Surgical aortic valve replacement in patients with reduced ejection fraction. Prevalence and follow-up.

INTRODUCTION: Limited information exists on the prevalence and outcomes of patients undergoing surgical aortic valve replacement (SAVR) for aortic stenosis (AS) with reduced left ventricular ejection fraction (LVEF). This study aims to describe the number of AS patients undergoing SAVR with LVEF less than 55 % and quantify LVEF improvement at follow-up. MATERIAL AND METHODS: We analyzed patients undergoing SAVR with LVEF less than 55 % and the number of patients that improved the LVEF at 6 months. We defined 'improved LVEF' as a 10 % increase of LVEF compared to baseline. RESULTS: Out of 685 patients, 11.4 % (n = 78) had SAVR with LVEF <55 %. The median pre-surgery LVEF was 45 % [IQR 37-51]. In-hospital mortality was 5.1 % (n = 4). Follow-up data for 69 patients showed 50.7 % (n = 35) had improved LVEF. CONCLUSIONS: In our cohort, 10 % of severe AS patients underwent SAVR with LVEF <55 %, with half showing LVEF improvement at follow-up.

Unconstrained Precision Mitochondrial Genome Editing with αDdCBEs.

DddA-derived cytosine base editors (DdCBEs) enable the targeted introduction of C•G-to-T•A conversions in mitochondrial DNA (mtDNA). DdCBEs are often deployed as pairs, with each arm comprised of a transcription activator-like effector (TALE), a split double-stranded DNA deaminase half, and a uracil glycosylase inhibitor. This pioneering technology has helped improve our understanding of cellular processes involving mtDNA and has paved the way for the development of models and therapies for genetic disorders caused by pathogenic mtDNA variants. Nonetheless, given the intrinsic properties of TALE proteins, several target sites in human mtDNA remain out of reach to DdCBEs and other TALE-based technologies. Specifically, due to the conventional requirement for a thymine immediately upstream of the TALE target sequences (i.e., the 5'-T constraint), over 150 loci in the human mitochondrial genome are presumed to be inaccessible to DdCBEs. Previous attempts at circumventing this constraint, either by developing monomeric DdCBEs or utilizing DNA-binding domains alternative to TALEs, have resulted in suboptimal specificity profiles with reduced therapeutic potential. Here, aiming to challenge and elucidate the relevance of the 5'-T constraint in the context of DdCBE-mediated mtDNA editing, and to expand the range of motifs that are editable by this technology, we generated αDdCBEs that contain modified TALE proteins engineered to recognize all 5' bases. Notably, 5'-T-noncompliant, canonical DdCBEs efficiently edited mtDNA at diverse loci. However, DdCBEs were frequently outperformed by αDdCBEs, which consistently displayed significant improvements in activity and specificity, regardless of the 5'-most bases of their TALE binding sites. Furthermore, we showed that αDdCBEs are compatible with DddA tox and its derivatives DddA6, and DddA11, and we validated TALE shifting with αDdCBEs as an effective approach to optimize base editing outcomes at a single target site. Overall, αDdCBEs enable efficient, specific, and unconstrained mitochondrial base editing.

Dataset about Mexico's forest diversity: Site locations of tree species, wood densities, and geographic database of forest-vegetation provinces.

A dataset about three topics is provided, as a follow-up to the article "Mexico's forest diversity: common tree species and proposed forest-vegetation provinces" by Ricker et al. [1]. Firstly, 6927 site locations are provided for 22,532 trees of 1452 species. Secondly, measurements of basic wood-densities are reported for 779 tree species, obtained from 5256 trunk-core samples from Mexico's national forest inventory, and ranging from 0.05 to 0.93 g/cm3. Third, the data and maps of the forest-vegetation provinces from [1] were updated with the new cartography of Mexico's vegetation and land use (base year 2018). The maps are available now in an adjusted presentation as a shapefile-set for ArcGIS, as well as map-package and image files.

Caustics and wavefronts produced by multiple refraction-reflections through plane-parallel plates.

We study the formation of caustics and wavefronts produced by multiple refraction-reflections through a plane-parallel transparent plate, assuming a point source placed at an arbitrary position along the optical axis. The caustic surfaces are obtained by using the envelope's method. Subsequently, the wavefronts are directly related to the involutes, which are associated with the envelopes for all the rays. Hence by using the Malus-Dupin theorem, we obtain their respective wavefronts produced by multiple refraction-reflections through a plane-parallel transparent plate. On the other hand, we implement Huygens' principle to obtain the wavefronts leaving the plate after undergoing multiple reflections inside the plate, which we have called zero-distance phase wavefronts. Finally, we establish the correspondence between the wavefronts obtained by Huygens' principle and the involutes associated with caustic surfaces; they are brought in coincidence assuming parallel curves from each other.

Heart transplantation in patients with anthracycline-induced cardiomyopathy / Trasplante cardiaco en pacientes con cardiotoxicidad inducida por antraciclinas

Abstract Objective: The objective of this study was to describe the clinical and imaging characteristics and the evolution of heart transplantation patients due to anthracycline-induced cardiomyopathy Methods: Patients with a diagnosis of ACM who received a heart transplantation in our institution in the period of November 2009-April 2021 were included. Clinical characteristics, pre-transplant studies, and clinical outcomes after transplantation were collected retrospectively from the electronic medical record. Results: A total of 11 patients were included in the study. The median age at the time of cancer diagnosis was 15 years (IQR 10-37 years), while the median age at the time of heart transplant was 56 years (IQR 39-62 years). Regarding post-transplant outcomes, three patients died in the post-operative period. One died 4 years after the intervention due to chronic rejection, while the other seven had a favorable evolution. No oncological relapse was observed with a median follow-up of 2.5 years (IQR 1.86-3.85 years). Conclusion: End-stage anthracycline-induced cardiomyopathy can occur many years after chemotherapy treatment, so close cardiovascular follow-up is extremely important. Heart transplantation is a treatment option after an exhaustive multidisciplinary evaluation, to minimize the risk of oncological relapse.

Resumen Objetivo: Describir las características clínicas, imagenológicas y la evolución de los pacientes trasplantados cardiacos por cardiotoxicidad inducida por antraciclinas. Métodos: Serie de casos descriptiva de pacientes consecutivos trasplantados cardiacos debido a cardiotoxicidad mediada por antraciclinas en el periodo de Noviembre de 2009 a Abril de 2021.Las características clínicas, los estudios complementarios pretrasplante y la información sobre la evolución posterior al trasplante fue recolectada de la historia clínica electrónica de forma retrospectiva. Resultados: Se incluyeron un total de 11 pacientes. La mediana de edad al diagnóstico de la patología oncológica fue de 15 años (RIC 10-37 años), mientras que la mediana de edad en la que recibieron el trasplante cardiaco fue de 56 años (RIC 39-62 años). Con respecto a la evolución posterior al trasplante, 3 pacientes murieron en el periodo del post operatorio inmediato. 1 paciente falleció a los 4 años del trasplante y los otros 7 pacientes tuvieron una evolución favorable. No se observó recaída oncológica en ningún paciente durante una mediana de seguimiento o de 2,5 años (RIC 1.86-3.85 años). Conclusión: La etapa final de la miocardiopatía inducida por antraciclinas puede ocurrir muchos años después del tratamiento con quimioterapia, por lo que es extremadamente importante un seguimiento cardiológico estricto. El trasplante cardiaco es una opción en este grupo de pacientes luego de una exhaustiva evaluación multidisciplinaria, con el fin de minimizar el riesgo de recaída oncológica.

Sustained participation in a Payments for Ecosystem Services program reduces deforestation in a Mexican agricultural frontier.

Payments for Ecosystem Services (PES) provide conditional incentives for forest conservation. PES short-term effects on deforestation are well-documented, but we know less about program effectiveness when participation is sustained over time. Here, we assess the impact of consecutive renewals of PES contracts on deforestation and forest degradation in three municipalities of the Selva Lacandona (Chiapas, Mexico). PES reduced deforestation both after a single 5-year contract and after two consecutive contracts, but the impacts are only detectable in higher deforestation-risk parcels. Enrollment duration increases PES impact in these parcels, which suggests a positive cumulative effect over time. These findings suggest that improved spatial targeting and longer-term enrollment are key enabling factors to improve forest conservation outcomes in agricultural frontiers.

Heart transplantation in patients with anthracycline-induced cardiomyopathy.

OBJECTIVE: The objective of this study was to describe the clinical and imaging characteristics and the evolution of heart transplantation patients due to anthracycline-induced cardiomyopathy. METHODS: Patients with a diagnosis of ACM who received a heart transplantation in our institution in the period of November 2009-April 2021 were included. Clinical characteristics, pre-transplant studies, and clinical outcomes after transplantation were collected retrospectively from the electronic medical record. RESULTS: A total of 11 patients were included in the study. The median age at the time of cancer diagnosis was 15 years (IQR 10-37 years), while the median age at the time of heart transplant was 56 years (IQR 39-62 years). Regarding post-transplant outcomes, three patients died in the post-operative period. One died 4 years after the intervention due to chronic rejection, while the other seven had a favorable evolution. No oncological relapse was observed with a median follow-up of 2.5 years (IQR 1.86-3.85 years). CONCLUSION: End-stage anthracycline-induced cardiomyopathy can occur many years after chemotherapy treatment, so close cardiovascular follow-up is extremely important. Heart transplantation is a treatment option after an exhaustive multidisciplinary evaluation, to minimize the risk of oncological relapse.

OBJETIVO: Describir las características clínicas, imagenológicas y la evolución de los pacientes trasplantados cardiacos por cardiotoxicidad inducida por antraciclinas. MÉTODOS: Serie de casos descriptiva de pacientes consecutivos trasplantados cardiacos debido a cardiotoxicidad mediada por antraciclinas en el periodo de Noviembre de 2009 a Abril de 2021.Las características clínicas, los estudios complementarios pretrasplante y la información sobre la evolución posterior al trasplante fue recolectada de la historia clínica electrónica de forma retrospectiva. RESULTADOS: Se incluyeron un total de 11 pacientes. La mediana de edad al diagnóstico de la patología oncológica fue de 15 años (RIC 10-37 años), mientras que la mediana de edad en la que recibieron el trasplante cardiaco fue de 56 años (RIC 39-62 años). Con respecto a la evolución posterior al trasplante, 3 pacientes murieron en el periodo del post operatorio inmediato. 1 paciente falleció a los 4 años del trasplante y los otros 7 pacientes tuvieron una evolución favorable. No se observó recaída oncológica en ningún paciente durante una mediana de seguimiento o de 2,5 años (RIC 1.86-3.85 años). CONCLUSIÓN: La etapa final de la miocardiopatía inducida por antraciclinas puede ocurrir muchos años después del tratamiento con quimioterapia, por lo que es extremadamente importante un seguimiento cardiológico estricto. El trasplante cardiaco es una opción en este grupo de pacientes luego de una exhaustiva evaluación multidisciplinaria, con el fin de minimizar el riesgo de recaída oncológica.

Imaging analysis reveals budding of filamentous human metapneumovirus virions and direct transfer of inclusion bodies through intercellular extensions.

IMPORTANCE: Human metapneumovirus is an important respiratory pathogen that causes significant morbidity and mortality, particularly in the very young, the elderly, and the immunosuppressed. However, the molecular details of how this virus spreads to new target cells are unclear. This work provides important new information on the formation of filamentous structures that are consistent with virus particles and adds critical new insight into the structure of extensions between cells that form during infection. In addition, it demonstrates for the first time the movement of viral replication centers through these intercellular extensions, representing a new mode of direct cell-to-cell spread that may be applicable to other viral systems.

Local adaptation to hummingbirds and bees in Salvia stachydifolia: insights into pollinator shifts in a Southern Andean sage.

BACKGROUND AND AIMS: Differences among populations in pollinator assemblages can lead to local adaptation mosaics in which plants evolve different floral morphologies and attractive traits. Mountain habitats may promote local adaptation because of differences in environmental conditions with altitude, causing changes in pollinators, and because mountaintops can act as isolated habitats. We studied if the differences in floral shape, size and nectar traits in Salvia stachydifolia can be attributed to variations in the relative contribution of hummingbirds and insects. METHODS: We studied eight populations of S. stachydifolia in natural and under common garden conditions, to assess whether population differences have a genetic component. We recorded pollinators, their behaviour and visitation rates, and characterized pollinator assemblages. In addition, we measured nectar volume and concentration, and collected flowers to describe floral shape and size variation using geometric morphometric methods. We then applied an unsupervised learning algorithm to identify ecotypes based on morphometric traits. Finally, we explored whether populations with different pollinator assemblages had different climatic and/or elevation preferences. KEY RESULTS: We found that variation in the identity of the main pollinators was associated with differences among populations in all traits, as expected under a local adaptation scenario. These differences persisted in the common garden, suggesting that they were not due to phenotypic plasticity. We found S. stachydifolia populations were pollinated either by bees, by hummingbirds or had mixed pollination. We identified two ecotypes that correspond to the identity of the main pollinator guilds, irrespective of climate or altitude. CONCLUSIONS: Variation in S. stachydifolia floral traits did not follow any evident association with bioclimatic factors, suggesting that populations may have diverged as the product of historical isolation on mountaintops. We suggest that differences among populations point to incipient speciation and an ongoing pollinator shift.

Mitochondrial Base Editing: Recent Advances towards Therapeutic Opportunities.

Mitochondria are critical organelles that form networks within our cells, generate energy dynamically, contribute to diverse cell and organ function, and produce a variety of critical signaling molecules, such as cortisol. This intracellular microbiome can differ between cells, tissues, and organs. Mitochondria can change with disease, age, and in response to the environment. Single nucleotide variants in the circular genomes of human mitochondrial DNA are associated with many different life-threatening diseases. Mitochondrial DNA base editing tools have established novel disease models and represent a new possibility toward personalized gene therapies for the treatment of mtDNA-based disorders.

Predictors of inappropriate antimicrobial prescription: Eight-year point prevalence surveys experience in a third level hospital in Spain.

Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. We aimed to describe the Point Prevalence Surveys (PPS) methodology implemented in our hospital as an efficient tool to guide ASP strategies. Annually repeated PPS were conducted from 2012 to 2019 at a 750-bed university hospital in South Spain. Key quality indicators and inappropriateness of antimicrobial treatment, defined strictly according to local guidelines, were described. Variables associated with inappropriate treatment were identified by bi/multivariable analysis. A total of 1,600 patients were included. We found that 49% of the prescriptions were inappropriate due to unnecessary treatment (14%), not first line drug recommended (14%), inadequate drug according to microbiological results (9%), unsuitable doses (8%), route (3%) or duration (7%). Samples collection presented a significant protective effect together with sepsis presentation at onset and intensive care unit admission. However, age, receiving an empirical treatment and an unknown or urinary source of the infections treated were independent risk factors for inappropriateness. Site and severity of infection were documented in medical charts by prescribers (75 and 61% respectively). PPS may allow identifying the main risk factors for inappropriateness. This simple methodology may be useful for ASP to select modifiable factors to be prioritized for targeted interventions.

Registro Nacional Argentino de Resonancia Cardíaca (RENAREC) / Argentine National Cardiac Magnetic Resonance Imaging Registry (RENAREC)

RESUMEN Introducción: La utilidad de la resonancia magnética cardíaca (RMC) ha crecido ampliamente en los últimos años, en los cuales se han publicado distintos registros internacionales sobre su uso e impacto clínico. Sin embargo, no contamos con este tipo de información en Argentina. Objetivo: Evaluar indicaciones, protocolos utilizados, seguridad y consecuencias terapéuticas de la RMC en la República Argentina. Material y métodos: Se diseñó un registro prospectivo a nivel nacional con recolección de datos demográficos, indicaciones de RMC, complicaciones asociadas, diagnósticos y consecuencias terapéuticas. Resultados: Participaron 34 centros de 10 provincias de Argentina (85% centros privados, 59% centros con internación). Se incluyeron 1131 pacientes (edad 54 ± 18 años, 61% varones). Las principales indicaciones para el estudio de RMC fueron la miocardiopatía hipertrófica (13,9%) y la arritmia ventricular (12,3%). El 99,7% de los estudios fueron reportados sin complicaciones. Los resultados más frecuentes de la RMC fueron: normal (31,2%), miocardiopatía no isquémica (14,7%), miocardiopatía isquémico-necrótica (11,6%) y miocardiopatía hipertrófica (8,9%). La sospecha clínica fue confirmada en el 23,6% de los casos y la RMC generó un diagnóstico nuevo no sospechado en el 48,7% de los casos. Las consecuencias terapéuticas más frecuentes fueron el alta hospitalaria (31,6%) seguida por el cambio en la medicación (28,1%). Conclusiones: La RMC es un estudio ampliamente utilizado en Argentina, principalmente en centros privados, con un número muy bajo de complicaciones. Las principales indicaciones son las miocardiopatías (hipertrófica y dilatada) y la arritmia ventricular, y provee un diagnóstico nuevo no sospechado en casi la mitad de los casos. Se requieren de otros estudios en el futuro para evaluar las implicancias clínicas y terapéuticas.

ABSTRACT Background: The usefulness of cardiac magnetic resonance imaging (MRI) has greatly increased in the last years. Different international registries have been published on its use; however, there is no data available from Argentina. Objective: The aim of this study was to evaluate different indications, protocols, safety and therapeutic consequences of cardiac MRI in Argentina. Methods: A prospective national registry was designed with collection of demographic data, indications for cardiac MRI, associated complications, diagnoses and therapeutic consequences. Results: A total of 34 centers from 10 provinces of Argentina (85% private and 59% with inpatient capacity) participated in the study, including 1131 patients (mean age 54±18 years and 61% males). The main indications for cardiac MRI were hypertrophic cardiomyopathy (13.9%), and ventricular arrhythmia (12.3%). In 99.7% of cases, no study complications were reported. The most frequent results of cardiac MRI were: normal (31.2%), non-ischemic cardiomyopathy (14.7%), ischemic-necrotic cardiomyopathy (11.6%) and hypertrophic cardiomyopathy (8.9%). Clinical suspicion was confirmed in 23.6% of cases and cardiac MRI generated an unsuspected new diagnosis in 48.7% of cases. The main therapeutic consequences were hospital discharge (31.6%) followed by change in medication (28.1%). Conclusions: Cardiac MRI is widely used in Argentina, mainly in private centers with a very low incidence of complications. Cardiomyopathies (hypertrophic and dilated) and ventricular arrhythmia are its main indication, and it provides a new unsuspected diagnosis in almost half of the cases. Further studies are required to assess its clinical and therapeutic impact.

An optimized FusX assembly-based technique to introduce mitochondrial TC-to-TT variations in human cell lines.

The FusX TALE Based Editor (FusXTBE) is a programmable base editing platform that can introduce specific TC-to-TT variations in the mitochondrial DNA (mtDNA). Here, we provide a protocol describing the synthesis and testing of the FusXTBE plasmids in cultured human cell lines. This tool is designed to be easily modified to work in diverse applications where editing of mitochondrial DNA is desired. For complete details on the use and execution of this protocol, please refer to Sabharwal et al. (2021) and Ma et al. (2016).

Anthropogenic microfibers are highly abundant at the Burdwood Bank seamount, a protected sub-Antarctic environment in the Southwestern Atlantic Ocean.

Microplastics debris in the marine environment have been widely studied across the globe. Within these particles, the most abundant and prevalent type in the oceans are anthropogenic microfibers (MFs), although they have been historically overlooked mostly due to methodological constraints. MFs are currently considered omnipresent in natural environments, however, contrary to the Northern Hemisphere, data on their abundance and distribution in Southern Oceans ecosystems are still scarce, in particular for sub-Antarctic regions. Using Niskin bottles we've explored microfibers abundance and distribution in the water column (3-2450 m depth) at the Burdwood Bank (BB), a seamount located at the southern extreme of the Patagonian shelf, in the Southwestern Atlantic Ocean. The MFs detected from filtered water samples were photographed and measured using ImageJ software, to estimate length, width, and the projected surface area of each particle. Our results indicate that small pieces of fibers are widespread in the water column at the BB (mean of 17.4 ± 12.6 MFs.L-1), from which, 10.6 ± 5.3 MFs.L-1 were at the surface (3-10 m depth), 20 ± 9 MFs.L-1 in intermediate waters (41-97 m), 24.6 ± 17.3 MFs.L-1 in deeper waters (102-164 m), and 9.2 ± 5.3 MFs.L-1 within the slope break of the seamount. Approximately 76.1% of the MFs were composed of Polyethylene terephthalate, and the abundance was dominated by the size fraction from 0.1 to 0.3 mm of length. Given the high relative abundance of small and aged MFs, and the oceanographic complexity of the study area, we postulate that MFs are most likely transported to the BB via the Antarctic Circumpolar Current. Our findings imply that this sub-Antarctic protected ecosystem is highly exposed to microplastic pollution, and this threat could be spreading towards the highly productive waters, north of the study area.

Mediciones de imágenes fotográficas del pie como una metodología no invasiva y válida en la exploración clínica / Measurements of the Foot Photo Images as a Non-Invasive and Valid Methodology in Clinical Examination

Introducción: La evaluación anatómica músculo esquelética por imagen en la exploración clínica del pie diabético es la fotografía digital que evalúa la morfología superficial. Objetivos: Validar la obtención de las imágenes fotográficas del pie, calcular las mediciones longitudinales, angulares y el índice del arco plantar, de las imágenes fotográficas del pie por fotogrametría, y basados en estas, categorizar la normalidad de la forma en sujetos sanos. Métodos: Estudio exploratorio en 30 individuos sanos evaluados en la Unidad clínica de pie diabético en la ciudad de Trujillo, mediante un prototipo de cámaras alrededor de un podoscopio y un software de análisis de imágenes. La imagen fotográfica fue evaluada por mediciones longitudinales, angulares y el índice del arco plantar. Resultados: Los pacientes evaluados tenían una edad media de 25,06+/-11,95 años, y predominaron las mujeres. La longitud total del pie y anchura del metatarso en el lado derecho fue de 226,55 ± 36,49 mm y 98,99 ± 22,71 mm respectivamente; y en el lado izquierdo fue de 229,81 ± 42,25 mm y 104,49 ± 16,84 mm respectivamente. El ángulo intermetatarsal del 1-2 rayo, ángulo intermetatarsal del 4-5 rayo y ángulo del retropié para el lado derecho fueron 14 ± 4º, 11 ± 3º y 2 ± 2º respectivamente; para el lado izquierdo 14 ± 3º, 9 ± 3º y 2 ± 2º respectivamente, y el índice plantar del arco derecho e izquierdo fueron 0,23 ± 0,2 y 0,22 ± 0,1 respectivamente. La variabilidad solo se presentó en el antepie en el 20 percent de los casos. Conclusiones: La obtención de las imágenes fotográficas del pie fueron válidas, las mediciones fueron menores o similares a otros estudios. La variabilidad de la normalidad solo se presentó en el antepie(AU)

Introduction: The musculoskeletal anatomical evaluation by imaging in the clinical examination of the diabetic foot is digital photography that assesses the superficial morphology. Objectives: To validate the obtaining of photographic images of the foot, to calculate the longitudinal and angular measurements and the index of the plantar arch, from the photographic images of the foot by photogrammetry, and to categorize the normality of the shape in healthy subjects, based on these photographic images. Methods: This an exploratory study in 30 healthy individuals evaluated at the Diabetic Foot Clinical Unit in Trujillo city, using a prototype of cameras around a podoscope and image analysis software. The photographic image was evaluated by longitudinal and angular measurements and the plantar arch index. Results: The patients evaluated had a mean age of 25.06+/-11.95 years, and women predominated. Total foot length and metatarsal width on the right side were 226.55 ± 36.49 mm and 98.99 ± 22.71 mm, respectively; and on the left side it was 229.81 ± 42.25 mm and 104.49 ± 16.84 mm, respectively. The 1st-2nd ray intermetatarsal angle, 4th-5th ray intermetatarsal angle and hindfoot angle for the right side were 14 ± 4º, 11 ± 3º and 2 ± 2º respectively; for the left side 14 ± 3º, 9 ± 3º and 2 ± 2º respectively, and the plantar index of the right and left arch were 0.23 ± 0.2 and 0.22 ± 0.1 respectively. Variability only occurred in the forefoot in 20 percent of cases. Conclusions: Obtaining of the photographic images of the foot was valid, measurements were smaller or similar to other studies. The variability of normality only appeared in the forefoot(AU)

Approach for designing thick cemented doublet lenses based on the caustic surface.

A new, to the best of our knowledge, method for designing a thick-lens achromatic doublet based on the concept of a caustic surface to correct both third- and fifth-order spherical aberration is presented. We consider two different wavelengths brought into coincidence at the back focal length instead of the effective focal length as it is usually done, to calculate the radii of curvature assuming predefined values for axial thicknesses and their indices of refraction for both lenses. Alternatively, we apply Taylor's series around the optical axis, and to vanish the approximate caustic surface, we obtain the values for the conic constants, which reduce at third- and fifth-order spherical aberration. Two designs for cemented doublets are provided assuming that the lenses are cemented. Finally, we propose a method to qualitatively test doublet lenses by using null screens, considering to place the detection plane at arbitrary positions.

Compatibility of prolonged infusion antibiotics during Y-site administration.

BACKGROUND: Antimicrobial resistance is a threat to global public health. The use of prolonged infusions in the hospital setting for certain antimicrobials is widely increasing in order to improve their efficacy and safety, including resistance development. Due to limited vascular access, it is important to clarify whether they can be infused through the same line with other drugs during Y-site administration. AIM: The aim of this review is to update and summarize the evidence on Y-site compatibility of antibacterial agents administered as prolonged infusions in intensive care units (ICUs). STUDY DESIGN: A literature review of PubMed, EMBASE and Trissel's Handbook on Injectable Drugs databases was conducted on the compatibility of selected antimicrobials administered simultaneously at a Y-site connection with parenteral nutrition and other widely used drugs in ICUs. All articles published up to October 30, 2021, in English or Spanish were included, regardless of the type of publication (original articles, case reports, letters, etc.). Eligible antimicrobials were those that can be administered as prolonged infusions: ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ceftolozane/tazobactam, ceftaroline, cloxacillin, ceftobiprole, vancomycin and fosfomycin. RESULTS: A total of 1302 drug-to-drug potential combinations were explored, 196 (15.05%) were found to be incompatible, and in 541 (41.55%), data were not available. The results were presented in a simple 2-dimensional consultation chart as a quick reference for health care professionals. CONCLUSIONS: This review provides useful and reliable information on the compatibility of antimicrobials administered as Y-site infusion with other drugs commonly used in the critical setting. This review contributes to patient safety in nursing practice. RELEVANCE TO CLINICAL PRACTICE: To our knowledge, this is the first review on Y-site compatibility of antimicrobials used as prolonged infusions with other commonly used drugs, including anti-emetics, analgesics and anti-epileptic and parenteral nutrition. The results of the current review need to be addressed to promote the knowledge sharing between health professionals and improve the quality and safety of patients. We believe that this review may serve as a simple and effective 2-dimensional updated drug-to-drug compatibility reference chart for critical care nurses.

Chimeric RNA: DNA TracrRNA Improves Homology-Directed Repair In Vitro and In Vivo.

Nearly 90% of human pathogenic mutations are caused by small genetic variations, and methods to correct these errors efficiently are critically important. One way to make small DNA changes is providing a single-stranded oligo deoxynucleotide (ssODN) containing an alteration coupled with a targeted double-strand break (DSB) at the target locus in the genome. Coupling an ssODN donor with a CRISPR-Cas9-mediated DSB is one of the most streamlined approaches to introduce small changes. However, in many systems, this approach is inefficient and introduces imprecise repair at the genetic junctions. We herein report a technology that uses spatiotemporal localization of an ssODN with CRISPR-Cas9 to improve gene alteration. We show that by fusing an ssODN template to the trans-activating RNA (tracrRNA), we recover precise genetic alterations, with increased integration and precision in vitro and in vivo. Finally, we show that this technology can be used to enhance gene conversion with other gene editing tools such as transcription activator like effector nucleases.