Stereochemistry-dependent thermotropic liquid crystalline phases of monosaccharide-based amphiphiles.

Conformational rigidity controls the bulk self-assembly and liquid crystallinity from amphiphilic block molecules to copolymers. The effects of block stereochemistry on the self-assembly have, however, been less explored. Here, we have investigated amphiphilic block molecules involving eight open-chain monosaccharide-based polyol units possessing different stereochemistries, derived from D-glucose, D-galactose, L-arabinose, D-mannose and L-rhamnose (allylated monosaccharides t-Glc*, e-Glc*, t-Gal*, e-Gal*, t-Ara*, e-Ara*, t-Man*, and t-Rha*), end-functionalized with repulsive tetradecyl alkyl chain blocks to form well-defined amphiphiles with block molecule structures. All compounds studied showed low temperature crystalline phases due to polyol crystallization, and smectic (lamellar) and isotropic phases upon heating in bulk. Hexagonal cylindrical phase was additionally observed for the composition involving t-Man*. Cubic phases were observed for e-Glc*, e-Gal*, e-Ara*, and t-Rha* derived compounds. Therein, the rich array of WAXS-reflections suggested that the crystalline polyol domains are not ultra-confined in spheres as in classic cubic phases but instead show network-like phase continuity, which is rare in bulk liquid crystals. Importantly, the transition temperatures of the self-assemblies were observed to depend strongly on the polyol stereochemistry. The findings underpin that the stereochemistry in carbohydrate-based assemblies involves complexity, which is an important parameter to be considered in material design when developing self-assemblies for different functions.

A Further Study on Calcium Phosphate Gardens Grown from the Interface of κ-Carrageenan-based Hydrogels and Counterion Solutions.

Originating from the concept of classical chemical gardens, a new field coined 'chemobrionics' has recently emerged. In the present work, two chemobrionic systems grown from a hydrogel/liquid interface at different time scales (for 1, 7, 14 or 28 days) were investigated, i. e., a calcium-based hydrogel with a phosphate counterion solution (Ca-gel) and a phosphate-based hydrogel with a calcium counterion solution (P-gel). The initial pH changes of the systems were investigated, and the obtained tubular structures were studied using optical microscopy, SEM, AFM, PXRD and TGA. One of the important findings is that the tubes obtained in the Ca-gel system were straight and long, which could be explained by the larger pH difference observed between the hydrogel and the counterion solution in this system (ΔpH∼2.1) compared to the P-gel system (ΔpH∼0). The Ca-gel structures remained overall more amorphous even though increased crystallinity was observed in both systems with increased time spent in counterion solution. Both systems contained hydroxyapatite phases, with additional calcite phases observed for the P-gel structures and traces of κ-carrageenan for the Ca-gel structures. Our study provides a promising method for controlling tubular macrostructures through adjusting the reaction conditions such as maturation time and pH.

Colorimetric Hydrogel from Natural Indicators: A Tool for Electrochemistry Education.

The electrolysis of water is popular both as lab work and as a demonstration. In this activity, the electrolysis of water in the presence of a pH indicator is used to produce text and symbols. This report describes the design of an environmentally friendly setup of a writing board utilizing the electrolysis of water in a hydrogel environment. The activity can be performed by only using chemicals and materials that are easily accessible to everyone, with no special permit needed. The writing board has been developed mainly as an outreach activity for our faculty and has been assessed during visits from upper secondary school students.

Distribution of Patients at Risk for Complications Related to COVID-19 in the United States: Model Development Study.

BACKGROUND: Coronavirus disease (COVID-19) has spread exponentially across the United States. Older adults with underlying health conditions are at an especially high risk of developing life-threatening complications if infected. Most intensive care unit (ICU) admissions and non-ICU hospitalizations have been among patients with at least one underlying health condition. OBJECTIVE: The aim of this study was to develop a model to estimate the risk status of the patients of a nationwide pharmacy chain in the United States, and to identify the geographic distribution of patients who have the highest risk of severe COVID-19 complications. METHODS: A risk model was developed using a training test split approach to identify patients who are at high risk of developing serious complications from COVID-19. Adult patients (aged ≥18 years) were identified from the Walgreens pharmacy electronic data warehouse. Patients were considered eligible to contribute data to the model if they had at least one prescription filled at a Walgreens location between October 27, 2019, and March 25, 2020. Risk parameters included age, whether the patient is being treated for a serious or chronic condition, and urban density classification. Parameters were differentially weighted based on their association with severe complications, as reported in earlier cases. An at-risk rate per 1000 people was calculated at the county level, and ArcMap was used to depict the rate of patients at high risk for severe complications from COVID-19. Real-time COVID-19 cases captured by the Johns Hopkins University Center for Systems Science and Engineering (CSSE) were layered in the risk map to show where cases exist relative to the high-risk populations. RESULTS: Of the 30,100,826 adults included in this study, the average age is 50 years, 15% have at least one specialty medication, and the average patient has 2 to 3 comorbidities. Nearly 28% of patients have the greatest risk score, and an additional 34.64% of patients are considered high-risk, with scores ranging from 8 to 10. Age accounts for 53% of a patient's total risk, followed by the number of comorbidities (29%); inferred chronic obstructive pulmonary disease, hypertension, or diabetes (15%); and urban density classification (5%). CONCLUSIONS: This risk model utilizes data from approximately 10% of the US population. Currently, this is the most comprehensive US model to estimate and depict the county-level prognosis of COVID-19 infection. This study shows that there are counties across the United States whose residents are at high risk of developing severe complications from COVID-19. Our county-level risk estimates may be used alongside other data sets to improve the accuracy of anticipated health care resource needs. The interactive map can also aid in proactive planning and preparations among employers that are deemed critical, such as pharmacies and grocery stores, to prevent the spread of COVID-19 within their facilities.

Molecular Dynamics on Wood-Derived Lignans Analyzed by Intermolecular Network Theory.

The dynamics of interactions to a solvent is a key factor in the proper characterization of new molecular structures. In molecular dynamics simulations, the solvent molecules are explicitly present, thereby defining a more accurate description on how the solvent molecules affect the molecular conformation. Intermolecular interactions in chemical systems, e.g., hydrogen bonds, can be considered as networks or graphs. Graph theoretical analyses can be an outstanding tool in analyzing the changes in interactions between solvent and solute. In this study, the software ChemNetworks is applied to interaction studies between TIP4P solvent molecules and organic solutes, i.e., wood-derived lignan-based ligands called LIGNOLs, thereby supporting the research of interaction networks between organic molecules and solvents. This new approach is established by careful comparisons to studies using previously available tools. In the hydration studies, tetramethyl 1,4-diol is found to be the LIGNOL which was most likely to form hydrogen bonds to the TIP4P solvent.

Modeling of a Hybrid Langmuir Adsorption Isotherm for Describing Interactions Between Drug Molecules and Silica Surfaces.

The interaction between disulfiram (Antabus®) and silica was studied experimentally by adsorption from apolar solvent onto highly porous silica material (Santa Barbara amorphous material-3) with large surface area. The adsorption isotherm was fitted to the Langmuir model by accounting 2 different affinities contributing to the overall behavior, which were attributed to 2 different types of silanol groups (i.e., geminal and vicinal) present on amorphous silica surfaces. This assumption was supported by theoretical calculations. In addition, the model could describe the adsorption of ibuprofen to the carrier material, indicating that the model bears big potential for describing the interactions between silica surfaces and drug molecules.

Electroencephalogram variability in patients with cirrhosis associates with the presence and severity of hepatic encephalopathy.

BACKGROUND & AIMS: The outputs of physiological systems fluctuate in a complex manner even under resting conditions. Decreased variability or increased regularity of these outputs is documented in several disease states. Changes are observed in the spatial and temporal configuration of the electroencephalogram (EEG) in patients with hepatic encephalopathy (HE), but there is no information on the variability of the EEG signal in this condition. The aim of this study was to measure and characterize EEG variability in patients with cirrhosis and to determine its relationship to neuropsychiatric status. METHODS: Eyes-closed, awake EEGs were obtained from 226 patients with cirrhosis, classified, using clinical and psychometric criteria, as neuropsychiatrically unimpaired (n=127) or as having minimal (n=21) or overt (n=78) HE, and from a reference population of 137 healthy controls. Analysis of EEG signal variability was undertaken using continuous wavelet transform and sample entropy. RESULTS: EEG variability was reduced in the patients with cirrhosis compared with the reference population (coefficient of variation: 21.2% [19.3-23.4] vs. 22.4% [20.8-24.5]; p<0.001). A significant association was observed between EEG variability and neuropsychiatric status; thus, variability was increased in the patients with minimal HE compared with their neuropsychiatrically unimpaired counterparts (sample entropy: 0.98 [0.87-1.14] vs. 0.83 [0.75-0.95]; p=0.02), and compared with the patients with overt HE (sample entropy: 0.98 [0.87-1.14] vs. 0.82 [0.71-1.01]; p=0.01). CONCLUSIONS: Variability of the EEG is associated with both the presence and severity of HE. This novel finding may provide new insights into the pathophysiology of HE and provide a means for monitoring patients over time. LAY SUMMARY: Decreased variability or increased regularity of physiological systems is documented in several disease states. Variability of the electroencephalogram was found to be associated with both the presence and severity of brain dysfunction in patients with chronic liver disease.

New spectral thresholds improve the utility of the electroencephalogram for the diagnosis of hepatic encephalopathy.

OBJECTIVE: The utility of the electroencephalogram (EEG) for the diagnosis of hepatic encephalopathy, using conventional spectral thresholds, is open to question. The aim of this study was to optimise its diagnostic performance by defining new spectral thresholds. METHODS: EEGs were recorded in 69 healthy controls and 113 patients with cirrhosis whose neuropsychiatric status was classified using clinical and psychometric criteria. New EEG spectral thresholds were calculated, on the parietal P3-P4 lead derivation, using an extended multivariable receiver operating characteristic curve analysis. Thresholds were validated in a separate cohort of 68 healthy controls and 113 patients with cirrhosis. The diagnostic performance of the newly derived spectral thresholds was further validated using a machine learning technique. RESULTS: The diagnostic performance of the new thresholds (sensitivity 75.0%; specificity 77.4%) was better balanced than that of the conventional thresholds (58.3%; 93.2%) and comparable to the performance of a machine learning technique (72.9%; 76.8%). The diagnostic utility of the new thresholds was confirmed in the validation cohort. CONCLUSIONS: Adoption of the new spectral thresholds would significantly improve the utility of the EEG for the diagnosis of hepatic encephalopathy. SIGNIFICANCE: These new spectral EEG thresholds optimise the performance of the EEG for the diagnosis of hepatic encephalopathy and can be adopted without the need to alter data recording or the initial processing of traces.

The Impact of Opioid Treatment on Regional Gastrointestinal Transit.

BACKGROUND/AIMS: To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact ofopioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GItransit times using the 3-dimensional (3D)-Transit system. METHODS: Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. AdverseGI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipationsymptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab(®) graphical user interface. RESULTS: GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P= 0.001). No associations between questionnaire scores and segmental transit times were detected. CONCLUSIONS: Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation.

Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI.

OBJECTIVE: Opioid treatment is associated with numerous gastrointestinal adverse effects collectively known as opioid-induced bowel dysfunction (OIBD). Most current knowledge of the pathophysiology derives from animal studies limited by species differences and clinical studies, which have substantial confounders that make evaluation difficult. An experimental model of OIBD in healthy volunteers in a controlled setting is therefore highly warranted. The aim of this study was to assess bowel function in healthy volunteers during opioid treatment using subjective and objective methods. METHODS: Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms and the Bristol stool form scale. Colorectal volumes were determined using a newly developed MRI method. RESULTS: Compared with baseline, oxycodone increased pain detection thresholds by 8% (P=0.02). Subjective OIBD was observed as increased bowel function index (464% increase; P<0.001), gastrointestinal symptom rating scale (37% increase; P<0.001) and patient assessment of constipation symptoms (198% increase; P<0.001). Objectively, stools were harder and drier during oxycodone treatment (P<0.001) and segmental colorectal volumes increased in the caecum/ascending colon by 41% (P=0.005) and in the transverse colon by 20% (P=0.005). No associations were detected between questionnaire scores and colorectal volumes. CONCLUSION: Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies to discriminate the efficacies of different laxatives, peripheral morphine antagonists and opioid treatments.

A novel semi-automatic segmentation method for volumetric assessment of the colon based on magnetic resonance imaging.

PURPOSE: To develop a novel semi-automatic segmentation method for quantification of the colon from magnetic resonance imaging (MRI). METHODS: Fourteen abdominal T2-weighted and dual-echo Dixon-type water-only MRI scans were obtained from four healthy subjects. Regions of interest containing the colon were outlined manually on the T2-weighted images. Segmentation of the colon and feces was obtained using k-means clustering and image registration. Regional colonic and fecal volumes were obtained. Inter-observer agreement between two observers was assessed using the Dice similarity coefficient as measure of overlap. RESULTS: Colonic segmentations showed wide variation in volume and morphology between subjects. Colon volumes of the four healthy subjects for both observers were (median [interquartile range]) ascending colon 200 mL [169.5-260], transverse 200.5 mL [113.5-242.5], descending 148 mL [121.5-178.5], sigmoid-rectum 277 mL [192-345], and total 819 mL [687-898.5]. Overlap agreement for the total colon segmentation between the two observers was high with a Dice similarity coefficient of 0.91 [0.84-0.94]. The colon volume to feces volume ratio was on average 0.7. CONCLUSION: Regional colon volumes were comparable to previous findings using fully manual segmentation. The method showed good agreement between observers and may be used in future studies of gastrointestinal disorders to assess colon and fecal volume and colon morphology. Novel insight into morphology and quantitative assessment of the colon using this method may provide new biomarkers for constipation and abdominal pain compared to radiography which suffers from poor reliability.

Conformational solvation studies of LIGNOLs with molecular dynamics and conductor-like screening model.

Molecular dynamics (MD) simulations were performed on sterically hindered α-conidendrin-based chiral 1,4-diols (LIGNOLs) from the naturally occurring lignan hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was to explore the conformational behaviour of the LIGNOLs in aqueous solution adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually and they were modeled with the OPLS-AA force field implemented in GROMACS. The four most relevant torsional angles in the LIGNOLs were properly analyzed during the simulations. The determining property for the conformation preferred in aqueous solution was found to be the lowest energy in gas phase. The solvation effects on the LIGNOLs were also studied by quantum chemical calculations applying the COnductor-like Screening MOdel (COSMO). The hydration studies of the MD simulations showed that several of these LIGNOLs, produced from a renewable source, have a great potential of acting as chiral catalysts.

Retail clinic versus office setting: do patients choose appropriate providers?

OBJECTIVE: To assess whether health plan members who used retail clinics chose that setting for minor conditions and continued to see other providers for more complex conditions. STUDY DESIGN: Retrospective analysis of claims data in a commercially insured population. METHODS: Health plan enrollment data were used to identify and describe the analysis population. Episode Treatment Groups were used to identify members with chronic conditions and to analyze reasons for retail clinic use, complexity of retail clinic visits, and care for chronic conditions in non-retail clinic settings. Logistic regression was used to study predictors of retail clinic use. RESULTS: Retail clinic users differed significantly from nonusers. The most significant predictors of retail clinic use were age, sex, and proximity to a retail clinic. Episodes of care treated in the retail clinic appeared to be less complex than similar episodes treated in other settings. Chronically ill members who used the retail clinic saw another provider for their chronic condition at rates similar to or higher than those of members who did not use the retail clinic. CONCLUSIONS: Individuals may be able to identify when conditions are minor enough to be treated in a retail clinic and serious enough to be treated by a traditional provider.

Improving the imputation of race: evaluating the benefits of stratifying by age.

Health plans and other health care institutions may use indirect methods such as geocoding and surname analysis to estimate race, ethnicity, and socioeconomic status in an effort to measure disparities in care or target specific demographics. This study investigated whether stratifying by age improved imputations of race and ethnicity made through geocoding. Self-reported race and ethnicity from Medicaid enrollment records and from a health risk assessment administered by a large employer were used to validate imputation results from both an age-stratified model and a standard model. Sensitivity, specificity, and positive predictive value were calculated. Both approaches successfully imputed race and ethnicity for whites, blacks, Asians, and Hispanics. The age-stratified approach identified more blacks than did the unstratified approach, and correctly identified more blacks and whites. The two approaches worked equally well for identifying Asians and Hispanics. Age stratification may improve the accuracy of imputation methods, and help health care organizations to better understand the demographics of the people they serve.

Conformational analysis of hydroxymatairesinol in aqueous solution with molecular dynamics.

Molecular dynamics simulations were performed on the naturally occuring lignan hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was to explore the conformational behavior of HMR in aqueous solution adopting the TIP4P model. The topology of HMR was constructed by hand and HMR was modeled with the OPLS-AA force field implemented in GROMACS. The five torsional angles in HMR were properly analyzed during the simulations. Correlations through certain patterns were observed between the angles. The determining property for the conformation preferred in aqueous solution was found to be the dipole moment and not the lowest energy in gas phase. The solvation effects on HMR was also studied by quantum chemical calculations applying the COnductorlike Screening MOdel (COSMO), the results of which were compared with results from a previous study using the Polarized Continuum Model (PCM). In the present work, COSMO was found to give more credible relative energies than PCM.