Promising tools for future drug discovery and development in antiarrhythmic therapy.

Arrhythmia refers to irregularities in the rate and rhythm of the heart, with symptoms spanning from mild palpitations to life-threatening arrhythmias and sudden cardiac death (SCD). The complex molecular nature of arrhythmias complicates the selection of appropriate treatment. Current therapies involve the use of antiarrhythmic drugs (class I-IV) with limited efficacy and dangerous side effects and implantable pacemakers and cardioverter-defibrillators with hardware-related complications and inappropriate shocks. The number of novel antiarrhythmic drug in the development pipeline has decreased substantially during the last decade and underscores uncertainties regarding future developments in this field. Consequently, arrhythmia treatment poses significant challenges, prompting the need for alternative approaches. Remarkably, innovative drug discovery and development technologies show promise in helping advance antiarrhythmic therapies. Here, we review unique characteristics and the transformative potential of emerging technologies that offer unprecedented opportunities for transitioning from traditional antiarrhythmics to next-generation therapies. We assess stem cell technology, emphasizing the utility of innovative cell profiling using multi-omics, high-throughput screening, and advanced computational modeling in developing treatments tailored precisely to individual genetic and physiological profiles. We offer insights into gene therapy, peptide and peptibody approaches for drug delivery. We finally discuss potential strengths and weaknesses of such techniques in reducing adverse effects and enhancing overall treatment outcomes, leading to more effective, specific, and safer therapies. Altogether, this comprehensive overview introduces innovative avenues for personalized rhythm therapy, with particular emphasis on drug discovery, aiming to advance the arrhythmia treatment landscape and the prevention of SCD. Significance Statement Arrhythmias and sudden cardiac death account for 15-20% of deaths worldwide. However, current antiarrhythmic therapies are ineffective and with dangerous side effects. Here, we review the field of arrhythmia treatment underscoring the slow progress in advancing the cardiac rhythm therapy pipeline and the uncertainties regarding evolution of this field. We provide information on how emerging technological and experimental tools can help accelerate progress and address the limitations of antiarrhythmic drug discovery.

Advancing mechanistic explanations through natural and artificial embodied cognitive systems.

Mougenot and Matheson propose that mechanistic models can explain behavior by describing the complex interactions among components of the brain, body, and environment as an integrated system, which aligns with embodied cognition. However, we suggest incorporating cognitive ontology theory and addressing degeneracy and neuronal reuse. We also recommend studying natural embodied cognition through artificial systems to develop a comprehensive mechanistic framework.

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024.

INTRODUCTION: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction. METHODS: This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis. RESULTS: Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth. CONCLUSIONS: Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive. CLINICAL TRIAL REGISTRATION: Not necessary. Not a clinical trial.

Is it Possible to Regenerate the Underactive Detrusor? Part 2 Electrical Stimulation Therapies, Treatment of Bladder Outlet Obstruction, Constipation, and Pelvic Floor Disorders ICI-RS 2024.

INTRODUCTION: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No clinical therapy has been proven to augment the strength of a detrusor contraction. METHODS: This subject was discussed at a think-tank at the International Consultation on Incontinence-Research Society (ICI-RS) held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This second part discusses the role of electrical stimulation therapies, treatment of bladder outlet obstruction, constipation, and pelvic floor disorders, in the enhancement of strength of a detrusor contraction. RESULTS: Electrical stimulation therapies, specifically sacral neuromodulation, have long been used in the salvage of patients with refractory nonobstructive voiding dysfunction. Clinical improvements can be noted in men following bladder outlet resistance reduction surgery especially, though not limited to those with demonstrable obstruction. Some patients may also show improvement with pelvic floor relaxation therapies and constipation care. However, there is a lack of high-quality urodynamic data to demonstrate an improvement in the strength of a detrusor contraction with these therapies. The think-tank recommends standards for future clinical studies examining treatments aimed at improving an underactive detrusor. CONCLUSIONS: Studies need to examine whether clinical improvement following treatment of patients with an underactive detrusor is associated with improvement in strength of the detrusor contraction. New therapeutic options should apply specified standards for assessing and reporting the impact on detrusor contraction.

South American monsoon intensification during the last millennium driven by joint Pacific and Atlantic forcing.

The South American summer monsoon (SASM) profoundly influences tropical South America's climate, yet understanding its low-frequency variability has been challenging. Climate models and oxygen isotope data have been used to examine the SASM variability over the last millennium (LM) but have, at times, provided conflicting findings, especially regarding its mean-state change from the Medieval Climate Anomaly to the Little Ice Age. Here, we use a paleoclimate data assimilation (DA) method, combining model results and δ18O observations, to produce a δ18O-enabled, dynamically coherent, and spatiotemporally complete austral summer hydroclimate reconstruction over the LM for tropical South America at 5-year resolution. This reconstruction aligns with independent hydroclimate and δ18O records withheld from the DA, revealing a centennial-scale SASM intensification during the MCA-LIA transition period, associated with the southward shift of the Atlantic Intertropical Convergence Zone and the strengthening Pacific Walker circulation (PWC). This highlights the necessity of accurately representing the PWC in climate models to predict future SASM changes.

The role of transitional probabilities in word holistic processing.

In recent years, increased attention has been devoted to visual word recognition under a perceptual expertise framework. Because the information required to identify words is distributed across the word, a holistic attentional strategy is optimal and develops with experience. It is, however, an open question the extent to which other information embedded in a word may contribute to word holistic processing, namely sublexical word properties. In the present research, we therefore explore the role of sublexical properties-specifically bigram transition probabilities-in this processing strategy. We used a common task in the holistic processing literature (i.e., composite task) and four-letter disyllabic words, where two of the bigrams reinforce the cohesiveness of each syllable and one of the bigrams reinforces the cohesiveness between the syllables. We found preliminary evidence of a role of these sublexical properties in word holistic processing.

Sex disparities in gallstone disease: insights from the MAUCO prospective population-based cohort study.

OBJECTIVE: To investigate factors associated with the prevalence and incidence of gallstone disease (GSD) in women and men of the MAUCO population-based prospective cohort. DESIGN: 8948 MAUCO participants (aged 38-74 years) underwent abdominal ultrasound at baseline (2015-2019); 4385 received follow-up ultrasound at years 2 or 4. Factors associated with prevalent GSD were assessed using Poisson multiple regression and with incident GSD using Cox regression models. RESULTS: GSD prevalence was 40.4% in women (13.1% gallstones, 27.3% cholecystectomies) and 17.1% in men (8.9% gallstones, 8.2% cholecystectomies). In men, GSD prevalence rate ratio (PRR) by age in >64 years was 3.85 (95% CI 3.00 to 4.94), doubling that of women's PRR 1.78 (95% CI 1.57 to 2.01). In women, waist circumference and diabetes were stronger GSD factors; a higher number of children and worse metabolic and socioeconomic conditions were also highlighted. GSD men had higher cardiovascular disease and a family history of GSD and gallbladder cancer. 198 GSD cases developed during follow-up, with incidence increasing by 2% (95% CI 1.005% to 1.03%) per each centimetre above the ideal waist circumference, statistically significant only in women. In men, age was the strongest factor for incidence, followed by a family history of GSD and low high-density lipoprotein increased incidence risk. CONCLUSIONS: GSD burden was high in this population; a third of women had their gallbladder removed, which may pose them at risk of other health problems. Abdominal obesity was the only preventable GSD risk factor, highlighting the need for effective public health policies promoting obesity reduction.

Results of Adjustable Trans-Obturator Male System for Stress Urinary Incontinence after Transurethral Resection or Holmium Laser Enucleation of the Prostate: International Multicenter Study.

Background: Male stress urinary incontinence (SUI) after surgical treatment of benign prostatic enlargement (BPE) is an infrequent but dreadful complication and constitutes a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS®) in these patients is rather unknown, mainly due to the rarity of this condition. We aimed to assess the results of ATOMS to treat SUI after transurethral resection (TURP) or holmium laser enucleation (HoLEP) of the prostate. Methods: Retrospective multicenter study evaluating patients with SUI after TURP or HoLEP for BPE primarily treated with silicone-covered scrotal port (SSP) ATOMS implants in ten different institutions in Europe and Canada between 2018 and 2022. Inclusion criteria were pure SUI for >1 year after endoscopic treatment for BPE and informed consent to receive an ATOMS. The primary endpoint of the study was a dry rate (pad test ≤ 20 mL/day after adjustment). The secondary endpoints were: the total continence rate (no pads and no leakage), complication rate (Clavien-Dindo classification) and self-perceived satisfaction (Patient Global Impression of Improvement (PGI-I) scale 1 to 3). Descriptive analytics, Wilcoxon's rank sum test and Fisher's exact test were performed. Results: A total of 40 consecutive patients fulfilled the inclusion criteria, 23 following TURP and 17 HoLEP. After ATOMS adjustment, 32 (80%) patients were dry (78.3% TURP and 82.4% HoLEP; p = 1) and total continence was achieved in 18 (45%) patients (43.5% TURP and 47% HoLEP; p = 0.82). The median pad test was at a 500 (IQR 300) mL baseline (648 (IQR 650) TURP and 500 (IQR 340) HoLEP; p = 0.62) and 20 (IQR 89) mL (40 (IQR 90) RTUP and 10 (IQR 89) HoLEP; p = 0.56) after adjustment. Satisfaction (PGI-I ≤ 3) was reported in 37 (92.5%) patients (95.6% TURP and 88.2% HoLEP; p = 0.5). There were no significant differences between patients treated with TURP or HoLEP regarding the patient age, radiotherapy and number of adjustments needed. After 32.5 (IQR 30.5) months, median follow-up postoperative complications occurred in seven (17.5%) cases (two grade I and five grade II; three after TURP and four HoLEP) and two devices were removed (5%, both HoLEP). Conclusions: ATOMS is an efficacious and safe alternative to treat SUI due to sphincteric damage produced by endoscopic surgery for BPE, both TURP and HoLEP. Future studies with a larger number of patients may identify predictive factors that would allow better patient selection for ATOMS in this scenario.

The effect of face race on metamemory: Examining its robustness and underlying mechanisms.

Perceivers typically exhibit better recognition memory for same-race faces than for cross-race faces, a phenomenon known as the cross-race effect (CRE). Despite its ubiquity, it is yet unclear whether people are metacognitively aware of the CRE. This research thoroughly investigates perceivers' metacognitive awareness of the CRE across five experiments. Experiments 1 and 2 demonstrated that both prospective (judgments of learning) and retrospective (confidence) metamemory judgments are sensitive to variations in the racial category and prototypicality of faces. Experiment 3 showed that participants' item-level prospective judgments are informed by beliefs about the impact of face race on memory performance. Experiment 4 revealed that global predictions are influenced by face race in the absence of direct stimulus experience, emphasizing the role of preexisting beliefs. Experiment 5 extended these findings by showing large crossover interactions between face race and participant race in both global predictions and item-level prospective judgments, indicating that both White and Black participants have higher metamemory estimates for ingroup faces. This experiment further showed that preexisting beliefs intensify the impact of face race on metamemory judgments yet do not fully account for it. Collectively, these experiments provide robust evidence of good metamemory accuracy for faces varying in racial categories and prototypicality among White participants and demonstrate that beliefs underlie the effect of face race on metamemory judgments among both White and Black participants, though this may not be the only mechanism involved. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy, Satisfaction, and Compliance: Insights from 15 Years of Botulinum Toxin Use for Female Urgency Urinary Incontinence.

Urgency urinary incontinence (UUI) refractory to medical treatment poses significant challenges despite advancements. This study evaluates the efficacy of intravesical botulinum toxin for UUI and identifies factors influencing treatment outcomes. Among 368 women receiving botulinum toxin injections, 74.5% achieved a complete discontinuation of pad usage. Predictors of efficacy included lower pre-treatment pad usage and the absence of prior sling placement. Patients often required repeat injections (60.3%), with younger age and satisfaction correlating with treatment repetition. The interval between injections averaged 18 months, influenced by logistical challenges and patient preferences. Despite concerns about diminishing efficacy, subjective perceptions did not align with objective findings. Limitations include retrospective analysis and heterogeneous clinical records. In conclusion, intravesical botulinum toxin is effective for UUI, with pre-treatment pad usage and sling placement history influencing outcomes and patient characteristics influencing treatment repetition.

Two Decades of Thyroid Nodule Cytology in Children: Malignancy Risk Assessment at a Tertiary Care Center.

INTRODUCTION: Pediatric thyroid nodules exhibit higher malignancy rates compared to adults and are associated with increased incidences of metastases and recurrences. The American Thyroid Association recommends surgery for indeterminate thyroid biopsies in children based on these higher malignancy risks, though this approach may lead to overtreatment. However, there remains a lack of comprehensive pediatric data to inform clinical decisions. This study examines the risk of malignancy (ROM) in pediatric thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and assesses the diagnostic accuracy of fine-needle aspiration (FNA) biopsy compared to histological outcomes. METHODS: A retrospective cross-sectional analysis was performed on patients under 19 years with thyroid nodules who underwent FNA and thyroidectomy at a tertiary care center. The sensitivity, specificity, positive predictive value, negative predictive value, and ROM of cytological biopsies were evaluated using TBSRTC criteria, with histology serving as the gold standard. Two analyses were conducted to assess diagnostic accuracy: (a) TBSRTC II as negative and TBSRTC VI as positive and (b) TBSRTC II as negative with TBSRTC V and VI as positive. For neoplasia detection, TBSRTC II was deemed negative, while TBSRTC IV, V, and VI were considered positive. TBSRTC categories III and I were excluded from the performance analysis and evaluated separately. Follicular neoplasm or lesions suspicious for follicular neoplasm (FN/SFN) were treated as positive outcomes, correlated with the presence of adenoma or carcinoma in the surgical specimen. RESULTS: Of 75 nodules from 73 patients, 28 (37.3%) were benign and 47 (62.6%) malignant. No significant differences in gender or age were noted between groups. The ROM in each TBSRTC was Bethesda I 0/2, 0%; II 0/13, 0%; III 2/7, 29%: IV 6/14, 43%; V 10/10, 100%, and VI 29/29, 100%. A sensitivity of 78.38% and specificity of 100% for FNA in detecting malignancy was found, with an even higher sensitivity (100%) for detecting neoplasia in TBSRTC IV. CONCLUSIONS: This study reveals that indeterminate thyroid nodules in pediatric patients exhibit a higher rate of malignancy compared to adults, yet align with rates previously reported in the pediatric population. These findings highlight the critical need for guidelines tailored specifically to the management of thyroid nodules and thyroid cancer in children.

A Pilot Study of Functional Brain Magnetic Resonance Imaging in BPS/IC Patients: Evidence of Central Sensitization.

Bladder pain syndrome/Interstitial cystitis (BPS/IC) is characterized by increased activity in bladder afferent pathways, recruitment of silent nociceptive neurons, and sensitization of the brain areas responsible for pain amplification. Default mode network (DMN) is a set of regions activated during the resting state, which reflect the brain's intrinsic activity. Conversely, the sensorimotor network (SMN) plays a key role in structural neuroplasticity. This study aimed to evaluate DMN and SMN activity in BPS/IC patients, both with and without bladder noxious stimulus, using functional brain magnetic resonance imaging (MRI). Six BPS/IC female patients underwent 3 Tesla fMRI brain scanners. Acquisitions consisted of 10-minute blood oxygen level-dependent echo-planar imaging. The first acquisition was with an empty bladder, painless, and the second was with suprapubic pain. Data were processed using the independent component analysis method with the MELODIC tool from the functional brain MRI of the Brain Software Library (FSL). A semi-quantitative analysis was performed afterward. The patients' age was 42.6 ± 5 years, pain intensity was 7 ± 0.7 (0-10), day and night frequency were 9.2 ± 2.2 and 2.8 ± 1.0, and maximal bladder capacity was 260 ± 54 mL. One patient was unable to complete the study. All patients showed a comparable DMN activation in both empty and full bladder states, and all presented high SMN activation whether the bladder was empty or full. The activation of DMN at both bladder states, empty and full, and constant SMN activation without and with pain supports the role of these networks in BPS/IC. Similar findings have been reported in other chronic pain syndromes.

Estudio Observacional Descriptivo de Pacientes Hemodializados Sospechosos de Nefritis Intersticial Crónica en Comunidades Agrícolas de Asunción y el Departamento Central / Descriptive Observational Study of Hemodialyzed Patients Suspected of Chronic Interstitial Nephritis in Agricultural Communities of Asunción and Central Department

Introducción: La Enfermedad Renal Crónica ha cobrado interés debido a su alta tasa de morbimortalidad. Además de las causas vasculares y de la diabetes mellitus, se ha identificado una causa de Origen Desconocido en jóvenes agricultores. Objetivo: El objetivo del estudio es determinar la prevalencia de la población en hemodiálisis, sospechosa de la Nefritis Intersticial Crónica en Comunidades Agrícolas, para categorizar la verdadera etiología de su patología renal. Metodología: Se aplicó un diseño observacional descriptivo durante los meses de diciembre de 2022, enero y febrero de 2023; y se encuestó a 684 pacientes de ambos sexos en 8 centros de hemodiálisis de la Capital y el Departamento Central del Paraguay. Resultados: La prevalencia de casos sospechosos por la exposición a factores de riesgo resultó ser del 18.1%. Esta cifra podría ser mayor, ya que 22.6% de los pacientes con diabetes mellitus tipo 2, no presentó retinopatía clínica ni otros signos clínicos de la enfermedad al momento del diagnóstico de la falla renal. Este panorama nos advierte de un probable diagnóstico desacertado en una cantidad considerable de pacientes. Conclusión: La importancia de esta investigación se sustenta en generar acciones preventivas en la población agrícola y concientizar a la sociedad médica de la relevancia diagnóstica de esta patología para mejorar la calidad y pronóstico de vida en la población paraguaya.

Introduction: Chronic Kidney Disease has gained interest due to its high morbidity and mortality rate. In addition to vascular causes and diabetes mellitus, an unknown cause has been identified in young farmers. Objective: This study aims to determine the prevalence of the population on hemodialysis, suspected of Chronic Interstitial Nephritis in agricultural communities, to categorize the true etiology of their renal pathology. Methodology: A descriptive observational design was applied during December 2022, January, and February 2023; and 684 patients of both sexes were surveyed in 8 hemodialysis centers in the Capital and the Central Department of Paraguay. Results: The prevalence of suspected cases due to the exposure to risk factors was 18.1%. This figure could be higher since 22.6% of patients with type 2 diabetes mellitus did not present clinical retinopathy or other clinical signs of the disease at the time of the diagnosis of kidney failure. This scenario warns us of a probable misdiagnosis in a considerable number of patients. Conclusion: The importance of this research lies in generating preventive actions in the agricultural population and raising awareness in the medical community about the diagnostic relevance of this pathology to improve the quality and prognosis of life in the Paraguayan population.

Learned Attentional Strategies in Word Holistic Processing.

Previous research has shown that, like faces, words are processed either holistically or through the automatic representation of their parts combined. The automaticity assumed to underlie the holistic processing of words presupposes that individuals have a relatively low level of control over these processes. However, they may also be capable of learning from their environments whether processing words as a whole is the most efficient processing strategy-which would require at least some control over the corresponding processes. In fact, previous research supports this latter account in the context of the holistic processing of faces: when provided a task in which participants should ignore half of a stimuli (the irrelevant part) and pay selective attention to the other half (the target part), the participants become better at ignoring the irrelevant part when it is commonly misleading (i.e., this suggests a response that is different from that of the relevant part in the context of the task). In the present work, we extend these considerations to holistic word processing. Our results support a learned attentional account in the context of holistic word processing. When an irrelevant word part is systematically helpful for the judgment of a target word half, participants engage more in holistic processing (vs. when the irrelevant word half is misleading). This reflects an incidental statistical learning process in which individuals identify the irrelevant word half as either providing helpful or misleading information about the target half.

Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP)).

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). DESIGN: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. SETTING: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). POPULATION OR SAMPLE: A total of 100 participants. METHODS: Descriptive and comparative analysis from flares questionnaire. MAIN OUTCOME MEASURES: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

Self-serving beliefs about science: Science justifies my weaknesses (but not other people's).

This research explored the strategic beliefs that people have about science and the extent to which it can explain moral and immoral behaviors. Although people do not believe that science is able to explain certain aspects of their mind, they might nevertheless accept a scientific explanation for their immoral behaviors if that explanation is exculpatory. In a first study, participants reflected on moral and immoral deeds that they performed or that other people performed. Participants were somewhat skeptic that science can account for people's behavior-except for when they reflected on the wrongdoings that they committed. Two further studies suggest that strategic belief in science arises because it enables external attributions for the behavior, outside of the wrongdoers' control. Implications are discussed for science understanding and communication.

Effect of Disinfection Protocols on Bacterial Reduction in Mandibular Molars.

OBJECTIVE: Evaluate the bacterial reduction effect of disinfection protocols used in lower molars infected by Enterococcus faecalis. METHODS: Eighty extracted lower molars were prepared and inoculated with E. faecalis for 2 months. The teeth were then distributed into 2 control groups (n = 4) and 4 experimental groups (n = 18) in function of the disinfection protocol utilized: G1. WaveOne Gold (WOG), passive ultrasonic irrigation (PUI) and Ultracal; G2. WOG, PUI and calcium hydroxide (CH); G3. WOG, XP-Endo Finisher (XPF) and Ultracal; G4. WOG, XPF and CH. Bacteriological samples were collected previously (S1), after preparation (S2), final agitation (S3) and intracanal dressing (S4). Microbial growth was assessed according to culture turbidity and UV spectrophotometry. Statistical analyses used the Friedman test for paired samples and Kruskal-Wallis test for non-paired data (p<0.05). RESULTS: No protocol eliminated E. faecalis effectively. The S2, S3 and S4 samples were statistically different from the S1 samples in G1, G2, G3 and G4 (p<0.05). Statistical differences were observed in bacterial reduction between G1 and G2 and G1 and G3 after the intracanal medicament (S4) (p<0.05). CONCLUSION: The WOG + PUI + CH disinfection protocol showed higher percentages of bacterial reduction.

Neurotrophin-3 Rescues Striatal Synaptic Plasticity in Model of Neurodegeneration by PLC Signaling Activation.

BACKGROUND: Neurotrophins are essential factors for neural growth and function; they play a crucial role in neurodegenerative diseases where their expression levels are altered. Our previous research has demonstrated changes in synaptic plasticity and neurotrophin expression levels in a pharmacological model of Huntington's disease (HD) induced by 3-nitropropionic acid (3-NP). In the 3-NP-induced HD model, corticostriatal Long Term Depression (LTD) was impaired, but neurotrophin- 3 (NT-3) restored striatal LTD. This study delves into the NT-3-induced signaling pathways involved in modulating and restoring striatal synaptic plasticity in cerebral slices from 3-NPinduced striatal degeneration in mice in vivo. METHODS: Phospholipase C (PLC), phosphatidylinositol-3-kinase (PI3K), and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways activated by NT-3 were analyzed by means of field electrophysiological recordings in brain slices from control and 3-NP treated in the presence of specific inhibitors of the signaling pathways. RESULTS: Using specific inhibitors, PLC, PI3K, and MEK/ERK signaling pathways contribute to NT-3-mediated plasticity modulation in striatal tissue slices recorded from control animals. However, in the neurodegeneration model induced by 3-NP, the recovery of striatal LTD induced by NT-3 was prevented only by the PLC inhibitor. Moreover, the PLC signaling pathway appeared to trigger downstream activation of the endocannabinoid system, evidenced by AM 251, an inhibitor of the CB1 receptor, also hindered NT-3 plasticity recovery. CONCLUSION: Our finding highlights the specific involvement of the PLC pathway in the neuroprotective effects of NT-3 in mitigating synaptic dysfunction under neurodegenerative conditions.

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Strategies for knowledge mobilization by advanced practice nurses in three hospitals in Spain: a qualitative study.

BACKGROUND: Evidence-based practice, in conjunction with optimum care quality, improves patients' clinical outcomes. However, its implementation in daily clinical practice continues to present difficulties. The aim of this study was to identify the strategies applied by Advanced Practice Nurses (APNs) to foster adherence to clinical practice guideline recommendations. METHODS: An exploratory qualitative study was conducted with six focus groups at three public hospitals belonging to the Balearic Islands Health Care Service (Spain). The study participants were 32 ward nurses and 5 advanced practice nurses working routinely with inpatients at these hospitals. The study was conducted from November 2020 to January 2021, using thematic analysis, based on the COREQ checklist. RESULTS: Four major themes related to the facilitation process were identified either by RNs and APNs: the context of the project, APN contribution to nursing team management, healthcare provision on the ward, and the acquisition and application of knowledge. CONCLUSIONS: The APNs adapted their actions to the characteristics and needs of the local context, employing strategies aimed at improving teamwork, healthcare, and knowledge management. Each of these contributions enhanced the sustainability of the changes made.