Autogenous Control of 5'TOP mRNA Stability by 40S Ribosomes.

Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5'TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5'TOP mRNAs, with disruption of this complex leading to induction of the impaired ribosome biogenesis checkpoint (IRBC) and p53 stabilization. The importance of this mechanism is underscored in 5q− syndrome, a macrocytic anemia caused by a large monoallelic deletion, which we found to also encompass the LARP1 gene. Critically, depletion of LARP1 alone in human adult CD34+ bone marrow precursor cells leads to a reduction in 5'TOP mRNAs and the induction of p53. These studies identify a 40S ribosome function independent of those in translation that, with LARP1, mediates the autogenous control of 5'TOP mRNA stability, whose disruption is implicated in the pathophysiology of 5q− syndrome.

Pilot study: a detailed analysis of the timing of immuno-inflammatory indices in gastric cancer, and their assessment together with TNM as supplementary prognostic factors.

An analysis of the prognostic impact of up to 36 immuno-inflammatory indices at 3 different times during the diagnostic-therapeutic process for gastric cancer. The dependent variable was disease-free survival at 3 years. The independent factors obtained were combined with TNM to provide an improved prognostic model.

Endoscopic ultrasound performed by surgical approach in a patient with pancreatic lesion and stenosing esophageal adenocarcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) performed in situations of altered anatomy has been described. Thus, in cases of Roux-en-Y gastric by-pass, several approaches have been documented for performing ERCP: by enteroscopy, guided by laparoscopic approach through the gastric remnant, and direct transgastric guided by endoscopic ultrasound through a stent between the reservoir or alimentary loop and the gastric remnant. However, there are clinical situations in which the anatomy is not altered, but there may be pancreatic lesions subsidiary to study by endoscopic ultrasound in situations where the endoscope cannot pass through the esophagus. Therefore, we present the clinical case of a patient with a pancreatic lesion subsidiary to study and a distal esophageal adenocarcinoma that prevented the passage of the endoscope.

Nanomicellar Formulations Loaded with Histamine and Paclitaxel as a New Strategy to Improve Chemotherapy for Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus® (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL). Their micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 70 and 90 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells rendering optimal antitumor efficacy in both cell lines for the nanoformulations with both drugs. In a model of TNBC developed in BALB/c mice with 4T1 cells, we found that all loaded micellar systems reduced tumor volume and that both HA and HA-PTX-loaded SG micelles reduced tumor weight and neovascularization compared with the empty micelles. We conclude that HA-PTX co-loaded micelles in addition to HA-loaded formulations present promising potential as nano-drug delivery systems for cancer chemotherapy.

Proton pump inhibitors (PPIs) and cancer. What should patients with gastroesophageal reflux disease candidates for PPIs therapy who refuse to comply with treatment know?

The relationship of proton pump inhibitors (PPIs) with gastric cancer is not clear. However, more and more patients with gastroesophageal reflux disease (GERD) who are candidates for therapy with PPIs reject such treatment. This situation is largely caused by global access to information, especially on the internet, where some news has recently been published linking PPIs to the development of gastric cancer. For this reason, patients with GERD who are candidates for therapy with PPIs, before rejecting such treatment and opting for antireflux surgery, should be aware of the morbidity and mortality of the surgery and the current scientific evidence regarding the relationship between PPIs and gastric cancer.

Large cell neuroendocrine carcinoma at the esophagogastric junction. An extremely rare entity.

We present the third case described to date of large cell neuroendocrine carcinoma located at the esophagogastric junction (LCNEC). Esophageal neuroendocrine tumours account for 0.03-0.05% of all malignant esophageal tumours. Within oesophageal NETs, LCNEC accounts for 1% of esophageal NETs. This tumour type is characterised by elevated levels of certain markers: synaptophysin, chromogranin A and CD56. In fact, 100% of patients will have chromogranin or synaptophysin, or at least one of these three markers. In turn, 78% will have lymphovascular invasion and 26% will have perineural invasion. Only 11% of patients will have stage I-II, which implies an aggressive course and worse prognosis.

Evolution of two unusual radiological findings in a patient with mesenteric ischemia.

Portal pneumatosis has been considered an ominous sign associated with intestinal ischemia, with a mortality rate of up to 90% as long as it is associated with sepsis. However, the prognosis of mesenteric ischemia depends on the etiology rather than the presence of portal pneumatosis. We present a patient with portal pneumatosis that disappeared 24 hours after the first surgery, but irreversible ischemic lesions were established in the terminal ileum. It should be noted that the excretion of the intravenous contrast is mainly through the kidneys, and it can be eliminated through alternative routes such as the bile duct or the mucosa of the small intestine (vicariant excretion), especially in patients with renal pathology.

Recurrence of gastric schwannoma.

Gastric schwannoma can be malignant in 13.8% of cases. The prognosis of malignant schwannoma is usually poor, characterized by a rapidly progressive disease course and a poor response to chemotherapy. Normally, the recurrence of schwannoma is due to involvement of the surgical resection margin. In turn, recurrence of malignant gastric schwannoma GS is approximately 50%, 25% locoregional and 25% with liver metastases. Even after a complete gastric resection with associated lymphadenectomy, schwannoma may present liver metastases during follow-up.

Intra-abdominal abscess caused by Streptococcus constellatus in an immunocompetent patient.

Streptococcus constellatus is a Gram-positive commensal bacterium of the oropharyngeal, gastrointestinal and urogenital flora. It can cause abscesses in different parts of the body, especially in immunocompromised patients. We present the clinical case of a 33-year-old female patient with a previous history of one anastomosis gastric bypass, among others. The patient was hospitalized two years after surgery for peritonitis secondary to a perforation in the biliopancreatic loop, underwent laparoscopic surgery and was hospitalised for two weeks. Fifteen days after being discharged from the hospital, she went to the emergency service for abdominal pain and fever. An abdominal and pelvic computerized tomography (CT) scan showed a multiloculated pelvic collection with thickened and hypercapillary walls.

Importance of immunohistochemistry in the differential diagnosis of gastric mesenchymal tumors.

Although morphology is the key to histological diagnosis, gastric mesenchymal tumors can share very similar growth and cellularity patterns, sometimes being indistinguishable. Therefore, immunohistochemical techniques are going to be crucial in the definitive diagnosis. The objective of this work is to perform an immunohistochemical differential diagnosis of gastric mesenchymal tumors.

Surgical indication of type I gastric neuroendocrine tumors.

Gastric neuroendocrine tumors (GNETs) account for less than 2% of gastric neoplasms and type 1 GNETs (GNETs-1), which are associated with chronic atrophic gastritis, account for 70-80% of all GNETs. Treatment of GNETs-1 is usually endoscopic, but surgery also has its indications. The aim of this study is to present five case reports of GNETs-1 treated with surgery and to analyze the surgical indications for this type of tumors.

Lymphoepithelioma-like gastric adenocarcinoma. Descriptive case series.

Lymphoepithelioma-like gastric adenocarcinoma is characterised by a large reactive lymphoplasmacytic infiltrate in the stroma and islets of undifferentiated cells, which express intense and widespread Epstein-Barr virus (EBV). This tumour type has higher survival rates than other gastric cancers, a more proximal location and less lymphatic spread. Our aim is to describe the clinical and pathological characteristics of our series of lymphoepithelioma-like gastric adenocarcinoma. We selected patients who underwent surgery for gastric adenocarcinoma lymphoepithelioma-like variant from 2014 onwards. The results of the following variables were collected: age (years), sex, pre-diagnostic clinical time (months), gastric tumour location, endoscopic biopsy histology, surgical technique, in situ hybridisation for EBER region (Epstein-Barr virus-associated non-coding RNA), microsatellite instability, degree of differentiation, level of resection, tumour size (cm), TNM T value, lymphadenopathy/resected node ratio, overall survival (months) and vital status. Our experience in the lymphoepithelioma-like variant presents as an advanced gastric cancer, possibly related to long-standing prediagnostic symptoms. It behaves as a tumour with expansive local growth with little capacity for lymphatic or metastatic involvement, which could be explained by the prominent intratumoral lymphoid stroma that acts as an antimetastatic barrier.

Dual esophageal compression secondary to two vascular abnormalities.

We report the case of a 65-year-old male with hypertension, diabetes and hypercholesterolemia, who presented due to pyrosis and regurgitation. A CT scan incidentally identified esophageal compression at two sites because of vascular abnormalities, which was asymptomatic. The proximal compression was due to a Kommerell's diverticulum (Fig. 1) and the distal one due to aortic tortuosity (Fig. 2). Esophageal manometry revealed a distal obstructive pattern of mechanical origin, which was consistent with the observed aortic kink. The esophagogram (Fig. 3) showed a proximal filling defect and a bend in the distal third.

Surgical indication for right hemicolectomy in goblet cell adenocarcinoma of the appendix.

We have read with interest the article by Pérez Montiel CA et al., in which goblet cell adenocarcinoma (GCA) is described as a cause of acute appendicitis. Although the article is brilliant in terms of histopathological description of the appendiceal GCA, the surgical indication for right hemicolectomy should be analyzed in depth due to the great controversy that exists in the scientific literature.

Children's use of demonstrative words: spatial deictics beyond infancy.

Demonstrative words are one of the most important ways of establishing reference in conversation. This work describes Spanish-speaking children's demonstrative production between ages 2 to 10 using data from the CHILDES corpora. Results indicate that children feature all demonstratives in their lexicon - however, the distal term is scarce throughout development. Moreover, patterns of demonstrative use are not adult-like at age 10. We compare adult and child data to conclude that children's development of demonstrative production is largely protracted. Adult use of the distal demonstrative is higher than in young children, although both older children and adults use the medial term ese more than any other demonstratives. In contrast, younger children use proximals relatively more frequently than older children and adults. Suggestions for future research and theoretical implications for the Spanish demonstrative system are discussed.

Surgical treatment of buried bumper syndrome in patients with Parkinson´s disease and duodenal levodopa/carbidopa infusion therapy.

We read with interest the article by Garrido Durán C, et al. in which endoscopic aspects of duodenal levodopa/carbidopa therapy in the treatment of advanced Parkinson's disease were analyzed. In this article, buried bumper syndrome (BBS) is documented in 5.4 % of cases. Normally, the initial treatment of BBS is endoscopic therapy, although sometimes surgery may be necessary. Thus, 4 cases of BBS treated with surgery are presented.

Single Image Dehazing Algorithm Analysis with Hyperspectral Images in the Visible Range.

In foggy or hazy conditions, images are degraded due to the scattering and attenuation of atmospheric particles, reducing the contrast and visibility and changing the color. This degradation depends on the distance, the density of the atmospheric particles and the wavelength. We have tested and applied five single image dehazing algorithms, originally developed to work on RGB images and not requiring user interaction and/or prior knowledge about the images, on a spectral hazy image database in the visible range. We have made the evaluation using two strategies: the first is based on the analysis of eleven state-of-the-art metrics and the second is two psychophysical experiments with 126 subjects. Our results suggest that the higher the wavelength within the visible range is, the higher the quality of the dehazed images. The quality increases for low haze/fog levels. The choice of the best performing algorithm depends on the criterion prioritized by the metric design strategy. The psychophysical experiment results show that the level of agreement between observers and metrics depends on the criterion set for the observers' task.

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease.

The ribosome is a remarkably complex machinery, at the interface with diverse cellular functions and processes. Evolutionarily conserved, yet intricately regulated, ribosomes play pivotal roles in decoding genetic information into the synthesis of proteins and in the generation of biomass critical for cellular physiological functions. Recent insights have revealed the existence of ribosome heterogeneity at multiple levels. Such heterogeneity extends to cancer, where aberrant ribosome biogenesis and function contribute to oncogenesis. This led to the emergence of the concept of 'onco-ribosomes', specific ribosomal variants with altered structural dynamics, contributing to cancer initiation and progression. Ribosomal proteins (RPs) are involved in many of these alterations, acting as critical factors for the translational reprogramming of cancer cells. In this review article, we highlight the roles of RPs in ribosome biogenesis, how mutations in RPs and their paralogues reshape the translational landscape, driving clonal evolution and therapeutic resistance. Furthermore, we present recent evidence providing new insights into post-translational modifications of RPs, such as ubiquitylation, UFMylation and phosphorylation, and how they regulate ribosome recycling, translational fidelity and cellular stress responses. Understanding the intricate interplay between ribosome complexity, heterogeneity and RP-mediated regulatory mechanisms in pathology offers profound insights into cancer biology and unveils novel therapeutic avenues targeting the translational machinery in cancer.