Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading.

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease.

JAZF1-SUZ12 dysregulates PRC2 function and gene expression during cell differentiation.

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis.

CircZNF609 as a prototype to elucidate the biological function of circRNA-mRNA interactions.

Circular RNAs (circRNAs) are expressed and are regulated in many biological processes but little is known about their ability to directly control mRNA homeostasis. We show that circRNA zinc finger protein 609 (circZNF609) interacts with several mRNAs increasing the final protein levels, which in the case of the cytoskeleton-associated protein 5 (CKAP5) leads to a stabilized microtubule cytoskeleton and an enhanced tumor cell proliferation.

Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response.

Impact of Cell of Origin on Outcomes After Autologous Hematopoietic Cell Transplant in Diffuse Large B-Cell Lymphoma.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Presión y área de contacto en reparación de manguito rotador: una revisión sistemática / Pressure and contact area in rotator cuff repair: a systematic review

OBJETIVO Proporcionar una sinopsis exhaustiva y un análisis de los estudios biomecánicos sobre la magnitud y distribución de la presión en la interfase tendón-huella de las roturas del manguito rotador, informadas en la literatura en los últimos cinco años. MÉTODOS La investigación se realizó de acuerdo con los métodos descritos en el Manual Cochrane. Los resultados se informan de acuerdo con el consenso de Ítems Preferidos de Reporte en Revisiones Sistemáticas y Metaanálisis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA, en inglés). La búsqueda se realizó el 1er de junio de 2020. Se identificaron e incluyeron estudios ex vivo de ciencia básica y estudios biomecánicos publicados, que evaluaran la magnitud y distribución de la presión en la interfase tendón-huella de las roturas del manguito rotador reparadas entre enero de 2015 y junio de 2020. Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE, Embase, Scopus y Google Scholar utilizando los términos y operadores booleanos: (Rotator Cuff OR Supraspinatus OR Infraspinatus OR Subscapularis OR Teres Minor) AND Pressure AND Footprint. En la base de datos Embase, respetando su sintaxis, se utilizó: Rotator Cuff AND Pressure AND Footprint. RESULTADOS Un total de 15 de los 87 artículos encontrados cumplieron con todos los criterios de elegibilidad y se incluyeron en el análisis. CONCLUSIÓN La presión y área de contacto sería optimizada biomecánicamente con una reparación transósea de doble fila equivalente, sin nudos en la hilera medial, y con el uso de cintas para su ejecución, conceptos de reparación específica para roturas delaminadas, y limitación de la abducción en el postoperatorio inmediato.

OBJETIVE To provide a comprehensive synopsis and analysis of biomechanical studies on the magnitude and distribution of pressure at the tendon-footprint interface of rotator cuff tears reported in the literature in the last five years. METHODS The research was performed according to the methods described in the Cochrane Manual. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus. The search was performed on June 1st, 2020. We identified and included ex vivo basic science studies and published biomechanical studies that evaluated the magnitude and distribution of pressure at the tendon-footprint interface of rotator cuff tears repaired between January 2015 and June 2020. Systematic searches on the MEDLINE, Embase, Scopus and Google Scholar databases were performed using the terms and Boolean operators: (Rotator Cuff OR Supraspinatus OR Infraspinatus OR Subscapularis OR Teres Minor) AND Pressure AND Footprint. In the Embase database, respecting its syntax, the following was used: Rotator Cuff AND Pressure AND Footprint. RESULTS In total, 15 of the 87 articles found fulfilled all the eligibility criteria and were included in the analysis. CONCLUSION The pressure and contact area would be biomechanically optimized with an equivalent transosseous double-row repair, without knots in the medial row, and with the use of tapes for its execution, specific repair concepts for delaminated tears, and a limitation of abduction in the immediate postoperative period.

Impact of Preoperative Testing on Patients Undergoing Ophthalmologic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Routine medical testing is not recommended before cataract surgery, but no consensus exists about preoperative testing before general ophthalmologic surgery. We aimed to assess the impact of preoperative testing on patients undergoing ophthalmologic surgery by analyzing their surgical outcomes and complications. METHODS: We retrospectively reviewed electronic health records of patients who had preoperative evaluations before cataract or noncataract ophthalmologic surgery at a tertiary care center from January 1, 2015, through December 31, 2019. RESULTS: The cohort consisted of 2268 patients (1270 [56.0%] women). The most frequent ophthalmologic procedure was cataract extraction (n = 1450 [63.9%]). Laboratory tests results were available for 489 patients (33.7%) in the cataract group; of these, 275 results (56.2%) had abnormal values, and 18 patients (6.5%) required preoperative interventions. Preoperative test results were available for 772 out of 818 patients (94.4%) having noncataract procedures. Of these, 384 results (49.7%) had abnormal values, and 10 patients (2.6%) required additional intervention. No significant differences were observed for the rate of surgery cancellations between the cataract and noncataract patient groups (0.6% vs 1.0%; P = .24). Of the 12 patients (0.5%) who had complications, all had undergone preoperative testing. CONCLUSIONS: No differences in outcomes and complications were observed among patients who underwent cataract or noncataract surgery. It is reasonable to consider avoiding preoperative testing in patients undergoing ophthalmologic surgery.

Early Cerebral Hypoperfusion in Patients with Orthostatic Intolerance Without Tachycardia During Head-Up Tilt Test is Independent of Vasovagal Response.

BACKGROUND: Cerebral hypoperfusion before syncope has been shown in patients with chronic orthostatic intolerance (OI) without tachycardia, but it is unknown if an initial decrease of cerebral blood flow velocity (CBFv) could be related to the vasovagal response (VVR) to head-up tilt test (HUTT). OBJECTIVE: The objective of the study was to compare cardiovascular, cerebrovascular, and autonomic variables during HUTT in OI patients with or without a VVR. METHODS: We included 74 subjects (58% female, mean age 33 ± 12 years) who underwent a 30-min HUTT and were divided into three groups: OI with VVR positive (VVR+), OI without VVR negative (VVR-), and asymptomatic healthy subjects with negative HUTT (control group). Cardiovascular, cerebrovascular, and autonomic variables were assessed beat-to-beat during HUTT with a Task Force monitor and a trans-cranial Doppler. Mean values were evaluated at baseline and throughout the first 10 min of tilting. RESULTS: Cardiovascular variables were similar in the three groups. Systolic, diastolic, and mean CBFv were similar in VVR+ and VVR-, but both groups had lower CBFv than the control group. Systolic and diastolic CBFv decreased from baseline since min 1 in VVR+ and VVR- and since min 5 in the control group. The mean CBFv had a significant decrease since min 1 compared to baseline in all groups. Spectral indices of heart rate and blood pressure variability showed a similar autonomic response to HUTT in all groups. CONCLUSION: Patients with chronic OI without tachycardia have early postural cerebral hypoperfusion, regardless of the VVR during HUTT.

Criterios radiográficos para la reducción rotatoria en fracturas diafisarias de húmero / Radiological criteria for rotational reduction in humeral shaft fractures

Introducción: La fractura diafisaria de húmero es frecuente y, en la actualidad, se privilegia el tratamiento quirúrgico. La consolidación en mala rotación puede causar un deterioro de la función y artrosis a largo plazo. Con las técnicas mínimamente invasivas, es difícil manejar la rotación intraoperatoria al no tener una visión directa de la reducción fracturaria. Objetivo: Describir criterios radiográficos para la reducción rotatoria en las fracturas diafisarias de húmero. Materiales y métodos: Estudio retrospectivo de radiografías de húmero comparando criterios radiográficos del húmero distal entre radiografías con rotación interna (sin retroversión proximal) y rotación externa (con retroversión fisiológica). Criterios estudiados: sobreproyección del epicóndilo lateral por sobre el capitellum >50%, esclerosis del borde inferior de la fosa olecraneana, esclerosis del borde lateral de la fosa olecraneana y asimetría de la fosa olecraneana. Resultados: El 97% de las 200 radiografías estudiadas cumplió con los criterios de inclusión y exclusión. Sobreproyección del epicóndilo por sobre el capitellum: 83,3% de los casos; esclerosis del borde inferior de la fosa olecraneana: 30%, esclerosis del borde lateral de la fosa olecraneana: 86,6% y asimetría: 80% de ellas. Todos los criterios con significancia estadística (p <0,001). Al analizar los tres signos positivos en conjunto, la sensibilidad fue del 70% y la especificidad, del 98%; valor predictivo positivo 95,5% y valor predictivo negativo 84,5%. Conclusiones: La rotación humeral correcta es difícil de reproducir en las cirugías mínimamente invasivas, en pacientes con una fractura diafisaria. Describimos cuatro criterios radiográficos que permiten inferir una correcta rotación humeral. Nivel de Evidencia: III

Introduction: Humeral shaft fractures are frequent and surgical treatment is currently favored. Consolidation in malrotation is a complication that can lead to impaired function and long-term osteoarthritis. In minimally invasive techniques, it is difficult to manage intraoperative rotation as there is no direct view of the fracture reduction. Objective: To describe radiological criteria for rotational reduction in humeral shaft fractures. Materials and methods: Retrospective study of humerus radiographs comparing radiological criteria of the distal humerus between radiographs with internal rotation (without proximal retroversion) and radiographs with external rotation (with physiological retroversion). Criteria studied: Overprojection of the lateral epicondyle over the capitellum of more than 50%; sclerosis of the lower border of the olecranon fossa (OF); sclerosis of the lateral border of the OF and asymmetry of the OF. Results: 200 radiographs were studied; 97% met the inclusion and exclusion criteria. Overprojection of the epicondyle over the capitellum was found in 83.3% of the cases. Sclerosis of the inferior border of the OF in 30%, sclerosis of the lateral border of the OF in 86.6%, and asymmetry of OF in 80%. All criteria with statistically significant (p<0.001). When analyzing the 3 positive signs, we found a sensitivity of 70% and a specificity of 98%. The positive predictive value was 95.5% and the negative predictive value was 84.5%. Conclusions: Correct humeral rotation is difficult to reproduce when performing minimally invasive surgeries in patients with a diaphyseal fracture. We describe 4 radiological criteria that allow inferring a correct humeral rotation. Level of Evidence: III

Nonimmunoglobulin Crystal-Storing Histiocytosis (CSH): Case Report and Literature Review.

Crystal-storing histiocytosis (CSH) is an uncommon condition in which histiocytes accumulate a crystalline matter within their cytoplasm. Generally, those crystals are composed of either monoclonal or polyclonal immunoglobulin chains, which have a strong association with an underlying lymphoproliferative or plasma cell disorder (LP-PCD). Rarely, CSH has been reported as local or generalized manifestation of a variety of benign disorders. These cases are associated with crystals composed of nonimmunoglobulin substances. We are reporting an exceptional case of a local colonic CSH with Charcot-Leyden crystals. This patient underwent a screening colonoscopy that detected some polyps. The biopsy reported tubular adenomas, with a markedly dense, transmural inflammatory infiltrates, which were predominantly composed of eosinophils and crystal-storing histiocytes containing Charcot-Leyden crystals. The patient had a negative workup for LP-PCD and autoimmune conditions, including a normal skeletal survey and bone marrow aspirate/biopsy. The only positive laboratory workup was an elevated absolute eosinophil count and a positive IgG anti-Strongyloides antibody. Giving those findings, this parasitic infection is the most likely etiology of the CSH in our patient. Although there was an initial negative evaluation for LP-PCD, close monitoring of patients with either immunoglobulin or nonimmunoglobulin CSH is recommended.

Glenoid size and orientation in the Chilean population / Tamaño y orientación glenoidea en la población chilena

Glenoid morphology is a key factor in determining the success of shoulder surgery. The purpose of this experimental study was to precisely determine the anatomical size and orientation of the glenoid in the Chilean population. 122 CT scans from asymptomatic Chilean patients were obtained. The mean age was 43.8 years (SD 12.3; range, 17-53 years) with 63 female and 59 male patients. For each of the scapulae, were obtained the glenoid version and inclination, maximum glenoid width and height, superior glenoid width, glenoid surface area, glenoid vault depth, and maximum scapular width. The glenoid size showed an average width of 26 ± 2.7 mm, a height of 40.3 ± 3.5 mm and a vault depth of 26.5 ± 3.7 mm. There were significant differences between men and women. The glenoid orientation showed an average of -13.9 ± 4.8° of retroversion and a superior inclination of 11.1 ± 4.7°. Significant differences between men and women were seen only for version. We conclude, that in this Chilean sample the morphological parameters of the glenoid correspond to the published literature, however, some characteristics in this cohort must be further confirmed using other methods.

La morfología glenoidea es un factor clave para determinar el éxito de la cirugía de hombro. El propósito de este estudio experimental fue determinar con precisión el tamaño anatómico y la orientación de la glenoides en la población chilena. Se obtuvieron 122 tomografías computarizadas de pacientes chilenos asintomáticos. La edad media fue de 43,8 años (DE 12,3; rango, 17-53 años) con 63 pacientes femeninos y 59 masculinos. Para cada una de las escápulas, se obtuvieron la versión glenoidea y la inclinación, el ancho y la altura glenoidea máxima, el ancho glenoideo superior, el área de superficie glenoidea, la profundidad de la bóveda glenoidea y el ancho escapular máximo. El tamaño glenoideo mostró un ancho promedio de 26 ± 2,7 mm, una altura de 40,3 ± 3,5 mm y una profundidad de bóveda de 26,5 ± 3,7 mm. Hubo diferencias significativas entre hombres y mujeres. La orientación glenoidea mostró un promedio de -13,9 ± 4,8 ° de retroversión y una inclinación superior de 11,1 ± 4,7 °. Se observaron diferencias significativas entre hombres y mujeres solo para la versión. Concluimos que en esta muestra chilena los parámetros morfológicos de la glenoides corresponden a la literatura publicada, sin embargo, algunas características de esta cohorte deben confirmarse aún más utilizando otros métodos.

Similar Cerebral Blood Flow and Autonomic Responses to Upright Tilt Test in Adult Patients With Different Hemodynamic Mechanisms Leading to Reflex Syncope.

PURPOSE: Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope. METHODS: The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt. RESULTS: At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge. CONCLUSIONS: Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

G-tract RNA removes Polycomb repressive complex 2 from genes.

Polycomb repressive complex 2 (PRC2) maintains repression of cell-type-specific genes but also associates with genes ectopically in cancer. While it is currently unknown how PRC2 is removed from genes, such knowledge would be useful for the targeted reversal of deleterious PRC2 recruitment events. Here, we show that G-tract RNA specifically removes PRC2 from genes in human and mouse cells. PRC2 preferentially binds G tracts within nascent precursor mRNA (pre-mRNA), especially within predicted G-quadruplex structures. G-quadruplex RNA evicts the PRC2 catalytic core from the substrate nucleosome. In cells, PRC2 transfers from chromatin to pre-mRNA upon gene activation, and chromatin-associated G-tract RNA removes PRC2, leading to H3K27me3 depletion from genes. Targeting G-tract RNA to the tumor suppressor gene CDKN2A in malignant rhabdoid tumor cells reactivates the gene and induces senescence. These data support a model in which pre-mRNA evicts PRC2 during gene activation and provides the means to selectively remove PRC2 from specific genes.

Primary Cutaneous T-Cell Lymphoblastic Lymphoma: Case Report and Literature Review.

Cutaneous involvement by precursor T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is rare, and almost all cases are seen in association with bone marrow, blood, and/or lymph node involvement. Presentation with isolated skin involvement is very rare. Literature review revealed only one case report of primary cutaneous T-cell LBL. We discuss here another patient diagnosed with primary cutaneous T-cell LBL at our institute. This patient was initially misdiagnosed as having peripheral T-cell lymphoma NOS. Cytogenetic analysis showed the CDKN2A deletion (-9p21×2) in addition to three intact copies of ABL1 (+9q34). Although she failed multiple lines of intensive chemotherapy, her disease remained confined to the skin. We believe that this presentation of T-LBL is underreported, and many patients are likely misdiagnosed as having high-grade cutaneous T-cell lymphomas. With this case and literature review, we would like to highlight the importance of keeping lymphoblastic lymphoma on the differential diagnosis of cutaneous T-cell lymphoma-like lesions to avoid delay in diagnosis and inappropriate treatment of this aggressive disease.

Efectividad de un programa de rehabilitación autoadministrado en el tratamiento del síndrome de hombro doloroso en atención primaria de salud: un estudio clínico aleatorizado, simple ciego / Effectiveness of a self-administered rehabilitation program for shoulder pain syndrome in primary health care

Background: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. Aim: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. Patients and Methods: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. Results: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. Conclusions: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.

Fractura de clavícula distal con cortical superior indemne: cirugía mínimamente invasiva / Distal clavicle fracture with intact upper cortex: minimally invasive surgery

INTRODUCCIÓN Las fracturas de clavícula distal desplazadas son manejadas generalmente de manera quirúrgica dada la alta probabilidad de no-unión con el tratamiento ortopédico. El propósito de este trabajo es evaluar el uso del sistema de fijación con doble botón cortical para la reducción y estabilización de la fractura de clavícula distal que presenten indemnidad de la cortical superior. MÉTODOS: Estudio retrospectivo observacional clínico-imagenológico de pacientes con fractura desplazada de clavícula distal operados con técnica mínimamente invasiva mediante reducción con sistema de fijación con doble botón cortical. Se describe como criterio radiológico de "Cortical Superior Indemne (CSI)" la presencia del rasgo de fractura a 1cm o más, hacia distal desde el tubérculo conoide, identificándose ese criterio como característica necesaria para la indicación del tratamiento propuesto. Se describen las complicaciones post-operatorias, progresión radiológica y resultados funcionales. RESULTADOS: 21 pacientes fueron tratados con esa técnica con un seguimiento promedio de 23,4 meses. No hubo casos de no unión, infección o herida dehiscente y ningún paciente requirió el retiro del dispositivo. Se encontró un Simple Shoulder Test (SST) promedio de 79,4 (66 - 91,7) y QuickDASH de 11 (6,8 - 15,9). El 87,5% de las fracturas desplazadas de clavícula distal tenían indemnidad de la cortical superior. CONCLUSIÓN: La técnica mínimamente invasiva para la reducción y fijación de la fractura de clavícula distal desplazada con botones corticales es una alternativa simple, reproducible, con pocas complicaciones y excelentes resultados funcionales.

BACKGROUND: Displaced distal clavicle fractures are commonly managed through surgery due to a high probability of nonunion with conservative treatments. The purpose of this study is to evaluate the use of Flip-buttons as a minimally invasive method for fixing and stabilizing displaced distal clavicle fractures when the upper cortical it́s intact. METHODS: A retrospective observational study of radiological and clinical results of patients with displaced distal clavicle fracture that were treated with the Flip-button technique. The indication for using this surgical method was based on the radiological criteria of "Intact Upper Cortical (IUC)" described by the authors as the presence of the fracture 1cm or more, distally to de conoid tubercle. Post-operative complications, radiologic and functional progress were recorded. RESULTS: 21 patients were treated with this technique, all with complete bony union. No patients presented infection or wound dehiscence and implant removal was not necessary in any case. The mean follow-up was of 23,4 months. The mean score in Simple Shoulder Test (SST) was 79,4 (66 - 91,7) and a mean QuickDASH of 11 (6,8 - 15,9). 87,5% of all the displaced distal clavicle fractures had IUC. CONCLUSION: The minimally invasive technique for the reduction and fixation of the displaced distal clavicle fracture with cortical buttons is a simple and reproducible alternative, with few complications and excellent functional results.

Does salt addiction exist? / ¿Existe la adicción a la sal?

Abstract: BACKGROUND: Salt consumption activates the brain reward system, inducing cravings and the search for salted food. Its excessive intake is associated with high blood pressure and obesity. The high quantity of salt in processed food is most likely a major cause of the global pandemic of hypertension (HT). OBJECTIVE: To review the current information on the topic of salt addiction and the health consequences this has. METHOD: A search in PubMed, ScienceDirect, and EBSCOhost databases was conducted with the keywords "salt", "salt addiction", and "food addiction". Articles with information relative to the topic of interest were checked, as were references of those articles and historical and culturally complementary information. RESULTS: We described the historical relationship between man and salt, the physiology of salty taste perception, its role in the reward system and the health consequences of a high sodium diet. DISCUSSION AND CONCLUSION: There is physiological and behavioural evidence that some people may develop a true addiction to food. Among these people, salt addiction seems to be of great importance in the development of obesity, HT and other diseases. Sodium is present in high quantities in processed food as salt and monosodium glutamate (MSG), used as flavour enhancers and food preservatives, including in non-salty foods like bread and soft drinks.

Resumen: ANTECEDENTES: El consumo de sal activa el sistema de recompensa cerebral, induciendo el deseo y búsqueda de alimentos salados. Su ingesta excesiva se asocia a presión arterial elevada y obesidad. La gran cantidad de sal en los alimentos procesados ha permitido que la hipertensión (HT) se instale hoy día como una pandemia. OBJETIVO: Revisar la bibliografía existente en el tema de adicción a la sal y sus consecuencias en la salud. MÉTODO: Se realizó una búsqueda en bases de datos PubMed, EBSCOhost y ScienceDirect con las palabras claves "salt", "salt addiction", "food addiction"; se revisaron los artículos que contuvieran información relativa al tema de interés así como referencias en estos mismos artículos e información histórica y cultural complementaria. RESULTADOS: Describimos la relación histórica entre el hombre y la sal, los mecanismos fisiológicos de percepción del sabor salado, su acción sobre el sistema de recompensa y las consecuencias en la salud de una dieta alta en sodio. DISCUSIÓN Y CONCLUSIÓN: Existe evidencia fisiológica y comportamental de que las personas pueden desarrollar una verdadera adicción a la ingestión de alimentos. Entre estas personas la adición a la sal juega un papel muy importante para el desarrollo de obesidad, hipertensión y otras enfermedades. El sodio está presente en altas cantidades en los alimentos procesados en forma de sal y glutamato monosódico (MSG), usados como conservadores o aditivos alimentarios, incluso en alimentos no salados como harinas y refrescos dulces.

Splicing of a non-coding antisense transcript controls LEF1 gene expression.

In this report we have analyzed the role of antisense transcription in the control of LEF1 transcription factor expression. A natural antisense transcript (NAT) is transcribed from a promoter present in the first intron of LEF1 gene and undergoes splicing in mesenchymal cells. Although this locus is silent in epithelial cells, and neither NAT transcript nor LEF1 mRNA are expressed, in cell lines with an intermediate epithelial-mesenchymal phenotype presenting low LEF1 expression, the NAT is synthesized and remains unprocessed. Contrarily to the spliced NAT, this unspliced NAT down-regulates the main LEF1 promoter activity and attenuates LEF1 mRNA transcription. Unspliced LEF1 NAT interacts with LEF1 promoter and facilitates PRC2 binding to the LEF1 promoter and trimethylation of lysine 27 in histone 3. Expression of the spliced form of LEF1 NAT in trans prevents the action of unspliced NAT by competing for interaction with the promoter. Thus, these results indicate that LEF1 gene expression is attenuated by an antisense non-coding RNA and that this NAT function is regulated by the balance between its spliced and unspliced forms.

In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.

Cerebral haemodynamics in cirrhotic patients with hepatic encephalopathy.

BACKGROUND & AIMS: Factors other than elevated levels of ammonia may be implicated in hepatic encephalopathy (HE) pathophysiology, including abnormal cerebral haemodynamics. Transcranial Doppler ultrasonography (TCD) evaluates cerebrovascular structural integrity and reactivity, through pulsatility index (PI) and breath-holding index (BHI) respectively. The aim of this study was to evaluate cerebral haemodynamics by TCD in patients with compensated and decompensated cirrhosis, and patients with and without HE. METHODS: We studied 90 subjects by TCD measuring PI and BHI in the middle cerebral artery: 30 with cirrhosis and no HE, 30 with cirrhosis and low-grade HE and 30 healthy subjects. Critical flicker frequency, psychometric hepatic encephalopathy score and West-Haven criteria were performed to assess MHE and HE respectively. RESULTS: Pulsatility index increased in decompensated cirrhotics (Child ≥ 7) when compared with compensated cirrhotics and healthy subjects [median (IQR) 1.07 (0.95-1.21) vs 0.90 (0.83-1.05) vs 0.87 (0.78-0.96); P < 0.001]. A reverse relationship was observed for BHI among the three groups [0.82 (0.45-1.11) vs 1.20 (0.82-1.52) vs 1.28 (1.06-1.68); P < 0.001]. Similar findings were observed in decompensation [model for end-stage liver disease (MELD) score ≥14]. Patients with HE showed higher PI and lower BHI [1.05 (1.00-1.16) and 0.89 (0.59-1.15)], when compared with patients without HE [0.96 (0.83-1.13) and 1.00 (0.60-1.53)] or controls [0.87 (0.78-0.96) and 1.28 (1.06-1.68)] (P < 0.001 for PI, and P = 0.007 for BHI). In multivariate regression models, only PI predicted HE, but it was outperformed by MELD-sodium and tumour necrosis factor-alpha. CONCLUSIONS: These results indicate that cerebral haemodynamics are altered in patients with cirrhosis, in relation to severity of disease and HE. Findings on impaired PI and BHI suggest that structural vascular damage and loss of vascular autoregulation are implicated in the pathophysiology of HE.