A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration.

Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches - like most structured RNAs - are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single-molecule and bulk approaches, we discover how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the representative Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.

A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration.

Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches - like most structured RNAs - are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single molecule and bulk approaches, we discovered how a single Mn 2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the paradigmatic Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.

Negation recognition in clinical natural language processing using a combination of the NegEx algorithm and a convolutional neural network.

BACKGROUND: Important clinical information of patients is present in unstructured free-text fields of Electronic Health Records (EHRs). While this information can be extracted using clinical Natural Language Processing (cNLP), the recognition of negation modifiers represents an important challenge. A wide range of cNLP applications have been developed to detect the negation of medical entities in clinical free-text, however, effective solutions for languages other than English are scarce. This study aimed at developing a solution for negation recognition in Spanish EHRs based on a combination of a customized rule-based NegEx layer and a convolutional neural network (CNN). METHODS: Based on our previous experience in real world evidence (RWE) studies using information embedded in EHRs, negation recognition was simplified into a binary problem ('affirmative' vs. 'non-affirmative' class). For the NegEx layer, negation rules were obtained from a publicly available Spanish corpus and enriched with custom ones, whereby the CNN binary classifier was trained on EHRs annotated for clinical named entities (cNEs) and negation markers by medical doctors. RESULTS: The proposed negation recognition pipeline obtained precision, recall, and F1-score of 0.93, 0.94, and 0.94 for the 'affirmative' class, and 0.86, 0.84, and 0.85 for the 'non-affirmative' class, respectively. To validate the generalization capabilities of our methodology, we applied the negation recognition pipeline on EHRs (6,710 cNEs) from a different data source distribution than the training corpus and obtained consistent performance metrics for the 'affirmative' and 'non-affirmative' class (0.95, 0.97, and 0.96; and 0.90, 0.83, and 0.86 for precision, recall, and F1-score, respectively). Lastly, we evaluated the pipeline against two publicly available Spanish negation corpora, the IULA and NUBes, obtaining state-of-the-art metrics (1.00, 0.99, and 0.99; and 1.00, 0.93, and 0.96 for precision, recall, and F1-score, respectively). CONCLUSION: Negation recognition is a source of low precision in the retrieval of cNEs from EHRs' free-text. Combining a customized rule-based NegEx layer with a CNN binary classifier outperformed many other current approaches. RWE studies highly benefit from the correct recognition of negation as it reduces false positive detections of cNE which otherwise would undoubtedly reduce the credibility of cNLP systems.

Single-shot, high-repetition rate carrier-envelope-phase detection of ultrashort laser pulses.

We propose a single-shot, high-repetition rate measurement scheme of the carrier-envelope phase offset of ultrashort laser pulses. The spectral fringes resulting from f-2f nonlinear interferometry, encoding the carrier-envelope-phase, are evaluated completely optically via an optical Fourier transform. For demonstration, the carrier-envelope-phase of a 200 kHz, few-cycle optical parametric chirped-pulse amplification (OPCPA) laser system was measured employing an interferometer as a periodic optical filter. The proposed method shows excellent agreement with simultaneous measurement of the spectral fringes by a fast line-scan camera.

Riboswitches as therapeutic targets: promise of a new era of antibiotics.

INTRODUCTION: The growth of antibiotic resistance among bacterial pathogens is an impending global threat that can only be averted through the development of novel antibacterial drugs. A promising answer could be the targeting of riboswitches, structured RNA elements found almost exclusively in bacteria. AREAS COVERED: This review examines the potential of riboswitches as novel antibacterial drug targets. The limited mechanisms of action of currently available antibiotics are summarized, followed by a delineation of the functional mechanisms of riboswitches. We then discuss the potential for developing novel approaches that target paradigmatic riboswitches in the context of their bacterial gene expression machinery. EXPERT OPINION: We highlight potential advantages of targeting riboswitches in their functional form, embedded within gene expression complexes critical for bacterial survival. We emphasize the benefits of this approach, including potentially higher species specificity and lower side effects.

Evolución y características de los ingresos por COVID-19 pediátricos en un hospital terciario

Introducción. La mayoría de infecciones por SARS-CoV2 en población pediátrica cursan asintomáticas o con síntomas leves, con porcentaje mínimo de casos graves descritos como síndrome inflamatorio multisistémico asociado al SARS-CoV2 (SIM-PEDs). El objetivo fue describir las características clínico-epidemiológicas de aquellos pacientes pediátricos ingresados con diagnóstico confirmado de SARS-CoV2, y las posibles diferencias de la enfermedad considerando dos períodos epidemiológicos. Material y métodos. Estudio retrospectivo observacional de pacientes pediátricos ingresados con diagnóstico de COVID-19, de un hospital terciario. Se recogieron de forma consecutiva, entre marzo de 2020 hasta febrero 2022, analizando datos demográficos, clínicos, pruebas complementarias, tratamiento administrado y evolución. Resultados. Se incluyeron 69 pacientes, clasificándose en 6 grupos según diagnóstico. Los pacientes con neumonía asociaban mayor hipoxemia, mayor edad y eran predominantemente varones (p<0.01), con respecto al grupo de infecciones respiratorias sin condensación. SIM-PEDs fueron pacientes más graves, con afectación analítica marcada y mayor ingreso en UCIP. Durante el 2º periodo se observa una tendencia a la disminución de la infección respiratoria (69% al 47%), menor estancia hospitalaria (de 4 a 3 días), y aumento de los ingresos por otra patología (7,7% al 30,6%). Conclusiones. Los cuadros clínicos de COVID-19 más frecuentes en niños son respiratorios leves-moderados con buena evolución. Hay una tendencia a menor duración de estancia hospitalaria y aumento de ingresos por otra patología en pacientes asintomáticos en el segundo periodo. SIM-PEDs es otra forma de expresión de infección por SARS-COV2 de mayor gravedad, pero habitualmente con buen pronóstico tras diagnóstico precoz y requiriendo frecuentemente ingreso en UCIP. (provisto por Infomedic International)

Introduction. Most SARS-CoV2 infections in pediatric population are asymptomatic or have mild symptoms, with a small percentage of severe cases described as SARS-CoV2-associated multisystem inflammatory syndrome (MIS-C). The objective was to describe the clinical-epidemiological characteristics of those pediatric patients admitted with a SARS-CoV2 confirmed diagnosis, and the possible differences in the disease considering two epidemiological periods. Methods. Observational retrospective study of pediatric patients admitted with a diagnosis of COVID-19, from a tertiary hospital. They were collected consecutively, between March 2020 and February 2022, analyzing demographic and clinical data, complementary tests, administered treatment and evolution. Results. 69 patients were included, classified into 6 groups according to diagnosis. Patients with pneumonia associated greater hypoxemia, older age and were predominantly male (p<0.01), with respect to the group of respiratory infections without condensation. MIS-C were more severe patients, with marked analytic involvement and greater admission to the PICU. During the 2nd period, there was a trend towards a decrease in respiratory infection (69% to 47%), a shorter hospital stays (4 to 3 days), and an increase in admissions for another pathology (7.7% to 30,6%). Discussion. The most frequent clinical manifestations of COVID-19 in children are mild-moderate respiratory symptoms with a good prognosis. There is a trend towards a shorter length of hospital stay and an increase in admissions for another pathology in asymptomatic patients in the second period. MIS-C is another form of expression of SARS-COV2 infection of greater severity, but usually with a good prognosis after early diagnosis and frequently requiring PICU admission. (provided by Infomedic International)

Integrative and Collaborative Approach in the Chronic Management of Obesity in Primary and Tertiary Care Setting: Vall Hebron-SAP Muntanya Healthcare Route.

INTRODUCTION: In the context of obesity pandemic, the health care providers involved in the primary care should have a significant role. Several guidelines for the management of obesity in primary care were proposed recently. In general lines, these guidelines include recommendation on the baseline assessment, therapy, and algorithm for referral to specialized obesity clinic and follow-up. Nevertheless, at present, there is no guideline or protocol that continuously and bidirectionally links the two settings: primary care and specialized obesity clinic. METHODS: We present a model of continuous, bilateral, and integrative interaction between primary care units and reference tertiary care setting in the chronic management of obesity that is already implemented in a public health system. RESULTS: The novelty of our algorithm is that incorporates the support and continuous communication with the specialized obesity clinic of the tertiary care setting from the beginning in the management of a patient with obesity, in a bidirectional manner. CONCLUSION: This kind of bidirectional and continuous collaboration will help engage health care providers in the management of obesity, optimize efforts, shorten the time until proper intervention, personalize the approach and, finally, save costs for the health system.

How can artificial intelligence optimize value-based contracting?

Efforts in the pharmaceutical market have been aimed at ensuring that the benefits obtained from the introduction of new therapies justify the associated costs. In recent years, drug payment models in healthcare have undergone a dramatic shift from focusing on volume (i.e., size of the target clinical population) to focusing on value (i.e., drug performance in real-world settings). In this context, value-based contracts (VBCs) were designed to align the payment of a drug to its clinical performance outside clinical trials by evaluating the effectiveness using real-word evidence (RWE). Despite their widespread implementation, different factors jeopardize the application of VBCs to most marketed drugs in a near future, including the need for easily measurable and relevant outcomes associated with clinical improvements, and access to a large patient population to assess said outcomes. Here, we argue that the extraction and analysis of massive amounts of RWE captured in patients' electronic health records (EHRs) will circumvent these issues and optimize negotiations in VBCs. Particularly, the use of Natural Language Processing (NLP) has proven successful in the analysis of structured and unstructured clinical information in EHRs in multicenter research studies. Thus, the application of NLP to analyze patient-centered information in EHRs in the context of innovative contracting can be utterly beneficial as it enables the real-time evaluation of treatment response and financial impact in real-world settings.

Few-cycle all-fiber supercontinuum laser for ultrabroadband multimodal nonlinear microscopy.

Temporally coherent supercontinuum sources constitute an attractive alternative to bulk crystal-based sources of few-cycle light pulses. We present a monolithic fiber-optic configuration for generating transform-limited temporally coherent supercontinuum pulses with central wavelength at 1.06 µm and duration as short as 13.0 fs (3.7 optical cycles). The supercontinuum is generated by the action of self-phase modulation and optical wave breaking when pumping an all-normal dispersion photonic crystal fiber with pulses of hundreds of fs duration produced by all-fiber chirped pulsed amplification. Avoidance of free-space propagation between stages confers unequalled robustness, efficiency and cost-effectiveness to this novel configuration. Collectively, the features of all-fiber few-cycle pulsed sources make them powerful tools for applications benefitting from the ultrabroadband spectra and ultrashort pulse durations. Here we exploit these features and the deep penetration of light in biological tissues at the spectral region of 1 µm, to demonstrate their successful performance in ultrabroadband multispectral and multimodal nonlinear microscopy.

Bacillary Layer Detachment in an Atypical Case of Central Serous Chorioretinopathy Associated with High Hyperopia.

A 16-year-old boy with elevated hyperopia presented to the office with a 24-h history of bilateral blurred vision, mainly of the left eye, and bilateral central serous chorioretinopathy. He showed a clinically recognizable bacillary layer detachment in one eye and excellent multimodal diagnostic image correlation, with the best-corrected visual acuity as 20/400. He had bilateral serous retinal detachment, as confirmed by optical coherence tomography. Laser photocoagulation was performed with good results, and reestablishment of the foveal anatomical structure was documented 16 days after treatment.

Factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según encuesta demográfica en Perú / Associated factors within the use of contraceptive methods in women of childbearing age between 15 to 49 years old according to a demographic survey in Peru

Introducción: Los métodos anticonceptivos son importantes herramientas para lograr una planificación familiar deseada. Objetivo: Determinar los factores asociados al uso de métodos anticonceptivos en mujeres en edad fértil de 15 a 49 años según ENDES 2018. Material y métodos: Estudio descriptivo, observacional, analítico y retrospectivo. Se analizó la muestra de la Encuesta Nacional Demográfica de Salud Familiar (ENDES), del año 2018 a mujeres peruanas entre 15 a 49 años que respondieron el módulo de métodos anticonceptivos. Resultados: Mayor prevalencia de usuarias de métodos anticonceptivos en el área urbana (RP=1,046, IC:1,037 ­ 1,054), según estado conyugal se evidencia un mayor uso en casadas o convivientes (RP=1,080 IC:1,071 ­ 1,090), en el nivel educativo se obtiene que mujeres con estudios superiores tiene mayor prevalencia de uso de anticonceptivos (RP= 1,021, IC:1,016 ­ 1,026) y, finalmente, la edad en la 1ª relación sexual menor a los 17 años tiene mayor prevalencia (RP = 1,017 IC:1,016 ­ 1,026). Conclusión: Existe asociación positiva entre residir en área urbana, edad de primera relación sexual menor a 17 años, ser casada o conviviente y tener grado de instrucción superior y el uso de métodos anticonceptivos.

Background: Contraceptive methods are an important tool to achieve the desired family planning.To determine the factors associated Objective:within the use of contraceptive methods in women of childbearing age between 15 to 49 years old according to the ENDES 2018. Material and methods: Descriptive, observational, analytical and retrospective study. The sample, of the National Demographic Survey of Family Health (ENDES) 2018, to Peruvian women between 15 to 49 years old who responded to the contraceptive methods module was analyzed. Results: There is a higher prevalence of women using contraceptive methods in the urban area (PR = 1,046, CI: 1,037 - 1,054), according the marital status there is a high use in married women of contraceptive use (PR = 1,080 CI: 1,071 - 1,090), in the educational level it's obtained that women with higher education have a higher prevalence of contraceptive use (PR = 1,021, CI: 1,016 - 1,026) and, finally, that the age in the first sex relationship before 17 years has a higher prevalence (PR = 1,017 CI: 1,016 - 1,026). Conclusion: There is a positive association between living in an urban area, age of first sexual intercourse less than 17 years, being married and having high educational level in the use of contraceptive methods.

Características clínicas de los niños hospitalizados por COVID-19 / Clinical characteristics of children hospitalized for COVID-19

Introducción:La mayoría de las infecciones por SARS-CoV-2 en población pediátrica cursan asintomáticas o con síntomas leves, con porcentaje mínimo de casos graves descritos como síndrome inflamatorio multisistémico asociado al SARS-CoV-2 (SIM-PEDs).El objetivo fue describir las características clínico-epidemiológicas de aquellos pacientes pediátricos ingresados, con diagnóstico confirmado de SARS-CoV-2 desde el inicio de la pandemia hasta mayo de 2021.Métodos:Estudio retrospectivo observacional de pacientes pediátricos ingresados con diagnóstico de COVID-19, de un hospital terciario. Se recogieron datos demográficos, clínicos, pruebas complementarias, tratamiento administrado y evolución.Resultados:Se incluyeron 30 pacientes, clasificándose en 3 grupos según diagnóstico: infección respiratoria, SIM-PEDs y síntomas compatibles. Los pacientes con neumonía asociaban mayor edad, comorbilidades y linfopenia. SIM-PEDs fueron pacientes más graves, con afectación analítica marcada y mayor ingreso en UCIP. La mayoría eran casos secundarios de contacto en el entorno familiar.Discusión:Los cuadros clínicos de COVID-19 más frecuentes en niños son respiratorios leves-moderados con buena evolución. SIM-PEDs es otra forma de expresión de infección por SARS-CoV-2 de mayor gravedad, pero habitualmente con buen pronóstico tras diagnóstico precoz y requiriendo frecuentemente ingreso en UCIP. (AU)

Introduction:Most SARS-CoV-2 infections in the pediatric population are asymptomatic or with mild symptoms, with a minimal proportion of severe cases described as SARS-CoV-2-associated multi-system inflammatory syndrome (MIS-C).The objective was to describe the clinical and epidemiological characteristics of pediatric patients admitted with confirmed diagnosis of SARS-CoV-2 infection from the beginning of the pandemic until May 2021.Methods:Retrospective observational study of pediatric patients hospitalized with confirmed COVID-19, in a tertiary hospital. Epidemiological and clinical data, additional tests, treatments administered and evolution were collected.Results:30 patients were included, classified into 3 groups according to diagnosis: respiratory infection, MIS-C and compatible symptoms. The patients with pneumonia were associated with age older, comorbidities and lymphopenia. MIS-C were more serious patients, with marked laboratory involvement and greater admission to PICU. Most of these were secondary cases of contact in the family environment.Discussion:The most frequent clinical manifestations of COVID-19 in children are mild−moderate respiratory with good evolution. MIS-C is another form of expression of SARS-CoV-2 infection of greater severity, but usually with good prognosis after early diagnosis and frequent PICU admission. (AU)

Clinical characteristics of children hospitalized for COVID-19.

Introduction: Most SARS-CoV2 infections in the pediatric population are asymptomatic or with mild symptoms, with a minimal proportion of severe cases described as SARS-CoV2-associated multi-system inflammatory syndrome (MIS-C).The objective was to describe the clinical and epidemiological characteristics of pediatric patients admitted with confirmed diagnosis of SARS-CoV2 infection from the beginning of the pandemic until May 2021. Methods: Retrospective observational study of pediatric patients hospitalized with confirmed COVID-19, in a tertiary hospital. Epidemiological and clinical data, additional tests, treatments administered and evolution were collected. Results: 30 patients were included, classified into 3 groups according to diagnosis: respiratory infection, MIS-C and compatible symptoms. The patients with pneumonia were associated with age older, comorbidities and lymphopenia. MIS-C were more serious patients, with marked laboratory involvement and greater admission to PICU. Most of these were secondary cases of contact in the family environment. Discussion: The most frequent clinical manifestations of COVID-19 in children are mild-moderate respiratory with good evolution. MIS-C is another form of expression of SARS-COV2 infection of greater severity, but usually with good prognosis after early diagnosis and frequent PICU admission.

Introducción: La mayoría de infecciones por SARS-CoV2 en población pediátrica cursan asintomáticas o con síntomas leves, con porcentaje mínimo de casos graves descritos como síndrome inflamatorio multisistémico asociado al SARS-CoV2 (SIM-PEDs).El objetivo fue describir las características clínico epidemiológicas de aquellos pacientes pediátricos ingresados, con diagnóstico confirmado de SARS-CoV2 desde el inicio de la pandemia hasta mayo 2021. Métodos: Estudio retrospectivo observacional de pacientes pediátricos ingresados con diagnóstico de COVID-19, de un hospital terciario. Se recogieron datos demográficos, clínicos, pruebas complementarias, tratamiento administrado y evolución. Resultados: Se incluyeron 30 pacientes, clasificándose en 3 grupos según diagnóstico: Infección respiratoria, SIM-PEDs y síntomas compatibles. Los pacientes con neumonía asociaban mayor edad, comorbilidades y linfopenia. SIM-PEDs fueron pacientes más graves, con afectación analítica marcada y mayor ingreso en UCIP. La mayoría eran casos secundarios de contacto en el entorno familiar. Discusión: Los cuadros clínicos de COVID-19 más frecuentes en niños son respiratorios leves-moderados con buena evolución. SIM-PEDs es otra forma de expresión de infección por SARS-COV2 de mayor gravedad, pero habitualmente con buen pronóstico tras diagnóstico precoz y requiriendo frecuentemente ingreso en UCIP.

Clinical characteristics of children hospitalized for COVID-19. / Características clínicas de los niños hospitalizados por COVID-19.

INTRODUCTION: Most SARS-CoV-2 infections in the pediatric population are asymptomatic or with mild symptoms, with a minimal proportion of severe cases described as SARS-CoV-2-associated multi-system inflammatory syndrome (MIS-C). The objective was to describe the clinical and epidemiological characteristics of pediatric patients admitted with confirmed diagnosis of SARS-CoV-2 infection from the beginning of the pandemic until May 2021. METHODS: Retrospective observational study of pediatric patients hospitalized with confirmed COVID-19, in a tertiary hospital. Epidemiological and clinical data, additional tests, treatments administered and evolution were collected. RESULTS: 30 patients were included, classified into 3 groups according to diagnosis: respiratory infection, MIS-C and compatible symptoms. The patients with pneumonia were associated with age older, comorbidities and lymphopenia. MIS-C were more serious patients, with marked laboratory involvement and greater admission to PICU. Most of these were secondary cases of contact in the family environment. DISCUSSION: The most frequent clinical manifestations of COVID-19 in children are mild-moderate respiratory with good evolution. MIS-C is another form of expression of SARS-CoV-2 infection of greater severity, but usually with good prognosis after early diagnosis and frequent PICU admission.

CHARACTERIZING COVID-19-RELATED RETINAL VASCULAR OCCLUSIONS: A Case Series and Review of the Literature.

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Bilaminar Graft of the Anterior Capsule and Internal Limiting Membrane: A Novel Surgical Technique for the Treatment of Macular Hole and Focal Macular Detachment Associated with High Myopia and Posterior Staphyloma.

This case report describes a novel surgical technique for the treatment of macular hole and focal macular detachment associated with high myopia and posterior staphyloma. A 65-year-old female presented with a stage 3C myopic traction maculopathy and VA of 20/600. OCT examination confirmed a macular hole of 958 µm diameter, posterior staphyloma, and macular detachment. We performed combined phacoemulsification surgery with 23G pars plana vitrectomy; the anterior capsule was preserved and divided into two equal circular laminar flaps. We proceeded with central and peripheral vitrectomy, brilliant blue staining, and partial ILM peeling; capsular sheets were introduced sequentially in the vitreous chamber, the first one was implanted below the hole and attached to pigment epithelium, the second lamina was inserted into the hole, and the remaining portion of ILM was implanted crosswise below the edges of the hole. Macular-hole closure and progressive reapplication of the macular detachment were obtained, with a final VA of 20/80. Treatment of macular holes and focal macular detachment in high myopic eyes is complex, even for experienced surgeons. We propose a new technique with additional mechanisms based on anterior lens capsule and internal limiting membrane tissue properties that showed functional and anatomical improvement and could be considered an alternative treatment.

Endothelial-Mesenchymal Transition in Heart Failure With a Preserved Ejection Fraction: Insights Into the Cardiorenal Syndrome.

BACKGROUND: The management of clinical heart failure with a preserved ejection fraction (HFpEF) is often complicated by concurrent renal dysfunction, known as the cardiorenal syndrome. This, combined with the notable lack of evidence-based therapies for HFpEF, highlights the importance of examining mechanisms and targetable pathways in HFpEF with the cardiorenal syndrome. METHODS: HFpEF was induced in mice by uninephrectomy, infusion of d-aldosterone (HFpEF; N=10) or saline (Sham; N=8), and given 1% NaCl drinking water for 4 weeks. Renal fibrosis and endothelial-mesenchymal transition (endo-MT) were evident once HFpEF developed. Human aortic endothelial cells were treated for 4 days with 10% serum obtained from patients with chronically stable HFpEF with the cardiorenal syndrome (N=12) and compared with serum-treated human aortic endothelial cells from control subjects (no cardiac/renal disease; N=12) to recapitulate the in vivo findings. RESULTS: Kidneys from HFpEF mice demonstrated hypertrophy, interstitial fibrosis (1.9-fold increase; P<0.05) with increased expression of endo-MT transcripts, including pdgfrß (platelet-derived growth factor receptor ß), snail, fibronectin, fsp1 (fibroblast-specific protein 1), and vimentin by 1.7- (P=0.004), 1.7- (P=0.05), 1.8- (P=0.005), 2.6- (P=0.001), and 2.0-fold (P=0.001) versus Sham. Immunostaining demonstrated co-localization of CD31 and ACTA2 (actin α2) in kidney sections suggesting evidence of endo-MT. Similar to the findings in HFpEF mice, comparable endo-MT markers were also significantly elevated in human aortic endothelial cells treated with serum from patients with HFpEF compared with human aortic endothelial cells treated with serum from control subjects. CONCLUSIONS: These translational findings demonstrate a plausible role for endo-MT in HFpEF with cardiorenal syndrome and may have therapeutic implications in drug development for patients with HFpEF and concomitant renal dysfunction.

α-Terpineol: An Aggregation Pheromone in Optatus palmaris (Coleoptera: Curculionidae) (Pascoe, 1889) Enhanced by Its Host-Plant Volatiles.

The Annonaceae fruits weevil (Optatus palmaris) causes high losses to the soursop production in Mexico. Damage occurs when larvae and adults feed on the fruits; however, there is limited research about control strategies against this pest. However, pheromones provide a high potential management scheme for this curculio. Thus, this research characterized the behavior and volatile production of O. palmaris in response to their feeding habits. Olfactometry assays established preference by weevils to volatiles produced by feeding males and soursop. The behavior observed suggests the presence of an aggregation pheromone and a kairomone. Subsequently, insect volatiles sampled by solid-phase microextraction and dynamic headspace detected a unique compound on feeding males increased especially when feeding. Feeding-starvation experiments showed an averaged fifteen-fold increase in the concentration of a monoterpenoid on males feeding on soursop, and a decrease of the release of this compound males stop feeding. GC-MS analysis of volatiles identified this compound as α-terpineol. Further olfactometry assays using α-terpineol and soursop, demonstrated that this combination is double attractive to Annonaceae weevils than only soursop volatiles. The results showed a complementation effect between α-terpineol and soursop volatiles. Thus, α-terpineol is the aggregation pheromone of O. palmaris, and its concentration is enhanced by host-plant volatiles.

Integrated health intervention on polypharmacy and inappropriate prescribing in elderly people with multimorbidity: Results at the end of the intervention and at 6 months after the intervention

Background and objective: To analyse the impact of an integrated health intervention focused on polypharmacy and inappropriate prescribing (IP) in elderly people with multimorbidity.Material and methodsPatients were referred for assessment and intervention from primary care or hospital to an interdisciplinary team composed of primary and hospital medical staff and nurses. Pharmacological assessment was centred on polypharmacy and IP using the STOPP/START criteria. Changes in polypharmacy and in IP were analysed at the end of the intervention and at 6 months.ResultsOne hundred consecutive patients (mean (SD) age 81.5(8.0) years, 54(54%) male) were analysed. Mean prescribed medicines at baseline was > 10. There were no significant changes at the end of the intervention and at 6 months. The proportion of patients with two or more STOPP criteria reduced from 37% at the beginning of the intervention to 18% at the end (p< .001), and the proportion of those with START criteria from 13% to 6% (p = .004). These differences persisted at 6 months. The number of STOPP and START criteria before the intervention was associated with a decrease in the STOPP and START criteria at the end of the intervention and at 6 months. A reduction in polypharmacy (p= .041) and in falls (p= .034) was observed at 6 months in those with a decrease in the STOPP criteria at the end of the intervention.ConclusionsAn integrated health intervention centred on polypharmacy and IP in elderly people improves inappropriate prescribing that persists beyond the intervention. (AU)

Fundamento y objetivo: Analizar el impacto de una intervención sanitaria integrada centrada en la polifarmacia y la prescripción inapropiada (PI) en pacientes de edad avanzada con multimorbilidad.Material y métodosLos pacientes fueron remitidos desde la atención primaria o el hospital a un equipo interdisciplinar compuesto por médicos y enfermeras de atención primaria y del hospital para la valoración e intervención. La valoración farmacológica se centró en la polifarmacia y en la PI utilizando los criterios STOPP/START. Se analizaron cambios en la polifarmacia y en la PI al final de la intervención y a los 6 meses.ResultadosSe analizaron 100 pacientes consecutivos con una edad media de 81,5 (8,0) años de los cuales el 54% fueron varones. La media de medicamentos basales fue >10. No hubo diferencias significativas al finalizar la intervención ni a los 6 meses. La proporción de pacientes con 2 o más criterios STOPP se redujo del 37% al comienzo de la intervención al 18% al final (p<0,001), y la proporción de aquellos con criterios START del 13 al 6% (p=0,004). Estos resultados se mantuvieron a los 6 meses. El número de criterios STOPP y START antes de la intervención se asoció a un descenso de los criterios STOPP y START, al final de la intervención y a los 6 meses. En aquellos con una disminución de los criterios STOPP al finalizar la intervención, se observó a los 6 meses una disminución en la polifarmacia (p=0,041) y en las caídas (p=0,034).ConclusionesUna intervención sanitaria integrada centrada en la polifarmacia y en la PI en pacientes de edad avanzada mejora la prescripción inapropiada, y dichas mejoras persisten después de la intervención. (AU)

Integrated health intervention on polypharmacy and inappropriate prescribing in elderly people with multimorbidity: Results at the end of the intervention and at 6 months after the intervention.

BACKGROUND AND OBJECTIVE: To analyse the impact of an integrated health intervention focused on polypharmacy and inappropriate prescribing (IP) in elderly people with multimorbidity. MATERIAL AND METHODS: Patients were referred for assessment and intervention from primary care or hospital to an interdisciplinary team composed of primary and hospital medical staff and nurses. Pharmacological assessment was centred on polypharmacy and IP using the STOPP/START criteria. Changes in polypharmacy and in IP were analysed at the end of the intervention and at 6 months. RESULTS: One hundred consecutive patients (mean (SD) age 81.5(8.0) years, 54(54%) male) were analysed. Mean prescribed medicines at baseline was > 10. There were no significant changes at the end of the intervention and at 6 months. The proportion of patients with two or more STOPP criteria reduced from 37% at the beginning of the intervention to 18% at the end (p< .001), and the proportion of those with START criteria from 13% to 6% (p = .004). These differences persisted at 6 months. The number of STOPP and START criteria before the intervention was associated with a decrease in the STOPP and START criteria at the end of the intervention and at 6 months. A reduction in polypharmacy (p= .041) and in falls (p= .034) was observed at 6 months in those with a decrease in the STOPP criteria at the end of the intervention. CONCLUSIONS: An integrated health intervention centred on polypharmacy and IP in elderly people improves inappropriate prescribing that persists beyond the intervention.