The potential of liquorpheresis to treat leptomeningeal disease.

Leptomeningeal disease (LMD) is a devastating sequela of many cancers with an extremely poor prognosis. Barriers to improving outcomes are related to the inability for many traditional therapies to effectively reach the cerebrospinal fluid (CSF) space within the central nervous system (CNS). Liquorpheresis is an emerging treatment modality specific to CSF pathologies, whose primary mechanism of action is direct targeted filtration of CSF content by neurosurgical access. In this review, we highlight the principles of liquorpheresis, and detail how LMD can be amenable to this for treatment. Further, we summarize the current in vitro and in vivo evidence supporting liquorpheresis as a feasible method to treat LMD and other CNS diseases, as well as describe its conceivable limitations.

Influence of Brainstem's Area A5 on Sympathetic Outflow and Cardiorespiratory Dynamics.

Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.

A study protocol of a comparative mixed study of the T-Control catheter.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterization by a multifactorial approach. The general purpose of this study is to determine the effectiveness, comfort, and experience of the patient catheterized with T-Control® compared with patients with a conventional Foley catheter. Study Design: This trial is a mixed-method study comprising a two-arm, pilot comparative study with random allocation to T-Control catheter or traditional Foley catheter in patients with long-term catheterization and a study with qualitative methodology, through discussion groups. Endpoints: The comfort and acceptability of the T-Control® device (qualitative) and the quality of life related to self-perceived health (quantitative) will be analysed as primary endpoints. As secondary endpoints, the following will be analysed: magnitude and rate of infections (symptomatic and asymptomatic); days free of infection; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterization's healthcare resources; and level of satisfaction and workload of health professionals. Patients and Methods: Eligible patients are male and female adults aged ≥18 years, who require a change of long-term bladder catheter. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 4 weeks later, plus the time until the discussion groups take place.

Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights.

Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies.

Comparison of Mechanical Insufflation-Exsufflation and Hypertonic Saline and Hyaluronic Acid With Conventional Open Catheter Suctioning in Intubated Patients.

BACKGROUND: Open respiratory secretion suctioning with a catheter causes pain and tracheobronchial mucosal injury in intubated patients. The goal of mechanical insufflation-exsufflation (MI-E) is to move secretions proximally and noninvasively by generating a high peak expiratory air flow. Nebulized hypertonic saline with hyaluronic acid (HS-HA) may facilitate suctioning by hydration. We assessed the safety and tolerance of a single session of airway clearance with MI-E and HS-HA in critically ill intubated patients. METHODS: Adults with a cuffed artificial airway were randomized to (1) open suctioning, (2) open suctioning after HS-HA, (3) MI-E, or (4) MI-E with HS-HA. Adverse events, pain and sedation/agitation scores, and respiratory and hemodynamic variables were collected before, during, and 5-min and 60-min post intervention. RESULTS: One-hundred twenty subjects were enrolled and completed the study. Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22 (16-28); median (IQR) age was 69.0 (57.0-75.7) y, and 90 (75%) were male. Baseline respiratory and hemodynamic variables were comparable. Adverse events occurred in 30 subjects (25%), with no between-group differences. Behavioral pain equivalents and Richmond Agitation-Sedation Scale were higher during suctioning in groups 1 (P < .001) and 2 (P < .001). Independent predictive variables for higher pain and agitation/sedation scores were study groups 1 and 2 and simultaneous analgosedation, respectively. Noradrenaline infusion rates were lower at 60 min in groups 2 and 4. PaO2 /FIO2 had decreased at 5 min after open suctioning in group 1 and increased at 60 min in group 3. CONCLUSIONS: We observed no difference in adverse events. MI-E avoids pain and agitation.

NFKB1 variants were associated with the risk of Parkinson´s disease in male.

The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson's disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the NFKB1 rs28362491 and rs7667496, NFKBIA rs696, and NFKBIZ rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient's vs. controls. We found that the two NFKB1 alleles were significantly associated with PD in our population (p = 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the NFKB1 variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (p = 0.02, OR = 1.52, 95%CI = 1.10-2.08) and rs28362491 C (p = 0.003, OR = 1.62, 95%CI = 1.18-2.22). The two NFKB1 variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (p = 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.

Central Autonomic Mechanisms Involved in the Control of Laryngeal Activity and Vocalization.

In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker-Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia.

Effectiveness of the T-Control catheter: A study protocol.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterisation by a multifactorial approach. The general purpose of this study is to evaluate the effectiveness and cost-effectiveness of the T-Control catheter versus the Foley-type catheter in patients with Acute Urine Retention (AUR). Study design: This is a pragmatic, open, multicentre, controlled clinical trial with random allocation to the T-Control catheter or a conventional Foley-type catheter in patients with AUR. Endpoints: The magnitude of infections will be analysed as a primary endpoint. While as secondary endpoint, the following will be analysed: rate of symptomatic and asymptomatic infections; days free of infection; quality of life-related to self-perceived health; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterisation's healthcare resources; level of satisfaction and workload of health professionals and acceptability of the T-Control device as well as the patient experience. Patients and methods: Eligible patients are male adults aged ≥50 years, with AUR and with an indication of bladder catheterisation for at least 2 weeks. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 2 weeks later, plus 2 weeks after this time when the patient will be called for an in-depth interview.

Utility of Targeted Positron Emission Tomography Imaging to Predict Schwannoma Growth in a Murine Tumor Model.

OBJECTIVE: To identify if targeted positron emission tomography (PET) imaging with radiolabeled antibodies can predict tumor growth rate and ultimate tumor size in a murine flank schwannoma model. STUDY DESIGN: Animal research study. METHODS: Rat schwannoma cells were cultured and implanted into 40 athymic nude mice. Once tumors reached 5 mm in diameter, 30 mice were injected with zirconium-89 labeled antibodies (HER2/Neu, vascular endothelial growth factor receptor 2 (VEGFR2), or IgG isotype). PET/CT was performed, and standardized uptake values (SUV) were recorded. Tumors were serially measured until mice were sacrificed per IACUC protocol. Statistical analysis was performed to measure correlations between SUV values, tumor size, and growth. RESULTS: Mean tumor sizes in mm3 on Day 0 were 144 ± 162 for anti-HER2/Neu, 212 ± 247 for anti-VEGFR2, and 172 ± 204 for IgG isotype groups respectively. Mean growth rates in mm3 /day were 531 ± 250 for HER2, 584 ± 188 for VEGFR2, and 416 ± 163 for the IgG isotype group. For both initial tumor size and growth rates, there was no significant difference between groups. There were significant correlations between maximum tumor volume and both the SUV max in the HER2 group (p = 0.0218, R2 = 0.5020), and we observed significant correlations between growth rate, and SUV values (p = 0.0156, R2 = 0.5394). Respectively, in the anti-VEGFR2 group, there were no significant correlations. CONCLUSION: In a murine schwannoma model, immunotargeted PET imaging with anti-HER2/Neu antibodies predicted tumor growth rate and final tumor size. Laryngoscope, 134:1372-1380, 2024.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Rotor-Stator Emulsification in the Turbulent Inertial Regime: Experiments toward a Robust Correlation for the Droplet Size.

The Sauter mean diameter, d32, is a representative parameter in emulsions that indicates the average size of the oil droplets once the emulsion becomes stable. Several mathematical and physical approaches have been employed in the literature to seek expressions for d32 under different conditions. The present work sheds light on this rich literature and emphasizes that the characterization of emulsions is still a fertile field for investigation. In this paper, a new Π-theorem-based model to predict the normalized Sauter mean diameter for the specific case of rotor-stator emulsification is sought by applying a multiple regression analysis on experimental data of oil-in-water (O-W) emulsions produced using three different oils: paraffin, soybean oil, and isopropyl myristate, at different oil-to-water (O/W) ratios and rotor speeds. The proposed model quantifies the roles of the viscous, inertial, and interfacial tension forces, besides the O/W ratio, in the emulsification process within the turbulent inertial subrange. The developed empirical correlation is then contrasted with relevant literature models for reliability assessment; predictions of the present explicit model are proven to be more accurate for the fluid properties and the experimental conditions under study.

Similar functional composition of fish assemblages despite contrasting levels of habitat degradation on shallow Caribbean coral reefs.

Functional trait-based approaches provide an opportunity to assess how changes in habitat affect the structure of associated communities. Global analyses have found a similarity in the composition of reef fish functional traits despite differences in species richness, environmental regimes, and habitat components. These large-scale patterns raised the question of whether this same stability can be observed at smaller spatial scales. Here, we compared the fish trait composition and their functional diversity in two Caribbean shallow coral reefs with contrasting levels of habitat degradation: Limones (>30% cover), constituted mainly by colonies of Acropora palmata and Bonanza, a reef with extensive areas of dead Acropora structures, dominated by algae. To characterize the functional structure of fishes on each reef, we calculated the community-weighted mean trait values (CWM), functional richness, functional evenness, functional dispersion, and functional originality. Despite the differences in habitat quality, reefs exhibited a similar proportion and common structure on fish functional traits. Functional richness and functional evenness differed significantly, but functional dispersion and functional originality did not show differences between reefs. The greater niche complexity driven by the high availability of microhabitats provided by A. palmata may explain the higher functional richness in Limones, whereas the reef degradation in Bonanza may contribute to a higher functional evenness because of a similar distribution of abundance per fish trait combinations. Our results suggest that widespread degradation on Caribbean reefs has limited the type, variety, and range of traits, which could lead to a functional homogenization of fish communities even at local scales.

Membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal tres años después

Fundamento la asociación de la membrana de fibrina rica en plaquetas con el colgajo de reposición coronal constituye una modalidad de la ingeniería de tejidos que aporta elementos regenerativos al proceso de reparación tisular. Objetivo evaluar la efectividad de la membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal en el tratamiento de la recesión periodontal tres años después. Métodos se realizó un cuasiexperimento en la facultad de Estomatología de Villa Clara, en el periodo marzo de 2017-julio de 2020, y con una población de estudio conformada por 46 pacientes portadores de recesión periodontal, quienes requerían recubrimiento radicular mediante el colgajo de reposición coronal. Se utilizó un muestreo no probabilístico intencional por criterios, y la muestra quedó conformada por 26 pacientes. Se establecieron sitios de estudio y sitios de control. Las variables estudiadas fueron: edad, sexo, largo de la recesión, clasificación de Miller, cobertura radicular, ancho y ganancia de la encía insertada, categorías de evaluación y efectividad del tratamiento. Resultados en el 88,68 % de los dientes ubicados en los sitios de estudio predominó la categoría de evaluación favorable. El porcentaje de efectividad a los tres años de la terapéutica fue superior en los sitios de estudio (54,71 %). Conclusiones se consideró más efectivo el tratamiento de la recesión periodontal con membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal a los tres años del proceder.

Foundation the association of the platelet-rich fibrin membrane with the coronal replacement flap constitutes a modality of tissue engineering that provides regenerative elements to the tissue repair process. Objective to evaluate the effectiveness of the platelet-rich fibrin membrane associated with the coronal repositioning flap in the treatment of periodontal recession three years later. Methods a quasi-experiment was carried out at the Villa Clara Dentistry Faculty, from March 2017 to July 2020, a study population of 46 patients with periodontal recession, who required root coverage using the replacement flap coronal. Intentional non-probabilistic sampling by criteria was used, and the sample of 26 patients. Study sites and control sites were established. The studied variables were: age, sex, recession length, Miller classification, root coverage, width and gain of the attached gingiva, evaluation categories and treatment effectiveness. Results in 88.68% of the teeth located in the study sites, the favorable evaluation category predominated. The effectiveness percentage three years after treatment was higher in the study sites (54.71%). Conclusions the treatment of periodontal recession with platelet-rich fibrin membrane associated with the coronal replacement flap was considered more effective three years after the procedure.

Comparison of Easy-to-Use Bronchiolitis Scores in the Post-COVID-19 Era-An Observational Study.

In the post-restrictions COVID-19 period, the incidence of bronchiolitis in infants has increased considerably. Several scores determine the degree of severity of the bronchiolitis episode, but few are clinician-friendly. The main aim of this research was to find the easy-to-use score that most accurately estimated the severity of patients' infections according to their clinical situations and most accurately predicted the need for hospital admission. An observational cross-sectional study was performed in a reference pediatric hospital during the post-restrictions period of the COVID-19 pandemic (2021 and 2022). A comparison was made between the severity estimate provided by five international acute bronchiolitis scales and the clinical severity of the acute bronchiolitis episode. Three hundred and seventy-seven patients participated in the investigation, with a mean age of 5.68 months; 68.7% of the participants had a mild episode of bronchiolitis, 24.5% had a moderate episode, and 6.9% had a severe episode. The severity estimated by the Tal scale modified by McCallum showed a statistically significant correlation with the clinical severity established by clinical criteria (0.836; p < 0.001). It showed a high correlation with other international scores, such as the Wang score (0.820; p < 0.05) and the Wood-Downes-Ferrés score (0.936; p < 0.001). In the multivariate analysis, the constituent variables of the modified Tal score appeared in the final model that predicts the need for hospital admission. In the context of increased incidence after COVID-19, the Tal score modified by McCallum is an easy-to-use measuring instrument that presents an excellent concordance with the clinical severity estimated at first care contact. It also offers a more significant prediction of the need for hospital admission.

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction.

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

A Nanostructured Protein Filtration Device for Possible Use in the Treatment of Alzheimer's Disease-Concept and Feasibility after In Vivo Tests.

BACKGROUND: Alzheimer's disease (AD), along with other neurodegenerative disorders, remains a challenge for clinicians, mainly because of the incomplete knowledge surrounding its etiology and inefficient therapeutic options. Considering the central role of amyloid beta (Aß) in the onset and evolution of AD, Aß-targeted therapies are among the most promising research directions. In the context of decreased Aß elimination from the central nervous system in the AD patient, the authors propose a novel therapeutic approach based on the "Cerebrospinal Fluid Sink Therapeutic Strategy" presented in previous works. This article aims to demonstrate the laborious process of the development and testing of an effective nanoporous ceramic filter, which is the main component of an experimental device capable of filtrating Aß from the cerebrospinal fluid in an AD mouse model. METHODS: First, the authors present the main steps needed to create a functional filtrating nanoporous ceramic filter, which represents the central part of the experimental filtration device. This process included synthesis, functionalization, and quality control of the functionalization, which were performed via various spectroscopy methods and thermal analysis, selectivity measurements, and a biocompatibility assessment. Subsequently, the prototype was implanted in APP/PS1 mice for four weeks, then removed, and the nanoporous ceramic filter was tested for its filtration capacity and potential structural damages. RESULTS: In applying the multi-step protocol, the authors developed a functional Aß-selective filtration nanoporous ceramic filter that was used within the prototype. All animal models survived the implantation procedure and had no significant adverse effects during the 4-week trial period. Post-treatment analysis of the nanoporous ceramic filter showed significant protein loading, but no complete clogging of the pores. CONCLUSIONS: We demonstrated that a nanoporous ceramic filter-based system that filtrates Aß from the cerebrospinal fluid is a feasible and safe treatment modality in the AD mouse model. The presented prototype has a functional lifespan of around four weeks, highlighting the need to develop advanced nanoporous ceramic filters with anti-biofouling properties to ensure the long-term action of this therapy.

CardioRVAR: A New R Package and Shiny Application for the Evaluation of Closed-Loop Cardiovascular Interactions.

CardioRVAR is a new R package designed for the complete evaluation of closed-loop cardiovascular interactions and baroreflex sensitivity estimated from continuous non-invasive heart rate and blood pressure recordings. In this work, we highlight the importance of this software tool in the context of human cardiovascular and autonomic neurophysiology. A summary of the main algorithms that CardioRVAR uses are reviewed, and the workflow of this package is also discussed. We present the results obtained from this tool after its application in three clinical settings. These results support the potential clinical and scientific applications of this tool. The open-source tool can be downloaded from a public GitHub repository, as well as its specific Shiny application, CardioRVARapp. The open-source nature of the tool may benefit the future continuation of this work.

Staging Parkinson's disease according to the MNCD classification correlates with caregiver burden.

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. PATIENTS AND METHODS: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers. CONCLUSION: Staging PD according to the MNCD classification is correlated with caregivers' strain and burden.

Teaching the physiology of the human body in non-formal spaces: pilot experience of a Service-Learning methodology and the interaction between students of different educational levels.

Research institutes and universities have strengthened the development of biomedicine outreach activities, constituing a non-formal education system of science literacy, although with little commitment from undergraduate students. However, as a Service-Learning methodology, these outreach activities could work as a tool for the acquisition of skills by students of Health Science Degrees. Described here is the development of the workshop entitled "Exploring the human body" at the Biodonostia Health Research Institute and the pilot experience of its implementation as a Service-Learning activity at the University of Málaga. Firstly, 359 secondary education students were mentored by Ph.D. students through a 5-station workshop with experiments and activities related to the physiology of the human body. Then, 301 undergraduate students of Medicine and Nursing Degrees advised 965 secondary education students. Both groups of students assessed the workshop via questionnaires and a debriefing. The data showed an overall score of 4.6 out of 5 for the workshop. Undergraduate students reported a positive impact on their academic background (4.8 out of 5), mainly due to the improvement of oral communication skills (34%). Therefore, this methodology could be a valid and applicable tool to develop the cross-disciplinary competences of undergraduate students.

Panitumumab-IRDye800 Improves Laryngeal Tumor Mapping During Transoral Laser Microsurgery.

Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor-targeted fluorescence-guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence-guided surgical resection of a T2N0M0 transglottic tumor using panitumumab-IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near-infrared (NIR) dye. Laryngoscope, 2023.