Compassion Versus Accuracy: Lenient Scoring of the Spatial Orientation Items on the Mini-mental State Exam Lowers Sensitivity.

The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.

Anti-SARS-CoV-2 Monoclonal Antibodies in Pediatrics: Statewide Experience in Rhode Island.

BACKGROUND: The pediatric population has suffered COVID-19 infections with measurable morbidity and mortality. Without oral options in those less than 12 years of age, practical treatment in this rapidly evolving disease is necessary. One treatment modality is monoclonal antibodies. Limited information describes the efficacy and safety of anti-SARS-CoV-2 monoclonal antibodies in pediatrics. This is the largest case series addressing efficacy and safety of monoclonal antibodies in this population. OBJECTIVE: To report patient characteristics, side effects encountered, and hospital admissions or emergency department visits within 30 days following treatment. DESIGN: This retrospective case series includes high-risk pediatric COVID-19 patients who received monoclonal antibody infusions in a tertiary care center as outpatients between January 2021 and January 2022. OUTCOMES: There were 108 patients included with seven patients (6.5%) having infusion-related reactions with no other adverse events reported. Following the monoclonal treatment, three patients presented to the emergency department for worsening symptoms, and one patient was admitted to the pediatric ICU for worsening respiratory status. No other admissions or emergency department visits were reported in the one month following the infusion. CONCLUSIONS: In this case series study, monoclonal antibody infusions were well tolerated.

Replicating a Meta-Analysis: The Search for the Optimal Word Choice Test Cutoff Continues.

This study was designed to expand on a recent meta-analysis that identified ≤42 as the optimal cutoff on the Word Choice Test (WCT). We examined the base rate of failure and the classification accuracy of various WCT cutoffs in four independent clinical samples (N = 252) against various psychometrically defined criterion groups. WCT ≤ 47 achieved acceptable combinations of specificity (.86-.89) at .49 to .54 sensitivity. Lowering the cutoff to ≤45 improved specificity (.91-.98) at a reasonable cost to sensitivity (.39-.50). Making the cutoff even more conservative (≤42) disproportionately sacrificed sensitivity (.30-.38) for specificity (.98-1.00), while still classifying 26.7% of patients with genuine and severe deficits as non-credible. Critical item (.23-.45 sensitivity at .89-1.00 specificity) and time-to-completion cutoffs (.48-.71 sensitivity at .87-.96 specificity) were effective alternative/complementary detection methods. Although WCT ≤ 45 produced the best overall classification accuracy, scores in the 43 to 47 range provide comparable objective psychometric evidence of non-credible responding. Results question the need for designating a single cutoff as "optimal," given the heterogeneity of signal detection environments in which individual assessors operate. As meta-analyses often fail to replicate, ongoing research is needed on the classification accuracy of various WCT cutoffs.

QTL mapping of yield components and kernel traits in wheat cultivars TAM 112 and Duster.

In the Southern Great Plains, wheat cultivars have been selected for a combination of outstanding yield and drought tolerance as a long-term breeding goal. To understand the underlying genetic mechanisms, this study aimed to dissect the quantitative trait loci (QTL) associated with yield components and kernel traits in two wheat cultivars `TAM 112' and `Duster' under both irrigated and dryland environments. A set of 182 recombined inbred lines (RIL) derived from the cross of TAM 112/Duster were planted in 13 diverse environments for evaluation of 18 yield and kernel related traits. High-density genetic linkage map was constructed using 5,081 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing (GBS). QTL mapping analysis detected 134 QTL regions on all 21 wheat chromosomes, including 30 pleiotropic QTL regions and 21 consistent QTL regions, with 10 QTL regions in common. Three major pleiotropic QTL on the short arms of chromosomes 2B (57.5 - 61.6 Mbps), 2D (37.1 - 38.7 Mbps), and 7D (66.0 - 69.2 Mbps) colocalized with genes Ppd-B1, Ppd-D1, and FT-D1, respectively. And four consistent QTL associated with kernel length (KLEN), thousand kernel weight (TKW), plot grain yield (YLD), and kernel spike-1 (KPS) (Qklen.tamu.1A.325, Qtkw.tamu.2B.137, Qyld.tamu.2D.3, and Qkps.tamu.6A.113) explained more than 5% of the phenotypic variation. QTL Qklen.tamu.1A.325 is a novel QTL with consistent effects under all tested environments. Marker haplotype analysis indicated the QTL combinations significantly increased yield and kernel traits. QTL and the linked markers identified in this study will facilitate future marker-assisted selection (MAS) for pyramiding the favorable alleles and QTL map-based cloning.

A new strategy for using historical imbalanced yield data to conduct genome-wide association studies and develop genomic prediction models for wheat breeding.

Using imbalanced historical yield data to predict performance and select new lines is an arduous breeding task. Genome-wide association studies (GWAS) and high throughput genotyping based on sequencing techniques can increase prediction accuracy. An association mapping panel of 227 Texas elite (TXE) wheat breeding lines was used for GWAS and a training population to develop prediction models for grain yield selection. An imbalanced set of yield data collected from 102 environments (year-by-location) over 10 years, through testing yield in 40-66 lines each year at 6-14 locations with 38-41 lines repeated in the test in any two consecutive years, was used. Based on correlations among data from different environments within two adjacent years and heritability estimated in each environment, yield data from 87 environments were selected and assigned to two correlation-based groups. The yield best linear unbiased estimation (BLUE) from each group, along with reaction to greenbug and Hessian fly in each line, was used for GWAS to reveal genomic regions associated with yield and insect resistance. A total of 74 genomic regions were associated with grain yield and two of them were commonly detected in both correlation-based groups. Greenbug resistance in TXE lines was mainly controlled by Gb3 on chromosome 7DL in addition to two novel regions on 3DL and 6DS, and Hessian fly resistance was conferred by the region on 1AS. Genomic prediction models developed in two correlation-based groups were validated using a set of 105 new advanced breeding lines and the model from correlation-based group G2 was more reliable for prediction. This research not only identified genomic regions associated with yield and insect resistance but also established the method of using historical imbalanced breeding data to develop a genomic prediction model for crop improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01287-8.

Genome-wide QTL mapping of yield and agronomic traits in two widely adapted winter wheat cultivars from multiple mega-environments.

Quantitative trait loci (QTL) analysis could help to identify suitable molecular markers for marker-assisted breeding (MAB). A mapping population of 124 F5:7recombinant inbred lines derived from the cross 'TAM 112'/'TAM 111' was grown under 28 diverse environments and evaluated for grain yield, test weight, heading date, and plant height. The objective of this study was to detect QTL conferring grain yield and agronomic traits from multiple mega-environments. Through a linkage map with 5,948 single nucleotide polymorphisms (SNPs), 51 QTL were consistently identified in two or more environments or analyses. Ten QTL linked to two or more traits were also identified on chromosomes 1A, 1D, 4B, 4D, 6A, 7B, and 7D. Those QTL explained up to 13.3% of additive phenotypic variations with the additive logarithm of odds (LOD(A)) scores up to 11.2. The additive effect increased yield up to 8.16 and 6.57 g m-2 and increased test weight by 2.14 and 3.47 kg m-3 with favorable alleles from TAM 111 and TAM 112, respectively. Seven major QTL for yield and six for TW with one in common were of our interest on MAB as they explained 5% or more phenotypic variations through additive effects. This study confirmed previously identified loci and identified new QTL and the favorable alleles for improving grain yield and agronomic traits.

Genome wide identification of QTL associated with yield and yield components in two popular wheat cultivars TAM 111 and TAM 112.

Two drought-tolerant wheat cultivars, 'TAM 111' and 'TAM 112', have been widely grown in the Southern Great Plains of the U.S. and used as parents in many wheat breeding programs worldwide. This study aimed to reveal genetic control of yield and yield components in the two cultivars under both dryland and irrigated conditions. A mapping population containing 124 F5:7 recombinant inbred lines (RILs) was developed from the cross of TAM 112/TAM 111. A set of 5,948 SNPs from the wheat 90K iSelect array and double digest restriction-site associated DNA sequencing was used to construct high-density genetic maps. Data for yield and yield components were obtained from 11 environments. QTL analyses were performed based on 11 individual environments, across all environments, within and across mega-environments. Thirty-six unique consistent QTL regions were distributed on 13 chromosomes including 1A, 1B, 1D, 2A, 2D, 3D, 4B, 4D, 6A, 6B, 6D, 7B, and 7D. Ten unique QTL with pleiotropic effects were identified on four chromosomes and eight were in common with the consistent QTL. These QTL increased dry biomass grain yield by 16.3 g m-2, plot yield by 28.1 g m-2, kernels spike-1 by 0.7, spikes m-2 by 14.8, thousand kernel weight by 0.9 g with favorable alleles from either parent. TAM 112 alleles mainly increased spikes m-2 and thousand kernel weight while TMA 111 alleles increased kernels spike-1, harvest index and grain yield. The saturated genetic map and markers linked to significant QTL from this study will be very useful in developing high throughput genotyping markers for tracking the desirable haplotypes of these important yield-related traits in popular parental cultivars.

Genomic, Phenotypic, and Virulence Analysis of Streptococcus sanguinis Oral and Infective-Endocarditis Isolates.

Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis (IE), particularly in people with predisposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. In this study, we compared the genomes of a collection of S. sanguinis strains comprised of both oral isolates and bloodstream isolates from patients diagnosed with IE. Oral and IE isolates could not be distinguished by phylogenetic analyses, and we did not succeed in identifying virulence genes unique to the IE strains. We then investigated the virulence of these strains in a rabbit model of IE using a variation of the Bar-seq (barcode sequencing) method wherein we pooled the strains and used Illumina sequencing to count unique barcodes that had been inserted into each isolate at a conserved intergenic region. After we determined that several of the genome sequences were misidentified in GenBank, our virulence results were used to inform our bioinformatic analyses, identifying genes that may explain the heterogeneity in virulence. We further characterized these strains by assaying for phenotypes potentially contributing to virulence. Neither strain competition via bacteriocin production nor biofilm formation showed any apparent relationship with virulence. Increased cell-associated manganese was, however, correlated with blood isolates. These results, combined with additional phenotypic assays, suggest that S. sanguinis virulence is highly variable and results from multiple genetic factors.

Manganese acquisition is essential for virulence of Enterococcus faecalis.

Manganese (Mn) is an essential micronutrient that is not readily available to pathogens during infection due to an active host defense mechanism known as nutritional immunity. To overcome this nutrient restriction, bacteria utilize high-affinity transporters that allow them to compete with host metal-binding proteins. Despite the established role of Mn in bacterial pathogenesis, little is known about the relevance of Mn in the pathophysiology of E. faecalis. Here, we identified and characterized the major Mn acquisition systems of E. faecalis. We discovered that the ABC-type permease EfaCBA and two Nramp-type transporters, named MntH1 and MntH2, work collectively to promote cell growth under Mn-restricted conditions. The simultaneous inactivation of EfaCBA, MntH1 and MntH2 (ΔefaΔmntH1ΔmntH2 strain) led to drastic reductions (>95%) in cellular Mn content, severe growth defects in body fluids (serum and urine) ex vivo, significant loss of virulence in Galleria mellonella, and virtually complete loss of virulence in rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI) models. Despite the functional redundancy of EfaCBA, MntH1 and MntH2 under in vitro or ex vivo conditions and in the invertebrate model, dual inactivation of efaCBA and mntH2 (ΔefaΔmntH2 strain) was sufficient to prompt maximal sensitivity to calprotectin, a Mn- and Zn-chelating host antimicrobial protein, and for the loss of virulence in mammalian models. Interestingly, EfaCBA appears to play a prominent role during systemic infection, whereas MntH2 was more important during CAUTI. The different roles of EfaCBA and MntH2 in these sites could be attributed, at least in part, to the differential expression of efaA and mntH2 in cells isolated from hearts or from bladders. Collectively, this study demonstrates that Mn acquisition is essential for the pathogenesis of E. faecalis and validates Mn uptake systems as promising targets for the development of new antimicrobials.

Differentiating epilepsy from psychogenic nonepileptic seizures using neuropsychological test data.

OBJECTIVE: Differentiating epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES) represents a challenging differential diagnosis with important treatment implications. This study was designed to explore the utility of neuropsychological test scores in differentiating ES from PNES. METHOD: Psychometric data from 72 patients with ES and 33 patients with PNES were compared on various tests of cognitive ability and performance validity. Individual measures that best discriminated the diagnoses were then entered as predictors in a logistic regression equation with group membership (ES vs. PNES) as the criterion. RESULTS: On most tests of cognitive ability, the PNES sample outperformed the ES sample (medium-large effect) and was less likely to fail the Reliable Digit Span. However, patients with PNES failed two embedded validity indicators at significantly higher rates (risk ratios (RR): 2.45-4.16). There were no group differences on the Test of Memory Malingering (TOMM). A logistic regression equation based on seven neuropsychological tests correctly classified 85.1% of patients. The cutoff with perfect specificity was associated with 0.47 sensitivity. CONCLUSIONS: Consistent with previous research, the utility of psychometric methods of differential diagnosis is limited by the complex neurocognitive profiles associated with ES and PNES. Although individual measures might help differentiate ES from PNES, multivariate assessment models have superior discriminant power. The strongest psychometric evidence for PNES appears to be a consistent lack of impairment on tests sensitive to diffuse neurocognitive deficits such as processing speed, working memory, and verbal fluency. While video-electroencephalogram (EEG) monitoring is the gold standard of differential diagnosis, psychometric testing has the potential to enhance clinical decision-making, particularly in complex or unclear cases such as patients with nondiagnostic video-EEGs. Adopting a standardized, fixed neuropsychological battery at epilepsy centers would advance research on the differential diagnostic power of psychometric testing.

Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections.

Use of nonsystemic antimicrobials with activity against enteropathogens is a promising approach for treatment of infectious diarrhea and other nonsystemic gastrointestinal infections. Rifaximin is approved by the US FDA for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients aged 12 years and older, and for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients aged 18 years or older. Rifaximin has been available in Italy since 1987 and overall is approved in 33 countries for various conditions, such as acute and chronic infections, bacterial diarrhea, HE, and pre- and postsurgical prophylaxis. There is accumulating evidence on the benefit of rifaximin for nonsystemic gastrointestinal infections. This article will serve as an update on rifaximin. The pharmacology and pharmacodynamics of rifaximin along with an updated review on the bacterial susceptibility to rifaximin will be presented. Finally, clinical trials with rifaximin for nonsystemic gastrointestinal indications will be updated.

Idiopathic gastroesophageal reflux disease in an adult horse.

Chronic gastroesophageal reflux disease was diagnosed in a 22-year-old female Tennessee Walking Horse that had signs of bruxism and ptyalism. Esophageal ulceration was detected via endoscopy. Compared with the damage to the proximal portions of the esophagus, the severity of the ulceration increased toward the gastroesophageal junction. Esophageal ulceration attributable to chronic gastric acid reflux is usually secondary to pyloric outflow obstruction in horses. In the horse of this report, there was no evidence of either a chronic pyloric or duodenal obstruction that could have resulted in esophageal ulceration. Esophageal ulceration in this horse was attributed to gastroesophageal reflux disease, a common condition in humans in which the underlying abnormality is functional incompetence of the gastroesophageal junction. Treatment is directed at decreasing gastric acidity and protecting the ulcerated mucosa. In the horse of this report, treatment was unsuccessful and the horse was euthanatized; a physical cause of gastroesophageal reflux disease was not identified during an extensive postmortem examination.

Characterization of the ftsZ gene from Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Rickettsia rickettsii, and use as a differential PCR target.

Degenerate primers corresponding to highly conserved regions of previously characterized ftsZ genes were used to PCR amplify a portion of the ftsZ gene from the genomic DNA of Ehrlichia chaffeensis (ftsZ(Ech)), Anaplasma phagocytophilum (ftsZ(Ap)), and Rickettsia rickettsii (ftsZ(Rr)). Genome walking was then used to amplify the 5' and 3' termini of the genes. The DNA sequences of the resulting amplification products yielded open reading frames coding for proteins with molecular masses of 42.0, 45.7, and 48.3 kDa for A. phagocytophilum, E. chaffeensis, and R. rickettsii, respectively. These homologs are 20 to 70 amino acids longer than the FtsZ proteins characterized in bacteria such as Escherichia coli and Bacillus subtilis, but do not possess the large extended carboxyl-termini found in the FtsZ proteins of Bartonella, Rhizobium, and Agrobacterium species. The functional domains important for FtsZ activity are conserved within the ehrlichial and rickettsial FtsZ protein sequences. The R. rickettsii FtsZ sequence is highly homologous to the FtsZ protein previously described for Rickettsia prowazekii (89% identity), and identical to the FtsZ protein of Rickettsia conorii. The percent identity observed between the A. phagocytophilum and E. chaffeensis FtsZ proteins is only 79% and is particularly low in the carboxyl-terminal region (15.8% identity). Primers were designed to PCR amplify a portion of the variable carboxyl-terminal region of the ftsZ gene, and used to differentiate each agent based on the size of the amplicons: A. phagocytophilum, 278 bp; E. chaffeensis, 341 bp; and Rickettsia spp., 425 bp.