Translational impacts of enzymes that modify ribosomal RNA around the peptidyl transferase centre.

Large ribosomal RNAs (rRNAs) are modified heavily post-transcriptionally in functionally important regions but, paradoxically, individual knockouts (KOs) of the modification enzymes have minimal impact on Escherichia coli growth. Furthermore, we recently constructed a strain with combined KOs of five modification enzymes (RluC, RlmKL, RlmN, RlmM and RluE) of the 'critical region' of the peptidyl transferase centre (PTC) in 23S rRNA that exhibited only a minor growth defect at 37°C (although major at 20°C). However, our combined KO of modification enzymes RluC and RlmE (not RluE) resulted in conditional lethality (at 20°C). Although the growth rates for both multiple-KO strains were characterized, the molecular explanations for such deficits remain unclear. Here, we pinpoint biochemical defects in these strains. In vitro fast kinetics at 20°C and 37°C with ribosomes purified from both strains revealed, counterintuitively, the slowing of translocation, not peptide bond formation or peptidyl release. Elongation rates of protein synthesis in vivo, as judged by the kinetics of ß-galactosidase induction, were also slowed. For the five-KO strain, the biggest deficit at 37°C was in 70S ribosome assembly, as judged by a dominant 50S peak in ribosome sucrose gradient profiles at 5 mM Mg2+. Reconstitution of this 50S subunit from purified five-KO rRNA and ribosomal proteins supported a direct role in ribosome biogenesis of the PTC region modifications per se, rather than of the modification enzymes. These results clarify the importance and roles of the enigmatic rRNA modifications.

Plasticity and conditional essentiality of modification enzymes for domain V of Escherichia coli 23S ribosomal RNA.

Escherichia coli rRNAs are post-transcriptionally modified at 36 positions but their modification enzymes are dispensable individually for growth, bringing into question their significance. However, a major growth defect was reported for deletion of the RlmE enzyme, which abolished a 2'O methylation near the peptidyl transferase center (PTC) of the 23S rRNA. Additionally, an adjacent 80-nt "critical region" around the PTC had to be modified to yield significant peptidyl transferase activity in vitro. Surprisingly, we discovered that an absence of just two rRNA modification enzymes is conditionally lethal (at 20°C): RlmE and RluC. At a permissive temperature (37°C), this double knockout was shown to abolish four modifications and be defective in ribosome assembly, though not more so than the RlmE single knockout. However, the double knockout exhibited an even lower rate of tripeptide synthesis than did the single knockout, suggesting an even more defective ribosomal translocation. A combination knockout of the five critical-region-modifying enzymes RluC, RlmKL, RlmN, RlmM, and RluE (not RlmE), which synthesize five of the seven critical-region modifications and 14 rRNA and tRNA modifications altogether, was viable (minor growth defect at 37°C, major at 20°C). This was surprising based on prior in vitro studies. This five-knockout combination had minimal effects on ribosome assembly and frameshifting at 37°C, but greater effects on ribosome assembly and in vitro peptidyl transferase activity at cooler temperatures. These results establish the conditional essentiality of bacterial rRNA modification enzymes and also reveal unexpected plasticity of modification of the PTC region in vivo.

Corrigendum to 'Anterior interosseous nerve lesion and distal myoclonus revealing a Parsonage Turner Syndrome associated with Hashimoto's thyroiditis' [Radiology Case Reports 16 (2021) 3176-3181].

[This corrects the article DOI: 10.1016/j.radcr.2021.07.067.].

Lumbar radiculopathy associated radicular schwannoma: A case report and literature review.

Lumbar radiculopathy is a clinical condition defined by symptoms of pain, weakness, numbness, or tingling due to lumbar nerve root compression in levels L1-L4. Typically, it is characterized by a narrowing near the nerve root possibly caused by stenosis, bone osteophytes, disc herniation, and similar conditions. Reports of lumbar radiculopathy brought about by the presence of a radicular schwannoma are exceedingly rare. In this paper, we discuss the case of a 67-year-old female patient, presenting with complaints of low back pain, numbness, and antalgic gait for the past eight months. Her physical examination revealed motor and sensor neurological deficits affecting the left lower limb. The electromyoneurography evaluation showed neurogenic atrophy of the left radicular area, while the MRI revealed the presence of a giant, radicular schwannoma at L4-L5 level. This case report aims to underscore the clinical course and management of lumbar radiculopathy caused by a rare L4-L5 radicular schwannoma. Our patient had no significant risk factors or previous spinal pathology.

Anterior interosseous nerve lession and distal myoclonus revealing a parsonage turner syndrome associated with hashimoto thyroiditys.

Parsonage-Turner Syndrome (PTS), also known as brachial neuritis or neuralgic amyotrophy, is a rare disorder affecting 2 to 3 individuals per 100,000 each year. Abrupt onset shoulder pain, followed by motor weakness, paresthesia and hypoesthesia, is usually reported, lasting several months with variable recovery. The etiology of the disease may be idiopathic or triggered by an underlying autoimmune disease in genetically susceptible individuals. Our report addresses a unique case of Parsonage-Turner Syndrome in a patient suffering from concurrent Hashimoto Thyroiditis. A previously healthy A 22 year-old female was referred to the Department of Neurology after complaints of sudden-onset motor weakness in her left upper limb. On physical examination, the patient could not make an "Ok sign" with her thumb and distal phalanx or form a complete fist, revealing weakness within the anterior interosseous branch of the median nerve. Further testing with electromyography demonstrated muscular atrophy within the arm's anterior compartment, forearm, and triceps brachii of the posterior compartment. Additional imaging and physical examination were unremarkable, confirming our diagnosis of PTS. Furthermore, lab reports revealed elevated levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies and our patient was concurrently diagnosed with Hashimoto's thyroiditis. This case aims to highlight the rare co-occurrence of Hashimoto's thyroiditis with Parsonage-Turner Syndrome in an otherwise healthy patient. A 2014 study published by Nugent et al. had also shed light on brachial neuritis in a patient suffering from autoimmune connective tissue disease, and through this case study, we hope to add to the growing literature regarding the correlation between PTS and autoimmune diseases. Symptoms of PTS can easily be misdiagnosed given its similarity to other peripheral neuropathies, and careful assessment and thorough understanding of the disease is required to successfully distinguish it from other neurological pathologies.

A Rare Case of Amyotrophic Lateral Sclerosis With Asymmetrical Phrenic Nerve Lesion Presenting With Acute Respiratory Failure as an Initial Manifestation.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that causes muscle weakness, disability, and eventually, death. Respiratory failure is the leading cause of death in ALS. It is common in the advanced stages of the disease. However, acute respiratory failure is a presenting symptom in only a small number of patients, such as in our case. Here, we present the case of a 54-year-old woman with ALS presenting with respiratory failure due to unilateral diaphragm paralysis as the first manifestation. Although rare, respiratory muscle function failure can be the first symptom of motor neuron disease. Therefore, a motor neuron disease such as ALS, which leads to respiratory muscle weakness and diaphragm paralysis, should be considered in cases of unexplained acute respiratory failure.

Generalized Hypotonia Revealing Spinal Muscular Atrophy Type 2: The First Case Reported From the Dominican Republic and a Review of the Literature.

Spinal muscular atrophy (SMA) is a rare, inherited autosomal recessive disease. Histopathological shreds of evidence related to the condition have suggested degenerative changes at the level of the spinal cord and brain stem. Deletions or mutations in the survival motor neuron 1 (SMN1) gene are the underlying cause of this disease. It is characterized by hypotonia, muscular atrophy, areflexia, fasciculations, and flaccid paralysis. It is further classified into five variants, depending upon the patient's age and clinical features. In this report, we present a rare case of SMA type 2 in a one-year-old female infant who presented with generalized hypotonia and axial body weakness. Besides clinical evaluation, her genetic analysis confirmed that she had a deletion of one of the SMN1 genes. Hence, the diagnosis of SMA type 2 was confirmed. Our study aims to emphasize that clinicians must consider this rare entity whenever a patient presents with the signs and symptoms mentioned above. As the most common cause of death in this disease is respiratory depression, an early diagnosis would prevent complications and help in the parents' genetic counseling.

Importancia de la imagen en la valoración de la respuesta al tratamiento con inmunoterapia del cáncer de pulmón / The Importance of Imaging Studies in the Assessment of Response to Immunotherapy in Lung Cancer

En los últimos años la inmunoterapia (particularmente los inhibidores de los puntos de control inmunitario) ha suscitado un gran interés en el tratamiento de los pacientes con cáncer de pulmón, revolucionando el manejo de los pacientes con tumores localmente avanzados/metastásicos y generando esperanzas entre los pacientes y los médicos que diagnostican y tratan a estos enfermos. Estos fármacos se han convertido (combinados o no con otras terapias) en el tratamiento estándar de muchos pacientes con cáncer de pulmón y se espera que su uso aumente significativamente en un futuro próximo. En este manuscrito revisaremos la importancia creciente de las técnicas de imagen en la valoración de respuesta al tratamiento con inmunoterapia de los pacientes con cáncer de pulmón, haciendo hincapié en los nuevos criterios radiológicos específicos de respuesta con inmunoterapia, en las respuestas radiológicas atípicas (seudoprogresión, respuestas disociadas, hiperprogresión) y en las principales manifestaciones radiológicas de los eventos adversos asociados a la inmunoterapia (reacciones sarcoideas, toxicidades pulmonares, etc.). Los neumólogos deben conocer no solo las respuestas radiológicas atípicas de la inmunoterapia y sus implicaciones pronósticas, sino también sus efectos secundarios y los nuevos criterios radiológicos de respuesta desarrollados para valorar la respuesta al tratamiento. En este trabajo se tratarán conceptos claves como «seudoprogresión», «respuesta paradójica», «hiperprogresión» o «progresión no confirmada» y su significado en el manejo de los pacientes con cáncer de pulmón tratados con inmunoterapia

Immunotherapy (particularly immune checkpoint inhibitors) in the treatment of patients with lung cancer has aroused great interest in recent years, revolutionized the management of patients with locally advanced/metastatic disease, and given hope to both patients and treating physicians. These drugs, in combination or in monotherapy, have become the standard treatment for many patients with lung cancer, and their use is expected to increase significantly in the near future. In this article, we will review the growing importance of imaging techniques in the evaluation of therapeutic response to immunotherapy in lung cancer patients, with emphasis on the new specific radiological criteria on response to immunotherapy, atypical radiological responses (pseudoprogresion, dissociative responses, hyperprogresion), and the main radiological manifestations of adverse events associated with immunotherapy (sarcoid reactions, pulmonary toxicities, etc.). Pulmonologists must be familiar not only with atypical radiological responses to immunotherapy and their prognostic implications, but also with their effects and the new radiological criteria of response to assess treatment response. In this study, we will address key concepts such as "pseudoprogresion", "paradoxical response", "hyperprogresion", or "unconfirmed progression", and their significance in the management of patients with lung cancer treated with immunotherapy

The Importance of Imaging Studies in the Assessment of Response to Immunotherapy in Lung Cancer. / Importancia de la imagen en la valoración de la respuesta al tratamiento con inmunoterapia del cáncer de pulmón.

Immunotherapy (particularly immune checkpoint inhibitors) in the treatment of patients with lung cancer has aroused great interest in recent years, revolutionized the management of patients with locally advanced/metastatic disease, and given hope to both patients and treating physicians. These drugs, in combination or in monotherapy, have become the standard treatment for many patients with lung cancer, and their use is expected to increase significantly in the near future. In this article, we will review the growing importance of imaging techniques in the evaluation of therapeutic response to immunotherapy in lung cancer patients, with emphasis on the new specific radiological criteria on response to immunotherapy, atypical radiological responses (pseudoprogresion, dissociative responses, hyperprogresion), and the main radiological manifestations of adverse events associated with immunotherapy (sarcoid reactions, pulmonary toxicities, etc.). Pulmonologists must be familiar not only with atypical radiological responses to immunotherapy and their prognostic implications, but also with their effects and the new radiological criteria of response to assess treatment response. In this study, we will address key concepts such as "pseudoprogresion", "paradoxical response", "hyperprogresion", or "unconfirmed progression", and their significance in the management of patients with lung cancer treated with immunotherapy.

Exposición a eventos traumáticos y priming perceptivo en población colombiana con desplazamiento forzado en Ecuador / Exposure to traumatic events and perceptual priming in forcedly displaced Colombian population in Ecuador

Los recientes estudios en priming perceptivo se han centrado en identificar las diferencias entre población con y sin Trastorno por Estrés Postraumático (TEPT) confirmando la hipótesis que el TEPT representa un trastorno de la memoria. En este trabajo, se pretende abordar el priming en personas que han estado expuestas a diversas experiencias traumáticas relacionadas con el desplazamiento forzado. Para ello, se diseñaron tres categorías de palabras "trauma" (i.e., de amenaza, emocional y judicial) y una categoría de palabras "neutra", las cuales compartían su raíz de tres letras. Participaron 44 colombianos refugiados y solicitantes de asilo que residen en Ecuador con presencia o ausencia de TEPT. Los resultados confirman que las personas con TEPT presentan mayor priming perceptivo en las categorías de amenaza y emociones y los solicitantes de asilo en la categoría judicial. Se discuten las implicaciones para los estudios que abordan el impacto de violencia política

In line with the hypothesis that PTSD is a memory disorder, recent studies on perceptual priming have focused on identifying the differences between population with and without Post-Traumatic Stress Disorder (PTSD). This study addresses priming in people who have been exposed to traumatic experiences of forced displacement. To that end, three categories of the word "trauma" (i.e., of threat, emotional and judicial) and a category of "neutral" words, which shared their three-letter root were chosen. The participants were 44 Colombian refugees and asylum seekers living in Ecuador with or without PTSD. The results of our study point that people with PTSD have higher perceptual priming in the threat and emotional categories, and asylum seekers show higher priming in the judicial category. The implications for studies that address the impact of political violence are discussed

Calidad de vida y enfermedad renal crónica avanzada. Influencia del aclaramiento renal / Quality of life and advanced chronic kidney disease. Influence of renal clearance

Objetivos: El objetivo del presente estudio fue analizar la Calidad de Vida Relacionada con la Salud en pacientes con Enfermedad Renal Crónica Avanzada en prediálisis y su relación con el aclaramiento renal. Material y Método: Se estudiaron 124 pacientes en prediálisis y edad de 67,2±14,3 años (45% mujeres). Se realizó un estudio descriptivo y transversal, en el Servicio de Nefrología de Hospital Reina Sofía de Córdoba. Se utilizó el cuestionario KDQOL-SF, para el análisis de la Calidad de Vida Relacionada con la Salud. También se analizó el aclaramiento renal y la comorbilidad asociada. Resultados: En el KDQOL, las dimensiones más afectadas fueron: Situación Laboral, Carga de la Enfermedad Renal y Sueño. Las mujeres presentaron peor puntuación en Listado de Síntomas/problemas. En las dimensiones del SF-36, Salud General, Vitalidad, Función Física y Rol Físico, fueron las más afectadas. Las mujeres obtuvieron peor puntuación en Salud General, Vitalidad, Rol Físico, Dolor y Rol Emocional. Los pacientes con menor aclaramiento renal presentaron peores puntuaciones en Efectos de la Enfermedad Renal, Carga de la Enfermedad Renal y Función Sexual; y en Rol Físico y Salud General. Conclusiones: Los pacientes en prediálisis tienen disminuida su calidad de vida en las dimensiones Carga de la enfermedad renal, Sueño, Salud general, Vitalidad, Función física y Rol físico. El aclaramiento renal, aunque influye directamente en los síntomas derivados de la enfermedad renal, no parece ser tan influyente en la calidad de vida, siendo el sexo femenino, la edad y la comorbilidad asociada, las variables que más se asocian con peor calidad de vida

Objectives: The aim of this study was to analyse the Health-Related Quality of Life in patients with Advanced Chronic Kidney Disease in pre-dialysis and the relationship with renal clearance. Material and Method: We studied 124 patients with ACKD in pre-dialysis and age of 67.2±14.3 years (56 women, 45%). A descriptive and cross-sectional study was carried out in the Nephrology Service of the Reina Sofía Hospital in Cordoba. The KDQOL-SF questionnaire was used to analyse the Health-Related Quality of Life. The renal clearance and associated comorbidity were also analysed. Results: In the KDQOL, the most affected dimensions were: work situation, burden of kidney disease and sleep. Women presented worse score in list of symptoms / problems. In the dimensions of SF-36, General health, Vitality, Physical function and Physical role were the most affected. Women rated worse scores, significantly, in: General health, Vitality, Physical role, Pain and Emotional role. Patients with lower renal clearance presented worse scores in Effects of kidney disease, burden of kidney disease and sexual function; and in Physical Role and General Health. Conclusion: Patients in pre-dialysis have reduced their Health-Related Quality of Life in dimensions Burden of kidney disease, Sleep, General health, Vitality, Physical function and Physical role. Renal clearance, although directly influence the symptoms derived from kidney disease, does not seem to be so decisive in quality of life, being the female sex, age and associated comorbidity, the variables most associated with poorer quality of life

Análisis de la sobrecarga del cuidador del paciente en diálisis / Analysis of caregiver burden on dialysis patient

Objetivo: Revisar la literatura científica existente sobre la sobrecarga del cuidador principal del paciente en diálisis. Método: Se realizó una búsqueda en las bases de datos PubMed, Proquest, Scopus y Google Académico. Se incluyeron artículos científicos escritos en inglés y español. Se analizaron los artículos que trataban sobre la sobrecarga de los cuidadores principales, excluyendo aquellos artículos que no presentaran resultados y aquellos donde los pacientes no estaban sometidos a diálisis. Resultados: Se incluyeron 19 artículos publicados entre 2010 y 2018. La sobrecarga aparece en la mayoría de los cuidadores, en mayor o menor grado. La mayoría de los cuidadores son mujeres con una edad entre 40 y 70 años, hijas/os o esposas/os y una mayoría con estudios primarios o sin estudios. Las variables más influyentes en la aparición de la sobrecarga del cuidador del paciente en diálisis son: mayor dependencia del paciente, mayor supervivencia del mismo en el tratamiento dialítico y tener menor apoyo social. También presentan mayor sobrecarga las cuidadoras hijas de los pacientes, las cuidadoras/es solteras/os, las cuidadoras jóvenes o mayores. Conclusiones: La sobrecarga está presente en la mayoría de cuidadores del paciente en diálisis, predominando los grados moderado y leve de sobrecarga. El cuidador principal suele ser mujer, de mediana edad, con un parentesco de hijas/os o esposas/os. Mayor dependencia y supervivencia del paciente en diálisis y menor apoyo social parecen ser las variables más influyentes en la aparición de sobrecarga. La técnica dialítica no parece influir en la sobrecarga del cuidador del paciente en diálisis

Objective: To know current scientific production about dialysis patients’s caregiver burden. Method: A search was conducted in the databases of PubMed, Proquest, Scopus and Google Scholar. Scientific articles written in English and Spanish were included. Articles that dealt with burden of caregivers were analysed, excluding those articles that did not present results and those in which the patients were not subjected to dialysis. Results: We included 19 articles published between 2010 and 2018. Overload appears in most of the caregivers, to a greater or lesser degree. The majority of the caregivers are women between 40 and 70 years of age, daughters or wives and a majority with primary education or without education. The most influential variables in the appearance of overload of the dialysis patient’s caregiver are: greater dependence on the patient, greater survival of the patient in the dialysis treatment and having less social support. Daughters caregivers, single caregivers, young or older caregivers present greater overload. Conclusions: Most dialysis patient’s caregivers suffer burden, prevailing moderate and mild degrees of burden. The main caregiver’s profile is a middle-aged woman, who is related as daughter/son or wife/husband. The most influential variables leading to this caregivers’ burden to appear are: greater dependence and survival of the patient with dialysis and a lower social support. Dialysis treatment does not seem to affect in the burden of the dialysis patient’s caregiver

Relación entre el optimismo disposicional y los síntomas somáticos en pacientes en hemodiálisis crónica / Relationship between dispositional optimism and somatic symptoms in patients on chronic hemodialysis

Objetivos: El objetivo del presente estudio fue analizar la relación existente entre el optimismo disposicional y el apoyo social, con los síntomas somáticos en un grupo de pacientes en hemodiálisis. Pacientes y Método: Se estudiaron 80 pacientes en hemodiálisis, con una edad de 65,20±16,47 años (36,3% mujeres). Se realizó un estudio descriptivo y transversal, en el Servicio de Nefrología de Hospital Reina Sofía de Córdoba. Se estudió el Optimismo Disposicional (cuestionario LOT-R), el Apoyo Social (cuestionario Duke-UNC), los síntomas (Escala de Síntomas Somáticos Revisada) y la comorbilidad asociada. Resultados: La media del LOT-R fue 21,19±5,04 puntos y la mediana 21 (8-30). Se utilizó la mediana del LOT-R para dividir a los pacientes en Pesimistas Disposicionales (<21) y Optimistas Disposicionales (≥21). Aunque edad y comorbilidad fueron más altas en el grupo Optimista, las diferencias no fueron significativas. Los Optimistas presentaron menos síntomas que los Pesimistas, aunque sin diferencias significativas. Los pacientes con Apoyo Social más bajo presentaron más síntomas, aunque sin diferencias significativas. Tampoco se encontraron diferencias significativas en el Apoyo Social recibido entre Optimistas frente a los Pesimistas. Las mujeres presentaron más síntomas gastrointestinales y músculoesqueléticos. La edad se correlacionó estadísticamente con la comorbilidad. Conclusiones: Al menos en nuestra muestra, en los pacientes en hemodiálisis, ni el Optimismo Disposicional ni el Apoyo Social parecen influir en la aparición de síntomas somáticos, ni tampoco el Apoyo Social tiene influencia en el Optimismo Disposicional. Las mujeres presentan más síntomas gastrointestinales y músculoesqueléticos que los hombres. A más edad más comorbilidad asociada

Objectives: The aim of the present study was to analyze the relationship between dispositional optimism and social support with somatic symptoms in a group of patients on hemodialysis. Patients and Method: We studied 80 patients on hemodialysis, with an average age of 65.20 ± 16.47 years (36.3% women and 63.7% men). A descriptive and cross-sectional study was carried out in the Nephrology Service of the Reina Sofía Hospital in Córdoba. The LOT-R questionnaire for Dispositional Optimism and the Revised Somatic Symptoms Scale were used. Social Support and associated comorbidity were also analyzed. Results: The mean LOT-R was 21.19±5.04 and the median 21 (8-30). The median LOT-R was used to divide patients between pessimists (<21) and optimists (≥21). Although age and comorbidity were higher in the optimistic group, not being significant differences. Although optimists presented fewer symptoms than pessimists, there were no significant differences. Similarly, although patients with lower Social Support presented more symptoms, also without significant differences. When the Social Support of the optimists was compared with the pessimists, no differences were found. Statistical relationship of age was found with comorbidity and cardiovascular symptoms. Conclusions: At least in our sample, in hemodialysis patients, neither Dispositional Optimism nor Social Support seem to influence the appearance of somatic symptoms, nor does Social Support influences Dispositional Optimism. Women have more gastrointestinal and musculoskeletal symptoms than men. The older, the more associated comorbidity

Spontaneous Bilateral Pneumothoraces in Erdheim-Chester Disease / Neumotórax bilateral espontáneo en un caso de enfermedad de Erdheim-Chester

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Hemorragia intraquística en paciente con afectación pulmonar quística secundaria a enfermedad por depósito de cadenas ligeras / Intracystic hemorrhage in a patient with pulmonary cystic disorder related to light-chain deposition disease

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Acrometástasis como presentación inicial de un adenocarcinoma de pulmón en una mujer joven / Acrometastasis as the initial presentation of lung adenocarcinoma in a young woman

No disponible