Insights into estrogen impact in oral health & microbiome in COVID-19.

BACKGROUND: COVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed. RESULTS: Our results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1ß, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7). CONCLUSIONS: Postmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

Proactive esophageal cooling during laser cardiac ablation: A computer modeling study.

BACKGROUND AND OBJECTIVES: Laser ablation is increasingly used to treat atrial fibrillation (AF). However, atrioesophageal injury remains a potentially serious complication. While proactive esophageal cooling (PEC) reduces esophageal injury during radiofrequency ablation, the effects of PEC during laser ablation have not previously been determined. We aimed to evaluate the protective effects of PEC during laser ablation of AF by means of a theoretical study based on computer modeling. METHODS: Three-dimensional mathematical models were built for 20 different cases including a fragment of atrial wall (myocardium), epicardial fat (adipose tissue), connective tissue, and esophageal wall. The esophagus was considered with and without PEC. Laser-tissue interaction was modeled using Beer-Lambert's law, Pennes' Bioheat equation was used to compute the resultant heating, and the Arrhenius equation was used to estimate the fraction of tissue damage (FOD), assuming a threshold of 63% to assess induced necrosis. We modeled laser irradiation power of 8.5 W over 20 s. Thermal simulations extended up to 250 s to account for thermal latency. RESULTS: PEC significantly altered the temperature distribution around the cooling device, resulting in lower temperatures (around 22°C less in the esophagus and 9°C in the atrial wall) compared to the case without PEC. This thermal reduction translated into the absence of transmural lesions in the esophagus. The esophagus was thermally damaged only in the cases without PEC and with a distance equal to or shorter than 3.5 mm between the esophagus and endocardium (inner boundary of the atrial wall). Furthermore, PEC demonstrated minimal impact on the lesion created across the atrial wall, either in terms of maximum temperature or FOD. CONCLUSIONS: PEC reduces the potential for esophageal injury without degrading the intended cardiac lesions for a variety of different tissue thicknesses. Thermal latency may influence lesion formation during laser ablation and may play a part in any collateral damage.

Unveiling the ChatGPT phenomenon: Evaluating the consistency and accuracy of endodontic question answers.

AIM: Chatbot Generative Pre-trained Transformer (ChatGPT) is a generative artificial intelligence (AI) software based on large language models (LLMs), designed to simulate human conversations and generate novel content based on the training data it has been exposed to. The aim of this study was to evaluate the consistency and accuracy of ChatGPT-generated answers to clinical questions in endodontics, compared to answers provided by human experts. METHODOLOGY: Ninety-one dichotomous (yes/no) questions were designed and categorized into three levels of difficulty. Twenty questions were randomly selected from each difficulty level. Sixty answers were generated by ChatGPT for each question. Two endodontic experts independently answered the 60 questions. Statistical analysis was performed using the SPSS program to calculate the consistency and accuracy of the answers generated by ChatGPT compared to the experts. Confidence intervals (95%) and standard deviations were used to estimate variability. RESULTS: The answers generated by ChatGPT showed high consistency (85.44%). No significant differences in consistency were found based on question difficulty. In terms of answer accuracy, ChatGPT achieved an average accuracy of 57.33%. However, significant differences in accuracy were observed based on question difficulty, with lower accuracy for easier questions. CONCLUSIONS: Currently, ChatGPT is not capable of replacing dentists in clinical decision-making. As ChatGPT's performance improves through deep learning, it is expected to become more useful and effective in the field of endodontics. However, careful attention and ongoing evaluation are needed to ensure its accuracy, reliability and safety in endodontics.

A tutorial on discourse analysis in healthy and pathological ageing.

BACKGROUND: Age is a key factor when dealing with language and speech disorders, as it entails a progressive loss of neuroplasticity even in healthy individuals. Apart from this, ageing also affects our word-retrieval abilities, and thus, our discursive skills, particularly in people suffering from neurodegenerative diseases. Therefore, descriptions and/or measures of communicative performance always need to be interpreted through the lens of variation across the lifespan. AIM: This paper's main objective is to create a general tutorial for researchers willing to start delving into discourse analysis, both in healthy and pathological ageing. METHODS: An eight-step tutorial on discourse analysis in the elderly is presented. Each of these steps starts with general recommendations and progresses to more specific topics that may be relevant when conducting this type of research. All of the steps have been extrapolated from an extensive literature review on discourse analysis. MAIN CONTRIBUTIONS: This work presents an easy-to-follow, step-by-step tutorial on discourse analysis in the elderly. It is aimed at clinical researchers who are taking their first steps in discourse analysis.It may also be useful for those who are already familiar with the methodology but may be interested in reading a general overview on the topic. Moreover, it offers new insights into the following topics: types of research questions, advantages and disadvantages of the different research methodologies and ethical considerations for data production in clinical linguistics. CONCLUSIONS: Discourse analysis in the elderly is a highly complex issue that may require researching from different approaches and disciplines. This implies following a well-planned and thorough process, which we have detailed through the following eight steps: (i) reviewing literature; (ii) formulating the research question; (iii) designing the study; (iv) producing data; (v) selecting technological tools for data treatment; (vi) transcribing the corpus; (vii) annotating the corpus and (viii) analysing and interpreting the results. WHAT THIS PAPER ADDS: What is already known on the subject Approaches in discourse analysis in elderly adults, and particularly, in people suffering from dementia have already been analysed by previous researchers and categorised into three main trends: the quantitative-experimental approach, the qualitative-naturalistic approach and an in-between path, the quantitative-naturalistic approach. Also, several handbooks on general discourse analysis have presented comprehensive revisions on potential resources and methodologies that can be applied to researching discourse in elderly populations. What this paper adds to existing knowledge This paper takes these three main approaches and analyses how the most recent research on language in ageing and dementia fits into them. Furthermore, it reviews the advantages and disadvantages each of them may bring for beginners in the field of discourse analysis. Moreover, it adds some studies that may fit into a fourth approach: the qualitative-experimental. This article also presents information about several of the main steps when analysing data from the pragmatic perspective: the formulation of the research question, data production and the transcription/annotation process. What are the potential or actual clinical implications of this work? This work has been devised for linguists who may want to read a systematization of the steps for analysing discourse in elderly populations. It may also be of interest to specialists from different fields such as speech therapy, psychology, gerontology or neurology who desire to start applying methods from discourse analysis in their work and aim to have a comprehensive scope of the main research trends within the field of clinical pragmatics.

ChatGPT performance in prosthodontics: Assessment of accuracy and repeatability in answer generation.

STATEMENT OF PROBLEM: The artificial intelligence (AI) software program ChatGPT is based on large language models (LLMs) and is widely accessible. However, in prosthodontics, little is known about its performance in generating answers. PURPOSE: The purpose of this study was to determine the performance of ChatGPT in generating answers about removable dental prostheses (RDPs) and tooth-supported fixed dental prostheses (FDPs). MATERIAL AND METHODS: Thirty short questions were designed about RDPs and tooth-supported FDP, and 30 answers were generated for each of the questions using ChatGPT-4 in October 2023. The 900 generated answers were independently graded by experts using a 3-point Likert scale. The relative frequency and absolute percentage of answers were described. Accuracy was assessed using the Wald binomial method, while repeatability was evaluated using percentage agreement, Brennan and Prediger coefficient, Conger generalized Cohen kappa, Fleiss kappa, Gwet AC, and Krippendorff alpha methods. Confidence intervals were set at 95%. Statistical analysis was performed using the STATA software program. RESULTS: The performance of ChatGPT in generating answers related to RDP and tooth-supported FDP was limited. The answers showed a reliability of 25.6%, with a confidence range between 22.9% and 28.6%. The repeatability ranged from substantial to moderate. CONCLUSIONS: The results show that currently ChatGPT has limited ability to generate answers related to RDPs and tooth-supported FDPs. Therefore, ChatGPT cannot replace a dentist, and, if professionals were to use it, they should be aware of its limitations.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages.

OBJECTIVE: Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis. METHODS: IgG and IgM serum levels of antibodies against HDL (anti-HDL) and apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients, 14 arthralgia individuals and 96 controls. Established RA patients (n = 42) were included for validation. Atherosclerosis and vascular stiffness were measured by Doppler ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high-throughput targeted proteomics. RESULTS: Anti-HDL and anti-ApoA1 responses were increased in early RA compared with controls (both P < 0.001) and were comparable to established disease. Only anti-ApoA1 antibodies were increased in arthralgia. IgG anti-HDL and anti-ApoA1 were associated with unfavourable lipoprotein traits in RA and arthralgia, respectively. A similar picture was observed for inflammatory mediators. No associations with clinical features or risk factors were found. IgG anti-HDL were independently associated with atherosclerosis occurrence in early RA, and outperformed patient stratification over conventional algorithms (mSCORE) and their anti-ApoA1 counterparts. Anti-HDL antibodies correlated with proteins involved in immune activation, remodelling and lipid metabolism pathways in early RA. CONCLUSION: Humoral responses against HDL particles are an early event along the arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers and underlying pathogenic circuits.

How far the zone of heat-induced transient block extends beyond the lesion during RF catheter cardiac ablation.

PURPOSE: While radiofrequency catheter ablation (RFCA) creates a lesion consisting of the tissue points subjected to lethal heating, the sublethal heating (SH) undergone by the surrounding tissue can cause transient electrophysiological block. The size of the zone of heat-induced transient block (HiTB) has not been quantified to date. Our objective was to use computer modeling to provide an initial estimate. METHODS AND MATERIALS: We used previous experimental data together with the Arrhenius damage index (Ω) to fix the Ω values that delineate this zone: a lower limit of 0.1-0.4 and upper limit of 1.0 (lesion boundary). An RFCA computer model was used with different power-duration settings, catheter positions and electrode insertion depths, together with dispersion of the tissue's electrical and thermal characteristics. RESULTS: The HiTB zone extends in depth to a minimum and maximum distance of 0.5 mm and 2 mm beyond the lesion limit, respectively, while its maximum width varies with the energy delivered, extending to a minimum of 0.6 mm and a maximum of 2.5 mm beyond the lesion, reaching 3.5 mm when high energy settings are used (25 W-20s, 500 J). The dispersion of the tissue's thermal and electrical characteristics affects the size of the HiTB zone by ±0.3 mm in depth and ±0.5 mm in maximum width. CONCLUSIONS: Our results suggest that the size of the zone of heat-induced transient block during RFCA could extend beyond the lesion limit by a maximum of 2 mm in depth and approximately 2.5 mm in width.

The Internet of Things for the Intelligent Management of the Heating of a Swimming Pool by Means of Smart Sensors.

By using various smart sensors integrated in a global domotic system, a proper solar thermal management is executed. The goal is to properly manage solar energy for heating swimming pool using various devices installed at home. Swimming pools are a necessity in many communities. In summer, they are a source of refreshment. However, maintaining a swimming pool at an optimal temperature can be a challenge even in the summer months. The use of the Internet of Things in homes has enabled proper management of solar thermal energy, thus significantly improving the quality of life by making homes more comfortable and safer without using additional resources. The houses built today have several smart devices that manage to optimize the energy consumption of the house. The solutions proposed in this study to improve energy efficiency in swimming pool facilities include the installation of solar collectors to heat swimming pool water more efficiently. The installation of smart actuation devices (to efficiently control energy consumption of a pool facility via different processes) together with sensors that provide valuable information on energy consumption in the different processes of a pool facility, can optimize energy consumption thus reducing overall consumption (by 90%) and economic cost (by more than 40%). Together, these solutions can help to significantly reduce energy consumption and economic costs and extrapolate it to different processes of similar characteristics in the rest of the society.

Immunometabolic Profile Associated with Progressive Damage of the Intestinal Mucosa in Adults Screened for Colorectal Cancer: Association with Diet.

Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.

Splicing Characterization and Isoform Switch Events in Human Keratinocytes Carrying Oncogenes from High-Risk HPV-16 and Low-Risk HPV-84.

Infection of epithelial cells with high-risk HPV (HR-HPV) types, followed by expression of virus oncogenic proteins (E5, E6, and E7), leads to genomic imbalance, suppression of tumor inhibitors, and induction of oncogenes. Low-risk HPV (LR-HPV) may slow the rate at which cervical cancer spreads to an invasive stage since co-infection with LR-HPV is linked to a decreased risk of future invasive cancer than infection with HR-HPV alone. We then propose that cancer-progressing changes may be distinguished through identifying the functional differences between LR-HPV and HR-HPV. Lentiviral strategies were followed to establish HaCaT cells with constitutive expression of HPV oncogenes. RNAseq experiments were designed to analyze the transcriptome modulations caused by each of the E5, E6, and E7 oncogenes of HPV-16 and HPV-84 in HaCaT cells. We identified enhanced RNA degradation, spliceosome, and RNA polymerase pathways related to mRNA processing. ATTS (alternative transcription termination site) was discovered to be more prevalent in cells with HPV-16E5 than HPV-84E5. In HPV-16E6-infected cells, ATTS gain was significantly higher than ATTS loss. Cells with HPV-16E7 had more isoforms with intron retention (IR) than those with HPV-84E7. We identified switches in ADAM10, CLSPN, and RNPS1 that led to greater expression of the coding isoforms in HR-HPV. The results of this work highlight differences between LR-HPV and HR-HPV in mRNA processing. Moreover, crucial cervical cancer-related switch events were detected.

Alzheimer's Disease: An Updated Overview of Its Genetics.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aß) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

Assessment of the Use of Common Juniper (Juniperus communis L.) Foliage following the Cascade Principle.

Juniperus communis L. is a species commonly grown in regions of the Northern Hemisphere, and is a good candidate to be cultivated in marginal lands. Plants coming from a pruning performed in a natural population located in Spain were used to assess the yield and quality of different products obtained following the cascade principle. A total of 1050 kg of foliage biomass were crushed, steam-distilled, and separated into fractions to produce biochar and absorbents for the pet industry using pilot plants. The obtained products were analysed. The essential oil, with a yield of 0.45% dry basis and a qualitative chemical composition similar to that described for the berries in international standards or monographs, showed antioxidant activity with promising CAA results (inhibition of 89% of the cell's oxidation). However, regarding antibacterial and antifungal activities, it only inhibited the growth of microorganisms at the maximum concentration tested, 2.5%. Concerning the hydrolate, it did not show bioactivity. Regarding the biochar, whose yield was 28.79% dry basis, interesting results were obtained for its characterisation as a possible soil improver for agronomic purposes (PFC 3(A)). Finally, promising results were obtained regarding the use of common juniper as absorbent, taking into account the physical characterisation and odour control capacity.

Urgent endoscopy versus early endoscopy: Does urgent endoscopy play a role in acute non-variceal upper gastrointestinal bleeding? / Endoscopia urgente frente a endoscopia precoz: ¿tiene algún papel la endoscopia urgente en la hemorragia digestiva alta aguda no varicosa?

INTRODUCTION: The main clinical practice guidelines recommend endoscopy within 24hours after admission to the Emergency Department in patients with non-variceal upper gastrointestinal bleeding. However, it is a wide time frame and the role of urgent endoscopy (<6hours) is controversial. MATERIAL AND METHODS: Prospective observational study carried out at La Paz University Hospital, where all patients were selected, from January 1, 2015 to April 30, 2020, who attended the Emergency Room and underwent endoscopy for suspected upper gastrointestinal bleeding. Two groups of patients were established: urgent endoscopy (<6hours) and early endoscopy (6-24hours). The primary endpoint of the study was 30-day mortality. RESULTS: A total of 1096 were included, of whom 682 underwent urgent endoscopy. Mortality at 30days was 6% (5% vs 7.7%, P=.064) and rebleeding was 9.6%. There were no statistically significant differences in mortality, rebleeding, need for endoscopic treatment, surgery and/or embolization, but there were differences in the necessity for transfusion(57.5% vs 68.4%, P<.001) and the number of concentrates of transfused red blood cells (2.85±4.01 vs 3.51±4.09, P=.008). CONCLUSION: Urgent endoscopy, in patients with acute upper gastrointestinal bleeding, as well as the high-risk subgroup (GBS ≥12), was not associated with lower 30-day mortality than early endoscopy. However, urgent endoscopy in patients with high-risk endoscopic lesions (ForrestI-IIB), was a significant predictor of lower mortality. Therefore, more studies are required for the correct identification of patients who benefit from this medical approach (urgent endoscopy).

Influence of the use of social media on patients changing dental practice: a web-based questionnaire study.

BACKGROUND: Recent years have seen an increase in the use of social media, by the healthcare sector, including dentistry. Indeed, social media may now be important communication tools for dental practices and patients. This work analyzes the influence of patient (male and female) use of dental practice social media on their decision to change practice. The results also provide insight into the factors patients considered important when choosing a dental practice. METHODS: This study was approved by the Ethics Committee of the Universidad Europea de Madrid (No. CIPI/22.022). Using a web-based questionnaire, a cross-sectional study was undertaken involving a Spanish population that made use of dental services. The questionnaire consisted of four parts covering provision of informed consent, the collection of sociodemographic data, patient use of dental practice social media, and the factors considered important when changing dental practice. RESULTS: All participants gave their informed consent regarding inclusion. No compensation was provided for participation. 588 people responded to the questionnaire, of whom 503 were eligible for inclusion. Most respondents were female (312/503; 62%). Most (151/503; 30%) last changed dental practice during the previous 2-5 years. 208/503 (41.4%) indicated that they had visited dental practice social media. 118/503 (23.5%) indicated that they had made use of such the last time they changed dental practice; 102 of these 118 (85.6%) reported their experience to have influenced their decision to change. Respondents who had changed practice in the last 5 years had interacted with dental practice social media more than those who changed over 11 years ago (p < .05), and those who changed practice in the present/past year were more influenced by these media (p < .05). The factor considered most important was 'Facilities and technology'. No gender-based differences were seen for any measured variable (p < .05). CONCLUSIONS: Different factors affect the selection of a new dental practice, but respondents who changed practice in the last few years were more likely to have made use of dental practice social media, which, for some, influenced their final decision to change. Dental practices might do well to consider using social media as communication and marketing tools.

Relationship between luminal esophageal temperature and volume of esophageal injury during RF ablation: In silico study comparing low power-moderate duration vs. high power-short duration.

OBJECTIVE: To model the evolution of peak temperature and volume of damaged esophagus during and after radiofrequency (RF) ablation using low power-moderate duration (LPMD) versus high power-short duration (HPSD) or very high power-very short duration (VHPVSD) settings. METHODS: An in silico simulation model of RF ablation accounting for left atrial wall thickness, nearby organs and tissues, as well as catheter contact force. The model used the Arrhenius equation to derive a thermal damage model and estimate the volume of esophageal damage over time during and after RF application under conditions of LPMD (30 W, 20 s), HPSD (50 W, 6 s), and VHPVSD (90 W, 4 s). RESULTS: There was a close correlation between maximum peak temperature after RF application and volume of esophageal damage, with highest correlation (R2 = 0.97) and highest volume of esophageal injury in the LPMD group. A greater increase in peak temperature and greater relative increase in esophageal injury volume in the HPSD (240%) and VHPSD (270%) simulations occurred after RF termination. Increased endocardial to esophageal thickness was associated with a longer time to maximum peak temperature (R2 > 0.92), especially in the HPSD/VHPVSD simulations, and no esophageal injury was seen when the distances were >4.5 mm for LPMD or >3.5 mm for HPSD. CONCLUSION: LPMD is associated with a larger total volume of esophageal damage due to the greater total RF energy delivery. HPSD and VHPVSD shows significant thermal latency (resulting from conductive tissue heating after RF termination), suggesting a requirement for fewer esophageal temperature cutoffs during ablation.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

PURPOSE: Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. METHODS: An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. RESULTS: The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. CONCLUSION: The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Role of MicroRNAs in Signaling Pathways Associated with the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Focus on Epithelial-Mesenchymal Transition.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.

A protocol for a randomized trial measuring flowmetry in risk areas for pressure ulcer: Hyperoxygenated fatty acids vs olive oil.

BACKGROUND: Pressure ulcers are a common adverse event in healthcare. To date, no flowmetry studies have been conducted to compare hyperoxygenated fatty acids (HFA) vs. extra-virgin olive oil (EVOO) in alleviating this condition. AIMS: To determine and evaluate the effect of the application of HFA vs. EVOO on tissue oxygenation and perfusion in heels under pressure, in healthy persons and in hospitalised patients. DESIGN: Two-phase experimental study. METHODS: Phase 1 will be conducted with healthy subjects, using a randomised, open study design, evaluating an intrasubject control group. Phase 2 will focus on hospitalised subjects, with a randomised, open study group vs. a control group. DISCUSSION: This Project is undertaken to identify the mechanisms that intervene in the genesis of pressure ulcers and to determine whether there are differences in outcomes between the application of HFA vs. EVOO as a preventive measure The results of this study are of economic importance (due to the price difference between the products used) and will also impact on usual clinical practice for patients with impaired mobility and liable to suffer from pressure ulcers, by considering an alternative to established preventive measures.

Effect of intracardiac blood flow pulsatility during radiofrequency cardiac ablation: computer modeling study.

PURPOSE: To assess the effect of intracardiac blood flow pulsatility on tissue and blood distributions during radiofrequency (RF) cardiac ablation (RFCA). METHODS: A three-dimensional computer model was used to simulate constant power ablations with an irrigated-tip electrode and three possible catheter orientations (perpendicular, parallel and 45°). Continuous flow and three different pulsatile flow profiles were considered, with four average blood velocity values: 3, 5.5, 8.5 and 24.4 cm/s. The 50 °C contour was used to assess thermal lesion size. RESULTS: The differences in lesion size between continuous flow and the different pulsatile flow profiles were always less than 1 mm. As regards maximum tissue temperature, the differences between continuous and pulsatile flow were always less than 1 °C, with slightly higher differences in maximum blood temperature, but never over 6 °C. While the progress of maximum tissue temperature was identical for continuous and pulsatile flow, maximum blood temperature with the pulsatile profile showed small amplitude oscillations associated with blood flow pulsatility. CONCLUSIONS: The findings show that intracardiac blood pulsatility has a negligible effect on lesion size and a very limited impact on maximum tissue and blood temperatures, which suggests that future experimental studies based on ex vivo or in silico models can ignore pulsatility in intracardiac blood flow.

High-power short-duration vs. standard radiofrequency cardiac ablation: comparative study based on an in-silico model.

PURPOSE: While the standard setting during radiofrequency catheter ablation (RFCA) consists of applying low power for long times, a new setting based on high power and short duration (HPSD) has recently been suggested as safer and more effective. Our aim was to compare the electrical and thermal performance of standard vs. HPSD settings, especially to assess the effect of the catheter orientation. METHODS: A 3D computational model was built based on a coupled electric-thermal-flow problem. Standard (20 W-45 s and 30 W-30 s) and HPSD settings (70 W-7 s and 90 W-4 s) were compared. Since the model only included a cardiac tissue fragment, the power values were adjusted to 80% of the clinical values (15, 23, 53 and 69 W). Three catheter-tissue orientations were considered (90°, 45° and 0°). Thermal lesions were assessed by the Arrhenius equation. Safety was assessed by checking the occurrence of steam pops (100 °C in tissue) and thrombus formation (80 °C in blood). RESULTS: The computed thermal lesions were in close agreement with the experimental data in the literature, in particular with in vivo studies. HPSD created shallower and wider lesions than standard settings, especially with the catheter at 45°. Steam pops occurred earlier with HPSD, regardless of catheter orientation. CONCLUSION: HPSD seems to be more effective in cases that need shallow and extensive lesions, especially when the catheter is at 0° or at 45°, as used in pulmonary vein isolation.