Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.

Solubility of CO2 in [1-n-butylthiolanium][Tf2N]+toluene mixtures: liquid-liquid phase split separation and modelling.

Carbon dioxide has been shown to be an effective antisolvent gas for separating organic compounds from ionic liquids (ILs) by inducing a liquid-vapour to liquid-liquid-vapour transition. Using carbon dioxide, toluene can be separated from imidazolium, phosphonium and pyridinum cation-based ILs with the bis(trifluoromethylsulfonyl)imide anion, which is relatively hydrophobic and has a high toluene solubility. A new IL with relatively low viscosity is tested here for the same toluene separation process: 1-n-butylthiolanium bis(trifluoromethylsulfonyl)imide. Carbon dioxide solubility in binary and ternary systems containing toluene and 1-n-butylthiolanium bis(trifluoromethylsulfonyl)imide is measured at 298.15 and 313.15 K up to 7.4 MPa. Solubility behaviour in this IL is similar to imidazolium-based ILs with the same anion. However, phase split pressures are lower when 1-n-butylthiolanium bis (trifluoromethylsulfonyl)imide is used instead of 1- n-hexyl-3-methylimidazolium bis(trifluoromethylsu- lfonyl)imide at the same conditions of temperature and initial composition of toluene in the IL. Solubility data are modelled with the conductor-like screening model for real solvents combined with the Soave-Redlich-Kwong equation of state, which provides good qualitative results.

Differential Extraction and Preliminary Identification of Polyphenols from Ugni candollei (White Murta) Berries.

Ugni candollei, commonly known as white murta, is a native Chilean berry with a polyphenol composition that has been underexplored. This study aimed to establish a comprehensive profile of white murta polyphenols using ultra-performance liquid chromatography electrospray ionization Orbitrap mass spectrometry (UPLC-ESI-ORBITRAP MS). Additionally, it compared the efficacy of conventional extraction methods with emerging techniques such as deep eutectic solvent (DES) extraction and hot pressurized water extraction (HPWE). The analysis tentatively identified 107 phenolic compounds (84 of them reported for the first time for this cultivar), including 25 phenolic acids, 37 anthocyanins, and 45 flavonoids. Among the prominent and previously unreported polyphenols are ellagic acid acetyl-xyloside, 3-p-coumaroylquinic acid, cyanidin 3-O-(6'-caffeoyl-glucoside, and phloretin 2'-O-xylosyl-glucoside. The study found HPWE to be a promising alternative to traditional extraction of hydroxybenzoic acids, while DES extraction was less effective across all categories. The findings reveal that white murta possesses diverse phenolic compounds, potentially linked to various biological activities.

Assessing the effect of deep eutectic solvents on α-chymotrypsin thermal stability and activity.

Optimizing the liquid reaction phase holds significant potential for enhancing the efficiency of biocatalytic pro- cesses since it determines reaction equilibrium and kinetics. This study investigates the influence of the addition of deep eutectic solvents on the stability and activity of α-chymotrypsin, a proteolytic enzyme with industrial rele- vance. Deep eutectic solvents, composed of choline chloride or betaine mixed with glycerol or sorbitol, were added in the reaction phase at various concentrations. Experimental techniques, including kinetic and fluorometry, were employed to assess the α-chymotrypsin activity, thermal stability, and unfolding reversibility. Atomistic molecular dynamics simulations were also conducted to assess the interactions and provide molecular-level insights between α-chymotrypsin and the solvent. The results showed that among all studied mixtures, adding choline chloride + sorbitol improved thermal stability up to 18 °C and reaction kinetic efficiency up to two-fold upon adding choline chloride + glycerol. Notably, the choline chloride + sorbitol system exhibited the most substantial stabilization effect, attributed to the surface preferential accumulation of sorbitol, as corroborated by the computational anal- yses. This work highlights the potential of tailoring liquid reaction phase of α-chymotrypsin catalyzed reaction using neoteric solvents to enhance α-chymotrypsin performance and stability in industrial applications.

Enhanced Polyphenols Recovery from Grape Pomace: A Comparison of Pressurized and Atmospheric Extractions with Deep Eutectic Solvent Aqueous Mixtures.

Deep eutectic solvents (DES) are emerging as potent polyphenol extractors under normal atmospheric conditions. Yet, their effectiveness in hot pressurized liquid extraction (HPLE) must be studied more. We explored the ability of various water/DES and water/hydrogen bond donors (HBDs) mixtures in both atmospheric solid liquid extraction (ASLE) and HPLE (50%, 90 °C) for isolating specific polyphenol families from Carménère grape pomace. We assessed extraction yields based on total polyphenols, antioxidant capacity, and recovery of targeted polyphenols. The HBDs ethylene glycol and glycerol outperformed DES in atmospheric and pressurized extractions. Ethylene glycol exhibited a higher affinity for phenolic acids and flavonols, while flavanols preferred glycerol. Quantum chemical computations indicated that a high-water content in DES mixtures led to the formation of new hydrogen bonds, thereby reducing polyphenol-solvent interactions. HPLE was found to be superior to ASLE across all tested solvents. The elevated pressure in HPLE has caused significant improvement in the recovery of flavanols (17-89%), phenolic acids (17-1000%), and flavonols (81-258%). Scanning electron microscopy analysis of post-extraction residues suggested that high pressures collapse the plant matrix, thus easing polyphenol release.

Integrating Biocatalysis with Viscous Deep Eutectic Solvents in Lab-On-A-Chip Microreactors.

The combination of deep eutectic solvents (DESs, ChCl/glycerol 1 : 2) with buffer (up to 15 % v/v) leads to solvent mixtures that exert viscosities below 25 mPa s-1 at 45 °C while keeping their non-aqueous nature. This enables the setup of efficient enzymatic esterifications, which can also be applied in different continuous systems. Following those premises, the use of microreactors in biocatalytic reactions was explored using (low-viscous) DES-buffer media, showing that reactions could be performed efficiently. Under non-optimized conditions, the microreactor devices led to specific productivities considerably higher than those observed in the batch reactor (14 vs. 0.24 mgproduct min-1 mgbiocat -1 ) at the same enzyme loadings and conversion of 6 % (to assure a fair comparison). Looking beyond, the combination of several microchannels (e. g., in scale-out fashion) with DES-water media may lead to powerful, sustainable, and efficient tools for industrial synthesis.

Emotional Intelligence: Changes Over the First Year of Physician Assistant Education.

PURPOSE: To investigate emotional intelligence (EI) development in physician assistant (PA) students as they progress through their didactic education. METHODS: Data were gathered through an online survey of EI distributed to a purposeful sample of 5 institutions with similar curriculum length and start dates. Program directors forwarded the survey to students at the start of their didactic education (pretest). Follow-up surveys were distributed via email to the students at the end of their didactic education (posttest). The survey consisted of 33 items related to 4 subscales of EI. Participants' age, gender, and previous healthcare experience were gathered. Five repeated measures ANOVAs were calculated for each EI summary score. Independent sample t-tests were conducted between pretest scores and a previously established EI mean. RESULTS: A total of 192 first-year students were solicited. A sample of 68 (16 males; 52 females) served as participants. No results were attained for gender or age due to unbalanced sample sizes. Significant results were realized for total EI and the Managing Others' Emotions subscale. CONCLUSION: Participants with more than one healthcare experience demonstrated significantly high emotional intelligence on the pretest. Participants with one healthcare experience demonstrated a significant increase in total EI and the Managing Others' Emotions subscale. The main limitation of the study was the attrition of participants between measures. Future research is needed to assess EI at the end of the clinical year, after a period of clinical experience, and to determine which educational activities are most likely to enhance EI.

Emotional Intelligence: one Component in the HeART of Medicine.

The increasing need for health care providers has contributed to a rise in the number of physician assistant (PA) programs. Unfortunately simply increasing the number of graduates to meet this increased need is not good enough. Not only must PA programs and educators make sure that graduates have the necessary medical knowledge and clinical skills but that graduates also have the ability to understand and manage emotions and behaviors which result from working with others and taking care of patients. How an individual acts and reacts to situations is an aspect of psychology that is rooted in the study of emotion and behaviors which result from emotions. This description serves as the basis for modern analysis of what it means to be emotionally intelligent (EQ). Research suggests that a curriculum which focuses on the development of specific emotional intelligence tenets at certain times in medical and health profession training would help to enhance the development of skill sets associated with EQ. However, before substantial curricular changes are undertaken research specific to PA education is necessary.

Amyloid imaging with carbon 11-labeled Pittsburgh compound B for traumatic brain injury.

OBJECTIVES: To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue. DESIGN, SETTING, AND PARTICIPANTS: In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for ß-amyloid (Aß) and ß-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes. MAIN OUTCOMES AND MEASURES: We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aß and ß-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue. RESULTS: Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aß and ß-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels. CONCLUSIONS AND RELEVANCE: [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.

Using positron emission tomography and Carbon 11-labeled Pittsburgh Compound B to image Brain Fibrillar ß-amyloid in adults with down syndrome: safety, acceptability, and feasibility.

OBJECTIVE: To investigate the safety, acceptability, and feasibility of positron emission tomography (PET) using carbon 11-labeled Pittsburgh Compound B ([(11)C]PiB) to measure cerebral ß-amyloid in adults with Down syndrome (DS) and to explore if the technique differentiates between participants with and without Alzheimer disease (AD). DESIGN: Proof-of-principle case-controlled study of a nonrandomly selected cohort of participants with DS (with or without AD) compared within group and with healthy controls without DS. All had dynamic [(11)C]PiB PET and magnetic resonance imaging. Carbon 11-labeled PiB binding in the regions of interest associated with AD was quantitatively analyzed. SETTING: Wolfson Brain Imaging Centre, Cambridge, England. PARTICIPANTS: Nine with DS (aged 25-64 years), of whom 5 had a diagnosis of AD, and 14 healthy controls without DS (aged 33-69 years). MAIN OUTCOME MEASURE: Positive [(11)C]PiB binding in regions of interest. RESULTS: The scanning process was feasible and acceptable with no adverse events or safety concerns. Maps and regional values of nondisplaceable binding potential were produced using the reference tissue-input Logan plot, with the cerebellum used as the reference tissue. When compared with the healthy control group without DS, only participants with DS older than 45 years had significant [(11)C]PiB binding in regions of interest usually associated with AD, whether or not they had clinical evidence of dementia. CONCLUSIONS: Dynamic [(11)C]PiB PET can be used successfully to measure cerebral ß-amyloid deposition in DS. A clinical diagnosis of AD and age appear to be predictors of [(11)C]PiB binding in regions of interest, but given the small numbers, we cannot generalize the results.

Admission variables as predictors of PANCE scores in physician assistant programs: a comparison study across universities.

PURPOSE: The purpose of this study was to create a model of cognitive and noncognitive measures that could estimate the probability of achieving a given level of performance on the Physician Assistant National Certifying Examination (PANCE). METHODS: A retrospective records review of admissions information used by six universities was conducted to discover which factor had the most impact on the dependent variable of the PANCE score. Multiple predictors were measured: undergraduate grade point average (uGPA), graduate GPA, prerequisite grades, Graduate Record Exam (GRE)-verbal, GRE-quantitative, GRE combined, interview scores, years of health care experience, age, gender, and first-year scores on the Physician Assistant Clinical Knowledge Rating and Assessment Tool (PACKRAT). While PACKRAT scores are not applicable to admission selection, they are a strong midpoint predictor of PANCE performance. Multiple regression analysis was used to develop prediction equations. Expectancy tables were developed to provide estimation of PANCE performance, given the various score ranges on each of the predictor variables. RESULTS: Four predictors made a significant contribution to the final regression equation: GPA, GRE-verbal, GRE-quantitative, and PACKRAT scores. The PACKRAT scores were consistently the best predictors of performance on the PANCE. Each of these four predictors can be plugged into predictability tables to estimate the probability of achieving various score intervals on the PANCE. CONCLUSION: A model of equations and predictors can be used to project how successful a physician assistant (PA) graduate will be on PANCE performance. Years of health care experience, grades on prerequisites, and demographics were not significant predictors across programs but did have significance in certain individual institutions. Future research should examine which specific noncognitive traits measured in interviews can add value to predictability.

Secuelas neurológicas y psicomotrices en niños de muy bajo peso al nacer: Clínica de Seguimiento Maternidad Nuestra Señora de la Altagracia 1982-1993 / Neurologics and psycomotors secuelae in children of very low birth wight: Maternidad Nuestra Señora de La Altagracia follow up clinic, 1982-1993

Antecedentes: El muy bajo peso al nacer, es todo niño que al momento del nacimiento pesa < 1,500 G. Hoy en día el pronóstico de estos niños ha mejorado sustancialmente; en primer lugar debido a la creación de las unidades de cuidados intensivos neonatales y en segundo lugar al seguimiento post natal que reciben. El objetivo de este estudio es comunicar, cuales son las secuelas neurológicas y psicomotrices en 31 niños de muy bajo peso al nacer, seguidos desde 1982-1993 en la clínica de seguimiento para niños de muy bajo peso al nacer en la Maternidad Nuestra Señora de la Altagracia, en Santo Domingo, República Dominicana. Materiales y métodos: Se siguieron los 31 niños durante un año cada mes, y luego cada 6 meses hasta los 5 años; durante el primer año se le realizaron medidas antropométricas (peso, talla, perímetro cefálico). Para el examen neurológico se utilizó la escala neurológica de Amiel Tisson; a los niños menores de 5 años se les aplicó el test de Gessel ya los de más de 5 años el Test de Bender, además se le realizó potenciales evocados para descartar problemas de audición. Resultados: Podemos destacar que a menor peso al nacer mayor el déficit neurológico, encontrándose que la mitad de los niños presentaron algún déficit. En las medidas antropométricas no se evidenciaron anormalidades. Las pruebas de Gessel y Bender demostraron que persisten alteraciones de diversos grados en el neurológico y psicomotor. Los potenciales evocados no evidenciaron ninguna alteración auditiva. Comentario: En nuestro estudio se evidenció que las secuelas neurológicas y psicomotrices, son muy frecuentes en niños de muy bajo peso al nacer

Vigilancia de la resistencia a los medicamentos antituberculosos en el Perú, 1995-96 / Surveillance about the antituberculosis drugs resistance in Peru, 1995-96

La tuberculosis es un importante y serio problema de salud en el Perú. La resistencia antibiótica constituye un problema emergente de magnitud no totalmente definida. A fin de determinar la prevalencia de la resistencia del M. tuberculosis a los medicamentos antituberculosos e iniciar un estudio de vigilancia, se efectuó un proyecto multicéntrico en 31 subregiones de salud del país, que incluyó muestras de esputo de pacientes diagnosticados de TB, con baciloscopia positiva precedentes de 814 hospitales y centros de salud. Se completó una muestra de 1958 pacientes nuevos y antes trabajos de quienes se obtuvo muestras de esputo, las cuales se cultivaron en los medios de Lowenstein-Jensen y Ogawa y los aislamientos fueron sometidos a pruebas de sensibilidad a los medicamentos anti TB por el método de las proporciones. Los resultados fueron: resistencia a uno o más medicamentos en el 15,4 de 1500 casos de TB no tratados previamente (NT), y en el 36,0 de 458 casos ya tratados (AT). la multirresistencia (MR) afectó a 2,4 de los pacientes NT y un 15,7 de los AT. En 9 casis (0,4) se reportó positividad para HIV, de los cuales seis no tratados (NT) fueron sensibles a los medicamentos anti TB y los otros 3 ya tratados (AT) un (1) caso fue sensible y 2 resistentes de éstos uno de ellos MR. El estudio permitió el fortalecimiento de la Red Nacional de Laboratorios en TB del país, contribuyendo a la seguridad y a la oportunidad en el diagnóstico y control de la enfermedad