Evaluation of the SpotChecks contrast sensitivity test in healthy adults.

PURPOSE: SpotChecks is a new contrast sensitivity (CS) test designed for self-monitoring of vision. This study assessed the test-retest repeatability of take-home SpotChecks, in-office SpotChecks and near Pelli-Robson charts in healthy adults. METHODS: One eye of 61 healthy adults with near visual acuity (VA) of 6/9 or better (age range 22-84, mean 49 [18] years) was tested during two office visits (mean 10 [8] days apart). Each visit included high-contrast VA, then 12 randomly ordered CS tests (6 different SpotChecks and 6 different Pelli-Robson) under the same lighting (luminance 110 cd/m2), all at near in the same eye with habitual correction. The same eye was self-tested with take-home SpotChecks once a day on 6 days between the office visits. SpotChecks was scored by the logCS at the highest line with ≥2 errors. Pelli-Robson was scored by [0.05 × number of letters read correctly - 0.15]. Repeatability of logCS was defined as 1.96 2 $$ \sqrt{2} $$ Sw, Sw representing within-subject standard deviation. Comparison for repeatability was performed with Bootstrap hypothesis test. RESULTS: SpotChecks and Pelli-Robson showed similar intra-session or inter-visit repeatability (p = 0.14-0.81). Inter-day repeatability for take-home SpotChecks was 0.18 logCS, the same as that from the first measurements of two office visits with SpotChecks or Pelli-Robson. Inter-visit repeatability improved to 0.15 by using the average of two repeated measurements for SpotChecks (p = 0.02) or three repeated measurements for Pelli-Robson (p = 0.04). Age showed a small effect on logCS (-0.015/decade, p = 0.02) for both SpotChecks and Pelli-Robson. Mean logCS was 0.05 lower in those ≥50 years (SpotChecks 1.84 [0.10] and Pelli-Robson 1.77 [0.10]) compared with those <50 years of age (SpotChecks 1.89 [0.07] and Pelli-Robson 1.83 [0.07]). CONCLUSIONS: SpotChecks showed good repeatability with take-home and in-office testing in healthy adults, making it a promising tool for monitoring disease progression at home.

Graham Patch Repair of a Prepyloric Ulcer Complicated by Recurrent Abdominal Abscesses and Leukocytosis: A Case Report.

This case report describes the clinical course of a 51-year-old Caucasian woman with a history of anemia who presented to the emergency department with worsening diffuse abdominal pain and weakness two days after dental surgery. The patient's condition rapidly deteriorated, manifesting as tachycardia, diaphoresis, and a peritonitic abdomen. A CT scan revealed a perforated gastric ulcer, prompting emergent laparoscopy, Graham patch repair, and abdominal washout. Postoperatively, the patient developed leukocytosis, and imaging indicated the formation of an abscess. Despite initial attempts at percutaneous drainage, a subsequent exploratory laparotomy was performed. The patient's leukocytosis eventually resolved, and she was discharged after 21 days with outpatient follow-up. The discussion delves into the declining incidence of peptic ulcer disease but a constant rate of complications, emphasizing the role of factors such as nonsteroidal anti-inflammatory drug use. The diagnostic approach using CT scans in suspected perforated peptic ulcers is highlighted. The study also explores risk stratification scoring systems, with a preference for operative management. The laparoscopic omental patch repair (Graham patch) is discussed, citing its safety and efficacy. The case presented an uncommon occurrence of failed primary percutaneous abscess drainage, leading to subsequent surgical drainage. The discussion concludes by noting variables that may contribute to drainage failure and emphasizes the need for further research to understand such complications.

Synthesis, Characterization, and Catalytic Application of Colloidal and Supported Manganese Nanoparticles.

Colloidal and supported manganese nanoparticles were synthesized following an organometallic approach and applied in the catalytic transfer hydrogenation (CTH) of aldehydes and ketones. Reaction parameters for the preparation of colloidal nanoparticles (NPs) were optimized to yield small (2-2.5 nm) and well-dispersed NPs. Manganese NPs were further immobilized on an imidazolium-based supported ionic phase (SILP) and characterized to evaluate NP size, metal loading, and oxidation states. Oxidation of the Mn NPs by the support was observed resulting in an average formal oxidation state of +2.5. The MnOx@SILP material showed promising performance in the CTH of aldehydes and ketones using 2-propanol as a hydrogen donor, outperforming previously reported Mn NPs-based CTH catalysts in terms of metal loading-normalized turnover numbers. Interestingly, MnOx@SILP were found to lose activity upon air exposure, which correlates with an additional increase in the average oxidation state of Mn as revealed by X-ray absorption spectroscopic studies.

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Intraepithelial lymphocytes (IELs), including αß and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/TCF7 and a reduced effector and cytotoxic profile, including low expression of granzymes. Targeted deletion of TCF-1 in γδ T-IELs induced a distinct effector profile and reduced colon tumor formation in mice. In addition, TCF-1 expression was significantly reduced in γδ T-IELs present in human colorectal cancers (CRCs) compared with normal healthy colon, which strongly correlated with an enhanced γδ T-IEL effector phenotype and improved patient survival. Our work identifies TCF-1 as a colon-specific T-IEL transcriptional regulator that could inform new immunotherapy strategies to treat CRC.

Readability and Suitability of Information Presented on a University Health Center Website.

This study evaluated the readability and suitability of a university health center public website. Readability formulas estimated the reading grade and age required for comprehension of health information. The Suitability Assessment of Materials (SAM) instrument determined adequacy of the webpages for the intended audience. Readability showed the reading grade level, representing the youngest reader able to process the material, ranged from 10.1 to 14.6, averaging 12.5 (midway through 12th grade in the US educational system). Full comprehension required higher education levels, up to postgraduate. Suitability scores for some webpages indicated deficiencies in readability, motivation to learn, and instructions for healthy behavior changes. Content on the website may be difficult for some students to comprehend based on the reading grade level, but overall suitability results are satisfactory. All webpage updates should bear these parameters in mind to ensure content is fully accessible to college students, faculty, and staff.

Kinetics of geopolymerization followed by rheology: a general model.

The geopolymerization process necessitates the activation of an aluminosilicate source by an alkaline solution. Its kinetics is followed by rheology. The storage modulus (G') and loss modulus (G'') are monitored through oscillatory rheological measurements from the early stage, geopolymer paste, to the gel point with the formation of a geopolymer network. The results show that the temperature increase shortens the reaction time. The principle of Reaction Time-Temperature Superposition (RTTS) is introduced to predict this phenomenon. Furthermore, it is pointed out that using metakaolin blends with different reactivities allows modifying and controlling the reaction time. A critical weight fraction of reactive metakaolin is identified as necessary for the formation of the geopolymer network. The reaction times of the different formulations are linked to the temperature and the weight fraction of metakaolin by the Arrhenius law. A model is established to predict the reaction time according to the temperature and the weight fraction between the two metakaolins used.

Conventional and nano-copper pesticides are equally toxic to the estuarine amphipod Leptocheirus plumulosus.

Modern nano-engineered pesticides have great promise for agriculture due to their extended, low dose release profiles that are intended to increase effectiveness but reduce environmental harm. Whether nanopesticides, including copper (Cu) formulations, cause reduced levels of toxicity to non-target aquatic organisms is unclear but important to assess. Predicting how aquatic species respond to incidental exposure to Cu-based nanopesticides is challenging because of the expected very low concentrations in the environment, and the two forms of exposure that may occur, namely to Cu ions and Cu nanoparticles. We conducted Cu speciation, tissue uptake, and 7-day toxicity laboratory experiments to test how a model estuarine organism, the amphipod Leptocheirus plumulosus, responded to two popular Cu-based nanopesticides, CuPRO and Kocide, and conventional CuCl2. Exposure concentrations ranged from 0 to 2.5 ppm, which were similar to those found in estuarine water located downstream of agricultural fields. Cu dissolution rates were much slower for the nanopesticides than the ionic formula, and Cu body burden in amphipods increased approximately linearly with the nominal exposure concentration. Amphipod survival declined in a normal dose-response manner with no difference among Cu formulations. Growth and movement rates after 7 days revealed no difference among exposure levels when analyzed with conventional statistical methods. By contrast, analysis of respiration rates, inferred from biomass measurements, with a bioenergetic toxicodynamic model indicated potential for population-level effects of exposure to very low-levels of the two nanopesticides, as well as the control contaminant CuCl2. Our results indicate that toxicity assessment of environmental trace pollutant concentrations may go undetected with traditional ecotoxicological tests. We present a process integrating toxicity test results and toxicodynamic modeling that can improve our capacity to detect and predict environmental impacts of very low levels of nanomaterials released into the environment.

Draft Genome Sequences of 16 Halophilic Prokaryotes Isolated from Diverse Environments.

Halophile-specific enzymes have wide-ranging industrial and commercial applications. Despite their importance, there is a paucity of available halophile whole-genome sequences. Here, we report the draft genome sequences of 16 diverse salt-tolerant strains of bacteria and archaea isolated from a variety of high-salt environments.

Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth.

Excessive signaling through gp130, the shared receptor for the interleukin (IL)6 family of cytokines, is a common hallmark in solid malignancies and promotes their progression. Here, we established the in vivo utility of bazedoxifene, a steroid analog clinically approved for the treatment of osteoporosis, to suppress gp130-dependent tumor growth of the gastrointestinal epithelium. Bazedoxifene administration reduced gastric tumor burden in gp130Y757F mice, where tumors arise exclusively through excessive gp130/STAT3 signaling in response to the IL6 family cytokine IL11. Likewise, in mouse models of sporadic colon and intestinal cancers, which arise from oncogenic mutations in the tumor suppressor gene Apc and the associated ß-catenin/canonical WNT pathway, bazedoxifene treatment reduces tumor burden. Consistent with the proposed orthogonal tumor-promoting activity of IL11-dependent gp130/STAT3 signaling, tumors of bazedoxifene-treated Apc-mutant mice retain excessive nuclear accumulation of ß-catenin and aberrant WNT pathway activation. Likewise, bazedoxifene treatment of human colon cancer cells harboring mutant APC did not reduce aberrant canonical WNT signaling, but suppressed IL11-dependent STAT3 signaling. Our findings provide compelling proof of concept to support the repurposing of bazedoxifene for the treatment of gastrointestinal cancers in which IL11 plays a tumor-promoting role.

Reduction potential calculations of the Fe-S clusters in Thermus thermophilus respiratory complex I.

Respiratory complex I facilitates electron transfer from NADH to quinone over ~95 Å through a chain of seven iron-sulfur (Fe-S) clusters in the respiratory chain. In this study, the reduction potentials of the Fe-S clusters in Thermus thermophilus complex I are calculated using a Density Functional Theory + Poisson-Boltzmann method. Our results indicate that the reduction potentials are influenced by a variety of factors including the clusters being deeply buried in the complex and the protonation state of buried ionizable residues. In addition, as several of the ionizable side chains have predicted pKa values near pH 7, relatively small structural fluctuations could lead to significant (0.2 V) shifts in the reduction potential of several of the Fe-S clusters, suggesting a dynamic mechanism for electron transfer. Moreover, the method used here is a useful computational tool to study other questions about complex I. © 2019 Wiley Periodicals, Inc.

A single-site multipole model for liquid water.

Accurate and efficient empirical potential energy models that describe the atomistic interactions between water molecules in the liquid phase are essential for computer simulations of many problems in physics, chemistry, and biology, especially when long length or time scales are important. However, while models with non-polarizable partial charges at four or five sites in a water molecule give remarkably good values for certain properties, deficiencies have been noted in other properties and increasing the number of sites decreases computational efficiency. An alternate approach is to utilize a multipole expansion of the electrostatic potential due to the molecular charge distribution, which is exact outside the charge distribution in the limits of infinite distances or infinite orders of multipoles while partial charges are a qualitative representation of electron density as point charges. Here, a single-site multipole model of water is presented, which is as fast computationally as three-site models but is also more accurate than four- and five-site models. The dipole, quadrupole, and octupole moments are from quantum mechanical-molecular mechanical calculations so that they account for the average polarization in the liquid phase, and represent both the in-plane and out-of-plane electrostatic potentials of a water molecule in the liquid phase. This model gives accurate thermodynamic, dynamic, and dielectric properties at 298 K and 1 atm, as well as good temperature and pressure dependence of these properties.

Molecular Multipole Potential Energy Functions for Water.

Water is the most common liquid on this planet, with many unique properties that make it essential for life as we know it. These properties must arise from features in the charge distribution of a water molecule, so it is essential to capture these features in potential energy functions for water to reproduce its liquid state properties in computer simulations. Recently, models that utilize a multipole expansion located on a single site in the water molecule, or "molecular multipole models", have been shown to rival and even surpass site models with up to five sites in reproducing both the electrostatic potential around a molecule and a variety of liquid state properties in simulations. However, despite decades of work using multipoles, confusion still remains about how to truncate the multipole expansions efficiently and accurately. This is particularly important when using molecular multipole expansions to describe water molecules in the liquid state, where the short-range interactions must be accurate, because the higher order multipoles of a water molecule are large. Here, truncation schemes designed for a recent efficient algorithm for multipoles in molecular dynamics simulations are assessed for how well they reproduce results for a simple three-site model of water when the multipole moments and Lennard-Jones parameters of that model are used. In addition, the multipole analysis indicates that site models that do not account for out-of-plane electron density overestimate the stability of a non-hydrogen-bonded conformation, leading to serious consequences for the simulated liquid.

A Systematic Investigation of p-Nitrophenol Reduction by Bimetallic Dendrimer Encapsulated Nanoparticles.

We demonstrate that the reduction of p-nitrophenol to p-aminophenol by NaBH4 is catalyzed by both monometallic and bimetallic nanoparticles (NPs). We also demonstrate a straightforward and precise method for the synthesis of bimetallic nanoparticles using poly(amido)amine dendrimers. The resulting dendrimer encapsulated nanoparticles (DENs) are monodisperse, and the size distribution does not vary with different elemental combinations. Random alloys of Pt/Cu, Pd/Cu, Pd/Au, Pt/Au, and Au/Cu DENs were synthesized and evaluated as catalysts for p-nitrophenol reduction. These combinations are chosen in order to selectively tune the binding energy of the p-nitrophenol adsorbate to the nanoparticle surface. Following the Brønsted-Evans-Polanyi (BEP) relation, we show that the binding energy can reasonably predict the reaction rates of p-nitrophenol reduction. We demonstrate that the measured reaction rate constants of the bimetallic DENs is not always a simple average of the properties of the constituent metals. In particular, DENs containing metals with similar lattice constants produce a binding energy close to the average of the two constituents, whereas DENs containing metals with a lattice mismatch show a bimodal distribution of binding energies. Overall, in this work we present a uniform method for synthesizing pure and bimetallic DENs and demonstrate that their catalytic properties are dependent on the adsorbate's binding energy.