Catalytic Olefin Transpositions Facilitated by Ruthenium N,N,N-Pincer Complexes.

In this report, we demonstrate olefin transposition/isomerization reactions catalyzed by a series of N,N,N-pincer (1,3-bis(2-pyridylimino)isoindoline) Ru-hydride complexes. The protocol proceeds at room temperature for most substrates, achieving excellent yields, regioselectivity, and diastereoselectivity in short reaction times. The air-stable Ru-chloride derivatives of these complexes exhibit comparable reactivity enabling benchtop setup and synthetic versatility. Furthermore, we demonstrate the potential for one-pot cascade sequences of the products derived from the transposition reactions.

STOP-AD portal: Selecting the optimal pharmaceutical for preclinical drug testing in Alzheimer's disease.

We propose an unbiased methodology to rank compounds for advancement into comprehensive preclinical testing for Alzheimer's disease (AD). Translation of compounds to the clinic in AD has been hampered by poor predictive validity of models, compounds with limited pharmaceutical properties, and studies that lack rigor. To overcome this, MODEL-AD's Preclinical Testing Core developed a standardized pipeline for assessing efficacy in AD mouse models. We hypothesize that rank-ordering compounds based upon pharmacokinetic, efficacy, and toxicity properties in preclinical models will enhance successful translation to the clinic. Previously compound selection was based solely on physiochemical properties, with arbitrary cutoff limits, making ranking challenging. Since no gold standard exists for systematic prioritization, validating a selection criteria has remained elusive. The STOP-AD framework evaluates the drug-like properties to rank compounds for in vivo studies, and uses an unbiased approach that overcomes the validation limitation by performing Monte-Carlo simulations. HIGHLIGHTS: Promising preclinical studies for AD drugs have not translated to clinical success. Systematic assessment of AD drug candidates may increase clinical translatability. We describe a well-defined framework for compound selection with clear selection metrics.

Analysis of alcohol use, consumption of micronutrient and macronutrients, and liver health in the 2017-2018 National Health and Nutrition Examination Survey.

BACKGROUND: Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol-associated diseases, including nutritional factors. The objective of the current study was to examine inter-relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Based on self-reported alcohol consumption, NHANES respondents were assigned to one of four categories: never drinkers (lifetime abstainers), non-drinkers (past-year abstainers), moderate drinkers (1/2 drinks per day for females/males, respectively), and heavy drinkers (>1/>2 drinks per day for females/males, respectively, and/or frequent binge drinking). Survey-weighted regression analyses (adjusted for gender, age, race, education, and body mass index) were performed to examine associations between alcohol intake, dietary, and liver health characteristics. RESULTS: Individuals categorized as heavy drinkers were significantly younger, most often well-educated males with low incidences of diabetes and other comorbidities. They consumed the most overall calories and various micronutrients, indicating a diet that was not necessarily nutrient poor. Neither moderate nor heavy drinkers had liver steatosis or fibrosis as measured by liver elastography, although heavy drinkers had modestly elevated plasma biomarkers of liver injury, including ALT, AST, and GGT, compared with the other groups. CONCLUSIONS: Our findings suggest that the category of heavy drinkers in the 2017-2018 NHANES consisted of generally healthy individuals with high-energy intake and no evidence of liver steatosis or fibrosis. However, slightly increased plasma liver markers may indicate a risk of future progression to more advanced stages of liver disease over time in some individuals. Several limitations should be considered when interpreting these data, including the potential misclassification of drinking categories and the lack of standardized cutoff scores for fatty liver as assessed by elastography, among others.

Survival after radiation for stage I and II non-small cell lung cancer with positive margins.

BACKGROUND: There is limited data guiding treatment for positive margins following lobectomy for early-stage non-small cell lung cancer (NSCLC). Using data from the National Cancer Data Base, we sought to determine whether radiation therapy following lobectomy for stage I or II NSCLC was associated with improved overall survival in patients with positive margins. METHODS: Patients who underwent lobectomy without induction therapy for stage I or II NSCLC (1998-2006) with positive resection margins were selected. Patients were stratified by administration of radiation therapy following surgery, and overall survival was estimated using the Kaplan-Meier method. The association between radiation therapy and survival was adjusted for nonrandom treatment selection using Cox proportional hazards regression modeling. RESULTS: Positive margins were recorded in 1934 of 49,563 (3.9%) patients who underwent lobectomy for stage I or II NSCLC. Positive margin status was associated with significantly worse 5-year survival (34.5% versus 57.2%, P < 0.001). After selection of patients with positive margins and known radiation status and exclusion of patients who had upstaged disease or received radiation therapy for palliative indications, radiation therapy was used in 579 of 1579 patients (38.2%) but was not associated with a significant difference in the likelihood of death during subsequent follow-up (hazard ratio: 1.10, 95% confidence interval: 0.90, 1.35). CONCLUSIONS: Positive margins following lobectomy for stage I or II NSCLC are associated with reduced 5-year survival. Postsurgical radiation is not strongly associated with an improvement in overall survival among these patients.

The effects of Desflurane and Sevoflurane on Nesfatin-1 levels in laparoscopic Cholecystectomy: a randomized controlled trial.

BACKGROUND: Nesfatin-1 is involved in cardiovascular regulation, stress-related responses. The objective of this study is to investigate the impact of volatile anesthetics on Nesfatin-1 levels. METHOD: Fourty-two patients aged 30-65 years with the American Society Anesthesiology (ASA) Class I-II who were scheduled for laparoscopic cholecystectomy were included in the study Patients were randomized into two group; desflurane administered group (Group I, n = 21) and sevoflurane administered group (Group II, n = 21). For anesthesia maintenance, the patients received 6% desflurane or 2% sevoflurane in 40% O2 and 60% air. The patient's heart rate (HR), mean, systolic and diastolic arterial pressures (MAP, SAP, DAP), peripheral O2 saturation (SpO2) were monitored and recorded before induction, after induction, after intubation, and during extubation. Blood samples were collected before induction (T1), and after extubation when aldrete score was 10 (T2). RESULTS: Demographic data were similar between the groups. The preoperative levels of nesfatin were similar in the two groups (p = 0.715). In desflurane group, post-operative nesfatin levels were similar compared to preoperative levels (p = 0.073). In sevoflurane group, post-operative nesfatin levels were similar (p = 0.131). The nesfatin levels (postoperative vs preoperative) were similar between the groups (p = 0.900). CONCLUSION: In conclusion, this study results suggest that nesfatin-1 levels are not affected by the use of sevoflurane or desflurane in patients undergoing laparoscopic cholecystectomy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001023347 , retrospectively registered on 17 July 2017.

Ecology under lake ice.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer 'growing seasons'. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.

Room-temperature phosphorescence determination of melamine in dairy products using l-cysteine-capped Mn-doped zinc sulfide (ZnS) quantum dots.

A simple, sensitive, and precise room-temperature phosphorescence method was developed for the determination of melamine in dairy products using l-cysteine-capped Mn-doped zinc sulfide (ZnS) quantum dots as a probe. This method is based on the quenching of the phosphorescence signal of quantum dots by the interaction with melamine. Under optimum conditions, phosphorescence intensity was quenched by various concentrations of melamine in a linear range from 50 to 500ng/mL, with a detection limit of 5.95ng/mL in 10 mM phosphate buffer (pH 7.4). The relative standard deviation for 5 replicate measurements was 0.15%. The developed method was applied to dairy products to determine melamine concentrations; recovery values ranged from 96.3 to 104.7%.

Effects of iron overload and exenatide on erythrocyte deformability in a rat model.

Iron overload is known to affect erythrocyte membrane properties and erythrocyte shape. We hypothesized that iron overload which directly affects the erythrocyte morphology may also interfere with erythrocyte deformability (ED). Exenatide, a glucagon like peptide -1 (GLP-1) analogue used in the treatment of diabetes, is known to have beneficial pleiotropic effects on endothelial function and blood flow which are different from its glucose-lowering effects. In our study we aimed to test the effect of iron overload on ED in a rat model (1) and to evaluate the effect of exenatide on ED in the same model (2). For this purpose, the animals were randomly divided into three groups, each containing 6 rats. Rats in the control group (Group C) were given intraperitoneal injections of saline as placebo. The second group (Group Fe) was given intraperitoneal iron dextran (60 mg/kg/day) five days a week for 4 weeks to develop iron overload. The third group (Group Fe +E) received subcutaneous injections of 10 mcg exenatide (Byetta® Lilly Pharma) in two divided doses for 4 weeks in addition to iron dextran. We observed that ED index was significantly higher in Group Fe when compared to Group C and Group Fe+E (p Keywords: erythrocyte deformability, iron, exenatide.

Effect of alprostadil on erythrocyte deformability in ischemia reperfusion injury.

BACKGROUND: Ischemia reperfusion injury (I/R) in lower extremity is a frequent and important clinical phenomenon. Protective effect of alprostadil on local and distant organ injury due to I/R has been well-documented but its effect on erythrocyte deformability needs further investigation. Our aim was to investigate the effect of alprostadil on erythrocyte deformability in infrarenal aorta of rats undergoing I/R. MATERIALS AND METHODS: Our study was conducted with 18 Wistar albino rats. Rats were divided into 3 groups; randomized control group (group C; n=6), I/R group without alprostadil (group I/R; n=6) and I/R group with alprostadil 20 mcg.kg(-1), intraperitoneal (group I/R-A; n=6). Packs of erythrocytes were prepared from heparinized blood samples and deformability measurements were done. RESULTS: Comparisons of the control and I/R-A groups revealed similar results (p=0.240). The values of the IR group were significantly higher than those of the control and IR-A groups (p=0.009, p=0.026, respectively). CONCLUSION: In our study, we detected unfavourable effects of I/R on erythrocyte deformability, which may lead to disturbance in blood flow and hence tissue perfusion in infrarenal rat aorta. We also found that alprostadil had beneficial effects by reversing undesirable effects of I/R (Fig. 1, Ref. 22).

Assessment of hygiene habits and attitudes among removable partial denture wearers in a university hospital.

AIMS: The aim of this study was conducting a survey of hygiene habits and use of removable partial dentures (RPDs) and correlate them with the social conditions of the interviewees. METHODS: A total of 145 RPD wearers were interviewed by experienced clinical staff using a structured questionnaire. A Chi-squared test was performed to evaluate statistical significance between the variables, and the level of significance was P<0.05. RESULTS: A total of 72 (49%) patients reported that they had not been well informed by the dentists. Brushing was the most frequent cleaning method (57.6%). 77 (53.1%) patients did not take off their dentures at night. The frequency of cleaning dentures and using cleansing tablet was significantly higher in females than in males (P<0.05). The frequency of denture cleaning, cleaned parts of denture, use of cleansing tablet, removal of dentures at night, frequency of tooth brushing, does not show any significant difference according to age, educational status or duration of denture usage (P>0.05). RPD wearers did not clean their dentures and natural teeth satisfactorily and had limited knowledge of denture cleansing and oral hygiene maintenance. CONCLUSIONS: Hygiene habits and attitudes may be affected by gender, but education level and hygiene attitudes may not always present positive correlation. Dentists should thoroughly inform patients about the harmful effects of overnight wearing and motivate to clean metal parts of RPD's and cleansing tablet use in order to minimize the abrasive effect of widely preferred cleaning method of brushing with toothpaste.

The effect of bleaching agents on the color stability of ceromer and porcelain restorative materials in vitro.

PURPOSE: The aim of this in vitro study was to determine the color changes of five different restorative materials after exposing these materials to two different home bleaching agents. METHODS: This study applied bleaching agents to an ultralow-fusing porcelain, a low-fusing porcelain, two types of heat-pressed glass ceramics, and a ceromer. A total of 24 disc-shaped specimens were fabricated (with a diameter of 10 mm and a thickness of 2 mm) from each material (n=12). The initial color measurements were taken with a spectrophotometer. The first set of specimens were bleached with 10% hydrogen peroxide (HP) for one hour daily for 10 days. The other set of specimens were bleached with 10% carbamide peroxide (CP) bleaching gel for eight hours daily for 14 days. Data were analyzed with the one-way analysis of variance and Kruskal-Wallis statistical test. The difference in the prebleaching and postbleaching color of each material was considered to be statistically significant at p < 0.05. RESULTS: The study found a statistically significant difference among the color changes of the test groups after exposing them to both bleaching agents (p<0.05). Appreciable color change was observed in the Estenia (ΔE=3.99) specimens that were bleached with the HP, and noticeable color changes were observed in the Estenia (ΔE=1.89) and IPS Empress 2 (ΔE=1.66) groups when they were treated with the CP. CONCLUSIONS: Restorations (especially polymer-containing restorative materials) should be protected before any bleaching procedure due to the high risk of color change.

Evaluation of hbetaD-1 and hbetaD-2 levels in saliva of patients with oral mucosal diseases.

OBJECTIVE: This study aimed to determine a possible correlation between oral mucosal disease and salivary concentrations of the antimicrobial peptides human beta-defensin-1 (hbetaD-1) and human beta-defensin-2 (hbetaD-2). METHOD: The present work focussed on the establishment of a reversed phase-high performance liquid chromatography (RP-HPLC) procedure to quantify human beta-defensins (hbetaD-1 and hbetaD-2) in saliva samples of patients with oral diseases such as lichen planus (n = 10), Behçet (n = 10) and recurrent apthous stomatitis (n = 10). RESULTS: Linear calibration range for hbetaD-1 and hbetaD-2 defensins was 1.67-200 microg mL-1 and 3.13 -100 PG mL-1 with R2 values of 0.9998 and 0.996, correspondingly. The concentration of beta-defensins in saliva was determined by comparing the peak areas of eluted hbetaD-1 and hbetaD-2 with that of their standards. The variation of the amount of beta-defensins was evaluated by comparisons of the results obtained from the patients with oral mucosal diseases before and after treatments and the control subjects. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.62 microg mL-Sand 5.39 microg mL-1 for hbetaD-1 and 0.94 mig mL-1 and 3.13 microg mL-1 for hbetalD-2, respectively. CONCLUSION: The salivary beta-defensin concentration was significantly higher in patients with oral mucosal diseases than in healthy volunteers; furthermore, in patients with oral mucosal diseases, the concentration was significantly higher before treatment than after treatment.

Clinical Decision Support for Precision Dosing: Opportunities for Enhanced Equity and Inclusion in Health Care.

Precision dosing aims to tailor doses to individual patients with the goal of improving treatment efficacy and avoiding toxicity. Clinical decision support software (CDSS) plays a crucial role in mediating this process, translating knowledge derived from clinical trials and real-world data (RWD) into actionable insights for clinicians to use at the point of care. However, not all patient populations are proportionally represented in clinical trials and other data sources that inform CDSS tools, limiting the applicability of these tools for underrepresented populations. Here, we review some of the limitations of existing CDSS tools and discuss methods for overcoming these gaps. We discuss considerations for study design and modeling to create more inclusive CDSS, particularly with an eye toward better incorporation of biological indicators in place of race, ethnicity, or sex. We also review inclusive practices for collection of these demographic data, during both study design and in software user interface design. Because of the role CDSS plays in both recording routine clinical care data and disseminating knowledge derived from data, CDSS presents a promising opportunity to continuously improve precision dosing algorithms using RWD to better reflect the diversity of patient populations.

Cluster formation restricts dynamic nuclear polarization of xenon in solid mixtures.

During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, (129)Xe nuclear magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical solid mixture exhibit a single peak, broadened by (1)H neighbors. A second peak appears upon annealing for several hours at 125 K. Its characteristic width and chemical shift indicate the presence of spontaneously formed pure Xe clusters. Microwave irradiation at the appropriate frequencies can bring both peaks to either positive or negative polarization. The peculiar time evolution of (129)Xe polarization in pure Xe clusters during DNP can be modelled as an interplay of spin diffusion and T(1) relaxation. Our simple spherical-cluster model offers a sensitive tool to evaluate major DNP parameters in situ, revealing a severe spin-diffusion bottleneck at the cluster boundaries and a significant sample overheating due to microwave irradiation. Subsequent DNP system modifications designed to reduce the overheating resulted in four-fold increase of (129)Xe polarization, from 5.3% to 21%.

Effects of motion paradigm on human perception of tilt and translation.

The effect of varying sinusoidal linear acceleration on perception of human motion was examined using 4 motion paradigms: off-vertical axis rotation, variable radius centrifugation, linear lateral translation, and rotation about an earth-horizontal axis. The motion profiles for each paradigm included 6 frequencies (0.01-0.6 Hz) and 5 tilt amplitudes (5°-20°). Subjects verbally reported the perceived angle of their whole-body tilt and the peak-to-peak translation of their head in space and used a joystick capable of recording 2-axis motion in the sagittal and transversal planes to indicate the phase between the perceived and actual motions. The amplitudes of perceived tilt and translation were expressed in terms of gain, i.e., the ratio of perceived tilt to equivalent tilt angle, and the ratio of perceived translation to equivalent linear displacement. Tilt perception gain decreased, whereas translation perception gain increased, with increasing frequency. During off-vertical axis rotation, the phase of tilt perception and of translation perception did not vary across stimulus frequencies. These motion paradigms elicited similar responses in roll tilt and interaural perception of translation, with differences likely due to the influence of naso-occipital linear accelerations and input to the semicircular canals that varied across motion paradigms.

Analysis of tinnitus severity and associated risk factors in patients with chronic otitis media: data from the multinational collaborative Chronic Otitis Media Questionnaire-12 study.

BACKGROUND: Subjective tinnitus is a common symptom, and there is often an underlying otological cause. This study investigated the degree of tinnitus-related annoyance in patients with chronic otitis media and analysed whether associations with tinnitus severity exist. METHOD: The multinational collaborative Chronic Otitis Media Questionnaire-12 study collected prospective data on 478 adult patients suffering from chronic otitis media across 9 otology referral centres in 8 countries. Based on this dataset, we investigated tinnitus severity using participant responses to item 7 of a native version of the Chronic Otitis Media Questionnaire-12. RESULTS: With respect to tinnitus severity, 23.8 per cent, 17.4 per cent, 15.5 per cent, and 43.4 per cent of participants reported no, minor, moderate, and major inconvenience or greater, respectively. The absence of ear discharge, absence of cholesteatoma, and poorer disease-specific health-related quality-of-life were associated with increased tinnitus severity in patients with chronic otitis media, whereas age, hearing disability and geographical region showed no association. CONCLUSION: This analysis provided novel insight into potential risk factors for tinnitus in patients with chronic otitis media.

A macroscopic comparison study on main branches of arteria brachialis and arteria subscapularis in Southern Karaman and Hasak sheep breeds.

BACKGROUND: The Southern Karaman sheep, which is very fertile in terms of meat and milk production and is often preferred in livestock raising, is known as a domestic sheep breed. The Hasak sheep is a breed formed by the triple crossbreeding of the German Black-headed, Hampshire and Akkaraman breeds. Arterial feeding of the forelimb is provided by arteria axillaris, a continuation of arteria subclavia. In this study, it was aimed to examine the forelimb arteries in Southern Karaman and Hasak sheep breeds. MATERIALS AND METHODS: Totally, 8 Southern Karaman and 8 Hasak sheep were obtained from Konya Bahri Dagdas International Agricultural Institute. The sheep were anesthetised with xylazine and ketamine and extravasated by cutting the arteria carotis communis in the neck area of the sheep. The forelimbs of the sheep separated from the body were fixed in 10% formaldehyde solution and then dissections were made and the course and branching of the arteries were examined. RESULTS: It was determined that the arteria brachialis was divided into two main branches as distal arteria brachialis and proximal arteria subscapularis at the articulatio humeri level of the arteria axillary. Arteria mediana, which is a continuation of arteria brachialis, was also examined in different parts of antebrachium and ended by splitting into branches. CONCLUSIONS: According to the findings of the Southern Karaman and Hasak sheep breeds, it was determined that the forelimb arteries had some anatomical differences but were similar in structure to many sheep breeds.

Olfactory dysfunction and coronavirus disease 2019 severity: a prospective cohort study.

OBJECTIVE: The primary goal of this study was to evaluate the association between olfactory dysfunction or taste impairment and disease severity and radiological findings in coronavirus disease-2019. The secondary goal was to assess the prevalence, severity and course of olfactory dysfunction or taste impairment in patients with coronavirus disease 2019. METHOD: This prospective observational cohort study evaluated patients hospitalised with coronavirus disease 2019 between April 1 and 1 May 2020. Olfactory dysfunction and taste impairment were evaluated by two questionnaires. Chest computed tomography findings and coronavirus disease-2019 severity were assessed. RESULTS: Among 133 patients, 23.3 per cent and 30.8 per cent experienced olfactory dysfunction and taste impairment, respectively, and 17.2 per cent experienced both. The mean age was 56.03 years, and 64.7 per cent were male and 35.3 per cent were female. No statistically significant association was found between olfactory dysfunction (p = 0.706) and taste impairment (p = 0.35) with either disease severity or chest computed tomography grading. CONCLUSION: Olfactory dysfunction or taste impairment does not have prognostic importance in patients with coronavirus disease 2019.

Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study.

PURPOSE: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). METHODS: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). CONCLUSION: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.