An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan Parasite Entamoeba histolytica.

E. histolytica is the etiological agent of intestinal amebiasis and liver abscesses, which still poses public health threat globally. Metronidazole is the drug of choice against amebiasis. However, metronidazole-resistant amoebic clinical isolates and strains have been reported recently, challenging the efforts for amebiasis eradication. In search of alternative treatments, E. histolytica transcriptomes have shown the association of genes involved in RNA metabolism with the virulence of the parasite. Among the upregulated genes in amoebic liver abscesses are the splicing factors EhU2AF2 and a paralog of EhSF3B1. For this reason and because EhU2AF2 contains unusual KH-QUA2 (84KQ) motifs in its lengthened C-terminus domain, here we investigated how the role of EhU2AF2 in pre-mRNA processing impacts the virulence of the parasite. We found that 84KQ is involved in splicing inhibition/intron retention of several virulence and non-virulence-related genes. The 84KQ domain interacts with the same domain of the constitutive splicing factor SF1 (SF1KQ), both in solution and when SF1KQ is bound to branchpoint signal RNA probes. The 84KQ-SF1KQ interaction prevents splicing complex E to A transition, thus inhibiting splicing. Surprisingly, the deletion of the 84KQ domain in EhU2AF2 amoeba transformants increased splicing and enhanced the in vitro and in vivo virulence phenotypes. We conclude that the interaction of the 84KQ and SF1KQ domains, probably involving additional factors, tunes down Entamoeba virulence by favoring intron retention.

Quality of life analysis after Whipple procedure. Retrospective cohort study / Análisis de calidad de vida en cirugía Whipple. Estudio de cohorte retrospectiva

Abstract Introduction Patient reported outcomes establish the patient's own perception about his/her health and enable the development of policies designed to improve health/disease processes. These are particularly helpful in the case of diseases with a significant impact on the patient's quality of life. Objective To compare the quality of life scores assessed using the EQ-5D-5L questionnaire in patients undergoing cephalic duodenopancreatectomy (Whipple procedure) and laparoscopic cholecystectomies in the same hospital. Methodology Retrospective cohort trial between July 2018 and February 2020. Patients programmed for cephalic duodenopancreatectomy were included, regardless of the type of pathology, and over 18 years old. Patients with carcinomatosis or vascular infiltration were excluded. The EQ-5D-5L was administered following Whipple surgery and compared against a control group (laparoscopic cholecystectomy). The demographic characteristics, the diagnosis, hospital stay and 60-day mortality were assessed. Results A total of 68 patients were included. The most frequent diagnosis was pancreatic cancer (30 %) in the Whipple group and lithiasis (100 %) in the control group. In the five dimensions assessed, there were no differences in terms of mobility (OR: 0.41, 95 % CI [0.30-0.57], p = 0.103) and in terms of personal care (OR: 0.42, 95 % CI [0.32-0.58], p = 0.254). There was a difference in daily life activities (OR: 0.38, 95 % CI [0.27-0.54], p = 0.017), pain/malaise (OR: 2.33, 95 % CI [0.99-5.48]), p = 0.013 and anxiety/depression (OR: 0.39, 95 % CI [0.28-0.55], p = 0.019). The overall health perception was 80 points for Whipple (IQR 60-90) vs. 100 points for the control group (IQR 90-100). Conclusions Patients undergoing a Whipple procedure experience a health perception slightly lower than patients undergoing laparoscopic cholecystectomy. This difference may be associated with increased pain, anxiety/depression and a reduction in their activities of daily life. The administration of the EQ-5D-5L questionnaire to measure quality of life is a friendly tool that used be used routinely to plan activities aimed at improving medical care.

Resumen Introducción Los desenlaces informados por el paciente permiten establecer cuál es la percepción que tiene de su salud y crear políticas que mejoren procesos en salud/enfermedad. Son particularmente útiles en enfermedad que afectan la calidad de vida de forma importante. Objetivo Comparar las puntuaciones de calidad de vida evaluadas mediante el cuestionario EQ-5D-5L en pacientes sometidos a duodenopancreatectomía cefálica (procedimiento de Whipple) y colecistectomías laparoscópicas en el mismo centro hospitalario. Metodología Estudio de cohorte retrospectivo entre julio de 2018 y febrero de 2020. Se incluyeron pacientes programados para duodenopancreatectomía cefálica independientemente del tipo de patología y mayor de 18 años de edad; se excluyeron pacientes con carcinomatosis o infiltración vascular. Se aplicó el cuestionario EQ-5D-5L después de cirugía Whipple y se comparó con un grupo control (colecistectomía laparoscópica). Se evaluaron características demográficas, diagnóstico, estancia hospitalaria y mortalidad a 60 días. Resultados Se incluyeron 68 pacientes. El diagnóstico más frecuente fue cáncer de páncreas (30 %) en el grupo Whipple y litiasis (100 %) en el grupo control. En las 5 dimensiones evaluadas no hubo diferencias en movilidad (OR: 0,41, IC 95 % [0,30-0,57], p = 0,103) y en cuidado personal (OR: 0,42, IC 95 % [0,32-0,58], p = 0,254). Se encontró diferencia en actividades cotidianas (OR: 0,38, IC 95 % [0,270,54], p = 0,017), dolor/malestar (OR: 2,33, IC 95 % [0,99-5,48]), p = 0,013 y angustia/depresión (OR: 0,39, IC 95 % [0,28-0,55], p = 0,019). La percepción general de salud fue 80 puntos para Whipple (RIQ60-90) vs. 100 puntos para el grupo control (RIC 90-100). Conclusiones Los pacientes sometidos a Whipple presentan una percepción de salud ligeramente menor que los pacientes de colecistectomía laparoscópica. Esta diferencia puede estar relacionada con el aumento en dolor, angustia/depresión y disminución en actividades cotidianas. La aplicación del cuestionario EQ-5D-5L para medición de calidad de vida es una herramienta fácil de aplicar que debería realizarse rutinariamente para planear intervenciones dirigidas a mejorar la atención médica.

Upgrading of Extra-Heavy Crude Oils by Dispersed Injection of NiO-PdO/CeO2±Î´ Nanocatalyst-Based Nanofluids in the Steam.

The main objective of this study is to evaluate the injection of a dispersed nanocatalyst-based nanofluid in a steam stream for in situ upgrading and oil recovery during a steam injection process. The nanocatalyst was selected through adsorption and thermogravimetric experiments. Two nanoparticles were proposed, ceria nanoparticles (CeO2±Î´), with and without functionalization with nickel, and palladium oxides (CeNi0.89Pd1.1). Each one was employed for static tests of adsorption and subsequent decomposition using a model solution composed of n-C7 asphaltenes (A) and resins II (R) separately and for different R:A ratios of 2:8, 1:1, and 8:2. Then, a displacement test consisting of three main stages was successfully developed. At the beginning, steam was injected into the porous media at a temperature of 210 °C, the pore and overburden pressure were fixed at 150 and 800 psi, respectively, and the steam quality was 70%. This was followed by CeNi0.89Pd1.1 dispersed injection in the steam stream. Finally, the treatment was allowed to soak for 12 h, and the steam flooding was carried out again until no more oil production was observed. Among the most relevant results, functionalized nanoparticles achieved higher adsorption of both fractions as well as a lower decomposition temperature. The presence of resins did not affect the amount of asphaltene adsorption over the evaluated materials. The catalytic activity suggests that the increase in resin content promotes a higher conversion in a shorter period of time. Also, for the different steps of the dynamic test, increases of 25% and 42% in oil recovery were obtained for the dispersed injection of the nanofluid in the steam stream and after a soaking time of 12 h, compared with the base curve with only steam injection, respectively. The upgraded crude oil reached an API gravity level of 15.9°, i.e., an increase in 9.0° units in comparison with the untreated extra-heavy crude oil, which represents an increase of 130%. Also, reductions of up to 71% and 85% in the asphaltene content and viscosity were observed.

Diseño y validación de un instrumento para evaluar la calidad de los registros de enfermería / Design and validation of an instrument to assess the quality of nursing records

El registro clínico de enfermería debe reflejar de forma concreta y precisa la actuación del profesional en la atención del paciente. Por ello, resulta importante contar con instrumentos que evalúen la documentación de enfermería y permitan la mejora del cuidado a partir de la continuidad y la calidad de este. El presente estudio describe el proceso de diseño y validación de un instrumento para evaluar los registros de enfermería. Estuvo conformado por cuatro fases que dieron como resultado la Cédula de Evaluación del Registro Clínico de Enfermería (CERCE), constituida por 48 reactivos de tipo dicotómico, divididos en seis indicadores, la cual reporta un coeficiente global de confiabilidad Kuder-Richardson (KR-20) de 0.917 y cuyos indicadores oscilaron entre 0.77 y 0.93. El producto final representa los esfuerzos para la mejora de los procesos de evaluación de los registros de enfermería como una medida que contribuya a una gestión de la calidad del cuidado.

The nursing record should reflect in a concrete and accurate way the performance of the nursing professional in care of the patient. That is why it is important to have instruments to evalúate the nursing documentation and allow the improvement of care through keeping a good nursing record. This study describes the process of design and validation of an instrument to evalúate nursing records. This instrument comprised four phases that resulted in the Evaluation Card of the Clinical Nursing Registry (CERCE, according to its initials in Spanish), consisting of 48 dichotomous items, divided into six indicators, reporting a Kuder- Richardson reliability coefficient (KR-20) of 0.917, and whose indicators ranged from 0.77 to 0.93. The final product represents the efforts to improve the evaluation processes of nursing records as a measure aimed at the management of quality of care.

Work Experiences and Satisfaction of International Medical School Graduates.

OBJECTIVES: We compared demographics and work, financial, and satisfaction experiences of early-career and midcareer pediatricians categorized by their childhood and medical school locations. METHODS: Data from the Pediatrician Life and Career Experience Study were used to examine the characteristics and experiences of 3 groups, which were categorized as (1) international childhood and medical school graduate (international-IMG), (2) United States childhood and international medical school graduate (US-IMG), and (3) United States or international childhood and United States medical school graduate (USMG). With multivariable logistic regression, we examined the experiences of the groups, controlling for participant characteristics. RESULTS: Data from 1467 of 1804 participants were analyzed; 13% were categorized as international-IMGs, 6% were categorized as US-IMGs, and 81% were categorized as USMGs. International-IMGs and US-IMGs were less likely than USMGs to report their race and ethnicity as white and non-Hispanic (26%, 32%, and 71%, respectively; P < .05) and more likely to report caring for patients with public insurance (adjusted odds ratio [aOR] 1.80 [95% confidence interval (CI) 1.27-2.56] and aOR 2.12 [95% CI 1.31-3.42], respectively). International-IMGs were less likely than USMGs to agree that physician colleagues value their work (aOR 0.35; 95% CI 0.21-0.56). Overall, 8 in 10 reported that their work was personally rewarding; international-IMGs were less likely than USMGs to report such satisfaction (P < .05). CONCLUSIONS: Among a national sample of pediatricians, international-IMGs and US-IMGs play important roles in workforce diversity. They also report unique challenges. Most are satisfied with their work, but international-IMGs are the least satisfied.

Postsplicing-Derived Full-Length Intron Circles in the Protozoan Parasite Entamoeba histolytica.

Noncoding circular RNAs are widespread in the tree of life. Particularly, intron-containing circular RNAs which apparently upregulate their parental gene expression. Entamoeba histolytica, the causative agent of dysentery and liver abscesses in humans, codes for several noncoding RNAs, including circular ribosomal RNAs, but no intron containing circular RNAs have been described to date. Divergent RT-PCR and diverse molecular approaches, allowed us to detect bona fide full-length intronic circular RNA (flicRNA) molecules. Self-splicing reactions, RNA polymerase II inhibition with Actinomycin D, and second step of splicing-inhibition with boric acid showed that the production of flicRX13 (one of the flicRNAs found in this work, and our test model) depends on mRNA synthesis and pre-mRNA processing instead of self-splicing. To explore the cues and factors involved in flicRX13 biogenesis in vivo, splicing assays were carried out in amoeba transformants where splicing factors and Dbr1 (intron lariat debranching enzyme 1) were silenced or overexpressed, or where Rabx13 wild-type and mutant 5'ss (splice site) and branch site minigene constructs were overexpressed. Whereas SF1 (splicing factor 1) is not involved, the U2 auxiliary splicing factor, Dbr1, and the GU-rich 5'ss are involved in postsplicing flicRX13 biogenesis, probably by Dbr1 stalling, in a similar fashion to the formation of ciRNAs (circular intronic RNAs), but with distinctive 5'-3'ss ligation points. Different from the reported functions of ciRNAs, the 5'ss GU-rich element of flicRX13 possibly interacts with transcription machinery to silence its own gene in cis. Furthermore, introns of E. histolytica virulence-related genes are also processed as flicRNAs.

Association between medical home characteristics and staff professional experiences in pediatric practices.

BACKGROUND: The patient-centered medical home (PCMH) model has been touted as a potential way to improve primary care. As more PCMH projects are undertaken it is critical to understand professional experiences as staff are key in implementing and maintaining the necessary changes. A paucity of information on staff experiences is available, and our study aims to fill that critical gap in the literature. METHODS: Eligible pediatric practices were invited to participate in the Florida Pediatric Medical Home Demonstration Project out which 20 practices were selected. Eligibility criteria included a minimum of 100 children with special health care needs and participation in Medicaid, a Medicaid health plan, or Florida KidCare. Survey data were collected from staff working in these 20 pediatric practices across Florida. Ware's seven-point scale assessed satisfaction and burnout was measured using the six-point Maslach scale. The Medical Home Index measured the practice's medical home characteristics. Descriptive and multivariate analyses were conducted. In total, 170 staff members completed the survey and the response rate was 42.6%. RESULTS: Staff members reported high job satisfaction (mean 5.54; SD 1.26) and average burnout. Multivariate analyses suggest that care coordination is positively associated (b = 0.75) and community outreach is negatively associated (b = -0.18) with job satisfaction. Quality improvement and organizational capacity are positively associated with increased staff burnout (OR = 1.37, 5.89, respectively). Chronic condition and data management are associated with lower burnout (OR = 0.05 and 0.20, respectively). Across all models adaptive reserve, or the ability to make and sustain change, is associated with higher job satisfaction and lower staff burnout. CONCLUSIONS: Staff experiences in the transition to becoming a PCMH are important. Although our study is cross-sectional, it provides some insight about how medical home, staff and practice characteristics are associated with job satisfaction and burnout. Many PCMH initiatives include facilitation and it should assist staff on how to adapt to change. Unless staff needs are addressed a PCMH may be threatened by fatigue, burnout, and low morale.

Assessing patient experiences in the pediatric patient-centered medical home: a comparison of two instruments.

The Patient-Centered Medical Home (PCMH) is a model of care that has been promoted as a way to transform a broken primary care system in the US. However, in order to convince more practices to make the transformation and to properly reimburse practices who are PCMHs, valid and reliable data are needed. Data that capture patient experiences in a PCMH is valuable, but which instrument should be used remains unclear. Our study aims to compare the validity and reliability of two national PCMH instruments. Telephone surveys were conducted with children who receive care from 20 pediatric practices across Florida (n = 990). All of the children are eligible for Medicaid or the Children's Health Insurance Program. Analyses were conducted to compare the Consumer Assessment of Health Plan Survey-Patient-Centered Medical Home (CAHPS-PCMH) and the National Survey of Children with Special Health Care Needs (NS-CSHCN) medical home domain. Respondents were mainly White non-Hispanic, female, under 35 years old, and from a two-parent household. The NS-CSHCN outperformed the CAHPS-PCMH in regard to scale reliability (Cronbach's alpha coefficients all ≥0.81 vs. 0.56-0.85, respectively). In regard to item-domain convergence and discriminant validity the CAHPS-PCMH fared better than the NS-CSHCN (range of convergence 0.66-0.93 vs. 0.32-1.00). The CAHPS-PCMH did not correspond to the scale structure in construct validity testing. Neither instrument performed well in the known-groups validity tests. No clear best instrument was determined. Further revision and calibration may be needed to accurately assess patient experiences in the PCMH.