Mechanisms of action behind the protective effects of proactive esophageal cooling during radiofrequency catheter ablation in the left atrium.

Proactive esophageal cooling for the purpose of reducing the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures is increasingly being used and has been Food and Drug Administration cleared as a protective strategy during left atrial RF ablation for the treatment of atrial fibrillation. In this review, we examine the evidence supporting the use of proactive esophageal cooling and the potential mechanisms of action that reduce the likelihood of atrioesophageal fistula (AEF) formation. Although the pathophysiology behind AEF formation after thermal injury from RF ablation is not well studied, a robust literature on fistula formation in other conditions (eg, Crohn disease, cancer, and trauma) exists and the relationship to AEF formation is investigated in this review. Likewise, we examine the abundant data in the surgical literature on burn and thermal injury progression as well as the acute and chronic mitigating effects of cooling. We discuss the relationship of these data and maladaptive healing mechanisms to the well-recognized postablation pathophysiological effects after RF ablation. Finally, we review additional important considerations such as patient selection, clinical workflow, and implementation strategies for proactive esophageal cooling.

In situ forming PLA and PLGA implants for the parenteral administration of Cannabidiol.

Cannabidiol (CBD) is the main non-psychotropic cannabinoid. It has attracted a great deal of interest in the treatment of several diseases such as inflammatory disorders and cancer. Despite its promising clinical interest, its administration is very challenging. In situ forming implants could be a simple and cheap strategy to administer CBD while obtaining a prolonged effect with a single administration. This work aims to design, develop, and characterize for the first time ISFIs for the parenteral administration of CBD with potential application in cancer disease. Formulations made of PLGA-502, PLGA-502H, and PLA-202 in NMP or DMSO and PLA-203 in DMSO at a polymer concentration of 0.25 mg/µL and loaded with CBD at a drug: polymer ratio of 2.5:100 and 5:100 (w/w) were developed. The formulations prepared with NMP exhibited a faster drug release. CBD implants elaborated with PLGA-502 and DMSO with the highest CBD: polymer ratio showed the most suitable drug release for one month. This formulation was successfully formed in ovo onto the chorioallantoic chick membrane without exhibiting signs of toxicity and exhibited a superior antiangiogenic activity than CBD in solution administered at the same doses. Consequently, implants made of PLGA-502 and DMSO represent a promising strategy to effectively administer CBD subcutaneously as combination therapy in cancer disease.

Intraoral Scanning for Monitoring Dental Wear and Its Risk Factors: A Prospective Study.

Dental wear arises from mechanical (attrition or abrasion) and chemical (erosion) factors. Despite its prevalence and clinical significance, accurately measuring and understanding its causes remain challenging in everyday practice. This one-year study with 39 participants involved comprehensive examinations and full-arch intraoral scans at the start and after 12 months. Volume loss exceeding 100 µ on each tooth's surfaces (buccal, lingual/palatine and incisal/occlusal) was measured by comparing three-dimensional scans from both time points. This study also assessed factors such as abrasion and erosion through clinical exams and questionnaires. There were no significant differences in dental wear in participants with sleep bruxism. However, noticeable wear occurred in the front teeth of those with waking bruxism and joint-related symptoms. Increased wear was associated with frequent consumption of acidic drinks, regular swimming, dry mouth, nocturnal drooling and heartburn, while no significant wear was found in patients with reflux. The used methodology proved effective in accurately assessing the progression of dental wear, which is important as many patients may initially be asymptomatic. The variability observed in dental wear patterns underscores the need to develop specific software applications that allow immediate and efficient comparison of wear areas based on extensive analysis of patient databases.

Particle swarm optimization solution for roll-off control in radiofrequency ablation of liver tumors: Optimal search for PID controller tuning.

The study investigates the efficacy of a bioinspired Particle Swarm Optimization (PSO) approach for PID controller tuning in Radiofrequency Ablation (RFA) for liver tumors. Ex-vivo experiments were conducted, yielding a 9th order continuous-time transfer function. PSO was applied to optimize PID parameters, achieving outstanding simulation results: 0.605% overshoot, 0.314 seconds rise time, and 2.87 seconds settling time for a unit step input. Statistical analysis of 19 simulations revealed PID gains: Kp (mean: 5.86, variance: 4.22, standard deviation: 2.05), Ki (mean: 9.89, variance: 0.048, standard deviation: 0.22), Kd (mean: 0.57, variance: 0.021, standard deviation: 0.14) and ANOVA analysis for the 19 experiments yielded a p-value ≪ 0.05. The bioinspired PSO-based PID controller demonstrated remarkable potential in mitigating roll-off effects during RFA, reducing the risk of incomplete tumor ablation. These findings have significant implications for improving clinical outcomes in hepatocellular carcinoma management, including reduced recurrence rates and minimized collateral damage. The PSO-based PID tuning strategy offers a practical solution to enhance RFA effectiveness, contributing to the advancement of radiofrequency ablation techniques.

Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Ablation catheter-induced mechanical deformation in myocardium: computer modeling and ex vivo experiments.

Cardiac catheter ablation requires an adequate contact between myocardium and catheter tip. Our aim was to quantify the relationship between the contact force (CF) and the resulting mechanical deformation induced by the catheter tip using an ex vivo model and computational modeling. The catheter tip was inserted perpendicularly into porcine heart samples. CF values ranged from 10 to 80 g. The computer model was built to simulate the same experimental conditions, and it considered a 3-parameter Mooney-Rivlin model based on hyper-elastic material. We found a strong correlation between the CF and insertion depth (ID) (R2 = 0.96, P < 0.001), from 0.7 ± 0.3 mm at 10 g to 6.9 ± 0.1 mm at 80 g. Since the surface deformation was asymmetrical, two transversal diameters (minor and major) were identified. Both diameters were strongly correlated with CF (R2 ≥ 0.95), from 4.0 ± 0.4 mm at 20 g to 10.3 ± 0.0 mm at 80 g (minor), and from 6.4 ± 0.7 mm at 20 g to 16.7 ± 0.1 mm at 80 g (major). An optimal fit between computer and experimental results was achieved, with a prediction error of 0.74 and 0.86 mm for insertion depth and mean surface diameter, respectively.

Present and Future Applications of Digital PCR in Infectious Diseases Diagnosis.

Infectious diseases account for about 3 million deaths per year. The advent of molecular techniques has led to an enormous improvement in their diagnosis, both in terms of sensitivity and specificity and in terms of the speed with which a clinically useful result can be obtained. Digital PCR, or 3rd generation PCR, is based on a series of technical modifications that result in more sensitive techniques, more resistant to the action of inhibitors and capable of direct quantification without the need for standard curves. This review presents the main applications that have been developed for the diagnosis of viral, bacterial, and parasitic infections and the potential prospects for the clinical use of this technology.

Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Discrepancies in Electronic Medical Prescriptions Found in a Hospital Emergency Department: A Prospective Observational Study.

The medication in an electronic prescribing system (EPS) does not always match the patient's actual medication. This prospective study analyzes the discrepancies (any inconsistency) between medication prescribed using an EPS and the medication revised by the clinical pharmacist upon admission to the observation area of the emergency department (ED). Adult patients with multimorbidity and/or polypharmacy were included. The pharmacist used multiple sources to obtain the revised medication list, including patient/carer interviews. A total of 1654 discrepancies were identified among 1131 patients. Of these patients, 64.5% had ≥1 discrepancy. The most common types of discrepancy were differences in posology (43.6%), commission (34.7%), and omission (20.9%). Analgesics (11.1%), psycholeptics (10.0%), and diuretics (8.9%) were the most affected. Furthermore, 52.5% of discrepancies affected medication that was high-alert for patients with chronic illnesses and 42.0% of medication involved withdrawal syndromes. Discrepancies increased with the number of drugs (ρ = 0.44, p < 0.01) and there was a difference between non-polypharmacy patients, polypharmacy ones and those with extreme polypharmacy (p < 0.01). Those aged over 75 years had a higher number of prescribed medications and discrepancies occurred more frequently compared with younger patients. The number of discrepancies was larger in women than in men. The EPS medication record requires verification from additional sources, including patient and/or carer interviews.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Difference between endocardial and epicardial application of pulsed fields for targeting Epicardial Ganglia: An in-silico modelling study.

BACKGROUND: Pulsed Field Ablation (PFA) has recently been proposed as a non-thermal energy to treat atrial fibrillation by selective ablation of ganglionated plexi (GP) embedded in epicardial fat. While some of PFA-technologies use an endocardial approach, others use epicardial access with promising pre-clinical results. However, as each technology uses a different and sometimes proprietary pulse application protocol, the comparation between endocardial vs. epicardial approach is almost impossible in experimental terms. For this reason, our study, based on a computational model, allows a direct comparison of electric field distribution and thermal-side effects of both approaches under equal conditions in terms of electrode design, pulse protocol and anatomical characteristics of the tissues involved. METHODS: 2D computational models with axial symmetry were built for endocardial and epicardial approaches. Atrial (1.5-2.5 mm) and fat (1-5 mm) thicknesses were varied to simulate a representative sample of what happens during PFA ablation for different applied voltage values (1000, 1500 and 2000 V) and number of pulses (30 and 50). RESULTS: The epicardial approach was superior for capturing greater volumes of fat when the applied voltage was increased: 231 mm3/kV with the epicardial approach vs. 182 mm3/kV with the endocardial approach. In relation to collateral damage to the myocardium, the epicardial approach considerably spares the myocardium, unlike what happens with the endocardial approach. Although the epicardial approach caused much more thermal damage in the fat, there is not a significant difference between the approaches in terms of size of thermal damage in the myocardium. CONCLUSIONS: Our results suggest that epicardial PFA ablation of GPs is more effective than an endocardial approach. The proximity and directionality of the electric field deposited using an epicardial approach are key to ensuring that higher electric field strengths and increased temperatures are obtained within the epicardial fat, thus contributing to selective ablation of the GPs with minimal myocardial damage.

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.

Type I interferon pathway activation across the antiphospholipid syndrome spectrum: associations with disease subsets and systemic antiphospholipid syndrome presentation.

Introduction: While the type I interferon (IFN-I) pathway is crucial in autoimmunity, its role in antiphospholipid antibody (aPL)-positive subjects, including aPL carriers and antiphospholipid syndrome (APS) patients, is poorly understood. This study aims at characterizing IFN-I pathway activation within the spectrum of aPL-positive subsets. Methods: A total of 112 patients [29 aPL carriers, 31 primary APS (PAPS), 25 secondary APS (SAPS), 27 systemic lupus erythematosus (SLE) patients without aPL, and 44 healthy controls (HCs)] were recruited. IFI6, IFI44, IFI44L, MX1, IFI27, OAS1, and RSAD2 gene expression was evaluated in whole blood, and a composite index (IFN score) was calculated. Results: An overall activation of the IFN-I pathway was observed across the entire APS spectrum, with differences among genes based on the specific disease subset. The composite score revealed quantitative differences across subsets, being elevated in aPL carriers and PAPS patients compared to HCs (both p < 0.050) and increasing in SAPS (p < 0.010) and SLE patients (p < 0.001). An unsupervised cluster analysis identified three clusters, and correspondence analyses revealed differences in clusters usage across APS subsets (p < 0.001). A network analysis revealed different patterns characterizing different subsets. The associations between IFN-I pathway activation and clinical outcomes differed across APS subsets. Although no differences in gene expression were observed in systemic APS, the network analyses revealed specific gene-gene patterns, and a distinct distribution of the clusters previously identified was noted (p = 0.002). Conclusion: IFN-I pathway activation is a common hallmark among aPL-positive individuals. Qualitative and quantitative differences across the APS spectrum can be identified, leading to the identification of distinct IFN-I signatures with different clinical values beyond traditional categorization.

HPV and Cervical Cancer: Molecular and Immunological Aspects, Epidemiology and Effect of Vaccination in Latin American Women.

Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores molecular and immunological aspects of HPV infection, its role in cervical cancer development, and the epidemiology in this region, highlighting the prevalence and diversity of HPV genotypes. The impact of vaccination initiatives on cervical cancer rates in Latin America is critically evaluated. The advent of HPV vaccines has presented a significant tool in combating the burden of this malignancy, with notable successes observed in various countries, the latter due to their impact on immune responses. The review synthesizes current knowledge, emphasizes the importance of continued research and strategies for cervical cancer prevention, and underscores the need for ongoing efforts in this field.

Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores.

Prostate cancer (PCa) is the most prevalent cause of death in the male population worldwide. The G Protein-Coupled Estrogen Receptor (GPER) has been gaining relevance in the development of PCa. Hedgehog (Hh) pathway activation is associated with aggressiveness, metastasis, and relapse in PCa patients. To date, no studies have evaluated the crosstalk between the GPER and the Hh pathway along different group grades in PCa. We conducted an analysis of paraffin-embedded tissues derived from patients with different prognostic grade of PCa using immunohistochemistry. Expression and correlation between GPER and glioma associated oncogene homologue (GLI) transcriptional factors in the parenchyma and stroma of PCa tumors were evaluated. Our results indicate that GPER is highly expressed in the nucleus and increases with higher grade groups. Additionally, GPER's expression correlates with pGLI3 nuclear expression across different grade groups in PCa tissues; however, whether the receptor induces the activation of GLI transcriptional factors, or the latter modulate the expression of GPER is yet to be discovered, as well as the functional consequence of this correlation.

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.

Pregnancy-Related Eccrine Angiomatous Hamartoma: Case Report.

Eccrine angiomatous hamartoma is rare, slow-growing, and benign neoplasm that is diagnosed based on clinical characteristics and histological findings. It usually presents as a solitary nodule on the extremities and may arise at birth or in childhood. Although it is usually asymptomatic, in some cases it can cause pain and hyperhidrosis. From a histological perspective, it is characterized by an increase in the number of eccrine glands and a proliferation of vascular channels. We present the case of a 26-year-old woman who developed an eccrine angiomatous hamartoma in her right leg. The rapid growth of the lesion during pregnancy coupled with the challenges posed by a superficial biopsy, complicated the differential diagnosis.

Beyond the Scalpel: Assessing ChatGPT's potential as an auxiliary intelligent virtual assistant in oral surgery.

AI has revolutionized the way we interact with technology. Noteworthy advances in AI algorithms and large language models (LLM) have led to the development of natural generative language (NGL) systems such as ChatGPT. Although these LLM can simulate human conversations and generate content in real time, they face challenges related to the topicality and accuracy of the information they generate. This study aimed to assess whether ChatGPT-4 could provide accurate and reliable answers to general dentists in the field of oral surgery, and thus explore its potential as an intelligent virtual assistant in clinical decision making in oral surgery. Thirty questions related to oral surgery were posed to ChatGPT4, each question repeated 30 times. Subsequently, a total of 900 responses were obtained. Two surgeons graded the answers according to the guidelines of the Spanish Society of Oral Surgery, using a three-point Likert scale (correct, partially correct/incomplete, and incorrect). Disagreements were arbitrated by an experienced oral surgeon, who provided the final grade Accuracy was found to be 71.7%, and consistency of the experts' grading across iterations, ranged from moderate to almost perfect. ChatGPT-4, with its potential capabilities, will inevitably be integrated into dental disciplines, including oral surgery. In the future, it could be considered as an auxiliary intelligent virtual assistant, though it would never replace oral surgery experts. Proper training and verified information by experts will remain vital to the implementation of the technology. More comprehensive research is needed to ensure the safe and successful application of AI in oral surgery.

Assessment of In Vitro Release Testing Methods for Colloidal Drug Carriers: The Lack of Standardized Protocols.

Although colloidal carriers have been in the pipeline for nearly four decades, standardized methods for testing their drug-release properties remain to be established in pharmacopeias. The in vitro assessment of drug release from these colloidal carriers is one of the most important parameters in the development and quality control of drug-loaded nano- and microcarriers. This lack of standardized protocols occurs due to the difficulties encountered in separating the released drug from the encapsulated one. This review aims to compare the most frequent types of release testing methods (i.e., membrane diffusion techniques, sample and separate methods and in situ detection techniques) in terms of the advantages and disadvantages of each one and of the key parameters that influence drug release in each case.