Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis.

BACKGROUND: MicroRNAs (miRNAs) are non-coding small RNAs, involved in post-transcriptional regulation of many target genes. METHODS: Five miRNAs that have been consistently found deregulated in PCa (miR-21, miR-141, miR-214, miR-375, and let-7c) were analyzed in urinary pellets from 60 prostate cancer (PCa) patients and 10 healthy subjects by qRT-PCR. Besides, urinary exosomes were isolated by differential centrifugation and analyzed for those miRNAs. RESULTS: Significant upregulation of miR-21, miR-141, and miR-375 was found comparing PCa patients with healthy subjects in urinary pellets, while miR-214 was found significantly downregulated. Regarding urinary exosomes, miR-21 and miR-375 were also significantly upregulated in PCa but no differences were found for miR-141. Significant differences were found for let-7c in PCa in urinary exosomes while no differences were observed in urinary pellets. A panel combining miR-21 and miR-375 is suggested as the best combination to distinguish PCa patients and healthy subjects, with an AUC of 0.872. Furthermore, the association of miRNAs with clinicopathological characteristics was investigated. MiR-141 resulted significantly correlated with Gleason score in urinary pellets and let-7c with clinical stage in urinary exosomes. Additionally, miR-21, miR-141, and miR-214 were found significantly deregulated in intermediate/high-risk PCa versus low-risk/healthy subjects in urinary pellets. Significant differences between both groups were found in urinary exosomes for miR-21, miR-375, and let-7c. CONCLUSIONS: These findings suggest that the analysis of miRNAs-especially miRNA-21 and miR-375- in urine could be useful as biomarkers in PCa. Prostate 77: 573-583, 2017. © 2016 Wiley Periodicals, Inc.

A population genomics insight into the Mediterranean origins of wine yeast domestication.

The domestication of the wine yeast Saccharomyces cerevisiae is thought to be contemporary with the development and expansion of viticulture along the Mediterranean basin. Until now, the unavailability of wild lineages prevented the identification of the closest wild relatives of wine yeasts. Here, we enlarge the collection of natural lineages and employ whole-genome data of oak-associated wild isolates to study a balanced number of anthropic and natural S. cerevisiae strains. We identified industrial variants and new geographically delimited populations, including a novel Mediterranean oak population. This population is the closest relative of the wine lineage as shown by a weak population structure and further supported by genomewide population analyses. A coalescent model considering partial isolation with asymmetrical migration, mostly from the wild group into the Wine group, and population growth, was found to be best supported by the data. Importantly, divergence time estimates between the two populations agree with historical evidence for winemaking. We show that three horizontally transmitted regions, previously described to contain genes relevant to wine fermentation, are present in the Wine group but not in the Mediterranean oak group. This represents a major discontinuity between the two populations and is likely to denote a domestication fingerprint in wine yeasts. Taken together, these results indicate that Mediterranean oaks harbour the wild genetic stock of domesticated wine yeasts.

Application of a new municipal management model of Home Care Service in Barcelona: Assessment of workers' labour conditions, health, and well-being.

BACKGROUND: In 2018, Barcelona City Council implemented a pilot phase of an organisational change in the municipal home care service (HCS) system. Inspired in the Buurtzorg model, the new model promotes the creation of self-managing teams operating in a restricted community setting. OBJECTIVE: To assess the pilot phase of the new model, focusing on employees' working and employment conditions as well as on their health and well-being outcomes. METHODS: Mixed-methods impact evaluation. First, a quantitative evaluation was conducted between October 2018 and October 2020, using a pre-post study design with one pretest and two posttest measurements in an intervention and a comparison group. The intervention group was composed of the members of the work teams implemented in the pilot phase from October 2018 onwards (baseline n = 44). The comparison group consisted of workers from the same districts working under the usual HCS system (baseline n = 72). Next, a qualitative study was conducted in workers from the intervention group in winter 2021-2022 (n = 10). RESULTS: The pre-post study results yielded positive changes for the intervention group in social support and autonomy, as well as in many of the employment conditions. This group also experienced increases in psychological demands, painful positions, fatigue and psychological distress. Two main themes affecting workers' well-being emerged from the interviews: factors inherent to the self-management model and external factors. CONCLUSIONS: Health and well-being outcomes seem to depend on the balance between job demands, resources, and ways of channelling conflicts within teams.

Dysphonia in children. Descriptive analysis of the factors involved, clinical parameters and impact on quality of life. / Disfonía en la edad pediátrica. Análisis descriptivo de los factores implicados, parámetros clínicos y repercusión en la calidad de vida.

INTRODUCTION: The prevalence of dysphonia in children is estimated at around 6%. Dysphonia in this age group is usually due to misuse of the voice that leads to the development of vocal fold injuries. This condition can negatively affect the child's self-esteem. The aim of the study is to describe the epidemiology of voice disorders in children in our area, perform an examination of the voice, as well as identify the impact of this pathology on quality of life. MATERIAL AND METHOD: We present a descriptive study with 87 patients aged between 5 and 14 years old, diagnosed with dysphonia. Data collection was carried out in our centre between January 2016 and April 2019. We analysed epidemiological and clinical factors. The impact on quality of life was studied using the Pediatric Voice Handicap Index questionnaire. RESULTS: 87 patients, 57 men (65.5%) and 30 women (34.5%) were included. Mean age 8.5 years (SD: 2.08; range 4-13). The most frequent phonatory disturbance was global muscle tension (88.5%). In the laryngoscopic examination, the most frequent finding was the presence of vocal nodules (45.9%). The average score on the Pediatric Voice Handicap Index was 24.3 points in total; 4.9 on the functional scale; 17.6 on the physical scale and 1.8 on the emotional scale. CONCLUSION: A correct anamnesis that includes the family environment and practice of team sport is essential. The physical examination should include a laryngoscopic examination. There is an impact on the quality of life of patients with dysphonia perceived by them and their families; the physical component is perceived to be most affected. We consider a multidisciplinary approach to this condition necessary.

Incidence and characteristics of diabetic foot ulcers in subjects with type 2 diabetes in Catalonian primary care centres: An observational multicentre study.

AIMS: The main objective was to assess the incidence of diabetic foot ulcers in type 2 diabetes individuals from primary care centres in Catalonia, Spain. METHODS: Prospective observational study in 36 Primary Care centres in Catalonia during February 2018 and July 2019 was conducted. We included participants with type 2 diabetes and a new foot ulcer. We estimated the annual foot ulcer incidence and described the characteristics: presence of comorbidities, clinical parameters and the characteristics of the diabetic foot ulcers (DFU) at inclusion in the study. RESULTS: The incidence of a new DFU during the 12-month recruitment period was 0.42%. The mean age of the participants was 72.2 years (± 12.7), the majority of them were males (n = 178; 69.5%). Overall, 43.8% of DFUs were located on the dorsal aspect of toes or interdigital spaces. A percentage of 43.4% of the participants had ulcers of less than 1 cm2 surface. Further, 44.1% of the participants had a neuroischemic, 20.3% a neuropathic, 20.3% an ischemic ulcer. A 25.3% of ulcers with a concomitant peripheral artery disease were infected. CONCLUSIONS: Although the incidence found was low, our study shows the great complexity of patients with foot ulcers treated in primary care.

Multifactorial control and treatment intensity of type-2 diabetes in primary care settings in Catalonia.

BACKGROUND: Many studies on diabetes have demonstrated that an intensive control of glycaemia and the main associated risk factors (hypertension, dislipidaemia, obesity and smoking) reduce cardiovascular morbi-mortality. Different scientific societies have proposed a multifactorial approach to type 2 diabetes.The objective of this study was to identify the degree of control of glycosylated haemoglobin (HbA1c) and of cardiovascular risk factors in type 2 diabetic patients, using the GedapS 2004 guidelines, and to analyse the type and intensity of drug treatment. METHODS: This cross-sectional, multicentre, epidemiological study was conducted in a primary care setting in Vallès Occidental South, Catalonia. Data were collected of 393 patients aged 18 and above who were diagnosed with diabetes mellitus type 2. Biodemographic and clinical data, cardiovascular risk factors, associated cardiovascular disease, and treatment were assessed. Descriptive and multivariable analysis with logistic regression was realized. RESULTS: A total of 392 patients with a mean age of 66.8 years (SD = 10.6) (45.4% male patients) were analyzed. The duration of diabetes was 8.4 years (SD = 7.6). The degree of multifactorial control of risk factors was only 2.6%, although in more than 50% individual cardiovascular risk factor was controlled, except for LDL cholesterol (40.6%) and systolic blood pressure (29.6%). Furthermore, only 13.0% of subjects had an optimal BMI, 27.5% an optimal waist circumference. Treatment for diabetes was prescribed in 82.7% of patients, for hypertension 70.7%, for dyslipidaemia 47.2% and 40.1% were taking antiplatelets. CONCLUSION: Over 50% of type 2 diabetic patients presented optimal control of the majority of individual cardiovascular risk factors, although the degree of multifactorial control of diabetes was insufficient (2.6%) and should be improved. Drug treatment can be intensified using a larger number of combinations, particularly in patients with target organ damage and associated clinical cardiovascular disease.

Dieulafoy lesion of the gallbladder: A rare cause of hemobilia and acute pancreatitis - Case report.

INTRODUCTION: Dieulafoy lesion of the gallbladder is very rare. It can cause hemobilia and, consequently, acute pancreatitis. After extensive research, the authors found six reported cases of this entity, none of them presenting as acute pancreatitis. CASE PRESENTATION: A 78-year-old woman presented to the emergency department a right upper-quadrant pain and nausea. Abdominal ultrasound showed a gallbladder full of a heterogenic content with no signs of lithiasis or acute cholecystitis. Blood lipase was significantly elevated. She was admitted for acute pancreatitis. During hospitalization she developed jaundice and hematemesis requiring blood transfusion. The upper gastrointestinal (GI) endoscopy with side-view duodenoscopy showed blood through the papilla of Vater. Computed tomography and magnetic resonance imaging confirmed the content of the gallbladder with no changes in the biliary tree. A laparoscopic cholecystectomy with intraoperative cholangiogram was performed. Histology revealed a Dieulafoy lesion. The patient was discharged three days after surgery and had no subsequent episodes. CONCLUSION: Hemobilia should be considered as a cause of upper GI bleeding and acute pancreatitis, especially if both are concurrent. Treatment is directed to the cause, with bleeding control and restoration of bile flow, which can be accomplished by a single minimally invasive surgery.

Amelanocytic anorectal malignant melanoma-Case report.

INTRODUCTION: Anorectal malignant melanoma (AMM), is a rare and aggressive form of melanoma. Accounts for <2% of melanomas, and <2% of anal tumors. It is more frequent at the 6th-7th decade, mostly in women. Surgery is the mainstay of treatment, but the extent is controversial. CASE PRESENTATION: 82-year-old male, presented with rectal mass in the Emergency Room (ER). After local excision, pathology observed that the mass corresponded to AMM. Despite being stage I (Local disease), a year later it presented with local recurrence and distant metastasis. The patient died 32 months after diagnosis. CONCLUSIONS: There is no optimal treatment, due to the lack of prospective studies. Wide local excision (WLE) has faster recovery, less post-operatory complications and similar survival rate compared to abdominal perineal resection (APR).

Sphenoid sinus mucocele: an unusual complication of head and neck irradiation in a North African woman.

Mucocele is a common benign lesion otherwise rarely located in the sphenoid sinus. Some complications after head and neck irradiation have been described in the literature until now. To our knowledge, this is the first report of a sphenoid sinus mucocele in a North African patient treated some years before with radiotherapy for a nasopharyngeal carcinoma (NPC). We extend the literature review about this infrequent finding, of which head and neck surgeons should be aware. Key words:Mucocele, sphenoid sinus mucocele, nasopharyngeal carcinoma, radiotherapy, North African.

Cell manipulation in autologous chondrocyte implantation: from research to cleanroom.

In the field of orthopaedics, autologous chondrocyte implantation is a technique currently used for the regeneration of damaged articular cartilage. There is evidence of the neo-formation of tissue displaying characteristics similar to hyaline cartilage. In vitro chondrocyte manipulation is a crucial phase of this therapeutic treatment consisting of different steps: cell isolation from a cartilage biopsy, expansion in monolayer culture and growth onto a three-dimensional biomaterial to implant in the damaged area. To minimise the risk of in vitro cell contamination, the manipulation must be performed in a controlled environment such as a cleanroom. Moreover, the choice of reagents and raw material suitable for clinical use in humans and the translation of research protocols into standardised production processes are important. In this study we describe the preliminary results obtained by the development of chondrocyte manipulation protocols (isolation and monolayer expansion) in cleanrooms for the application of autologous implantation.

Cystic mass of the floor of the mouth.

BACKGROUND: Epidermoid and dermoid cysts in the oral cavity are relatively uncommon lesions of developmental origin. They often remain asymptomatic for years until they grow enough to interfere with speech, deglutition and less often with breathing which can pose a critical risk to the airway and require immediate surgery. CASE DESCRIPTION: A case of an epidermoid cyst of the floor of the mouth affecting a 37-year-old man is presented; this lesion was surgically enucleated with an intraoral approach. Patient did well postoperatively and there was no evidence of recurrence up to 2 years of follow up. CLINICAL IMPLICATIONS: Floor of the mouth is a challenging site for the diagnosis of a broad variety of lesions which the surgeon should be aware. Depending on the anatomical relation to the muscles of the floor of the mouth dermoid cysts are classified as supramylohyoid or inframylohyoid, and they will both have different clinical and radiological features. This article also includes literature review about the etiopathological, clinical, radiological and histological features, the differential diagnosis and its treatment. Key words:Epidermoid cyst, dermoid cyst, floor of mouth.

Nevus azul celular parotídeo, una tumoración inusual / Parotid cellular blue nevi, an unusual mass

Introducción: el nevus azul celular es una tumoración melanocítica dérmica benigna. En ocasiones, puede ser falsamente diagnosticada como lesiones malignas, entre ellas, el melanoma. Caso clínico: se trata de una mujer de 37 años que presentó una masa parotídea izquierda de cuatro meses de evolución correspondiente con un nevus azul celular. Discusión: la región de la cabeza y cuello es la tercera en frecuencia, tras la sacrococcígea y las extremidades. Ante una tumoración melanocítica, es importante la confirmación diagnóstica, debido a las similitudes, tanto clínicas como anatomopatológicas, del nevus azul celular con el melanoma maligno. Conclusiones: es muy importante el diagnóstico diferencial correcto, para lo cual es de ayuda el uso de las tinciones inmunohistoquímicas. El tratamiento de esta tumoración es la exéresis quirúrgica con márgenes, esto presenta un comportamiento benigno y baja tasa de recidiva.

Introduction: Cellular blue nevi is a benign dermal melanocytic tumor. Occasionally, it can be falsely diagnosed as malignant lesions, including melanoma. Clinical case: This is a 37-year-old woman who presented with a left parotid mass of four months of evolution, corresponding with a cellular blue nevi. Discussion: The region of the head and neck is the third in frequency, after the sacrococcygeal and the extremities. During the study of a melanocytic tumor, diagnostic confirmation with a biopsy is important, due to the similarities, both clinical and pathological, of cellular blue nevi with malignant melanoma. Conclusions: the correct differential diagnosis is very important, for which immunohistochemical study is helpful. The treatment of this tumor is the surgical excision with margins, presenting benign behaviour and low recurrence rate.

Distinct Domestication Trajectories in Top-Fermenting Beer Yeasts and Wine Yeasts.

Beer is one of the oldest alcoholic beverages and is produced by the fermentation of sugars derived from starches present in cereal grains. Contrary to lager beers, made by bottom-fermenting strains of Saccharomyces pastorianus, a hybrid yeast, ale beers are closer to the ancient beer type and are fermented by S. cerevisiae, a top-fermenting yeast. Here, we use population genomics to investigate (1) the closest relatives of top-fermenting beer yeasts; (2) whether top-fermenting yeasts represent an independent domestication event separate from those already described; (3) whether single or multiple beer yeast domestication events can be inferred; and (4) whether top-fermenting yeasts represent non-recombinant or recombinant lineages. Our results revealed that top-fermenting beer yeasts are polyphyletic, with a main clade composed of at least three subgroups, dominantly represented by the German, British, and wheat beer strains. Other beer strains were phylogenetically close to sake, wine, or bread yeasts. We detected genetic signatures of beer yeast domestication by investigating genes previously linked to brewing and using genome-wide scans. We propose that the emergence of the main clade of beer yeasts is related with a domestication event distinct from the previously known cases of wine and sake yeast domestication. The nucleotide diversity of the main beer clade more than doubled that of wine yeasts, which might be a consequence of fundamental differences in the modes of beer and wine yeast domestication. The higher diversity of beer strains could be due to the more intense and different selection regimes associated to brewing.

Análisis clínico y terapéutico ante la patología obstructiva crónica de las glándulas salivales / Clinical and therapeutic analysis to the chronic obstructive pathology of the salivary glands

Introducción: gran parte de la población sufre procesos relacionados con las glándulas salivales, que, con los avances técnicos, se tiende cada vez más a tratar de una manera mínimamente invasiva. Objetivos: remarcar las indicaciones y las diferencias entre los abordajes comunes y los mínimamente invasivos, guiados por el sialoendoscopio. Además, describir la presentación clínica y el estudio de dichos pacientes. Diseño: realizamos un estudio descriptivo, observacional, longitudinal y retrospectivo sobre un grupo de 67 pacientes diagnosticados con patología obstructiva crónica no tumoral de las glándulas. Material y métodos: revisamos los datos referentes a la edad, sexo, hábitos tóxicos, enfermedades sistémicas o autoinmunes asociadas, radioterapia o tratamiento con yodo radiactivo (I131), síntomas asociados y resultados del examen físico y radiológico efectuados, así como el tratamiento efectuado. En mayo de 2019 incorporamos la técnica de sialoendoscopia al manejo de esta patología. Resultados: desde la incorporación de la sialoendoscopia, los casos de patología litiásica a nivel del tercio distal del conducto de Wharton se abordaron mediante exéresis de la litiasis sobre el suelo de la boca con ayuda del sialoendoscopio. Realizamos una sialoendoscopia diagnóstico-terapéutica en pacientes con clínica obstructiva crónica no litiásica. Discusión: el abordaje mínimamente invasivo permite una recuperación más temprana con una adecuada función glandular tras la cirugía. No solo es útil en la patología litiásica, sino que también presenta buenos resultados en patología autoinmune. Conclusión: las técnicas mínimamente invasivas han hecho que el manejo haya cambiado, limitando la realización de resecciones glandulares.

Introduction: A large part of the population suffers from processes related to the salivary glands, which with new advances in technology tends to be treated in a minimally invasive way. Goals: To highlight the indications and differences between common and minimally invasive approaches, guided by the sialoendoscope. In addition, to describe the clinical presentation and the study of these patients. Design: We carried out a descriptive, observational, longitudinal and retrospective study on a group of 67 patients diagnosed with non-tumorous chronic obstructive pathology of the glands. Material and methods: We review the data regarding age, sex, toxic habits, associated systemic or autoimmune diseases, radiotherapy or treatment with I131 (radioactive iodine), associated symptoms and results of the physical and radiological examination carried out. As well as the given treatment. In May 2019 we incorporated the sialoendoscopy to the management of this pathology. Results: Since the incorporation of sialoendoscopy, cases of lithiasic pathology at the distal 1/3 of Wharton's duct were approached by excision of the stone on the floor of the mouth using sialoendoscopy. We perform diagnostic-therapeutic sialoendoscopy in patients with non-lithiasic chronic obstructive symptoms. Discussion: The minimally invasive approach allows an earlier recovery with adequate glandular function after surgery. It is not only useful in lithiasic pathology, but it also has good results in autoimmune pathology. Conclusion: Minimally invasive techniques have changed management, limiting the neck open surgeries.

Standard operating procedure for the good manufacturing practice-compliant production of human bone marrow mesenchymal stem cells.

According to the European Regulation (EC 1394/2007), Mesenchymal Stem Cells expanded in culture for clinical use are considered as Advanced Therapy Medicinal Products. As a consequence, they must be produced in compliance with Good Manufacturing Practice in order to ensure safety, reproducibility, and efficacy. Here, we report a Standard Operating Procedure describing the Good Manufacturing Practice-compliant production of Bone Marrow-derived Mesenchymal Stem Cells suitable for autologous implantation in humans. This procedure can be considered as a template for the development of investigational medicinal Mesenchymal Stem Cells-based product protocols to be enclosed in the dossier required for a clinical trial approval. Possible clinical applications concern local uses in the regeneration of bone tissue in nonunion fractures or in orthopedic and maxillofacial diseases characterized by a bone loss.

Media fill for validation of a good manufacturing practice-compliant cell production process.

According to the European Regulation EC 1394/2007, the clinical use of Advanced Therapy Medicinal Products, such as Human Bone Marrow Mesenchymal Stem Cells expanded for the regeneration of bone tissue or Chondrocytes for Autologous Implantation, requires the development of a process in compliance with the Good Manufacturing Practices. The Media Fill test, consisting of a simulation of the expansion process by using a microbial growth medium instead of the cells, is considered one of the most effective ways to validate a cell production process. Such simulation, in fact, allows to identify any weakness in production that can lead to microbiological contamination of the final cell product as well as qualifying operators. Here, we report the critical aspects concerning the design of a Media Fill test to be used as a tool for the further validation of the sterility of a cell-based Good Manufacturing Practice-compliant production process.