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The interplay between bacterial biofilms, encrustation, and wall shear stress in ureteral stents: a review across scales
Get PDFDramatic Acceleration of the Hopf Cyclization on Gold(111): From Enediynes to Peri-Fused Diindenochrysene Graphene Nanoribbons.
Get PDFHopf et al. reported the high-temperature 6π-electrocyclization of cis-hexa-1,3-diene-5-yne to benzene in 1969. Subsequent studies using this cyclization have been limited by its very high reaction barrier. Here, we show that the reaction barrier for two model systems, (E)-1,3,4,6-tetraphenyl-3-hexene-1,5-diyne (1a) and (E)-3,4-bis(4-iodophenyl)-1,6-diphenyl-3-hexene-1,5-diyne (1b), is decreased by nearly half on a Au(111) surface. We have used scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc-AFM) to monitor the Hopf cyclization of enediynes 1a,b on Au(111). Enediyne 1a undergoes two sequential, quantitative Hopf cyclizations, first to naphthalene derivative 2, and finally to chrysene 3. Density functional theory (DFT) calculations reveal that a gold atom from the Au(111) surface is involved in all steps of this reaction and that it is crucial to lowering the reaction barrier. Our findings have important implications for the synthesis of novel graphene nanoribbons. Ullmann-like coupling of enediyne 1b at 20 °C on Au(111), followed by a series of Hopf cyclizations and aromatization reactions at higher temperatures, produces nanoribbons 12 and 13. These results show for the first time that graphene nanoribbons can be synthesized on a Au(111) surface using the Hopf cyclization mechanism
Red blood cell distribution width (RDW) - A new nutritional biomarker to assess nutritional risk and response to nutritional therapy?
No full textBACKGROUND & AIMS
Red cell distribution width (RDW) has been proposed as a surrogate marker for acute and chronic diseases and may be influenced by nutritional deficits. We assessed the prognostic value of RDW regarding clinical outcomes and nutritional treatment response among medical inpatients at nutritional risk.
METHODS
This is a secondary analysis of EFFORT, a randomized, controlled, prospective, multicenter trial investigating the effects of nutritional support in patients at nutritional risk in eight Swiss hospitals. We examined the association between RDW and mortality in regression analysis.
RESULTS
Among 1,244 included patients (median age 75 years, 46.6 % female), high RDW (≥15 %) levels were found in 38 % of patients (n = 473) with a significant association of higher malnutrition risk [OR 1.48 (95%CI 1.1 to 1.98); p = 0.009]. Patients with high RDW had a more than doubling in short-term (30 days) mortality risk [adjusted HR 2.12 (95%CI 1.44 to 3.12); p < 0.001] and a signficant increase in long-term (5 years) mortality risk [adjusted HR 1.73 (95%CI 1.49 to 2.01); p < 0.001]. Among patients with high RDW, nutritional support reduced morality within 30 days [adjusted OR 0.56 (95%CI 0.33 to 0.96); p = 0.035], while the effect of the nutritional intervention in patients with low RDW was markedly smaller.
CONCLUSIONS
Among medical patients at nutritional risk, RDW correlated with several nutritional parameters and was a strong prognostic marker for adverse clinical outcomes at short- and long-term, respectively. Patients with high baseline RDW levels also showed a strong benefit from the nutritional intervention. Further research is needed to understand whether monitoring of RDW over time severs as a nutritional biomarker to assess effectiveness of nutritional treatment in the long run.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02517476
MSCs mediate long-term efficacy in a Crohn's disease model by sustained anti-inflammatory macrophage programming via efferocytosis.
Get PDFMesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis
Taxonomy of teaching methods and their use in health professions education: a scoping review protocol.
Get PDFINTRODUCTION
Applying the lens of social constructivist theory, teaching methods facilitate the process of learning and may be used differently across settings to align learning goals. Teaching methods are used across disciplines, occupations and learning settings, yet terminology, descriptions and application for use vary widely. This scoping review will identify eligible literature of reported teaching methods with documented descriptions across disciplines with a focus of how teaching methods are applied to health professions education. A literary description of a teaching method was used as a basis from which to select eligible articles based on two criteria, a specified method and delivery of that teaching by a teacher figure.
METHODS AND ANALYSIS
Using the extension of the Joanna Briggs Institute methodology aligned to Arksey and O'Malley's six-stage framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, this scoping review will systematically search ERIC, Embase, Web of Science and PubMed databases. The search strategy was supported by an information specialist. Eligible studies will be identified in a two-stage screening process with four researchers. To complement eligible peer-reviewed literature, we will also search out relevant grey literature including University Websites, Conference Programmes and handsearched reference lists. Data extraction will be performed using a developed data extraction tool. A narrative summary will accompany charted results and describe the results aligned to the study objectives.
ETHICS AND DISSEMINATION
As no intervention or patient recruitment is required for this research, ethics board approval is not required. Results will be disseminated via publication in a peer-reviewed journal, conference presentations and where feasible reaching out to those organisations and universities with published glossaries of terms for teaching
Impact of Socioeconomic Inequalities on Dental Caries Status in Sardinian Children.
Get PDFBACKGROUND
The association between oral health of schoolchildren living in the North Sardinia area and socioeconomic deprivation was assessed to evaluate a potential spatial correlation.
METHODS
A total of 10,947 subjects were examined (5281 aged 3-5-years, and 5666 aged 6-11-years). The WHO dmft index score was calculated following clinical examination by calibrated examiners. The Sardinian Deprivation Index (IDMS) of the children's municipalities was also considered. Descriptive, bivariate and multinomial data analysis was conducted to assess the association between clinical data and socioeconomic deprivation. The presence of systematic spatial variation regarding caries experience (dmft) and deprivation status was investigated using a spatial autoregressive analysis.
RESULTS
Caries figures were statistically different in the two age groups (dmf > 0, 13.79% in the younger group vs. dmf > 0, 34.20% in the older one, p < 0.01). In a multinomial logistic regression model for caries experience, all the covariates were statistically significantly associated (p < 0.01) in comparison with the base outcome "caries-free". Linear regression analysis showed a dependence of dmft on IDMS (p < 0.01). Based on this equation, the dmft of the 39 municipalities that did not participate in the survey was estimated. IDMS was statistically significantly associated (p < 0.01) with caries prevalence in the spatial regression model.
CONCLUSIONS
The deprivation index significantly increased the risk of caries for all categories of caries experience and prevalence compared to caries-free. The relationship between IDMS and caries data was also confirmed by spatial analysis
Associations between sex, body mass index and the individual microglial response in Alzheimer's disease.
Get PDFBACKGROUND AND OBJECTIVES
18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer's disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between β-amyloid-accumulation and microglial activation in AD.
METHODS
49 patients with AD (29 females, all Aβ-positive) and 15 Aβ-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and β-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional Aβ-PET on TSPO-PET was used to determine the Aβ-plaque-dependent microglial response (slope) and the Aβ-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI).
RESULTS
In AD, females showed higher mean cortical TSPO-PET z-scores (0.91 ± 0.49; males 0.30 ± 0.75; p = 0.002), while Aβ-PET z-scores were similar. The Aβ-plaque-independent microglial response was stronger in females with AD (+ 0.37 ± 0.38; males with AD - 0.33 ± 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the Aβ-plaque-dependent microglial response was not different between sexes. The Aβ-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the Aβ-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005).
CONCLUSION
While microglia response to fibrillar Aβ is similar between sexes, women with AD show a stronger Aβ-plaque-independent microglia response. This sex difference in Aβ-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the Aβ-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD
Intraoperative hypotension and postoperative outcomes: just the tip of the iceberg. Comment on Br J Anaesth 2023; 131: 823-31.
No full textChallenges in developing and validating machine learning models for TAVI mortality risk prediction: reply.
Get PDFMultiple independent de novo mutations are associated with the development of schistosoma reflexum, a lethal syndrome in cattle.
Get PDFSchistosoma reflexum (SR) is a lethal congenital syndrome characterized by U-shaped dorsal retroflexion of the spine and exposure of abdominal viscera. SR is usually associated with severe dystocia. The syndrome is thought to be inherited as a Mendelian trait. We collected a series of 23 SR-affected calves from four breeds (20 Holstein, one Red Danish, one Limousin, one Romagnola) and performed whole-genome sequencing (WGS). WGS was performed on 51 cattle, including 14 cases with parents (trio-based; Group 1) and nine single cases (solo-based; Group 2). Sequencing-based genome-wide association studies with 20 Holstein cases and 154 controls showed no association (above Bonferroni threshold; P-value<3×10-09). Assuming a monogenic recessive inheritance, no region of shared homozygosity was observed, suggesting heterogeneity. Alternatively, the presence of possible dominant acting de novo mutations were assessed. In Group 1, heterozygous private variants, absent in both parents, were found in seven cases. These involved the ACTL6A, FLNA, GLG1, IQSEC2, MAST3, MBTPS2, and MLLT1 genes. In addition, heterozygous private variants affecting the genes DYNC1LI1, PPP2R2B, SCAF8, SUGP1, and UBP1 were identified in five cases from Group 2. The detected frameshift and missense variants are predicted to cause haploinsufficiency. Each of these 12 affected genes belong to the class of haploinsufficient loss-of-function genes or are involved in embryonic and pre-weaning lethality or are known to be associated with severe malformation syndromes in humans and/or mice. This study presents for the first time a detailed genomic evaluation of bovine SR, suggesting that independent de novo mutations may explain the sporadic occurrence of SR in cattle
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