Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows

Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury.

BACKGROUND: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators. METHODS: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool. RESULTS: The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N = 24, 48%) and neurosurgeons (N = 7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N = 49, 98%) and indicated routine measurement in registries (N = 41, 82%), benchmarking (N = 42, 84%), and quality improvement programs (N = 41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N = 48, 98%). CONCLUSIONS: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury

BackgroundWe aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.MethodsA preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.ResultsThe expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).ConclusionsThis Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future

Converting homogeneous to heterogeneous in electrophilic catalysis using monodisperse metal nanoparticles

A continuing goal in catalysis is the transformation of processes from homogeneous to heterogeneous. To this end, nanoparticles represent a new frontier in heterogeneous catalysis, where this conversion is supplemented by the ability to obtain new or divergent reactivity and selectivity. We report a novel method for applying heterogeneous catalysts to known homogeneous catalytic reactions through the design and synthesis of electrophilic platinum nanoparticles. These nanoparticles are selectively oxidized by the hypervalent iodine species PhICl{sub 2}, and catalyze a range of {pi}-bond activation reactions previously only homogeneously catalyzed. Multiple experimental methods are utilized to unambiguously verify the heterogeneity of the catalytic process. The discovery of treatments for nanoparticles that induce the desired homogeneous catalytic activity should lead to the further development of reactions previously inaccessible in heterogeneous catalysis. Furthermore, our size and capping agent study revealed that Pt PAMAM dendrimer-capped nanoparticles demonstrate superior activity and recyclability compared to larger, polymer-capped analogues

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Evaluación de la contaminación del aire por hongos microscópicos en dos colecciones biológicas y dos museos de la ciudad de Guatemala

Evaluation of air pollution by microscopic fungi in two biological collections and two museums of Guatemala Abstract Air quality was determined both inside and outside the Micoteca Licenciado Rubén Mayorga Peralta (MICG), the Herbarium of the School of Biology (BIGU), the Museum of Natural History (MUSHNAT) and the Museum of the University of San Carlos of Guatemala (MUSAC). Volumetric sampling (impaction) with a bio-colector was used to gather microscopic fungi. The samples were collected from Oct 2011 to Mar 2012. Microscopic identification was performed using slides with lactophenol blue; while API 20C AUX was used for the identification of yeasts. The results obtained were 1,780 CFU/m3 outside and 1,270 CFU/m3 inside for MICG; 2,790 CFU/m3 outside and 1,450 CFU/m3 inside for BIGU; 990 CFU/m3 outside and 1,010 CFU/m3 inside for MUSAC, and finally 1,630 CFU/m3 outside and 2,850 CFU/m3 inside for MUSHNAT. The predominant genera found in both environments of all sites were Penicillium sp., Cladosporium sp. and Aspergillus sp. It was also possible to isolate other extremely important fungal genera such as Fusarium sp. and Paecilomyces sp. A guide was developed with information about the proper cleaning and biosafety procedures according to the infrastructure and raw materials of each site.Se determinó la calidad del aire en el interior y exterior de la Micoteca Licenciado Rúben Mayorga Peralta (MICG), el Herbario de Biología de Guatemala (Herbario BIGU), el Museo de Historia Natural (MUSHNAT) y el Museo de la Universidad de San Carlos de Guatemala (MUSAC). Para la recolección de los hongos microscópicos se utilizó la técnica volumétrica por impactación haciendo uso de un biocolector. Los muestreos fueron realizados de octubre de 2011 a marzo de 2012, la identificación microscópica se realizó por medio de preparaciones con azul de lactofenol y para la identificación de levaduras se utilizó el API 20C AUX. Los resultados obtenidos en los ambientes Micoteca Licenciado Rúben Mayorga Peralta indican que la mayor concentración fúngica fue de 1,780, (unidad formadora de colonias por metro cúbico UFC/m3) en el exterior y para el interior fue de 1,270 UFC/m3, en el caso del Herbario BIGU en el exterior fue de 2,790 UFC/m3 y en el interior de 1,450 UFC/m3, para el MUSAC la mayor concentración observada fue de 990 UFC/m3 para el exterior y de 1,010 UFC/m3 para el interior, y para el MUSHNAT en el caso del ambiente exterior fue de 1,630 UFC/m3 y para el interior fue de 2,850 UFC/m3. Los géneros predominantes durante los muestreos en ambos ambientes en todas las áreas muestreadas fueron Penicillium sp., Cladosporium sp. y Aspergillus sp. Se logró el aislamiento de otros géneros fúngicos de gran importancia Fusarium sp. y Paecilomyces sp. Se llevó a cabo la elaboración de una guía que contiene información acerca de procedimientos de limpieza y bioseguridad acorde a la infraestructura y materia prima de cada establecimiento