New dental simulator for microsurgical training preliminary overview

Objective: To present a new simulator designed at the Minimally Invasive Surgery Centre (Cáceres) which offers an integral, effective and viable training system that can be used for learning microsurgical techniques. Study design: A square methacrylate block was used. Animal jaws were fixed to the sides by means of butterfly screws. This block also has a drainage tube to facilitate the escape of fluids. Results: Excellent results were obtained using this simulator in microsurgical suturing training in dental, Oral and Maxillofacial Surgery Conclusions: We believe that this simulator is an essential component in microsurgical training. It is an ethically and morally valid training method with which various suturing techniques can be practised before using live animals and before applying these to daily clinical practice

Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study

Background: This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine. Methods: Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an ‘up-down' design to determine the toxicity contour of the combination. Results: Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m−2 twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients. Conclusions: In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed

Tryptophan synthase uses an atypical mechanism to achieve substrate specificity

Tryptophan synthase (TrpS) catalyzes the final steps in the biosynthesis of L-tryptophan from L-serine (Ser) and indole-3-glycerol phosphate (IGP). We report that native TrpS can also catalyze a productive reaction with L-threonine (Thr), leading to (2S,3S)-β-methyltryptophan. Surprisingly, β-substitution occurs in vitro with a 3.4-fold higher catalytic efficiency for Ser over Thr using saturating indole, despite >82,000-fold preference for Ser in direct competition using IGP. Structural data identify a novel product binding site and kinetic experiments clarify the atypical mechanism of specificity: Thr binds efficiently but decreases the affinity for indole and disrupts the allosteric signaling that regulates the catalytic cycle

Density functional electronic spectrum of the CuO−6−10Cu O_{-6}^{-10} cluster and possible local Jahn-Teller distorsions in the La-Ba-Cu-O superconductor

We present a density functional theory (DFT) calculation in the generalized gradient approximation to study the possibility for the existence of Jahn-Teller (JT) or pseudo Jahn-Teller (PJT) type local distortions in the La-Ba-Cu-O superconducting system. We performed the calculation and correspondingly group theory classification of the electronic ground state of the CuO${_{6}}^{-10}$ elongated octahedra cluster, immersed in a background simulating the superconductor. Part of the motivation to do this study is that the origin of the apical deformation of the CuO${_{6}}^{-10}$ cluster is not due to a pure JT effect, having therefore a non {\it a priori} condition to remove the degeneracy of the electronic ground state of the parent regular octahedron. We present a comparative analysis of the symmetry classified electron spectrum with previously reported results using unrestricted Hartree-Fock calculations (UHF). Both the DFT and UHF calculations produced a non degenerate electronic ground state, not having therefore the necessary condition for a pure JT effect. However, the appearance of a degenerate E$_{g}$ state near to the highest occupied molecular orbital in the DFT calculation, suggests the possibility for a PJT effect responsible for a local distortion of the oxidized CuO$_{6}^{-9}$ cluster.Comment: 12 pages, 3 figures, submitted to International Journal of Modern Physics B (IJMPB

Increased Glycemic Variability Is Independently Associated With Length of Stay and Mortality in Noncritically Ill Hospitalized Patients

OBJECTIVE To investigate the association between glycemic variability (GV) and both length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This study retrospectively analyzed 4,262 admissions to the general medicine or surgery services during a 2 year period. Patients with point-of-care glucose monitoring and a minimum of two glucose values per day on average were selected. GV was assessed by SD and coefficient of variation (CV). Data were analyzed with linear and logistic multivariate regression analysis in separate models for SD and CV. Analysis was performed with generalized estimating equations to adjust for correlation between multiple admissions in some individual cases. RESULTS After exclusions, 935 admissions comprised the sample. Results of adjusted analysis indicate that for every 10 mg/dL increase in SD and 10–percentage point increase in CV, LOS increased by 4.4 and 9.7%, respectively. Relative risk of death in 90 days also increased by 8% for every 10-mg/dL increase in SD. These associations were independent of age, race, service of care (medicine or surgery), previous diagnosis of diabetes, HbA1c, BMI, the use of regular insulin as a sole regimen, mean glucose, and hypoglycemia occurrence during the hospitalization. CONCLUSIONS Our results indicate that increased GV during hospitalization is independently associated with longer LOS and increased mortality in noncritically ill patients. Prospective studies with continuous glucose monitoring are necessary to investigate this association thoroughly and to generate therapeutic strategies targeted at decreasing GV. Inpatient hyperglycemia is common, and it has been associated with increased morbidity and mortality in patients with and without diabetes (1–7). In the intensive care unit (ICU) setting, hypoglycemia has also been independently associated with a significant increase in mortality (8–10). Recently, a third metric of glucose control, known as glycemic variability (GV), has been proposed to be additionally implicated in the disease-associated process of dysglycemia (11). GV refers to fluctuations of blood glucose values around the mean and has been posited as a novel marker for poor glycemic control (12,13). In vitro and human studies suggest that high GV leads to greater oxidative stress than does sustained hyperglycemia (14,15). Studies of ICU patients have consistently demonstrated that increased GV is independently associated with higher mortality (16–19). Notably, results from a large multicenter study concluded that GV was a stronger predictor of ICU mortality than was mean glucose concentrations (20). Although there is no consensus as to the best method to determine GV in hospitalized patients, the use of SD of glucose values has been well validated by previous ICU studies (16,20). Coefficient of variation (CV) has also been suggested as a strong independent index for measuring GV because it corrects for mean glucose levels (21,22). Despite substantial scientific evidence from the ICU, no previous studies have investigated the association between GV and clinical outcomes in patients admitted to the general medical and surgical wards. The purpose of this study was therefore to investigate the association between GV and length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients. We hypothesize that increased GV in this setting is associated with increased LOS and mortality

Prospective Study of Pre-Gravid Sugar-Sweetened Beverage Consumption and the Risk of Gestational Diabetes Mellitus

ObjectiveConsumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older-aged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM).Research design and methodsThis was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses' Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk.ResultsDuring 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed <1 serving/month, those who consumed >or=5 servings/week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01-1.47]).ConclusionsFindings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (>or=5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages

The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study

Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy

Comparison of circulation patterns of mumps virus in the Netherlands and Spain (2015–2020)

BackgroundMumps is a viral infection mainly characterized by inflammation of the parotid glands. Despite of vaccination programs, infections among fully vaccinated populations were reported. The World Health Organization (WHO) recommends molecular surveillance of mumps based on sequencing of the small hydrophobic (SH) gene. The use of hypervariable non-coding regions (NCR) as additional molecular markers was proposed in multiple studies. Circulation of mumps virus (MuV) genotypes and variants in different European countries were described in the literature. From 2010 to 2020, mumps outbreaks caused by genotype G were described. However, this issue has not been analyzed from a wider geographical perspective. In the present study, sequence data from MuV detected in Spain and in The Netherlands during a period of 5  years (2015- March 2020) were analyzed to gain insights in the spatiotemporal spread of MuV at a larger geographical scale than in previous local studies.MethodsA total of 1,121 SH and 262 NCR between the Matrix and Fusion protein genes (MF-NCR) sequences from both countries were included in this study. Analysis of SH revealed 106 different haplotypes (set of identical sequences).ResultsOf them, seven showing extensive circulation were considered variants. All seven were detected in both countries in coincident temporal periods. A single MF-NCR haplotype was detected in 156 sequences (59.3% of total), and was shared by five of the seven SH variants, as well as three minor MF-NCR haplotypes. All SH variants and MF-NCR haplotypes shared by both countries were detected first in Spain.DiscussionOur results suggest a transmission way from south to north Europe. The higher incidence rate of mumps in Spain in spite of similar immunization coverage in both countries, could be associated with higher risk of MuV exportation. In conclusion, the present study provided novel insights into the circulation of MuV variants and haplotypes beyond the borders of single countries. In fact, the use of MF-NCR molecular tool allowed to reveal MuV transmission flows between The Netherlands and Spain. Similar studies including other (European) countries are needed to provide a broader view of the data presented in this study

Pollinators and Other Insect Visitations on Native and Ornamental Perennials in Two Landscapes

Many pollinator insects, especially honey bees [Apis mellifera Linnaeus (Apidae)] and wild bees, are experiencing population decline because of forage and habitat losses. Planting perennial flowering taxa is one method of increasing pollinator habitat. The objectives of this study were to evaluate the potential of 27 native species and ornamental perennial cultivars to determine their ability to attract insect pollinators in a rural and an urban landscape in North Dakota, assess the potential of these perennials to attract other beneficial insects and insect pests, and identify the bee species visiting these perennials. Five to eight native species and/or ornamental cultivars each from four genera, Monarda L. (bee balm), Hylotelephium H. Ohba (stonecrop), Baptisia Vent. (wild indigo), and Symphyotrichum Nees (aster), were tested. Weekly observations of individual plants during flowering and their pollinator visitations from 2018 to 2020 indicated that insect pollinators were present for the earliest flowering perennials in June and until the latest flowering perennials during the second week of October or the first freeze. A total of 16,194 insect pollinators were observed, and 87.8% of these pollinator visitations were Hymenoptera and Diptera. Significant landscapes × perennial flowering taxa interactions were detected for all insect groups, except for syrphid flies, for which both main effects were significantly different. Overall, honey bees and beetles preferred to visit Hylotelephium and Symphyotrichum. The wild bees, lepidopterans, and syrphids preferred Hylotelephium, Symphyotrichum, and Monarda. Tachinids preferred Symphyotrichum. Blow flies preferred Hylotelephium. More beneficial insect visitations (i.e., 96.0%) and fewer insect pest visitations (i.e., 30.4%) were counted on the rural landscape. A total of 3311 bee individuals were identified as species from the following families: Apidae, Andrenidae, Colletidae, Megachilidae, and Halictidae. Thirty-one and 21 bee species were unique to the rural and urban landscapes, respectively. The two most common wild bees were Ceratina calcarata Robertson on the cultivar S. oblongifolium (Nutt.) G.L. Nessom October Skies and Lasioglossum imitatum (Smith) on some Monarda and Hylotelephium. These findings suggest that pollinator visitations are influenced by the landscape and varied among the perennial flowering taxa in some cases. However, all evaluated perennial flower taxa would be suitable for attracting and supporting pollinators in rural or urban landscape settings in the northern Great Plains

Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.SCOPUS: re.jinfo:eu-repo/semantics/publishe