCLUSION: Our results suggest that OVP might decrease CDI rates in at-risk populations, although this conclusion should be interpreted with caution. Higher daily doses of OVP might increase CDI. Although the use of OVP in high-risk patients may reduce CDI, this suggestion has yet to be validated by prospective blinded randomized controlled trials.

Tomato Domestication Attenuated Responsiveness to a Beneficial Soil Microbe for Plant Growth Promotion and Induction of Systemic Resistance to Foliar Pathogens.

Crop domestication events followed by targeted breeding practices have been pivotal for improvement of desirable traits and to adapt cultivars to local environments. Domestication also resulted in a strong reduction in genetic diversity among modern cultivars compared to their wild relatives, though the effect this could have on tripartite relationships between plants, belowground beneficial microbes and aboveground pathogens remains undetermined. We quantified plant growth performance, basal resistance and induced systemic resistance (ISR) by Trichoderma harzianum, a beneficial soil microbe against Botrytis cinerea, a necrotrophic fungus and Phytophthora infestans, a hemi-biotrophic oomycete, in 25 diverse tomato genotypes. Wild tomato related species, tomato landraces and modern commercial cultivars that were conventionally or organically bred, together, representing a domestication gradient were evaluated. Relationships between basal and ISR, plant physiological status and phenolic compounds were quantified to identify potential mechanisms. Trichoderma enhanced shoot and root biomass and ISR to both pathogens in a genotype specific manner. Moreover, improvements in plant performance in response to Trichoderma gradually decreased along the domestication gradient. Wild relatives and landraces were more responsive to Trichoderma, resulting in greater suppression of foliar pathogens than modern cultivars. Photosynthetic rate and stomatal conductance of some tomato genotypes were improved by Trichoderma treatment whereas leaf nitrogen status of the majority of tomato genotypes were not altered. There was a negative relationship between basal resistance and induced resistance for both diseases, and a positive correlation between Trichoderma-ISR to B. cinerea and enhanced total flavonoid contents. These findings suggest that domestication and breeding practices have altered plant responsiveness to beneficial soil microbes. Further studies are needed to decipher the molecular mechanisms underlying the differential promotion of plant growth and resistance among genotypes, and identify molecular markers to integrate selection for responsiveness into future breeding programs.

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals.

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

A case of gastrointestinal histoplasmosis with esophageal involvement.

Histoplasmosis is a common infection endemic to the Ohio and Mississippi River Valleys caused by the inhalation of Histoplasma capsulatum spores from contaminated soil. Most infections are asymptomatic; however, patients with impaired cellular immunity (HIV infection, hematologic malignancy, solid organ transplant, hematopoietic stem cell transplant or TNF-⍺ inhibitor use) are at risk for disseminated disease. Disseminated histoplasmosis commonly affects the lungs, liver, spleen, bone marrow and gastrointestinal tract. Esophageal involvement is rare and usually due to extrinsic compression from affected mediastinal/hilar lymph nodes. Herein, we report a case of disseminated histoplasmosis in an AIDs patient involving the esophagus, without evidence of mediastinal involvement.

Decreased GABA-A Receptor Binding in Association With ß-Lactam Antibiotic Use.

ß-Lactam antibiotics are proconvulsive. In laboratory animals, this effect seems to be predominantly mediated through inhibition of GABA-A receptors, but it has not been demonstrated in humans in vivo. We report images of a [C]Ro15-4513 PET from a 40-year-old man who had completed a 1-week course of flucloxacillin before it. Relative to healthy controls, the participant had significantly lower mean gray matter binding. These novel data suggest that, in humans, the proconvulsive effect of ß-lactam antibiotics is mediated via either competition for the same benzodiazepine-binding site as [C]Ro15-4513 or downregulation of GABA-A receptor expression.