Pharmacy Data for Tuberculosis Surveillance and Assessment of Patient Management

Pharmacy data help locate tuberculosis cases and assess their management

Reproducibility of Brain Responses: High for Speech Perception, Low for Reading Difficulties

Neuroscience findings have recently received critique on the lack of replications. To examine the reproducibility of brain indices of speech sound discrimination and their role in dyslexia, a specific reading difficulty, brain event-related potentials using EEG were measured using the same cross-linguistic passive oddball paradigm in about 200 dyslexics and 200 typically reading 8-12-year-old children from four countries with different native languages. Brain responses indexing speech and non-speech sound discrimination were extremely reproducible, supporting the validity and reliability of cognitive neuroscience methods. Significant differences between typical and dyslexic readers were found when examined separately in different country and language samples. However, reading group differences occurred at different time windows and for different stimulus types between the four countries. This finding draws attention to the limited generalizability of atypical brain response findings in children with dyslexia across language environments and raises questions about a common neurobiological factor for dyslexia. Our results thus show the robustness of neuroscience methods in general while highlighting the need for multi-sample studies in the brain research of language disorders

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p <2.8 x 10(-6)) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atp(T) = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 x 10(-13)), bipolar disorder (1.53[1.44; 1.63];p = 1 x 10(-43)), schizophrenia (1.36[1.28; 1.45];p = 4 x 10(-22)), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 x 10(-12)), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 x 10(-4)), educational attainment (0.86[0.82; 0.91];p = 2 x 10(-7)), and intelligence (0.72[0.68; 0.76];p = 9 x 10(-29)). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.Peer reviewe

Readability of Spanish-Language Online Patient Educational Materials for Peripheral Artery Disease Do Not Meet Recommended Standards and Represent a Literacy Barrier to Care

BackgroundOnline resources are a valuable source of information for patients and have been reported to improve engagement and adherence to medical care. However, readability of online patient educational materials (OPEMs) is crucial for them to serve their intended purpose. The American Medical Association (AMA) recommends that OPEM be written at or below the sixth grade reading level. To avoid disparities in access to comprehensible health information on peripheral artery disease (PAD), it is imperative that the readability of PAD OPEM is appropriate for both English-speaking and Spanish-speaking patients. The aim of this study is to evaluate the readability of PAD OPEM in Spanish and compare to English-language OPEM.MethodsWe conducted a Google search in English and Spanish using "peripheral arterial disease" and "enfermedad arterial periferica", respectively, and the top 25 patient-accessible articles were collected for each. Articles were categorized by source type: hospital, professional society, or other. Readability of English-language OPEM was measured using the Flesch Reading Ease Readability Formula, Automated Readability Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Gunning Fog, Linsear Write Formula, and the Simple Measure of Gobbledygook Index. Readability of Spanish OPEM was measured using the Fernández-Huerta Index and Índice Flesch-Szigriszt Scale. Readability of the articles was compared to the AMA recommendation, between English- and Spanish-language, and across sources using statistical tests appropriate to the data.ResultsOPEM from professional societies represented the fewest number of English- (n&nbsp;=&nbsp;7, 28%) and Spanish-language (n&nbsp;=&nbsp;6, 24%) articles. Most English-speaking (n&nbsp;=&nbsp;18, 72%) and Spanish-language (n&nbsp;=&nbsp;20, 80%) OPEM were considered difficult as measured by the Flesch Reading Ease Readability Formula and Fernández-Huerta Index, respectively, but did not significantly differ between languages (P&nbsp;=&nbsp;0.59). There were no significant differences in the average readability of all readability measurements across sources (hospital, professional society, or other). All the average readability grade levels for English-speaking and Spanish-language OPEM was significantly higher than the sixth grade reading level (P&nbsp;&lt;&nbsp;0.01). Only 3 (6%) OPEM met the AMA recommended reading level and there was no significant difference between English-language and Spanish-language OPEM (P&nbsp;=&nbsp;1.0).ConclusionsNearly all Spanish-language and English-language PAD OPEM assessed were written at a reading grade level higher than recommended by the AMA. There was no significant difference in the readability of materials from hospitals or professional societies. To prevent further widening of health disparities related to literacy, health content creators, particularly hospitals and professional societies, should prioritize, develop, and ensure that English-language and Spanish-language patient education materials are written at a level appropriate for the public

Crystallographic Trapping of the Glutamyl-CoA Thioester Intermediate of Family I CoA Transferases

Coenzyme A transferases are involved in a broad range of biochemical processes in both prokaryotes and eukaryotes, and exhibit a diverse range of substrate specificities. The YdiF protein from Escherichia coli O157:H7 is an acyl-CoA transferase of unknown physiological function, and belongs to a large sequence family of CoA transferases, present in bacteria to humans, which utilize oxoacids as acceptors. In vitro measurements showed that YdiF displays enzymatic activity with short-chain acyl-CoAs. The crystal structures of YdiF and its complex with CoA, the first co-crystal structure for any Family I CoA transferase, have been determined and refined at 1.9 and 2.0 A resolution, respectively. YdiF is organized into tetramers, with each monomer having an open {alpha}/{beta} structure characteristic of Family I CoA transferases. Co-crystallization of YdiF with a variety of CoA thioesters in the absence of acceptor carboxylic acid resulted in trapping a covalent {gamma}-glutamyl-CoA thioester intermediate. The CoA binds within a well defined pocket at the N- and C-terminal domain interface, but makes contact only with the C-terminal domain. The structure of the YdiF complex provides a basis for understanding the different catalytic steps in the reaction of Family I CoA transferasesPeer reviewed: YesNRC publication: Ye

Pharmacy data for tuberculosis surveillance and assessment of patient management.

Underreporting tuberculosis (TB) cases can compromise surveillance. We evaluated the contribution of pharmacy data in three different managed-care settings and geographic areas. Persons with more than two anti-TB medications were identified by using pharmacy databases. Active TB was confirmed by using state TB registries, medical record review, or questionnaires from prescribing physicians. We identified 207 active TB cases, including 13 (6%) missed by traditional surveillance. Pharmacy screening identified 80% of persons with TB who had received their medications through health plan-reimbursed sources, but missed those treated solely in public health clinics. The positive predictive value of receiving more than two anti-TB medications was 33%. Pharmacy data also provided useful information about physicians' management of TB and patients' adherence to prescribed therapy. Pharmacy data can help public health officials to find TB cases and assess their management in populations that receive care in the private sector

Electronic Structure and Bonding in Iron(II) and Iron(I) Complexes Bearing Bisphosphine Ligands of Relevance to Iron-Catalyzed C–C Cross-Coupling

Chelating phosphines are effective additives and supporting ligands for a wide array of iron-catalyzed cross-coupling reactions. While recent studies have begun to unravel the nature of the in situ-formed iron species in several of these reactions, including the identification of the active iron species, insight into the origin of the differential effectiveness of bisphosphine ligands in catalysis as a function of their backbone and peripheral steric structures remains elusive. Herein, we report a spectroscopic and computational investigation of well-defined FeCl₂(bisphosphine) complexes (bisphosphine = SciOPP, dpbz, ^tBudppe, or Xantphos) and known iron­(I) variants to systematically discern the relative effects of bisphosphine backbone character and steric substitution on the overall electronic structure and bonding within their iron complexes across oxidation states implicated to be relevant in catalysis. Magnetic circular dichroism (MCD) and density functional theory (DFT) studies demonstrate that common <i>o</i>-phenylene and saturated ethyl backbone motifs result in small but non-negligible perturbations to 10<i>Dq</i>(<i>T</i>_<i>d</i>) and iron–bisphosphine bonding character at the iron­(II) level within isostructural tetrahedra as well as in five-coordinate iron­(I) complexes FeCl­(dpbz)₂ and FeCl­(dppe)₂. Notably, coordination of Xantphos to FeCl₂ results in a ligand field significantly reduced relative to those of its iron­(II) partners, where a large bite angle and consequent reduced iron–phosphorus Mayer bond orders (MBOs) could play a role in fostering the unique ability of Xantphos to be an effective additive in Kumada and Suzuki–Miyaura alkyl–alkyl cross-couplings. Furthermore, it has been found that the peripheral steric bulk of the SciOPP ligand does little to perturb the electronic structure of FeCl₂(SciOPP) relative to that of the analogous FeCl₂(dpbz) complex, potentially suggesting that differences in the steric properties of these ligands might be more important in determining in situ iron speciation and reactivity

Transition-Metal-Free Formation of C–E Bonds (E = C, N, O, S) and Formation of C–M Bonds (M = Mn, Mo) from <i>N</i>‑Heterocyclic Carbene Mediated Fluoroalkene C–F Bond Activation

Herein, a recently reported polyfluoroalkenyl imidazolium salt is shown to react with nitrogen-, oxygen- and sulfur-based nucleophiles at the C_β position in a stereoselective and regioselective fashion, without the use of a transition metal. In contrast, reactivity with 1-methylimidazole demonstrates net substitution at C_α. This product reacts quantitatively with water, affording clean transformation of a difluoromethylene group to give an α,β-unsaturated trifluoromethyl ketone. Further reactivity studies demonstrate that the difluoromethyl fragment of an N-heterocyclic fluoroalkene is capable of direct C–C bond formation with NaCp through loss of sodium fluoride and double C–F bond activation (Cp = cyclopentadienide). TD-DFT calculations of this product indicate that both the HOMO and LUMO are of mixed π/π* character and are delocalized over the <i>N</i>-heterocyclic and Cp fragments, giving rise to a very intense absorption feature in the UV–vis spectrum. Additionally, two carbonylmetalate-substituted fluorovinyl imidazolium complexes featuring Mn and Mo were isolated and fully characterized