La unión de Candida albicans y Malassezia spp. a células de piel promueve cambios de expresión en los genes responsables de la síntesis de las cadenas de heparán y condroitín sulfato / Adherence of Candida albicans and Malassezia Species to Skin Cells Induces Changes in the Expression of Genes Responsible for Heparan and Chondroitin Sulfate Chain Synthesis

Las micosis superficiales son patologías prevalentes en dermatología, causadas frecuentemente por hongos oportunistas de los géneros Candida y Malassezia. El objetivo de este trabajo es analizar, mediante qRT-PCR, la existencia de alteraciones en la expresión génica de las enzimas biosintéticas de las cadenas de glicosaminoglicanos (GAGs) tras la adhesión de dichas levaduras a líneas celulares de piel. La interacción de C.albicans y Malassezia spp. produjo las siguientes modificaciones en genes implicados en la biosíntesis del heparán y condroitín sulfato: la subexpresión de CHPF en los queratinocitos y 4 subexpresiones (EXT1, EXT2, CHSY3 y CHPF) en los fibroblastos. Las enzimas implicadas en la modificación de las cadenas de dichos GAG se ven más alteradas en los fibroblastos, produciendo 13 subexpresiones y 2 sobreexpresiones (CHST15 y CHST7). Como consecuencia, la afinidad de las cadenas de GAGs por sus ligandos puede verse afectada, pudiendo alterar su papel como receptores de microorganismos, paso clave para el inicio de su proceso infeccioso (AU)

Superficial fungal infections are common in dermatology and are often caused by opportunistic species in the Candida and Malassezia genera. The aim of this study was to analyze changes in the expression of genes coding for enzymes involved in the biosynthesis of glycosaminoglycans (GAGs) chains following the adherence of Candida and Malassezia yeasts to skin cell lines. Gene expression was analyzed using reverse transcriptase–quantitative polymerase chain reaction assays. Interactions between the yeasts and the skin cells induced the following changes in genes involved in the biosynthesis of heparan sulfate and chondroitin sulfate: downregulation of CHPF in keratinocytes and downregulation of EXT1, EXT2, CHSY3, and CHPF in fibroblasts. Adherence to fibroblasts had an even greater effect on GAG biosynthetic enzymes, inducing the downregulation of 13 genes and the upregulation of two (CHST15 and CHST7). Interactions between yeasts and skin cells might affect the binding affinity of GAG chains, possibly changing their ability to function as receptors for pathogens and interfering with a key stage at the start of infection (AU)

[Translated article] Adherence of Candida albicans and Malassezia Species to Skin Cells Induces Changes in the Expression of Genes Responsible for Heparan and Chondroitin Sulfate Chain Synthesis / La unión de Candida albicans y Malassezia spp. a células de piel promueve cambios de expresión en los genes responsables de la síntesis de las cadenas de heparán y condroitín sulfato

Superficial fungal infections are common in dermatology and are often caused by opportunistic species in the Candida and Malassezia genera. The aim of this study was to analyze changes in the expression of genes coding for enzymes involved in the biosynthesis of glycosaminoglycans (GAGs) chains following the adherence of Candida and Malassezia yeasts to skin cell lines. Gene expression was analyzed using reverse transcriptase–quantitative polymerase chain reaction assays. Interactions between the yeasts and the skin cells induced the following changes in genes involved in the biosynthesis of heparan sulfate and chondroitin sulfate: downregulation of CHPF in keratinocytes and downregulation of EXT1, EXT2, CHSY3, and CHPF in fibroblasts. Adherence to fibroblasts had an even greater effect on GAG biosynthetic enzymes, inducing the downregulation of 13 genes and the upregulation of two (CHST15 and CHST7). Interactions between yeasts and skin cells might affect the binding affinity of GAG chains, possibly changing their ability to function as receptors for pathogens and interfering with a key stage at the start of infection (AU)

Las micosis superficiales son patologías prevalentes en dermatología, causadas frecuentemente por hongos oportunistas de los géneros Candida y Malassezia. El objetivo de este trabajo es analizar, mediante qRT-PCR, la existencia de alteraciones en la expresión génica de las enzimas biosintéticas de las cadenas de glicosaminoglicanos (GAGs) tras la adhesión de dichas levaduras a líneas celulares de piel. La interacción de C.albicans y Malassezia spp. produjo las siguientes modificaciones en genes implicados en la biosíntesis del heparán y condroitín sulfato: la subexpresión de CHPF en los queratinocitos y 4 subexpresiones (EXT1, EXT2, CHSY3 y CHPF) en los fibroblastos. Las enzimas implicadas en la modificación de las cadenas de dichos GAG se ven más alteradas en los fibroblastos, produciendo 13 subexpresiones y 2 sobreexpresiones (CHST15 y CHST7). Como consecuencia, la afinidad de las cadenas de GAGs por sus ligandos puede verse afectada, pudiendo alterar su papel como receptores de microorganismos, paso clave para el inicio de su proceso infeccioso (AU)

Adherence of Candida albicans and Malassezia Species to Skin Cells Induces Changes in the Expression of Genes Responsible for Heparan and Chondroitin Sulfate Chain Synthesis. / La unión de Candida albicans y Malassezia spp. a células de piel promueve cambios de expresión en los genes responsables de la síntesis de las cadenas de heparán y condroitín sulfato.

Superficial fungal infections are common in dermatology and are often caused by opportunistic species in the Candida and Malassezia genera. The aim of this study was to analyze changes in the expression of genes coding for enzymes involved in the biosynthesis of glycosaminoglycans (GAGs) chains following the adherence of Candida and Malassezia yeasts to skin cell lines. Gene expression was analyzed using reverse transcriptase-quantitative polymerase chain reaction assays. Interactions between the yeasts and the skin cells induced the following changes in genes involved in the biosynthesis of heparan sulfate and chondroitin sulfate: downregulation of CHPF in keratinocytes and downregulation of EXT1, EXT2, CHSY3, and CHPF in fibroblasts. Adherence to fibroblasts had an even greater effect on GAG biosynthetic enzymes, inducing the downregulation of 13 genes and the upregulation of two (CHST15 and CHST7). Interactions between yeasts and skin cells might affect the binding affinity of GAG chains, possibly changing their ability to function as receptors for pathogens and interfering with a key stage at the start of infection.

Los glicosaminoglicanos se encuentran implicados en la adherencia de Candida albicans y Malassezia spp. a queratinocitos, pero no a fibroblastos dérmicos / Glycosaminoglycans Are Involved in the Adhesion of Candida albicans and Malassezia Species to Keratinocytes But Not to Dermal Fibroblasts

Antecedentes y objetivo Las micosis superficiales son algunas de las enfermedades más comunes en todo el mundo, siendo los agentes causales más frecuentes las levaduras de los géneros Malassezia y Candida, comensales habituales de la piel que pueden actuar como patógenos oportunistas. El objetivo de este trabajo es investigar si los glicosaminoglicanos (GAG) de las células epiteliales son utilizados por estos microrganismos como receptores de adhesión a las mismas. Materiales y métodos Se utilizaron cultivos de queratinocitos y fibroblastos dérmicos. La participación de los GAG en la adhesión de Candida albicans (C. albicans) y Malassezia spp. se estudió mediante inhibición específica de la síntesis de estas moléculas empleando rodamina B o genisteína. También se analizó mediante digestión enzimática in situ empleando liasas específicas. Resultados El tratamiento con rodamina B produjo una inhibición parcial de la adherencia de ambas especies fúngicas a queratinocitos, pero no a fibroblastos. La digestión selectiva del heparán sulfato produjo un aumento de la unión de Malassezia a los queratinocitos y de ambas especies a los fibroblastos. La digestión del condroitín sulfato redujo la unión de C. albicans en los queratinocitos, pero favoreció la unión de la forma filamentada de esta levadura en los fibroblastos. Conclusiones Los GAG de superficie celular de queratinocitos parecen estar implicados en la adherencia de Candida y Malasezzia a la superficie celular. En los fibroblastos, por el contrario, su eliminación favorece la adherencia, sugiriendo la implicación de otro tipo de receptores (AU)

Background and objective Superficial mycoses are some of the most common diseases worldwide. The usual culprits — yeasts belonging to the genera Malassezia and Candida — are commensal species in the skin that can cause opportunistic infections. We aimed to determine whether these yeasts use glycosaminoglycans (GAGs) as adhesion receptors to mediate binding to epithelial cells. Material and methods In keratinocyte and dermal fibroblast cultures, we used rhodamine B and genistein to inhibit GAG synthesis to study the role these molecules play in the adhesion of Candida albicans (C. albicans) and Malassezia species to cells. We also analyzed GAG involvement by means of enzyme digestion, using specific lyases. Results Rhodamine B partially inhibited the adhesion of both fungi to keratinocytes but not to fibroblasts. Selective digestion of heparan sulfate enhanced the binding of Malassezia species to keratinocytes and of both fungi to fibroblasts. Chondroitin sulfate digestion decreased C. albicans adhesion to keratinocytes, but increased the adhesion of the filamentous forms of this species to fibroblasts. Conclusions Cell surface GAGs appear to play a role in the adhesion of C albicans and Malasezzia species to keratinocytes. In contrast, their adhesion to fibroblasts appears to be enhanced by GAG inhibition, suggesting that some other type of receptor is the mediator (AU)

Glycosaminoglycans Are Involved in the Adhesion of Candida albicans and Malassezia Species to Keratinocytes But Not to Dermal Fibroblasts.

BACKGROUND AND OBJECTIVE: Superficial mycoses are some of the most common diseases worldwide. The usual culprits-yeasts belonging to the genera Malassezia and Candida-are commensal species in the skin that can cause opportunistic infections. We aimed to determine whether these yeasts use glycosaminoglycans (GAGs) as adhesion receptors to mediate binding to epithelial cells. MATERIAL AND METHODS: In keratinocyte and dermal fibroblast cultures, we used rhodamine B and genistein to inhibit GAG synthesis to study the role these molecules play in the adhesion of Candida albicans and Malassezia species to cells. We also analyzed GAG involvement by means of enzyme digestion, using specific lyases. RESULTS: Rhodamine B partially inhibited the adhesion of both fungi to keratinocytes but not to fibroblasts. Selective digestion of heparan sulfate enhanced the binding of Malassezia species to keratinocytes and of both fungi to fibroblasts. Chondroitin sulfate digestion decreased Calbicans adhesion to keratinocytes, but increased the adhesion of the filamentous forms of this species to fibroblasts. CONCLUSIONS: Cell surface GAGs appear to play a role in the adhesion of Calbicans and Malasezzia species to keratinocytes. In contrast, their adhesion to fibroblasts appears to be enhanced by GAG inhibition, suggesting that some other type of receptor is the mediator.

Glycosaminoglycans Are Involved in the Adhesion of Candida albicans and Malassezia Species to Keratinocytes But Not to Dermal Fibroblasts. / Los glicosaminoglicanos se encuentran implicados en la adherencia de Candida albicans y Malassezia spp. a queratinocitos, pero no a fibroblastos dérmicos.

BACKGROUND AND OBJECTIVE: Superficial mycoses are some of the most common diseases worldwide. The usual culprits - yeasts belonging to the genera Malassezia and Candida - are commensal species in the skin that can cause opportunistic infections. We aimed to determine whether these yeasts use glycosaminoglycans (GAGs) as adhesion receptors to mediate binding to epithelial cells. MATERIAL AND METHODS: In keratinocyte and dermal fibroblast cultures, we used rhodamine B and genistein to inhibit GAG synthesis to study the role these molecules play in the adhesion of Candida albicans (C. albicans) and Malassezia species to cells. We also analyzed GAG involvement by means of enzyme digestion, using specific lyases. RESULTS: Rhodamine B partially inhibited the adhesion of both fungi to keratinocytes but not to fibroblasts. Selective digestion of heparan sulfate enhanced the binding of Malassezia species to keratinocytes and of both fungi to fibroblasts. Chondroitin sulfate digestion decreased C. albicans adhesion to keratinocytes, but increased the adhesion of the filamentous forms of this species to fibroblasts. CONCLUSIONS: Cell surface GAGs appear to play a role in the adhesion of C albicans and Malasezzia species to keratinocytes. In contrast, their adhesion to fibroblasts appears to be enhanced by GAG inhibition, suggesting that some other type of receptor is the mediator.

Pretreatment neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte, and neutrophil/monocyte ratios and outcome in elderly breast cancer patients.

PURPOSE: Several studies have found an association between peripheral inflammatory cells and outcome. However, no study has explored their impact specifically in elderly patients. We have retrospectively examined pretreatment peripheral neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and neutrophil/monocyte ratio (NMR) in 113 elderly breast cancer patients and correlated our findings with disease-free survival (DFS) and overall survival (OS). METHODS: All patients ≥ 65 years diagnosed from 2004 to 2018 with locally advanced breast cancer were included and classified as high vs low NLR, PLR, LMR, and NMR based on previously identified cutoffs. Estimated 1-, 3-, and 5-year DFS and OS were compared by Chi square analysis. RESULTS: Among 104 evaluable patients, only PLR was significantly associated with estimated 3-year DFS (85.1% vs 63.6%; P = 0.04) and OS (89.3% vs 68.1%; P = 0.03). Among 69 patients with three or more years of follow-up, PLR (P = 0.05), absolute lymphocyte count (ALC) (P = 0.01), polychemotherapy (P = 0.04), number of comorbidities (P = 0.02), polypharmacy (P = 0.005), and clinical stage (P = 0.03) were associated with 3-year DFS. Polypharmacy (OR 4.9; P = 0.02) and ALC (OR 4.6; P = 0.04) retained their significance in the multivariate analysis. CONCLUSIONS: We have found an association between low PLR and longer DFS in elderly breast cancer patients that is in line with findings in patients with a wider range of ages. Our findings on NLR contrast with those of other studies, indicating a potential differential effect in elderly patients. In addition, the effect of polypharmacy on outcome in elderly patients warrants further investigation.

Geriatric oncology in Spain: survey results and analysis of the current situation

Introduction: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. Objectives: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. Methods: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. Results: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. Conclusions: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived

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Geriatric oncology in Spain: survey results and analysis of the current situation.

INTRODUCTION: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. OBJECTIVES: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. METHODS: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. RESULTS: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. CONCLUSIONS: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived.

Carcinoma mucinoso primario cutáneo: presentación de un caso / Primary Mucinous Carcinoma of the Skin: A Case Report

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[Olmesartan-associated enteropathy: attention to an emerging iatrogenic phenomenon]. / Enteropatía asociada a olmesartán: atención a un fenómeno iatrogénico emergente.

Olmesartan is an angiotensin II type 1 receptor blocker commonly used in the treatment of hypertension. Several cases of sprue-like enteropathy associated with the use of this drug have been described which, even with important signs and limitations for the patient, present a full recovery after discontinuing the use of olmesartan. The case of a 64 year-old patient is presented, diagnosed with hypertension, under treatment with olmesartan-amlodipine, with chronic diarrhoea and villous atrophy on intestinal biopsies without diagnostic criteria for celiac disease and with complete remission after suspending discontinuing the use of olmesartan. Based on the clinical features presented by the case reported, the clinical and anatomopathological findings are described as well as the evolution of drug-induced enteropathy.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Computer-assisted method development in liquid chromatography-mass spectrometry: new proposals.

A new approach is proposed for computer-assisted method development in LC-MS. The procedure consists of three stages. Firstly, an accurate retention model is developed for the peaks in the mixture to be separated by use of an iterative approach with isocratic priming data, which is calibrated and validated by means of a few gradient runs. Secondly, a specially developed LC-MS objective function, based on selectivity targets (the selectivity matrix), is calculated and used to evaluate the simulated chromatograms and drive the optimization process. Thirdly, the retention model and the selectivity matrix objective function are used with an evolutionary algorithm in which the concepts of constrained Pareto optimality are applied, to carry out the unattended optimization process. The system was applied to real data for a complex separation and compared with the results provided by a commercial tool for computer-assisted method development.