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1.
Mol Microbiol ; 121(2): 291-303, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38169053

RESUMEN

Pseudomonas aeruginosa is an important opportunistic pathogen. Several of its virulence-related processes, including the synthesis of pyocyanin (PYO) and biofilm formation, are controlled by quorum sensing (QS). It has been shown that the alternative sigma factor RpoS regulates QS through the reduction of lasR and rhlR transcription (encoding QS regulators). However, paradoxically, the absence of RpoS increases PYO production and biofilm development (that are RhlR dependent) by unknown mechanisms. Here, we show that RpoS represses pqsE transcription, which impacts the stability and activity of RhlR. In the absence of RpoS, rhlR transcript levels are reduced but not the RhlR protein concentration, presumably by its stabilization by PqsE, whose expression is increased. We also report that PYO synthesis and the expression of pqsE and phzA1B1C1D1E1F1G1 operon exhibit the same pattern at different RpoS concentrations, suggesting that the RpoS-dependent PYO production is due to its ability to modify PqsE concentration, which in turn modulates the activation of the phzA1 promoter by RhlR. Finally, we demonstrate that RpoS favors the expression of Vfr, which activates the transcription of lasR and rhlR. Our study contributes to the understanding of how RpoS modulates the QS response in P. aeruginosa, exerting both negative and positive regulation.


Asunto(s)
Percepción de Quorum , Factor sigma , Percepción de Quorum/genética , Factor sigma/genética , Factor sigma/metabolismo , Pseudomonas aeruginosa/metabolismo , Biopelículas , Piocianina , Operón , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica
2.
Bioethics ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857488

RESUMEN

Our society, in general, and health care, in particular, faces notable challenges due to the emergence of innovative digital technologies. The use of socially assistive robots in aged care is a particular digital application that provokes ethical reflection. The answers we give to the ethical questions associated with socially assistive robots are framed by ontological and anthropological considerations of what constitutes human beings and how the meaning of being human relates to how these robots are conceived. Religious beliefs and secular worldviews, each of which may participate fully in pluralist societies, have an important responsibility in this foundational debate, as anthropological theories can be inspired by religious and secular viewpoints. This article identifies seven anthropological considerations grounded in the synthesis of biblical scriptures, Roman Catholic documents, and recent research literature. We highlight the inspirational quality of these anthropological considerations when dealing with ethical issues regarding the development and use of socially assistive robots in aged care. With this contribution, we aim to foster a global and inclusive dialogue on digitalization in aged care that deeply challenges our basic understanding of what constitutes a human being and how this notion relates to machine artefacts.

3.
Eur Arch Otorhinolaryngol ; 281(4): 2081-2086, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37405455

RESUMEN

INTRODUCTION: Sialendoscopy has emerged in the last decades as a groundbreaking technique, offering a minimally invasive approach for exploring and managing salivary gland disorders. More recently, the advent of chatbots, powered by advanced natural processing language and artificial intelligence algorithms, has revolutionized the way healthcare professionals and patients access and analyze medical information and potentially will support soon the clinical decision-making process. MATERIALS AND METHODS: A prospective, cross-sectional study was designed to assess the level of agreement between Chat-GPT and 10 expert sialendoscopists aiming the capabilities of Chat-GPT to further improve the management of salivary gland disorders. RESULTS: The mean level of agreement was 3.4 (SD: 0.69; Min: 2, Max: 4) for Chat-GPT's answers while it was 4.1 (SD: 0.56; Min: 3, Max: 5) for the group of EESS (p < 0.015). The overall Wilcoxon signed-rank test yielded a significance level of p < 0.026 when comparing the level of agreement between Chat-GPT and EESS. The mean number of therapeutic alternatives suggested by Chat-GPT was 3.33 (SD: 1.2; Min: 2, Max: 5), while it was 2.6 (SD: 0.51; Min: 2, Max: 3) for the group of EESS; p = 0.286 (95% CI - 0.385 to 1.320). CONCLUSION: Chat-GPT represents a promising tool in the clinical decision-making process within the salivary gland clinic, particularly for patients who are candidates for sialendoscopy treatment. Additionally, it serves as a valuable source of information for patients. However, further development is necessary to enhance the reliability of these tools and ensure their safety and optimal use in the clinical setting.


Asunto(s)
Inteligencia Artificial , Enfermedades de las Glándulas Salivales , Humanos , Estudios Prospectivos , Estudios Transversales , Reproducibilidad de los Resultados , Endoscopía/métodos , Enfermedades de las Glándulas Salivales/cirugía , Alanina Transaminasa
4.
Eur Arch Otorhinolaryngol ; 281(4): 1835-1841, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38189967

RESUMEN

PURPOSE: This study aimed to evaluate the utility of large language model (LLM) artificial intelligence tools, Chat Generative Pre-Trained Transformer (ChatGPT) versions 3.5 and 4, in managing complex otolaryngological clinical scenarios, specifically for the multidisciplinary management of odontogenic sinusitis (ODS). METHODS: A prospective, structured multidisciplinary specialist evaluation was conducted using five ad hoc designed ODS-related clinical scenarios. LLM responses to these scenarios were critically reviewed by a multidisciplinary panel of eight specialist evaluators (2 ODS experts, 2 rhinologists, 2 general otolaryngologists, and 2 maxillofacial surgeons). Based on the level of disagreement from panel members, a Total Disagreement Score (TDS) was calculated for each LLM response, and TDS comparisons were made between ChatGPT3.5 and ChatGPT4, as well as between different evaluators. RESULTS: While disagreement to some degree was demonstrated in 73/80 evaluator reviews of LLMs' responses, TDSs were significantly lower for ChatGPT4 compared to ChatGPT3.5. Highest TDSs were found in the case of complicated ODS with orbital abscess, presumably due to increased case complexity with dental, rhinologic, and orbital factors affecting diagnostic and therapeutic options. There were no statistically significant differences in TDSs between evaluators' specialties, though ODS experts and maxillofacial surgeons tended to assign higher TDSs. CONCLUSIONS: LLMs like ChatGPT, especially newer versions, showed potential for complimenting evidence-based clinical decision-making, but substantial disagreement was still demonstrated between LLMs and clinical specialists across most case examples, suggesting they are not yet optimal in aiding clinical management decisions. Future studies will be important to analyze LLMs' performance as they evolve over time.


Asunto(s)
Inteligencia Artificial , Sinusitis , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Lenguaje
5.
Eur Arch Otorhinolaryngol ; 281(4): 2167-2173, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38329526

RESUMEN

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.


Asunto(s)
Asma , Productos Biológicos , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Interleucina-5 , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Inteligencia Artificial , Calidad de Vida , Asma/epidemiología , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/epidemiología , Enfermedad Crónica , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Sinusitis/epidemiología , Productos Biológicos/uso terapéutico , Terapia Biológica
6.
Artículo en Inglés | MEDLINE | ID: mdl-38703195

RESUMEN

BACKGROUND: The widespread diffusion of Artificial Intelligence (AI) platforms is revolutionizing how health-related information is disseminated, thereby highlighting the need for tools to evaluate the quality of such information. This study aimed to propose and validate the Quality Assessment of Medical Artificial Intelligence (QAMAI), a tool specifically designed to assess the quality of health information provided by AI platforms. METHODS: The QAMAI tool has been developed by a panel of experts following guidelines for the development of new questionnaires. A total of 30 responses from ChatGPT4, addressing patient queries, theoretical questions, and clinical head and neck surgery scenarios were assessed by 27 reviewers from 25 academic centers worldwide. Construct validity, internal consistency, inter-rater and test-retest reliability were assessed to validate the tool. RESULTS: The validation was conducted on the basis of 792 assessments for the 30 responses given by ChatGPT4. The results of the exploratory factor analysis revealed a unidimensional structure of the QAMAI with a single factor comprising all the items that explained 51.1% of the variance with factor loadings ranging from 0.449 to 0.856. Overall internal consistency was high (Cronbach's alpha = 0.837). The Interclass Correlation Coefficient was 0.983 (95% CI 0.973-0.991; F (29,542) = 68.3; p < 0.001), indicating excellent reliability. Test-retest reliability analysis revealed a moderate-to-strong correlation with a Pearson's coefficient of 0.876 (95% CI 0.859-0.891; p < 0.001). CONCLUSIONS: The QAMAI tool demonstrated significant reliability and validity in assessing the quality of health information provided by AI platforms. Such a tool might become particularly important/useful for physicians as patients increasingly seek medical information on AI platforms.

7.
Allergol Immunopathol (Madr) ; 51(2): 168-176, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36916103

RESUMEN

OBJECTIVE: Dental caries is one of the most common chronic diseases affecting millions of people globally. Some studies revealed the presence of bidirectional relationship between allergic rhinitis (AR) and oral diseases, with each disease having a potential impact on the other. In this study we aimed to systematically review the literature and analyze the available evidence regarding whether AR contributes to the development of dental caries. METHODS: Three authors, members of the YO-IFOS rhinology study group, independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing the relationship between rhinitis and caries, in adult and pediatric patients. RESULTS: Eight studies met the inclusion criteria (87612 participants). Six studies were performed in children. A total of three studies found an association between AR and dental caries. Only two studies had adjusted the measure of effect for potentially confounding variables. Regarding the quality of the selected studies according to the NICE classification, the most observed methodological limitations detected were: (1) the cross-sectional design of the included studies which could have introduced a simultaneity bias, and (2) not clearly reporting the inclusion and exclusion criteria. CONCLUSION: This systematic review can neither confirm nor deny the presence of an association between AR and caries. Despite the evidence is very scarce to conclude a relationship between AR and caries, the option for examining patients with repetitive caries by an otolaryngologist and those with AR by odontologist should be considered, as these examinations do not possess any risk for the patient.


Asunto(s)
Caries Dental , Rinitis Alérgica , Adulto , Niño , Humanos , Estudios Transversales , Caries Dental/epidemiología , Rinitis Alérgica/epidemiología
8.
Eur Arch Otorhinolaryngol ; 280(2): 869-876, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36102986

RESUMEN

INTRODUCTION: Nowadays, 70% of patients in Europe and the USA are affected by a p16 + , potentially HPV driven oropharyngeal squamous cell carcinoma. However, despite the improved survival rate in this group, the quality-of-life remains low in cases which neck dissection took place. In this vein, in recent years, some surgeons have considered to avoid dissection of level IIB, proposing a supra-selective non-IIb neck dissection. MATERIALS AND METHODS: A retrospective, longitudinal, multicentric study was conducted, including patients with pathologically confirmed primary HPV + or HPV - OPSCC who went through surgical treatment for the primary lesion and neck dissection. RESULTS: 141 patients were included. Among them, 99 (70.2%) were male and 42 (29.8%) were female. The mean age was 62 ± 9 years (range 36-81). The most frequent anatomical location was the tonsil in 63 (44.7%) of patients. The most common approach was the classic transoral oropharyngectomy in 51 (36.2%) patients. Immunohistochemistry for p16 was positive in 62 (44%) patients. One-hundred and five (74.5%) patients received a unilateral ND, and a 36 (25.5%) a bilateral ND. Of those, a 12.8% (18/141) of patients were level IIb LN + . According to our results, level IIb ND should be considered in patients underwent therapeutic ND with positive LN metastasis in level IIa (OR = 9.83; 95% CI 3.463-27.917) or III (OR = 6.25; 95% CI 2.158-18.143), advanced (T3/T4) oropharyngeal primary tumors (OR = 3.38; 95% CI 1.366-8.405), and patients with ENE (OR = 6.56; 95% CI 2.182-19.770), regardless of p16 status. CONCLUSIONS: According to our results, level IIb ND should be considered in patients who underwent therapeutic ND with positive LN metastasis in level IIa or III, advanced oropharyngeal primary tumors, and patients with ENE, independently of p16 status. Prospective data are necessary to definitively ensure the safety of omitting ipsilateral or contralateral level IIb ND in cN - patients with early stage disease.


Asunto(s)
Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Disección del Cuello/métodos , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/cirugía , Infecciones por Papillomavirus/patología , Estudios Prospectivos , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
9.
J Basic Microbiol ; 63(1): 51-63, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36207285

RESUMEN

Pyocyanin is a phenazine with redox activity produced by Pseudomonas aeruginosa that is harmful to other bacteria and eukaryotic organisms by generating reactive oxygen species. Gene regulation of pyocyanin synthesis has been addressed in the PAO1 and PA14 strains and involves the three-quorum sensing systems Las, Rhl, and Pqs; the regulators RsaL, MvaU, and RpoS, and the posttranscriptional Rsm system, among others. Here, we determined how RsmA regulates pyocyanin synthesis in P. aeruginosa ID4365, an overproducer strain. We found that, in the protease peptone glucose ammonium salts medium, rsmA inactivation increases pyocyanin production compared with the wild-type strains ID4365, PAO, and PA14. We showed that RsmA regulates inversely the expression of both phz operons involved in pyocyanin synthesis; particularly the phz2 operon is positively regulated at the transcriptional level indirectly through MvaU. In addition, we found that the phz1 operon contributes mainly to pyocyanin synthesis and that RsmA negatively regulates phzM and phzS expression. Finally, we showed that translation of the sigma factor RpoS is positively regulated by RsmA, and the expression of rpoS under an independent promoter decreases pyocyanin production in the IDrsmA strain. These results indicate that RsmA regulates not only the genes for pyocyanin production but also their regulators.


Asunto(s)
Pseudomonas aeruginosa , Piocianina , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Bacterias/metabolismo
10.
Clin Otolaryngol ; 48(4): 515-526, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37012583

RESUMEN

OBJECTIVES: Tracheoesophageal puncture (TEP) is considered the gold standard for voice rehabilitation after total laryngectomy. One of the main causes of treatment failure, and a potentially serious complication, is the TEP enlargement and/or leakage around the voice prosthesis. The injection of biocompatible material to increase the volume of the puncture surrounding tissue has been studied as a popular option for conservative treatment of enlarged tracheoesophageal fistula. The aim of this paper was to perform a systematic review of the efficacy and safety of such treatment. DESINGN: Search conducted in PubMed/MEDLINE, the Cochrane Library, Google Scholar, Scielo and Web of Science and through the meta-searcher Trip Database based on Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) statement. SETTINGS: Human experiments published in peer-reviewed journals, where investigators assessed the use of peri-fistular tissue augmentation for periprosthetic leakage were evaluated. PARTICIPANTS: Laryngectomized patients with voice prosthesis, presenting periprosthetik leak due to enlarged fistula. MAIN OUTCOMES MEASURES: mean-duration without new leak. RESULTS: A total of 196 peri-fistular tissue augmentation procedures in 97 patients were found in the 15 selected articles. The 58.8% of patients had a time without periprosthetic leak after treatment of >6 months. The 88.7% of tissue augmentation treatments resulted in periprosthetic leakage cessation. The general level of evidence of the studies included in this review was low. CONCLUSIONS: Tissue augmentation treatment is a minimally invasive, biocompatible and safe solution that temporarily resolves periprosthetic leaks in many cases. There is no standard technique or material, and treatment needs to be individualised according to the experience of the practitioner and the characteristics of the patient. Future randomised studies are needed to confirm these results.


Asunto(s)
Neoplasias Laríngeas , Laringe Artificial , Fístula Traqueoesofágica , Humanos , Neoplasias Laríngeas/cirugía , Laringectomía/métodos , Laringe Artificial/efectos adversos , Punciones/efectos adversos , Estudios Retrospectivos , Fístula Traqueoesofágica/cirugía
11.
Medicina (Kaunas) ; 59(7)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37512129

RESUMEN

Background and Objectives: This study aimed to assess the comparative effectiveness of continuous positive airway pressure (CPAP) therapy and sildenafil pharmacological therapy in improving sexual function among patients with obstructive sleep apnea (OSA) and erectile dysfunction (ED). Materials and methods: Population: Patients affected by OSA and ED; Intervention: CPAP therapy vs. Comparison: Sildenafil pharmacological therapy; Outcomes: Improvement in erectile function, as measured by the International Index of Erectile Function 5 (IIEF-5) scoring system; Time: A systematic review of the literature from the past 20 years; Study Design: Observational studies comparing erectile function improvements after OSA treatment. Results: A total of eight papers were included in the qualitative summary, involving four hundred fifty-seven patients with ED and OSA. Erectile function improvements were observed in both treatment groups. After sildenafil and CPAP treatment, the mean IIEF-5 domain scores were 37.7 and 27.3, respectively (p < 0.001). Sildenafil 100 mg demonstrated a higher therapeutic impact compared to CPAP treatment. Conclusions: CPAP therapy significantly improved sexual parameters in most studies for OSA patients with ED. The findings suggest that CPAP therapy effectively alleviates erectile dysfunction symptoms, resulting in improved sexual performance in OSA patients. The comparison of the two treatments indicates that sildenafil has a more substantial therapeutic impact on erectile function than CPAP therapy; however, a combined treatment will provide a cumulative effect.


Asunto(s)
Disfunción Eréctil , Disfunciones Sexuales Fisiológicas , Apnea Obstructiva del Sueño , Masculino , Humanos , Citrato de Sildenafil/uso terapéutico , Disfunción Eréctil/tratamiento farmacológico , Presión de las Vías Aéreas Positiva Contínua/métodos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/tratamiento farmacológico
12.
Medicina (Kaunas) ; 59(8)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37629765

RESUMEN

Background and Objective: To examine the effects of the lockdown on diet adherence and stress levels in patients with laryngopharyngeal reflux (LPR). Materials and Methods: Patients with a positive LPR diagnosis at the hypopharyngeal-esophageal impedance-pH monitoring were treated from a pre- to lockdown period with a 3-month high-protein, low-fat, alkaline, plant-based diet, with behavioral changes, and an association of pantoprazole (20 MG/d) and alginate (Gaviscon 3/d). The following patient-reported outcomes questionnaire and findings instrument were used: Reflux Symptom Score-12 (RSS-12) and Reflux Sign Assessment (RSA). At the posttreatment time, patients were invited to evaluate the impact of lockdown on diet adherence and stress management with a predefined grid of foods and beverages and the perceived stress scale (PSS), respectively. Results: Thirty-two patients completed the evaluations. RSS-12 and RSA significantly improved from baseline to 3-month posttreatment. Most patients experienced mild-to-severe stress levels at the end of the lockdown. The level of stress substantially increased in 11 patients (34%) due to the lockdown, while it did not change in 11 patients (44%). In 11 cases (34%), patients reported that the adherence to the anti-reflux diet was better than initially presumed thanks to the lockdown period, while 44% (N = 14) reported that the lockdown did not impact the adherence to a diet. PSS and RSS-12 were significantly correlated at the end of the pandemic (rs = 0.681; p < 0.001). The increase in stress level was positively associated with the lack of adherence to diet (rs = 0.367; p = 0.039). Conclusions: During the lockdown, the diet habits of LPR patients were improved in one-third and unchanged in 44% of cases. The stress level was increased in one-third of patients, which was associated with an increase in symptom scores.


Asunto(s)
COVID-19 , Reflujo Laringofaríngeo , Humanos , Cuarentena , Control de Enfermedades Transmisibles , Bebidas
13.
Mol Microbiol ; 116(4): 1113-1123, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34418194

RESUMEN

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an opportunistic pathogen that represents an important health hazard. The quorum-sensing response regulates the expression of several virulence factors and involves three regulons: Las, Rhl, and Pqs. The P. aeruginosa ATCC 9027 strain, which belongs to the genetically diverse PA7 clade, contains a frame-shift mutation in the pqsR gene that encodes a transcriptional activator necessary for pyocyanin (PYO) synthesis in type strains PAO1 and PA14. Here we characterize the PqsE-dependent production of PYO in strain ATCC 9027. We show that this strain expresses pqsE independently of PqsR and in the absence of quinolone production, and that PqsE promotes the RhlR-dependent production of PYO, yet this production is not strictly dependent on PqsE. In addition, we show that in both strains ATCC 9027 and PAO1, PqsE overexpression causes an increased concentration of RhlR and enhances PYO production but does not affect rhamnolipids (RL) production in the same way. These results suggest that PqsE interaction with RhlR preferentially modifies its ability to activate transcription of genes involved in PYO production and provide new evidence about PqsE-dependent RhlR activation, highlighting the variability of the QS response among different P. aeruginosa clades and strains. HIGHLIGHTS: Pseudomonas aeruginosa ATCC 9027 is able to produce pyocyanin in phosphate limiting conditions, even in the absence of a functional PqsR. This strain does not produce alkyl quinolones like PQS and HHQ, but expresses pqsE. Synthesis of pyocyanin by ATCC 9027 is only partially dependent on pqsE. The overexpression of pqsE in the ATCC 9027 and PAO1 strains causes pyocyanin overproduction. The overexpression of pqsE in these strains causes an increased RhlR concentration without affecting rhlR transcription or translation. Rhamnolipids production is not affected to the same extent as pyocyanin by overexpression of pqsE in these strains.


Asunto(s)
Proteínas Bacterianas/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/biosíntesis , Percepción de Quorum , Tioléster Hidrolasas/genética , Tioléster Hidrolasas/metabolismo , Proteínas Bacterianas/genética , Mutación del Sistema de Lectura , Regulación Bacteriana de la Expresión Génica , Glucolípidos/metabolismo , Humanos , Mutación , Operón , Infecciones por Pseudomonas/microbiología , Quinolonas/metabolismo , Regulón , Transactivadores , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
14.
Microbiology (Reading) ; 168(10)2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36301076

RESUMEN

Several Pseudomonas aeruginosa virulence-related traits like pyocyanin are regulated by an intricate regulatory network called quorum sensing (QS) that relies on transcriptional regulators that are activated through binding to a self-produced molecule called an autoinducer (AI). QS is composed of three systems, Las, Rhl and Pqs. In the Las system, the regulatory protein LasR interacts with its AI to activate the other two QS systems. In turn, the Rhl and Pqs systems regulate the expression of multiple virulence-related genes, such as the genes of the reiterated operons phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2 involved in pyocyanin production. The Las system also regulates the negative regulator RsaL, which provides negative feedback to the QS-response, including repression of pyocyanin synthesis genes. In this work, we describe that LasR can act as a negative regulator of phzA1 transcription and hence of pyocyanin production and that this regulation is independent of RsaL activity. This work contributes to the understanding of QS-dependent pyocyanin production and demonstrates a previously uncharacterized role of LasR as a repressor.


Asunto(s)
Pseudomonas aeruginosa , Piocianina , Piocianina/metabolismo , Pseudomonas aeruginosa/metabolismo , Regulación Bacteriana de la Expresión Génica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Percepción de Quorum/genética , Factores de Transcripción/genética , Fosfatos/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
15.
Eur Arch Otorhinolaryngol ; 279(12): 5741-5753, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35652941

RESUMEN

OBJECTIVE: To investigate epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer (LC). METHODS: PubMed, Scopus and Cochrane Library were searched by three researchers for studies investigating epidemiological, clinical and oncological outcomes of patients with age < 40 years old and LC. The following outcomes were investigated with PRISMA criteria: age; ethnicity; gender; tobacco/alcohol habits; anatomical, pathological, therapeutic and survival features. Authors performed a bias analysis of papers and provided recommendations for future studies. RESULTS: Seventeen papers published between 1982 and 2021 met our inclusion criteria, accounting for 928 patients with age < 40 years (female/male ratio: 2:5). There were on average 54.2 and 45.8% of smokers and drinkers. The tumor location mainly consisted of glottis (70.1%), supraglottis (27.7%) and subglottis (2.2%). Radiation therapy was the main therapeutic strategy used in young adults with LC. The 2-year overall survival ranged from 50 to 100% and depended on tumor stage, treatment, and cohort features. Four studies reported better overall survival in young compared with old adults, while there were no significant differences in three studies. There was an important heterogeneity between studies regarding the inclusion/exclusion criteria, epidemiological, clinical, pathological and treatment. CONCLUSION: It was suggested that young patients with LC had lower proportion of smokers and drinkers and better overall survival compared with older but both data of the current literature and heterogeneity between studies limit us to draw definitive conclusions.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Laringe , Adulto Joven , Humanos , Masculino , Femenino , Adulto , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patología , Carcinoma de Células Escamosas/patología , Glotis/cirugía , Laringe/patología , Estudios de Cohortes
16.
Eur Arch Otorhinolaryngol ; 279(8): 4167-4172, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35217904

RESUMEN

PURPOSE: Tracheoesophageal speech is considered the gold standard for rehabilitation following total laryngectomy. The main reason of voice prosthesis failure is the endoprosthesis leakage. Provox ActiValve® incorporates a magnet-based valve system to achieve active closure of the valve to treat these leakages, with the drawback of being significantly more expensive. The aim of the study was to compare the Provox Vega® and Provox ActiValve® duration and costs in patients with replacements increase due to endoprosthetic leakage. METHODS: Prospective case-crossover study in laryngectomized patients with Provox Vega® and endoprosthesis leakage to whom a Provox ActiValve® was placed. Survival and possible factors that affect voice prosthesis were studied using Kaplan-Meier curves and Cox Proportional Hazards Regression. Cost-effectiveness analysis from the perspective of the Spanish Public National Health System with incremental cost-effectiveness calculation was performed. RESULTS: A total of 159 prostheses were evaluated. The most frequent reason for replacement was the endoprosthesis leakage (N = 129; 83.77%) in both models. The mean duration-time of Provox Vega® was 44.77 ± 2.82 days (CI 95%, 39.18-50.35; median 36 days), and 317.34 ± 116.8 days (CI 95% 86.66-548; median 286 days) for the Provox ActiValve® (p < 0.000). For every replacement not made thanks to the Provox ActiValve® there was saving of 133.97€ CONCLUSIONS: The Provox ActiValve® is a cost-effective solution in patients with increased prosthesis replacements due to endoprosthetic leakage, reducing the number of changes and cost compared to Provox Vega®.


Asunto(s)
Laringe Artificial , Análisis Costo-Beneficio , Estudios Cruzados , Humanos , Laringectomía/efectos adversos , Laringectomía/rehabilitación , Imanes , Diseño de Prótesis , Falla de Prótesis
17.
ORL J Otorhinolaryngol Relat Spec ; 84(4): 278-288, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35021182

RESUMEN

INTRODUCTION: Despite multiple prognostic indicators described for oral cavity squamous cell carcinoma (OCSCC), its management still continues to be a matter of debate. Machine learning is a subset of artificial intelligence that enables computers to learn from historical data, gather insights, and make predictions about new data using the model learned. Therefore, it can be a potential tool in the field of head and neck cancer. METHODS: We conducted a systematic review. RESULTS: A total of 81 manuscripts were revised, and 46 studies met the inclusion criteria. Of these, 38 were excluded for the following reasons: use of a classical statistical method (N = 16), nonspecific for OCSCC (N = 15), and not being related to OCSCC survival (N = 7). In total, 8 studies were included in the final analysis. CONCLUSIONS: ML has the potential to significantly advance research in the field of OCSCC. Advantages are related to the use and training of ML models because of their capability to continue training continuously when more data become available. Future ML research will allow us to improve and democratize the application of algorithms to improve the prediction of cancer prognosis and its management worldwide.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Algoritmos , Inteligencia Artificial , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Humanos , Aprendizaje Automático , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/terapia , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia
18.
J Bacteriol ; 203(5)2021 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-33288622

RESUMEN

Pseudomonas aeruginosa is a major nosocomial pathogen that presents high-level resistance to antibiotics. Its ability to cause infections relies on the production of multiple virulence factors. Quorum sensing (QS) regulates the expression of many of these virulence factors through three QS systems: Las, Rhl, and PQS. The Las system positively regulates the other two systems, so it is at the top of a hierarchized regulation. Nevertheless, clinical and environmental strains that lack a functional Las system have been isolated, and, surprisingly, some of them still have the ability to produce virulence factors and infect animal models, so it has been suggested that the hierarchy is flexible under some conditions or with atypical strains. Here, we analyze the PAO1 type strain and its ΔlasR-derived mutant and report, for the first time, a growth condition (phosphate limitation) where LasR absence has no effect either on virulence factor production or on the gene expression profile, in contrast to a condition of phosphate repletion where the LasR hierarchy is maintained. This work provides evidence on how the QS hierarchy can change from being a strictly LasR-dependent to a LasR-independent RhlR-based hierarchy under phosphate limitation even in the PAO1 type strain.IMPORTANCEPseudomonas aeruginosa is an important pathogen, considered a priority for the development of new therapeutic strategies. An important approach to fight its infections relies on blocking quorum sensing. The Las system is the main regulator of the quorum-sensing response, so many research efforts aim to block this system to suppress the entire response. In this work, we show that LasR is dispensable in a phosphate-limited environment in the PAO1 type strain, which has been used to define the quorum-sensing response hierarchy, and that under this condition RhlR is at the top of the regulation hierarchy. These results are highly significant, since phosphate limitation represents a similar environment to the one that P. aeruginosa faces when establishing infections.


Asunto(s)
Fosfatos/deficiencia , Pseudomonas aeruginosa/fisiología , Piocianina/biosíntesis , Percepción de Quorum/fisiología , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Operón , Elastasa Pancreática/biosíntesis , Pseudomonas aeruginosa/metabolismo , Percepción de Quorum/genética , Transactivadores/biosíntesis , Transactivadores/genética , Transcripción Genética
19.
Am J Otolaryngol ; 42(2): 102865, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33450479

RESUMEN

OBJECTIVES: To analyze the characteristics of the visits attended to in an ENT Emergency Department (ENT-ED) during the first wave of COVID-19, comparing them with the emergencies attended to during the same period of time in 2019. METHODS: Descriptive and analytical observational retrospective study of all emergency consultations between March 1, 2020, and May 21, 2020, carried out by the Otorhinolaryngology-Head and Neck Surgery Department of a tertiary university hospital. The adequacy of consultations was assessed with the Hospital Emergency Suitability Protocol (HESP). The correlation between the emergencies and the SARS-CoV-2 confirmed cases was assessed with a generalized linear model. RESULTS: Although there was a decrease of almost 50% in ENT-ED visits during the first wave of COVID-19, the pattern of most cases remained similar to the pre-COVID-19 era: non-urgent consultations, not previously assessed by Primary Care (PC), being considered inadequate by the HESP. The three main reasons for consultation were otalgia, odynophagia, and epistaxis. The number of ENT-ED visits and the total number of confirmed cases of SARS-CoV-2 in the health area were correlated. CONCLUSIONS: SARS-CoV-2 pandemic was a challenge for the Spanish health system. The critical epidemiological situation experienced during March, April, and May explains the reduction in the number of visits to the ENT-ED. However, this condition did not affect the predominant pattern of visits with respect to the pre-COVID-19 era, which were mostly inadequate. A strengthening of PC and an improvement in the population's health education is essential.


Asunto(s)
COVID-19/epidemiología , Servicio de Urgencia en Hospital , Enfermedades Otorrinolaringológicas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , Derivación y Consulta , Estudios Retrospectivos , España/epidemiología , Adulto Joven
20.
Eur Arch Otorhinolaryngol ; 278(7): 2569-2575, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33237476

RESUMEN

PURPOSE: Oropharyngeal cancer is estimated to continue to increase in the next decades. Prevention strategies and knowing the current situation of knowledge and concern of the population about this disease is necessary. Infodemiology is valuable to monitor health information-seeking behaviour trends and epidemiology. The objective of this study is to analyze the use and evolution, through Google trends as a source of information, of internet-based information-seeking behaviour related to the oropharyngeal cancer in Spain and related to mass media stories. METHODS: Using Google Trends, the terms "throat cancer', "HPV", "laryngeal cancer", "tonsil cancer" and "oral cancer". The searches volume and trend were analyzed using a Jointpoint regression method from January 2009 to July 2019. RESULTS: The most searched term was "HPV", with a search volume index of 61, followed by "throat cancer" (SVI = 25). The trend of the term "HPV" increased 6.1% annually (p < 0.000), with a linear correlation of both terms of 0.52 (p < 0.000). The greatest number of searches was carried out in the north of Spain, the most repeated query being "oral sex AND cancer". A correlation between the news in the media and the increase in the volume of searches for the terms was found. CONCLUSION: Any news stories, new interventions or aetiology related to oropharyngeal cancer can manifest as an increase in information-seeking behaviours for "throat cancer" on Google. Understanding healthcare information-seeking behaviour is essential in order to control and plan the quality of knowledge provided by health organisations, advocacy groups and health professionals regarding head and neck cancers.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Humanos , Conducta en la Búsqueda de Información , Internet , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/terapia , Motor de Búsqueda , España/epidemiología
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