Daily discrimination, church support, personal mastery, and psychological distress in black people in the United States.

OBJECTIVE: This study used the stress process model to test the mediating effects of personal mastery and moderating effects of church-based social support on the relationship between daily discrimination and psychological distress across three age groups of African American and Afro-Caribbean adults. METHODS: Using a national sample of 5008 African Americans and Afro-Caribbean adults from the National Survey of American Life Study, this study employs structural equation modeling to investigate the relationships between daily discrimination, personal mastery, church-based social support, and psychological distress. RESULTS: Daily discrimination was an independent predictor of psychological distress across all groups. Group- and age-specific comparisons revealed significant differences in the experience of daily discrimination and psychological distress. Mastery was a partial mediator of the relationship between discrimination and psychological distress among Afro-Caribbeans while church support was a significant moderator only among the young and older African Americans. IMPLICATIONS: Together, our study findings provide useful first steps towards developing interventions to reduce the adverse psychological impacts of daily discrimination on African Americans and Afro-Caribbeans. Intervention efforts such as individual psychotherapy aimed to improve Afro-Caribbean individuals' sense of mastery would be a partial solution to alleviating the adverse effects of discrimination on their psychological health.

How can clinicians choose between conflicting and discordant systematic reviews? A replication study of the Jadad algorithm.

INTRODUCTION: The exponential growth of published systematic reviews (SRs) presents challenges for decision makers seeking to answer clinical, public health or policy questions. In 1997, an algorithm was created by Jadad et al. to choose the best SR across multiple. Our study aims to replicate author assessments using the Jadad algorithm to determine: (i) if we chose the same SR as the authors; and (ii) if we reach the same results. METHODS: We searched MEDLINE, Epistemonikos, and Cochrane Database of SRs. We included any study using the Jadad algorithm. We used consensus building strategies to operationalise the algorithm and to ensure a consistent approach to interpretation. RESULTS: We identified 21 studies that used the Jadad algorithm to choose one or more SRs. In 62% (13/21) of cases, we were unable to replicate the Jadad assessment and ultimately chose a different SR than the authors. Overall, 18 out of the 21 (86%) independent Jadad assessments agreed in direction of the findings despite 13 having chosen a different SR. CONCLUSIONS: Our results suggest that the Jadad algorithm is not reproducible between users as there are no prescriptive instructions about how to operationalise the algorithm. In the absence of a validated algorithm, we recommend that healthcare providers, policy makers, patients and researchers address conflicts between review findings by choosing the SR(s) with meta-analysis of RCTs that most closely resemble their clinical, public health, or policy question, are the most recent, comprehensive (i.e. number of included RCTs), and at the lowest risk of bias.

Chirality-driven self-assembly: application toward renewable/exchangeable resin-immobilized catalysts.

Resin-immobilized catalysts were prepared through chirality-driven self-assembly. The method allows the resin-immobilized catalyst to be regenerated under mild conditions and in situ catalyst exchange to be carried out quantitatively. The uniqueness of the methodology was demonstrated by the preparation of a catalyst for TEMPO oxidation as well as a two-step sequential TEMPO oxidation/aldol condensation sequence enabled by facile catalyst exchange.

The Conformational Landscape, Internal Rotation, and Structure of 1,3,5-Trisilapentane using Broadband Rotational Spectroscopy and Quantum Chemical Calculations.

The rotational spectrum of 1,3,5-trisilapentane was observed on a chirped-pulse Fourier transform microwave spectrometer and is reported. During assignment, multiple conformations of the molecule were identified in the molecular beam. Prior quantum-chemical calculations performed on the molecule show that the identified spectra correspond to the lowest three calculated energetic structures. These structures are of C2 (Conf.1), C2v (Conf.2), and C1 (Conf.3) symmetry, with relative energy ordering of Conf.1 < Conf.3 < Conf.2, which is in stark contrast to n-pentane and all known silicon-substituted n-pentane derivatives. This is found to most likely arise from the elongation of the Si-C bond and the size of the silicon atoms providing for the C2 and C1 structures relieving steric hindrance in comparison to that of the C2v. In the C2v and C1 conformers, splitting in the spectra due to internal rotation of the -SiH3 end groups of 1,3,5-trisilapentane was observed and determined. The C2v equivalent V3 values are 368.46(33) cm-1, and the C1V3 values are 347.78(21) and 360.18(88) cm-1, respectively. These barriers are compared to similar species in order to help verify their veracity and are determined to be accurate based on similar molecular silyl rotors.

The impact of small-scale land cover and groundwater interactions on base flow solute and nutrient export in a small agricultural stream.

Central Kentucky could be considered a critical source area of nutrients in water ways because of low permeability soils, fast groundwater flow through bedrock fractures, and pervasive agriculture and development. Of particular concern is rising development in rural areas, which creates mixed land cover (MLC) watersheds, i.e., watersheds with development, agriculture, and other land cover types. MLC watersheds add complexity to spatial and temporal releases of dissolved constituents, leading to less predictable water quality patterns. The goal of this research was to examine the export of dissolved substances from a small, upland MLC catchment in central Kentucky with a focus on how the interaction between discharges from developed agricultural land cover and groundwater influence base flow water quality. Our approach was to spatially sample a representative catchment monthly over 1 year, characterize the major dissolved constituents, and evaluate catchment processes with statistical analyses and Piper diagrams. Principal component analysis, factor analysis, and Piper diagrams indicate base flow was composed of groundwater influenced by two different host rocks and an outfall draining a developed region. Base flow nutrient export was dominated by mixing nitrate-sulfate rich groundwater with ammonium-phosphate-chloride rich outfall drainage. High nitrate groundwater dominated nitrogen export in the winter, whereas high ammonium outfall drainage dominated summer export. Spatial analysis revealed that ~ 10% of the basin may have similar land cover and hydrologic processes, suggesting that MLC catchments are small but collectively significant nitrogen sources to river networks due to development and agriculturally impacted groundwater.

Borepin Rings as "Sigma-Free" Reporters of Aromaticity within Polycyclic Aromatic Scaffolds.

The definition and measurement of local and global aromaticity in fused ring polycyclic aromatic compounds is a complex issue. Historically, these types of molecules have been explored in this capacity by way of experimental (NMR, thermochemistry) and computational (NICS, HOMA) analyses. We previously showed how borepin rings with [ b, f] arene fusions can be used as experimental magnetic aromaticity reporters via the remaining protons attached to the borepin rings. In this report, we describe a joint experimental and computational analysis of several borepin-containing polycyclic aromatic molecules in order to draw conclusions about the influence of ring fusion on aromaticity. We find that the borepin ring within these extended structures is a unique motif with limited σ-contribution to aromaticity while still displaying a wide range of structural and magnetic aromatic character.

Engineering dynamical control of cell fate switching using synthetic phospho-regulons.

Many cells can sense and respond to time-varying stimuli, selectively triggering changes in cell fate only in response to inputs of a particular duration or frequency. A common motif in dynamically controlled cells is a dual-timescale regulatory network: although long-term fate decisions are ultimately controlled by a slow-timescale switch (e.g., gene expression), input signals are first processed by a fast-timescale signaling layer, which is hypothesized to filter what dynamic information is efficiently relayed downstream. Directly testing the design principles of how dual-timescale circuits control dynamic sensing, however, has been challenging, because most synthetic biology methods have focused solely on rewiring transcriptional circuits, which operate at a single slow timescale. Here, we report the development of a modular approach for flexibly engineering phosphorylation circuits using designed phospho-regulon motifs. By then linking rapid phospho-feedback with slower downstream transcription-based bistable switches, we can construct synthetic dual-timescale circuits in yeast in which the triggering dynamics and the end-state properties of the ON state can be selectively tuned. These phospho-regulon tools thus open up the possibility to engineer cells with customized dynamical control.

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study.

Background: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). Patients and methods: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy. Results: Sixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4-NR], not yet reached, and 10.7 months (95% CI 4.3-21.0), respectively. Conclusions: This study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL. Trial registered: Clinicaltrials.gov, NCT01594229.

Benzo[b]thiophene Fusion Enhances Local Borepin Aromaticity in Polycyclic Heteroaromatic Compounds.

This report documents the synthesis, characterization, and computational evaluation of two isomeric borepin-containing polycyclic aromatics. The syntheses of these two isomers involved symmetrical disubstituted alkynes that were reduced to Z-olefins followed by borepin formation either through an isolable stannocycle intermediate or directly from the alkene via the trapping of a transient dilithio intermediate. Comparisons of their magnetic, crystallographic, and computational characterization to literature compounds gave valuable insights about the aromaticity of these symmetrically fused [b,f]borepins. The fusion of benzo[b]thiophene units to the central borepin cores forced a high degree of local aromaticity within the borepin moieties relative to other known borepin-based polycyclic aromatics. Each isomer had unique electronic responses in the presence of fluoride anions. The experimental data demonstrate that the local borepin rings in these two compounds have a relatively high amount of aromatic character. Results from quantum chemical calculations provide a more comprehensive understanding of local and global aromatic characters of various rings in fused ring systems built upon boron heterocycles.

Aromaticity Competition in Differentially Fused Borepin-Containing Polycyclic Aromatics.

This report describes the synthesis and characterization of a series of borepin-based polycyclic aromatics bearing two different arene fusions. The borepin synthesis features streamlined Ti-mediated alkyne reduction, leading to Z-olefins, followed by direct lithiation and borepin formation. These molecules allow for an assessment of aromatic competition between the fused rings and the central borepin core. Crystallographic, magnetic, and computational studies yielded insights about the aromaticity of novel, differentially fused [b,f]borepins and allowed for comparison to literature compounds. Multiple borepin motifs were also incorporated into polycyclic aromatics with five or six rings in the main backbone, and their properties were also evaluated.

Microwave, r0 Structural Parameters, Conformational Stability, and Vibrational Assignment of (Chloromethyl)fluorosilane.

The FT-microwave spectrum (6.5-26 GHz) of (chloromethyl)fluorosilane (ClCH2-SiH2F) has been recorded and 250 transitions for the parent species along with (13)C, (37)Cl, (29)Si, and (30)Si isotopologues have been assigned for trans conformer. Infrared spectra (3100 to 400 cm(-1)) of gas, solid, and the variable temperature (-100 to -60 °C) studies of the infrared spectra of the sample dissolved in xenon have been recorded. Additionally, the variable temperature (-153 to -133 °C) studies of the Raman spectra of the sample dissolved in krypton have been recorded. The enthalpy difference between the trans and gauche conformers in xenon solutions has been determined to be 109 ± 15 cm(-1) (1.47 ± 0.16 kJ mol(-1)), and in krypton solution, the enthalpy difference has been determined to be 97 ± 16 cm(-1) (1.16 ± 0.19 kJ mol(-1)) with the trans conformer as the more stable form. Approximately 46 ± 2% of the trans form is present at ambient temperature. By utilizing the microwave rotational constants of five isotopologues for trans and the structural parameters predicted from MP2(full)/6-311+G(d,p) calculations, adjusted r0 parameters have been obtained for trans conformer. The r0 structural parameter values for the trans form are for the heavy atom distances (Å): Si-F = 1.608 (3); C-Cl = 1.771 (3); Si-C = 1.884 (3); and angles (deg): ∠FSiC = 108.9 (5); ∠ClCSi = 104.9 (5). The results are discussed and compared to some related molecules.

Full-dose challenge of moderate, severe, and unknown beta-lactam allergies in the emergency department.

OBJECTIVE: This study aims to assess the outcome of challenging documented moderate, severe, or unknown beta-lactam allergies with full dose administration of a beta-lactam antibiotic in emergency department (ED) patients admitted for acute bacterial infection. METHODS: A single-center, retrospective, descriptive study of adult patients challenged with a full dose of beta-lactam in the ED from January 2021 to December 2022 was conducted. Included patients had at least one documented moderate, severe, or unknown beta-lactam allergy in the electronic medical record (EMR) without documentation of prior tolerance. Patient demographics, prior beta-lactam antibiotic reaction, beta-lactam administered in the ED, inpatient beta-lactam continuation, adverse drug reactions, and updates to allergy profiles were collected. Descriptive statistics for data analysis were performed using SPSS Version 22. RESULTS: Of the 184 ED encounters with full-dose beta-lactam challenges, five (2.7%) patients with documented moderate, severe, or unknown beta-lactam allergies experienced an allergic reaction after the challenge; one (0.5%) patient had an allergic reaction in the ED, and the remaining four (2.2%) occurred after admission. No anaphylactic reactions occurred. All allergic reactions were limited to mild rash or itching. Most patients (98.9%) were challenged with a cephalosporin. A beta-lactam was continued in 86.4% of cases, and the allergy profile was updated for future utilization in 73.4% of patients. CONCLUSIONS: This study suggests that full-dose challenge of moderate, severe, or unknown beta-lactam allergies can be safely accomplished in the ED. This approach avoids unnecessary penicillin allergy skin testing and reduces utilization of suboptimal alternative antibiotic regimens.

Policies during COVID-19 and their impact on immigrant families' psychological well-being: A critically engaged practice.

INTRODUCTION: The COVID-19 pandemic has exacerbated, and complicated stressors related to immigrant families' experience with U.S. immigration policies. METHOD: This article uses a critically engaged practice (CEP) framework to examine three policies and their implications for the health and well-being of immigrant families during the COVID-19 pandemic (a) Detention and Removal of Alien Parents or Legal Guardians policy, (b) Order Suspending the Right to Introduce Certain Persons from Countries where a Quarantinable Communicable Disease Exists, and (c) Field Guidance on Deportability and Inadmissibility on Public Charge Grounds. RESULTS: Our article presents a CEP framework to empower clinicians in integrated healthcare settings to better understand and communicate policies with their patients. DISCUSSION: Policy-informed CEP asks clinicians to (a) remain current with policy change; (b) have the ability to interpret policy and or policy change to clients; and (c) be aware of not only the primary effects of policy on the family but also the secondary impacts to their system. Clinical implications are provided. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Low-Cost Programmable Reversing Flow Column Apparatus for Investigating Mixing Zones.

This note describes the development and testing of a novel, programmable reversing flow 1D (R1D) experimental column apparatus designed to investigate reaction, sorption, and transport of solutes in aquifers within dynamic reversing flow zones where waters with different chemistries mix. The motivation for constructing this apparatus was to understand the roles of mixing and reaction on arsenic discharging through a tidally fluctuating riverbank. The apparatus can simulate complex transient flux schedules similar to natural flow regimes The apparatus uses an Arduino microcontroller to control flux magnitude through two peristaltic pumps. Solenoid valves control flow direction from two separate reservoirs. In-line probes continually measure effluent electrical conductance, pH, oxidation-reduction potential, and temperature. To understand how sensitive physical solute transport is to deviations from the real hydrograph of the tidally fluctuating river, two experiments were performed using: (1) a simpler constant magnitude, reversing flux direction schedule (RCF); and (2) a more environmentally relevant variable magnitude, reversing flux direction schedule (RVF). Wherein, flux magnitude was ramped up and down according to a sine wave. Modeled breakthrough curves of chloride yielded nearly identical dispersivities under both flow regimes. For the RVF experiment, Peclet numbers captured the transition between diffusion and dispersion dominated transport in the intertidal interval. Therefore, the apparatus accurately simulated conservative, environmentally relevant mixing under transient, variable flux flow regimes. Accurately generating variable flux reversing flow regimes is important to simulate the interaction between flow velocity and chemical reactions where Brownian diffusion of solutes to solid-phase reaction sites is kinetically limited.

Iron Sequestration by Galloyl-Silane Nano Coatings Inhibits Biofilm Formation of Sulfitobacter sp.

Microbially-induced corrosion is the acceleration of corrosion induced by bacterial biofilms. The bacteria in the biofilms oxidize metals on the surface, especially evident with iron, to drive metabolic activity and reduce inorganic species such as nitrates and sulfates. Coatings that prevent the formation of these corrosion-inducing biofilms significantly increase the service life of submerged materials and significantly decrease maintenance costs. One species in particular, a member of the Roseobacter clade, Sulfitobacter sp., has demonstrated iron-dependent biofilm formation in marine environments. We have found that compounds that contain the galloyl moiety can prevent Sulfitobacter sp. biofilm formation by sequestering iron, thus making a surface unappealing for bacteria. Herein, we have fabricated surfaces with exposed galloyl groups to test the effectiveness of nutrient reduction in iron-rich media as a non-toxic method to reduce biofilm formation.

Membrane curvature recognition by C-reactive protein using lipoprotein mimics.

It has been reported that the oxidation of phosphatidylcholine (PC) is necessary for C-reactive protein (CRP) to bind to lipid membranes, but it remains elusive why CRP only binds oxidized membranes. Here we offer a new perspective on the role of membrane curvature and CRP binding using engineered lipoprotein particle (LPP) mimics. We show that CRP binds preferentially to LPP mimics with diameters of ≤ 28 nm, and binding of CRP to these mimics leads to the dissociation of native CRP into monomeric CRP, exposing CRP neo-epitopes that bind C1q. We also show that the smaller LPP mimics compete for CRP binding to oxidized low density lipoproteins (oxLDLs), suggesting that these mimics expose the same PC epitopes as those found on oxLDLs. Results from this study suggest that membrane curvature could be an additional factor influencing CRP binding of damaged membranes distinct from the oxidation of PC lipids.

Ten-Year Trends in Level of Evidence in Hand Surgery.

BACKGROUND: The purposes of this study were to analyze the trends in Oxford level of evidence (LOE), LOE of most-cited articles, and association between LOE and journal impact factor (IF) and SCImago Journal Rank (SJR) over a 10-year period (2009-2018) in 3 prominent hand surgery journals, specifically HAND, Journal of Hand Surgery (American Volume) (JHS), and Journal of Hand Surgery (European Volume) (JHSE). METHODS: All articles published from 2009 to 2018 in HAND, JHS, and JHSE were reviewed for assigned or available LOE. Data were pooled and analyzed for trends in LOE; relationship among IF, SJR, and LOE; and citation density. RESULTS: A total of 3921 total publications were tabulated from 2009 to 2018, with the majority of studies being level V (1700, 43%) and fewer studies being level I (146, 4%). Over the 10-year study period, there was no significant change in frequency of level I studies for any journal. HAND trended significantly toward higher LOE, JHS trended toward higher LOE, and JHSE trended toward decreased LOE without significance. Among all journals, the annual number of articles and the average LOE were independent significant predictors of IF and SJR. Statistically significant correlations were found between citation density and LOE for JHS and HAND. CONCLUSIONS: Higher quality evidence is becoming more prevalent in the hand surgery literature over the past 10 years. Annual articles, average LOE, and level I and II and level IV articles were significant predictors of increasing IF and SJR.

Clinical utility of transoesophageal echocardiography in low resource environments: the Jamaican experience.

OBJECTIVE: To provide the first detailed review of the indications and clinical utility of transoesophageal echocardiogram (TEE) in the Caribbean. DESIGN AND METHODS: Data for patients who had TEE performed at the Heart Institute of the Caribbean over a three-year period were abstracted and reviewed. Information gathered included demographic data, indications for the procedure, findings and clinical recommendations. The effect of age and sex on these variables was assessed using the Chi-square or Fishers Exact tests. Significance was set at a p < or = 0.05. RESULTS: Of the 116 procedures performed between 2005 and 2008, medical records were reviewed for 107 (50 male, 57 female) patients. The patients ranged in age from 15-86 years with a mean age of 45.4 +/- 18.5 years. With the exception of four patients, all attempted TEE were completed. The most common indications for the procedure were valvular heart disease (41.1%), strokes (17.8%), shunts (10.3%) and infective endocarditis (11.2%). Less common indications included arrhythmias, cardiac masses, aortic dissection and shortness of breath. Transoesophageal echocardiogram altered the treatment course in about 30% of all patients including 66.6% of patients referred for suspected infective endocarditis. Furthermore, TEE resulted in recommendation for surgery in 43% of patients referred for evaluation of severity of valvular disease. Minor complications occurred in two persons. No severe complications or deaths occurred as a result of the procedure. CONCLUSIONS: Transoesophageal echocardiogram has been most commonly performed to evaluate valvular heart disease in Jamaica without any major complications resulting from the procedure. It provides additional information that supplements transthoracic echocardiography in a wide range of clinical conditions. Measures should be put in place to make TEE more widely available and accessible in Jamaica.

Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype.

Mutation of the atlastin gene (SPG3A) is responsible for approximately 10% of autosomal dominant hereditary spastic paraplegia (AD-HSP) cases. The goal of this study was to identify novel disease causing atlastin mutations. Atlastin nucleotide variations were detected by direct sequencing of all 14 exons in 70 autosomal dominant (AD), 16 single sibship and 14 sporadic spastic paraplegia patients. Six mis-sense mutations (four of which were novel) were identified in six unrelated AD-HSP kindreds in exons 4, 7 and 8 of the atlastin gene. One kindred with a novel mutation showed variability in clinical phenotype and age of onset. Mutations are predicted to decrease GTPase activity, cause morphological abnormalities of the endoplasmic reticulum and prevent maturation of the Golgi complex resulting in impaired vesicle trafficking. Our study significantly adds to the spectrum of mutations and clinical phenotype of SPG3A. We advocate that all spastin mutation negative AD-HSP kindreds should be screened for pathogenic atlastin mutations regardless of age of onset or phenotypic complexity.

Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion.

The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the 'steal phenomenon' within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage.