Salt-sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity.

In humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/- rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active polyunsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregulated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.

The learning curve of transoral condylectomy; a retrospective analysis of 100 consecutive cases of unilateral condylar hyperplasia.

In this study, 100 consecutive scheduled transoral condylectomies for unilateral condylar hyperplasia were included. The safety and surgical performances were assessed, using the operating time, conversion rate and complication rate. The conversion rate learning curve was evaluated with a learning curve cumulative summation (LC-CUSUM). The total conversion rate was 8.0%. The LC-CUSUM for conversion signaled at the 53th procedure, indicating sufficient evidence had accumulated that the surgeon had achieved competence. For procedures 54-100, the conversion rate was 4.0%. The operating time for the transoral condylectomy was 41.5 ± 15.3 min; when a conversion was necessary, the operating time was 101.4 ± 28.3 min (p < 0.05). The estimated operating time in the post-learning phase was 37 min, this was reached after approximately 47 procedures. There was 1 major complication of a permanent inferior alveolar nerve hypoesthesia. The complication rate was not significantly decreased after the learning curve. Within the limitations of the study, it seems that transoral condylectomy for UCH is a safe procedure with several advantages over the traditional preauricular approach. Surgeons starting this procedure should be aware of the potential complications and of the learning curve of approximately 53 procedures.

Enfrentamiento de lesiones de cavidad oral: clasificación y diagnóstico diferencial / Assessment of oral cavity lesions: classification and differential diagnosis

Las lesiones de la cavidad oral corresponden a un hallazgo frecuente y muchas veces difíciles de diagnosticar. Su correcto reconocimiento podría ser clave en detectar patologías que podrían cambiar el pronóstico del paciente. El objetivo de esta revisión es describir una clasificación de las lesiones de la cavidad oral que permita ayudar al diagnóstico en la práctica clínica. Para esto, se detallan y se describen las lesiones, orientando al diagnóstico y a la necesidad de biopsiar. Para simplificar la orientación diagnóstica, las lesiones se clasifican en 2 grandes grupos: tumorales y no tumorales. Las lesiones no tumorales se subdividen en lesiones de la mucosa oral y lesiones de la lengua.

Lesions of the oral cavity are frequent and often difficult to diagnose. However, correct recognition could change the patient's prognosis. This review aims to describe a classification of oral mucosa lesions, to help the diagnosis in clinical practice. The lesions are described for this, guiding the diagnosis and the need for biopsy. To simplify the diagnostic orientation, the lesions are classified into two groups: tumor and non-tumor lesions. Non-tumor lesions are subdivided into lesions of the oral mucosa and lesions of the tongue.

El buceo recreativo y la otorrinolaringología: ¿qué sabemos y deberíamos saber? / Recreational diving and otolaryngology: what do we know and should we know?

El buceo recreativo es una práctica cada vez más popular en la población mundial, sin embargo, no está exenta de riesgos. A medida que transcurre una inmersión, el buzo es susceptible a una serie de cambios de presión que afectan las distintas cavidades que contienen aire dentro del cuerpo humano, tales como el oído, cavidades paranasales y los pulmones. Existe un gran espectro de patologías asociadas al buceo, explicándose la mayoría de ellas por el barotrauma asociado, cuya gravedad depende de la magnitud del daño asociado, pudiendo presentar desde manifestaciones a nivel local, así como también a nivel sistémico. Las patologías otológicas suelen ser las más frecuentes y el principal motivo de consulta en este tipo de pacientes. Sin embargo, las afecciones otoneurológicas, rinosinusales, de vía aérea y sistémicas pueden ser comunes dependiendo de cada perfil de buceo. Actualmente no existen recomendaciones locales sobre esta práctica, por lo que el conocimiento de la fisiología, fisiopatología y el tratamiento de las patologías otorrinolaringológicas asociadas deben ser conocidas a medida que este deporte se vuelve cada vez más popular. Se realizó una revisión de la literatura sobre las distintas afecciones otorrinolaringológicas con el fin de sistematizarlas y elaborar recomendaciones para establecer una práctica segura.

Recreational diving is an increasingly popular practice in the world; however, it is not without risks. As a dive progresses, the diver is susceptible to a series of pressure changes that affect the air-containing cavities, such as the ear, paranasal cavities, and lungs. There is a large spectrum of pathologies associated with diving, most of them being explained by associated barotrauma, the severity of which depends on the magnitude of the associated damage, could present local manifestations, as well as at systemic level. Otological pathologies are usually the most frequent and the main reason for consultation in this type of patients, however, otoneurological, rhinosinusal, airway and systemic conditions can be common depending on each diving profile. Currently there are no local recommendations on this practice, therefore, knowledge of the physiology, pathophysiology and treatment of associated otorhinolaryngological pathologies should be known as this sport becomes increasingly popular. A review of the literature on the different ear, nose and throat conditions was carried out in order to systematize them and develop recommendations to establish a safe practice.

Enfermedad de Rosai-Dorfman nasosinusal: actualización a propósito de un caso de obstrucción nasal progresiva / Nasosinusal Rosai-Dorfman disease: update on a case of progressive nasal obstruction

Resumen La histiocitosis sinusal con linfadenopatías masivas, conocida como enfermedad de Rosai-Dorfman (ERD), es una patología poco frecuente cuya presentación clásica consiste en el desarrollo de grandes adenopatías cervicales bilaterales indoloras. La manifestación extranodal puede involucrar compromiso cutáneo, del sistema nervioso central, hematológico, óseo, de la vía aérea, entre otros. Su diagnóstico es un desafío y requiere una evaluación completa del paciente incluyendo historia clínica, examen físico, exámenes de laboratorio, imágenes y estudio histopatológico que confirme el diagnóstico. El tratamiento debe ser individualizado para cada paciente. Las alternativas incluyen la observación, corticoides sistémicos, radioterapia, quimioterapia, inmunomoduladores y cirugía. Se presenta el caso de una paciente de 65 años con antecedente de enfermedad de Rosai-Dorfman localizada en glándulas lagrimales y linfoma no Hodgkin, que comienza con obstrucción nasal bilateral progresiva refractaria a tratamiento médico, por lo que se decide realizar cirugía, cuyo estudio histopatológico confirmó enfermedad de Rosai-Dorfman.

Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare pathology, with a classic clinical presentation of painless bilateral massive cervical lymphadenopathy. The extranodal manifestations may involve skin, central nervous system, hematological, bones, and airway compromise, among others. Its diagnosis is challenging and requires a complete evaluation of the patient including medical history, physical examination, laboratory testing, imaging and histopathological study to confirm the diagnosis. Treatment should be individualized for each patient, including follow-up, systemic corticosteroids, radiotherapy, chemotherapy, immunomodulators and surgery. We present the case of a 65-year-old patient with a history of RDD located in the lacrimal glands and lymphoma, which begins with progressive bilateral obstruction refractory to medical treatment, for which it is decided to perform surgery, whose histopathological study confirmed RDD.

Prehabilitation in rectal surgery: a narrative review.

AIM: Neoadjuvant chemotherapy (NACRT) can make decompensated patients more vulnerable prior to rectal surgery. Prehabilitation is an intervention which enhances functional capacity to withstand the stress of surgery. The aim of this review was to evaluate the impact of prehabilitation for patients undergoing rectal surgery on physical fitness and clinical outcomes and to establish feasibility of prehabilitation. METHODS: An analysis of the literature was conducted of PubMed, the Cochrane Library, MEDLINE, EMBASE and ScienceDirect. Articles were initially included based on their title and abstracts reviewed. Full-text copies of those selected were obtained for confirmation of inclusion. RESULTS: Eight studies were included. Heterogenicity was observed in the structure of exercise programmes. Improvements in physical fitness were observed in six studies. One study demonstrated a statistically significant improvement in quality of life. The prehabilitation programmes were shown to be feasible, with high completion rates. No adverse events were reported. There was limited data regarding the impact of prehabilitation on postoperative outcomes. CONCLUSION: Current evidence on prehabilitation in rectal surgery has considerable heterogenicity in both structure of programmes and outcome measures. Standardisation is required for future evaluation of the impact on outcomes. A trimodal approach of exercise, nutritional and psychological interventions has been employed in similar programmes, and should be used in rectal surgery. The intervention should be tailored to the patient and environment. This review highlights the benefits, safety and feasibility of prehabilitation and provides a platform for consensus-building for international trials.

Muir-Torre syndrome: a case of unusual coexisting genetic mutations.

Patients with Muir-Torre syndrome (MTS) commonly have germline mismatch repair mutations in MLH1, MSH2 or MSH6, with a strong predominance in MSH2. A subset of approximately one-third of patients will instead have an autosomal recessive base excision repair mutation in MUTYH called MUTYH polyposis. To the best of our knowledge, this is the first report of coexisting germline MSH2 and MUTYH mutations in a patient with MTS.

[Successful deployment of a percutaneous aortic valve in a patient with a mitral prosthesis. Risks and technical considerations]. / Implante de válvula aórtica percutánea en paciente con prótesis mitral previa: riesgos y consideraciones técnicas.

The deployment of a percutaneous aortic valve is challenging in patients with a mitral prosthesis. The risk of prosthetic deformation, embolization or dysfunction is higher in this group of patients, which requires a series of technical considerations. We report a successful implantation of an Evolut Pro # 29 self-expanding valve in a 67-year-old female with a previous Starr-Edwards caged-ball mitral prosthesis.

3D test sample for the calibration and quality control of stimulated emission depletion (STED) and confocal microscopes.

Multiple samples are required to monitor and optimize the quality and reliability of quantitative measurements of stimulated emission depletion (STED) and confocal microscopes. Here, we present a single sample to calibrate these microscopes, align their laser beams and measure their point spread function (PSF) in 3D. The sample is composed of a refractive index matched colloidal crystal of silica beads with fluorescent and gold cores. The microscopes can be calibrated in three dimensions using the periodicity of the crystal; the alignment of the laser beams can be checked using the reflection of the gold cores; and the PSF can be measured at multiple positions and depths using the fluorescent cores. It is demonstrated how this sample can be used to visualize and improve the quality of STED and confocal microscopy images. The sample is adjustable to meet the requirements of different NA objectives and microscopy techniques and additionally can be used to evaluate refractive index mismatches as a function of depth quantitatively.

Manifestaciones otorrinolaringológicas en la infección por virus de inmunodeficiencia humana

Resumen La infección por el virus de la inmunodeficiencia humana (VIH) es una pandemia global que afecta a 38 millones de personas en el mundo. En Chile, se ha visto un alza sostenida en la incidencia de VIH, aumentando un 57% entre 2010 y 2019, reportándose 74.000 personas que viven con VIH en el país. Las manifestaciones en cabeza y cuello ascienden a un 80% de los pacientes con VIH. Éstas pueden presentarse durante el síndrome retroviral agudo, en etapas más avanzadas, incluso como forma de debut, o aparecer en casos de falla de tratamiento o complicaciones derivadas del síndrome inflamatorio de reconstitución inmune. Con la mayor cobertura de terapia antirretroviral (TARV) se ha visto a lo largo del tiempo un cambio en la frecuencia de las manifestaciones otorrinolaringológicas. Las lesiones de la cavidad oral han representado un signo de avance de la enfermedad o de falla al tratamiento, siendo más frecuentes la candidiasis y la leucoplasia vellosa. En el área rinosinusal predominan la rinitis y rinosinusitis, en el cuello las linfadenopatías e hipertrofia parotídea, y en el oído la hipoacusia, alteraciones vestibulares y del oído medio. Para la especialidad de otorrinolaringología es fundamental conocer estas manifestaciones para mantener un alto índice de sospecha del diagnóstico. De esta forma, se permite un diagnóstico precoz y tratamiento oportuno para así mejorar la calidad de vida del paciente. Además, se requiere un seguimiento cercano de forma de detectar signos tempranos de falla al tratamiento o progresión a etapas más avanzadas.

Abstract The human immunodeficiency virus (HIV) infection is a global pandemic, affecting 38 million people worldwide. In Chile, its incidence has risen continuously, increasing to 57% from 2010 to 2019, with 74,000 infected people in the country. Head and neck manifestations account to 80% of HIV patients. These manifestations may be present during the acute retroviral syndrome, in more advanced stages, even as a debut, or appear in treatment failure or complications secondary to the immune reconstitution inflammatory syndrome. With the increase in antiretroviral therapy (ART) coverage, the prevalence of otorhinolaryngological manifestations has changed. Oral lesions may be an early sign for advanced stages or treatment failure, with a predominance of candidiasis and hairy leukoplakia. Rhinitis and rhinosinusitis are the main manifestations in the sinonasal area, lymphadenopathy and parotid hypertrophy in the neck, and hearing loss, vestibular and middle ear disorders in the ear. It is essential for otorhinolaryngologists to be aware of these manifestations in order to maintain a high index of clinical suspicion, allowing an early diagnosis and opportune treatment to improve the patient's quality of life. In addition, a close follow-up is required to identify early signs of treatment failure or progression to more advanced stages.

Topographic features of nano-pores within the osteochondral interface and their effects on transport properties -a 3D imaging and modeling study.

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral interface. Using scanning electron microscopy (SEM), we found a continuous transition of mineralization architecture from the non-calcified cartilage towards the calcified cartilage. This refurbishes the classical picture of the so-called tidemark; a well-defined discontinuity at the osteochondral interface. Using focused-ion-beam SEM (FIB-SEM) on one osteochondral plug derived from a human cadaveric knee, we elucidated that the pore structure gradually varies from the calcified cartilage towards the subchondral bone plate. We identified nano-pores with radius of 10.71 ± 6.45 nm in calcified cartilage to 39.1 ± 26.17 nm in the subchondral bone plate. The extracted pore sizes were used to construct 3D pore-scale numerical models to explore the effect of pore sizes and connectivity among different pores. Results indicated that connectivity of nano-pores in calcified cartilage is highly compromised compared to the subchondral bone plate. Flow simulations showed a permeability decrease by about 2000-fold and solute transport simulations using a tracer (iodixanol, 1.5 kDa with a free diffusivity of 2.5 × 10-10 m2/s) showed diffusivity decrease by a factor of 1.5. Taken together, architecture of the nano-pores and the complex mineralization pattern in the osteochondral interface considerably impacts the cross-talk between cartilage and bone.

Oncological outcomes of laparoscopic versus open rectal cancer resections: meta-analysis of randomized clinical trials.

BACKGROUND: The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. METHODS: A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. RESULTS: Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. CONCLUSION: Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.

Implante de válvula aórtica percutánea en paciente con prótesis mitral previa: riesgos y consideraciones técnicas / Successful deployment of a percutaneous aortic valve in a patient with a mitral prosthesis: risks and technical considerations

The deployment of a percutaneous aortic valve is challenging in patients with a mitral prosthesis. The risk of prosthetic deformation, embolization or dysfunction is higher in this group of patients, which requires a series of technical considerations. We report a successful implantation of an Evolut Pro # 29 self-expanding valve in a 67-year-old female with a previous Starr-Edwards caged-ball mitral prosthesis.

Prostaglandin E2 receptors and their role in gastrointestinal motility - Potential therapeutic targets.

Prostaglandin E2 (PGE2) is found throughout the gastrointestinal tract in a diverse variety of functions and roles. The recent discovery of four PGE2 receptor subtypes in intestinal muscle layers as well as in the enteric plexus has led to much interest in the study of their roles in gut motility. Gut dysmotility has been implicated in functional disease processes including irritable bowel syndrome (IBS) and slow transit constipation, and lubiprostone, a PGE2 derivative, has recently been licensed to treat both conditions. The diversity of actions of PGE2 in the intestinal tract is attributed to its differing effects on its downstream receptor types, as well as their varied distribution in the gut, in both health and disease. This review aims to identify the role and distribution of PGE2 receptors in the intestinal tract, and aims to elucidate their distinct role in gut motor function, with a specific focus on functional intestinal pathologies.