Vanishing spin alignment : experimental indication of triaxial 28Si+28Si\bf ^{28}Si + {^{28}Si} nuclear molecule

Fragment-fragment-$\gamma$ coincidences have been measured for $\rm ^{28}Si + {^{28}Si}$ at an energy corresponding to the population of a conjectured resonance in $^{56}$Ni. Fragment angular distributions as well as $\gamma$-ray angular correlations indicate that the spin orientations of the outgoing fragments are perpendicular to the orbital angular momentum. This differs from the $\rm ^{24}Mg+{^{24}Mg}$ and the $\rm ^{12}C+{^{12}C}$ resonances, and suggests two oblate $\rm ^{28}Si$ nuclei interacting in an equator-to-equator molecular configuration.Comment: 14 pages standard REVTeX file, 3 ps Figures -- Accepted for publication in Physical Review C (Rapid Communication

Intention to Inform Relatives, Rates of Cascade Testing, and Preference for Patient-Mediated Communication in Families Concerned with Hereditary Breast and Ovarian Cancer and Lynch Syndrome: The Swiss CASCADE Cohort.

Cascade screening for Tier 1 cancer genetic conditions is a significant public health intervention because it identifies untested relatives of individuals known to carry pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). The Swiss CASCADE is a family-based, open-ended cohort, including carriers of HBOC- and LS-associated pathogenic variants and their relatives. This paper describes rates of cascade screening in relatives from HBOC- and LS- harboring families, examines carriers' preferences for communication of testing results, and describes theory-based predictors of intention to invite relatives to a cascade screening program. Information has been provided by 304 index cases and 115 relatives recruited from September 2017 to December 2021. On average, 10 relatives per index case were potentially eligible for cascade screening. Approximately 65% of respondents wanted to invite relatives to the cohort, and approximately 50% indicated a preference for patient-mediated communication of testing results, possibly with the assistance of digital technology. Intention to invite relatives was higher for first- compared to second- and third-degree relatives, but was not different between syndromes or based on relatives' gender. The family environment and carrying pathogenic variants predicts intention to invite relatives. Information helps optimize delivery of tailored genetic services

The effect of Spirulina sauce, as a functional food, on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease patients:A randomized double-blinded clinical trial

OBJECTIVE: This study sought to investigate the effect of Spirulina on cardiometabolic risk factors, oxidative stress biomarkers, glycemic profile, and liver enzymes in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: This randomized, double‐blind clinical trial was performed on 46 NAFLD patients. Subjects were allocated to consume either Spirulina sauce or placebo, each 20 g/day for 8 weeks. Fatty liver grade, liver enzymes, anthropometric parameters, blood pressure, and serum lipids, glucose, insulin, malondialdehyde, and antioxidant capacity were assessed pre‐ and postintervention. RESULTS: Fatty liver grade was significantly different between the two groups. A significant change for ALT (alanine aminotransferase) and AST (aspartate aminotransferase) was seen between the two groups (p = .03 and .02, respectively), while ALP (alkaline phosphatase) serum levels were not significantly different within or between groups. Pertaining to glycemic profile, all variables, except HOMA‐IR, were not significantly different within or between groups. Finally, statistically significant changes were seen in both MDA (malondialdehyde) and TAC (total antioxidant capacity) among the groups (p = .04 and <.001, respectively). CONCLUSIONS: Spirulina may improve fatty liver grade by modifying liver enzymes, oxidative stress, and some lipid profiles; however, there was effect of Spirulina on anthropometric characteristics and blood pressure

Purification and immobilization of engineered glucose dehydrogenase: A new approach to producing gluconic acid from breadwaste

Background Platform chemicals are essential to industrial processes. Used as starting materials for the manufacture of diverse products, their cheap availability and efficient sourcing are an industrial requirement. Increasing concerns about the depletion of natural resources and growing environmental consciousness have led to a focus on the economics and ecological viability of bio-based platform chemical production. Contemporary approaches include the use of immobilized enzymes that can be harnessed to produce high-value chemicals from waste. Results In this study, an engineered glucose dehydrogenase (GDH) was optimized for gluconic acid (GA) production. Sulfolobus solfataricus GDH was expressed in Escherichia coli. The Km and Vmax values for recombinant GDH were calculated as 0.87 mM and 5.91 U/mg, respectively. Recombinant GDH was immobilized on a hierarchically porous silica support (MM-SBA-15) and its activity was compared with GDH immobilized on three commercially available supports. MM-SBA-15 showed significantly higher immobilization efficiency (> 98%) than the commercial supports. After 5 cycles, GDH activity was at least 14% greater than the remaining activity on commercial supports. Glucose in bread waste hydrolysate was converted to GA by free-state and immobilized GDH. After the 10th reuse cycle on MM-SBA-15, a 22% conversion yield was observed, generating 25 gGA/gGDH. The highest GA production efficiency was 47 gGA/gGDH using free-state GDH. Conclusions This study demonstrates the feasibility of enzymatically converting BWH to GA: immobilizing GDH on MM-SBA-15 renders the enzyme more stable and permits its multiple reuse

Cyclen-Based Cationic Lipids for Highly Efficient Gene Delivery towards Tumor Cells

Gene therapy has tremendous potential for both inherited and acquired diseases. However, delivery problems limited their clinical application, and new gene delivery vehicles with low cytotoxicity and high transfection efficiency are greatly required.In this report, we designed and synthesized three amphiphilic molecules (L1-L3) with the structures involving 1, 4, 7, 10-tetraazacyclododecane (cyclen), imidazolium and a hydrophobic dodecyl chain. Their interactions with plasmid DNA were studied via electrophoretic gel retardation assays, fluorescent quenching experiments, dynamic light scattering and transmission electron microscopy. The in vitro gene transfection assay and cytotoxicity assay were conducted in four cell lines.Results indicated that L1 and L3-formed liposomes could effectively bind to DNA to form well-shaped nanoparticles. Combining with neutral lipid DOPE, L3 was found with high efficiency in gene transfer in three tumor cell lines including A549, HepG2 and H460. The optimized gene transfection efficacy of L3 was nearly 5.5 times more efficient than that of the popular commercially available gene delivery agent Lipofectamine 2000™ in human lung carcinoma cells A549. In addition, since L1 and L3 had nearly no gene transfection performance in normal cells HEK293, these cationic lipids showed tumor cell-targeting property to a certain extent. No significant cytotoxicity was found for the lipoplexes formed by L1-L3, and their cytotoxicities were similar to or slightly lower than the lipoplexes prepared from Lipofectamine 2000™.Novel cyclen-based cationic lipids for effective in vitro gene transfection were founded, and these studies here may extend the application areas of macrocyclic polyamines, especially for cyclen

Energy security and shifting modes of governance

The concept of energy security fits uneasily into contemporary security debates. It is neither a clearly traditional nor a fully ‘non-traditional’ security issue. There are also limits to the social constructedness of the concept. This article argues that, while it is important to identify the differing securitizations of energy, these must be contextualized within the material realities and the differing historical modes of governance of the political economy of resources. This is essential for understanding the differing meanings accorded to energy security, the shifting modes through which energy is governed, and the extent to which energy security concerns drive international politics. In this context, contemporary concerns over energy security have both material and ideological dimensions: anxiety over the dual shift of power from West to East and from resource-importing to resource-exporting countries; and concern over the normative weakening of the neo-liberal mode of energy governance

Site-Specific Bioconjugation of a Murine Dihydrofolate Reductase Enzyme by Copper(I)-Catalyzed Azide-Alkyne Cycloaddition with Retained Activity

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is an efficient reaction linking an azido and an alkynyl group in the presence of copper catalyst. Incorporation of a non-natural amino acid (NAA) containing either an azido or an alkynyl group into a protein allows site-specific bioconjugation in mild conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme has been hampered by several issues including low yield, poor solubility of a ligand, and protein structural/functional perturbation by CuAAC components. In the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine dihydrofolate reductase (mDHFR), in high cell density cultivation of Escherichia coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate enzyme compatibility of various CuAAC conditions comprising combination of commercially available Cu(I)-chelating ligands and reductants. The condensed culture improves the protein yield 19-fold based on the same amount of non-natural amino acid, and the enzyme incubation under the optimized reaction condition did not lead to any activity loss but allowed a fast and high-yield bioconjugation. Using the established conditions, a biotin-azide spacer was efficiently conjugated to mDHFR with retained activity leading to the site-specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated plate. These results demonstrate that the combination of reactive non-natural amino acid incorporation and the optimized CuAAC can be used to bioconjugate enzymes with retained enzymatic activityope

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin