Single Institutional Cross-Sectional Phone Survey Study: Evaluation of Causes for Loss to Follow-up After Spinal Cord Stimulator Implantation.

BACKGROUND: Spinal cord stimulation (SCS) is often an option of last resort for patients with post-laminectomy syndrome or an alternative option for patients with complex regional pain syndrome, chronic nonsurgical low back pain, or painful diabetic peripheral neuropathy when conservative management has failed. Although SCS is a helpful option, it is not without complications that can frequently lead to explantation of the SCS device and dissatisfaction with the treatment. Furthermore, as with any technology, SCS has potential issues that may lead to patient frustration and ultimately result in patient noncompliance and lack of follow-up visits. OBJECTIVES: The goals of this study are to explore the magnitude of and reasons for patient loss to follow-up after SCS device implantation. STUDY DESIGN: A cross-sectional phone survey. SETTING: A tertiary-care academic hospital. METHODS: A cross-sectional phone survey was performed on 49 patients who were deemed lost to follow-up when they did not return to the clinic one month after being implanted with permanent SCS devices at Beth Israel Deaconess Medical Center. Patients were administered an institutional review board-approved questionnaire exploring their reasons for not returning to the clinic. RESULTS: Over a 5-year period, 257 patients underwent full implantation of an SCS device. Of the 49 patients lost to follow-up, 24 were able to be contacted, and they completed the questionnaire. Twenty of the patients continued to use the SCS device but were lost to follow-up for the following reasons: 58% (14/24) due to improvement of pain, 13% (3/24) due to minimal improvement in pain control, 4% (1/24) due to other urgent health conditions, and 8% (2/24) due to patient noncompliance and missing follow-up appointments (4/24). Four patients discontinued using the SCS device after an average of 1.5 years +/- one year, 12% (3/24) due to inadequate pain control and 4% (1/24) due to inability to recharge the device (1/24). Of these patients, 2 of the 4 contacted their SCS representatives for help with troubleshooting prior to discontinuation. None of the patients was explanted. LIMITATIONS: The main limitation of this study was the incompletion rate, which was 51.0% (25 out of 49 patients). CONCLUSIONS: This paper, the first cross-sectional study of loss to follow-up among patients who are implanted with SCS devices, identifies that up to 19% of patients are quickly lost to follow-up after implantation. Only half of the patients in this study could be reached, with most successfully using their device for meaningful pain control, but a substantial number of patients likely required additional device optimization for pain relief.

Case Report: Glossopharyngeal Allodynia-Related Odynophagia and Dysphagia Post Anterior Cervical Discectomy and Fusion Managed with Glossopharyngeal Nerve Block.

Dysphagia after anterior cervical spine surgery has a 5% to 15% incidence beyond 1-year postsurgery, often attributed to mechanical factors such as pharyngeal thickening and epiglottis inversion. Despite normal neurological examination and electromyography, nerve distortion related to stretching also remains a possibility in these patients and may cause allodynia resulting in odynophagia and dysphagia. Current treatment options for dysphagia after anterior cervical discectomy and fusion are limited to local intraoperative steroid injections and tracheal traction exercises. In our patient, a glossopharyngeal nerve block was effectively used to manage the glossopharyngeal allodynia, thereby reducing the odynophagia and dysphagia, ultimately enhancing oral tolerance.

Artificial Intelligence and Virtual Reality in Headache Disorder Diagnosis, Classification, and Management.

PURPOSE OF REVIEW: This review provides an overview of the current and future role of artificial intelligence (AI) and virtual reality (VR) in addressing the complexities inherent to the diagnosis, classification, and management of headache disorders. RECENT FINDINGS: Through machine learning and natural language processing approaches, AI offers unprecedented opportunities to identify patterns within complex and voluminous datasets, including brain imaging data. This technology has demonstrated promise in optimizing diagnostic approaches to headache disorders and automating their classification, an attribute particularly beneficial for non-specialist providers. Furthermore, AI can enhance headache disorder management by enabling the forecasting of acute events of interest, such as migraine headaches or medication overuse, and by guiding treatment selection based on insights from predictive modeling. Additionally, AI may facilitate the streamlining of treatment efficacy monitoring and enable the automation of real-time treatment parameter adjustments. VR technology, on the other hand, offers controllable and immersive experiences, thus providing a unique avenue for the investigation of the sensory-perceptual symptomatology associated with certain headache disorders. Moreover, recent studies suggest that VR, combined with biofeedback, may serve as a viable adjunct to conventional treatment. Addressing challenges to the widespread adoption of AI and VR in headache medicine, including reimbursement policies and data privacy concerns, mandates collaborative efforts from stakeholders to enable the equitable, safe, and effective utilization of these technologies in advancing headache disorder care. This review highlights the potential of AI and VR to support precise diagnostics, automate classification, and enhance management strategies for headache disorders.

Scoping Review: The Role of Psychedelics in the Management of Chronic Pain.

Introduction: Amid a lack of effective chronic pain treatments, psychedelics have gained attention as a potential solution, although their Schedule 1 classification poses challenges. Psychedelics, such as lysergic acid diethylamide (LSD) and psilocybin, have gained popularity as alternatives and adjuncts for chronic pain treatment. Studies suggest that they may modulate pain processing through agonism primarily at the serotonin receptor, 5-HT2A. One of the first of its nature, we present an artificial intelligence (AI)-powered scoping review primarily focusing on evaluating psychedelics for chronic pain conditions such as cluster headache, phantom limb pain, and fibromyalgia. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we used an AI-powered comprehensive search strategy utilizing the ChatGPT4.0 Bing chat to search Medline, Embase, Cochrane, and Google Scholar for articles addressing chronic pain. The query was performed on June 1, 2023, focusing on psychedelics for chronic, non-cancer pain including headache disorders. Inclusion criteria were English-only, peer-reviewed articles involving human participants >18 years, focusing on chronic pain conditions (eg, phantom limb pain and cluster headache), using LSD, 2.5-dimethoxy-4-bromophenethylamine (2C-B), N, N-dimethyltryptamine (DMT), psilocybin, or mescaline. Exclusion criteria were reviews, editorials, and opinion articles and studies focusing on tetrahydrocannabinol/cannabis and/or ketamine. Results: A total of 186 unique database entries were retrieved, of which nine studies were included in the scoping review. These included four case reports/series, an open-label study, a cohort study, two online surveys, and a randomized, double-blind, placebo-controlled trial. They comprised three studies addressing phantom limb pain, four addressing cluster headaches, and two addressing fibromyalgia, spinal cord injury, complex regional pain syndrome, and lumbar radiculopathy. Conclusion: Psychedelics may have potential in alleviating pain symptoms secondary to a multitude of chronic pain conditions. However, further randomized, double-blind, placebo-controlled trials are needed to further explore and evaluate the role of psychedelics in chronic, non-cancer pain.

Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids.

BACKGROUND: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS). RESULTS: Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu. CONCLUSIONS: Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

PURPOSE OF REVIEW: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. RECENT FINDINGS: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain.

Neurotensin (8-13) and Neuromedin N Neuropeptides Radiolabelling with Copper-64 Produced on Solid or Liquid Targets.

On the verge of a theranostic approach to personalised medicine, copper-64 is one of the emerging radioisotopes in nuclear medicine due to its exploitable nuclear and biochemical characteristics. The increased demand for copper-64 for preclinical and clinical studies has prompted the development of production routes. This research aims to compare the (p,n) reaction on nickel-64 solid versus liquid targets and evaluate the effectiveness of [64Cu]CuCl2 solutions prepared by the two routes. As new treatments for neurotensin receptor-overexpressing tumours have developed, copper-64 was used to radiolabel Neurotensin (8-13) and Neuromedin N. High-quality [64Cu]CuCl2 solutions were prepared using ACSI TR-19 and IBA Cyclone Kiube cyclotrons. The radiochemical purity after post-irradiation processing reached 99% (LT) and 99.99% (ST), respectively. The irradiation of a solid target with 11.8 MeV protons and 150 µAh led to 704 ± 84 MBq/µA (17.6 ± 2.1 GBq/batch at EOB). At the end of the purification process (1 h, 90.90% activity yield), the solution for peptide radiolabelling had a radioactive concentration of 1340.4 ± 70.1 MBq/mL (n.d.c.). The irradiation of a liquid target with 16.9 MeV protons and 230 µAh resulted in 3.7 ± 0.2 GBq/batch at EOB, which corresponds to an experimental production yield of 6.89 GBq.cm3/(g.µA)sat. Benefiting from a shorter purification process (40 min), the activity yielded 90.87%, while the radioactive concentration of the radiolabelling solution was lower (492 MBq/mL, n.d.c.). The [64Cu]CuCl2 solutions were successfully used for the radiolabelling of DOTA-NT(8-13) and DOTA-NN neuropeptides, resulting in a high RCP (>99%) and high molar activity (27.2 and 26.4 GBq/µmol for LT route compared to 45 and 52 GBq/µmol for ST route, respectively). The strong interaction between the [64Cu]Cu-DOTA-NT(8-13) and the colon cancerous cell lines HT29 and HCT116 proved that the specificity for NTR had not been altered, as shown by the uptake and retention data.

Artificial intelligence: ChatGPT as a disruptive didactic strategy in dental education.

PURPOSE: To evaluate the influence of ChatGPT on academic tasks performed by undergraduate dental students. METHOD: Fifty-five participants completed scientific writing assignments. First, ChatGPT was utilized; subsequently, a conventional method involving the search of scientific articles was employed. Each task was preceded by a 30-min training session. The assignments were reviewed by professors, and an anonymous questionnaire was administered to the students regarding the usefulness of ChatGPT. Data were analyzed by Mann-Whitney U-test. RESULTS: Final scores and scores for the criteria of utilization of evidence, evaluation of arguments, and generation of alternatives achieved higher values through the traditional method than with ChatGPT (p = 0.019, 0.042, 0.017, and <0.001, respectively). No differences were found between the two methods for the remaining criteria (p > 0.05). A total of 64.29% of the students found ChatGPT useful, 33.33% found it very useful, and 3.38% not very useful. Regarding its application in further academic activities, 54.76% considered it useful, 40.48% found it very useful, and 4.76% not very useful. A total of 61.90% of the participants indicated that ChatGPT contributed to over 25% of their productivity, while 11.9% perceived it contributed to less than 15%. Concerning the relevance of having known ChatGPT for academic tasks, 50% found it opportune, 45.24% found it very opportune, 2.38% were unsure, and the same percentage thought it is inopportune. All students provided positive feedback. CONCLUSION: Dental students highly valued the experience of using ChatGPT for academic tasks. Nonetheless, the traditional method of searching for scientific articles yield higher scores.

Fully Automated Production of [68Ga]GaFAPI-46 with Gallium-68 from Cyclotron Using Liquid Targets.

68Ga-based radiopharmaceuticals are routinely used for PET imaging of multiple types of tumors. Gallium-68 is commonly obtained from 68Ge/68Ga generators, which are limited in the quantity of activity produced. Alternatively, gallium-68 can easily be produced on a cyclotron using liquid targets. In this study, we optimized the GMP production of [68Ga]GaFAPI-46 using gallium-68 produced via a standard medical cyclotron using liquid targets. Starting from the published synthesis and quality control procedures described for other 68Ga-based radiopharmaceuticals, we have validated the synthesis process and the analytical methods to test the quality parameters of the final product to be used for routine clinical studies. [68Ga]GaFAPI-46 was successfully produced with high radiochemical purity and yield using an IBA Synthera® Extension module. Gallium chloride was produced on a medical cyclotron using a liquid target with activity of 4.31 ± 0.36 GBq at the end of purification (EOP). Analytical methods were established and validated, meeting Ph. Eur. standards. Full GMP production was also validated in three consecutive batches, producing 2.50 ± 0.46 GBq of [68Ga]GaFAPI-46 at the end of synthesis (EOS), with 98.94 ± 0.72% radiochemical purity measured via radio-HPLC. Quality was maintained for up to 3 h after the EOS. Production of [68Ga]GaFAPI-46 was performed and validated using a standard medical cyclotron with liquid targets. The quality control parameters (e.g., sterility, purity, and residual solvents) conformed to Ph. Eur. and a shelf life of 3 h was established. The activity of [68Ga]GaFAPI-46 produced was substantially higher than the one obtained with generators, enabling a better response to the clinical need for this radiopharmaceutical.

Antibody and Nanobody Radiolabeling with Copper-64: Solid vs. Liquid Target Approach.

Antibody and nanobody-based copper-64 radiopharmaceuticals are increasingly being proposed as theranostic tools in multiple human diseases. While the production of copper-64 using solid targets has been established for many years, its use is limited due to the complexity of solid target systems, which are available in only a few cyclotrons worldwide. In contrast, liquid targets, available in virtually in all cyclotrons, constitute a practical and reliable alternative. In this study, we discuss the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. Copper-64 production from solid targets was performed on a TR-19 cyclotron with an energy of 11.7 MeV, while liquid target production was obtained by bombarding a nickel-64 solution using an IBA Cyclone Kiube cyclotron with 16.9 MeV on target. Copper-64 was purified from both solid and liquid targets and used to radiolabel NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab conjugates. Stability studies were conducted on all radioimmunoconjugates in mouse serum, PBS, and DTPA. Irradiation of the solid target yielded 13.5 ± 0.5 GBq with a beam current of 25 ± 1.2 µA and an irradiation time of 6 h. On the other hand, irradiation of the liquid target resulted in 2.8 ± 1.3 GBq at the end of bombardment (EOB) with a beam current of 54.5 ± 7.8 µA and an irradiation time of 4.1 ± 1.3 h. Successful radiolabeling of NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab with copper-64 from both solid and liquid targets was achieved. Specific activities (SA) obtained with the solid target were 0.11, 0.19, and 0.33 MBq/µg for NODAGA-Nb, NOTA-Nb, and DOTA-trastuzumab, respectively. For the liquid target, the corresponding SA values were 0.15, 0.12, and 0.30 MBq/µg. Furthermore, all three radiopharmaceuticals demonstrated stability under the testing conditions. While solid targets have the potential to produce significantly higher activity in a single run, the liquid process offers advantages such as speed, ease of automation, and the feasibility of back-to-back production using a medical cyclotron. In this study, successful radiolabeling of antibodies and nanobodies was achieved using both solid and liquid targets approaches. The radiolabeled compounds exhibited high radiochemical purity and specific activity, rendering them suitable for subsequent in vivo pre-clinical imaging studies.

Osteosarcoma-Derived Exosomes as Potential PET Imaging Nanocarriers for Lung Metastasis.

Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma-related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected with current clinical tools. Herein, an exosome (EX)-based imaging tool is developed for lung micrometastasis by positron emission tomography (PET) using osteosarcoma-derived EXs as natural nanocarriers of the positron-emitter copper-64 (64 Cu). Exosomes are isolated from metastatic osteosarcoma cells and functionalized with the macrocyclic chelator NODAGA for complexation with 64 Cu. Surface functionalization has no effect on the physicochemical properties of EXs, or affinity for donor cells and endows them with favorable pharmacokinetics for in vivo studies. Whole-body PET/magnetic resonance imaging (MRI) images in xenografted models show a specific accumulation of 64 Cu-NODAGA-EXs in metastatic lesions as small as 2-3 mm or in a primary tumor, demonstrating the exquisite tropism of EXs for homotypic donor cells. The targetability for lung metastasis is also observed by optical imaging using indocyanine green (ICG)-labeled EXs and D-luciferin-loaded EXs. These findings show that tumor-derived EXs hold great potential as targeted imaging agents for the noninvasive detection of small lung metastasis by PET. This represents a step forward in the biomedical application of EXs in imaging diagnosis with increased translational potential.

Multiplex measurement of proinflammatory cytokines around miniscrews during orthodontic treatment / Medición múltiple de citocinas proinflamatorias alrededor de mini-implantes durante el tratamiento ortodóntico

ABSTRACT Objective : To determine the levels of proinflammatory cytokines around miniscrews with and without loading, used during orthodontic treatment. Material and Methods : A descriptive longitudinal study was executed with a sample of ten miniscrews inserted in patients that attended a dental clinic. Saliva and peri-implant crevicular fluid samples were taken: at baseline (T0), 24 hours after insertion (T1), 1 week after insertion (T2), 24 hours after loading (T3). The samples obtained were processed by immunoassay and read with a flow cytometer. Results : Data analysis was performed using the SPSS program version 21.0. To verify normal distribution, Kolmogorov-Smirnov test was used, followed by ANOVA to compare and determine statistical significance. Levels of inflammatory mediators in the peri-implant crevicular fluid at T1 had the following order of average values: IL-8>IL-1β >IL-6>TNF-α>IL-10>IL-12p70. Higher values were found 24 hours post-insertion. Salivary levels found were lower but the previously mentioned order was maintained. Statistically significant intergroup differences were found for IL-1β and IL-8 in the peri-implant crevicular fluid. The Scheffe post hoc test showed that there were no statistically significant differences when making an intragroup pair comparison of each mediator level in a given evaluation time. No statistically significant differences were found in saliva inter and intra-group for all the evaluated inflammatory mediators. Conclusions : The miniscrew loading did not generate an increase of the concentrations of the cytokines greater than the effect caused by the insertion per se. The highest levels of inflammatory mediators were found 24 hours post-insertion of the miniscrew.

RESUMEN Objetivo : Determinar los niveles de citocinas inflamatorias alrededor de mini-implantes con y sin carga, durante el tratamiento ortodóntico. Material y métodos : Se realizó un estudio descriptivo longitudinal con una muestra de diez mini-implantes. La toma de muestras de saliva y líquido crevicular peri-implantario fue realizada en cuatro tiempos: basal (T0), 24 horas post-inserción (T1), 1 semana post-inserción (T2), 24 horas post-carga (T3). Fueron procesadas mediante una técnica de inmunoensayo y citometría de flujo. Resultados : El análisis de los datos se realizó con el programa SPSS versión 21.0. Para verificar la distribución normal se utilizó la prueba de Kolmogorov-Smirnov, seguida de la prueba ANOVA para comparar y determinar la significancia estadística. Los niveles de mediadores inflamatorios en el líquido crevicular peri-implantario en T1 tuvieron el siguiente orden de valores promedio: IL-8> IL-1β> IL-6> TNF-α> IL-10> IL-12p70. Los valores más altos se encontraron 24 horas post-inserción. Los niveles en saliva fueron menores pero se mantuvo el orden mencionado. Se hallaron diferencias estadísticamente significativas entre grupos para IL-1β e IL-8 en el líquido crevicular peri-implantario. Posteriormente, la prueba post hoc de Scheffe demostró la ausencia de diferencias estadísticamente significativas en la comparación de pares intragrupo de cada mediador. No se encontraron diferencias estadísticamente significativas inter e intragrupo para todos los mediadores inflamatorios evaluados en saliva. Conclusiones : La carga del mini-implante no generó un aumento en la concentración de citocinas mayor que el provocado por la inserción per se. Los niveles más altos se encontraron 24 horas después de la inserción.

Detection of oral biomarkers as a diagnostic tool for orthodontically induced inflammatory root resorption: a literature review / Detección de biomarcadores orales como herramienta de diagnóstico para la reabsorción radicular inflamatoria inducida ortodónticamente: una revisión de la literatura

ABSTRACT Orthodontically induced inflammatory root resorption (OIIRR) is one of the most common complications of orthodontic treatment. Historically, only radiographic methods were available, while offering ease of use and accessibility, many limitations exist. Problems of technique, standardization, limited points of view and radiation exposure remain. Resorption can only be detected after a significant portion of the root has been lost (60% to 70% mineralized tissue). Moreover, these methods are static and cannot indicate if the process of root resorption has arrested or is ongoing. Recently, oral fluids have been used as a tool for the diagnosis and monitoring of oral and systemic diseases through the detection of biomarkers. The purpose of this review is to describe the scientific evidence related to the prevalence, etiology, the traditional diagnostic methods and the advances in the detection of oral biomarkers through molecular biology for this pathology.

RESUMEN La reabsorción radicular inflamatoria inducida ortodónticamente (RRIIO) es una de las complicaciones más comunes del tratamiento de Ortodoncia. Históricamente, solo estaban disponibles los medios radiográficos para detectarla, sin embargo, requieren de exposición a radiaciones ionizantes potencialmente dañinas, la técnica radiográfica es sensible, detecta la reabsorción después de que se ha perdido una porción significativa de la raíz (60% al 70% del tejido mineralizado) y no proporciona información sobre su actividad. Recientemente, los fluidos orales vienen siendo utilizados como herramienta para el diagnóstico y monitoreo de enfermedades orales y sistémicas mediante la detección de biomarcadores. El propósito de esta revisión es describir la evidencia científica relacionada con la prevalencia y etiología, los métodos diagnósticos tradicionales y los avances en la detección de biomarcadores orales mediante biología molecular.

Production of GMP-Compliant Clinical Amounts of Copper-61 Radiopharmaceuticals from Liquid Targets.

PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t1/2 = 3.33 h, 61% ß+, Emax = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of 61Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [61Cu]Cu-DOTA-NOC, [61Cu]Cu-DOTA-TOC and [61Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of 61Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce 18F-based radiopharmaceuticals.

Preferencia y aceptabilidad sobre diferentes diseños de aparatos ortodónticos fijos en adolescentes peruanos / Peruvian adolescent preferences and acceptability of orthodontic fixed appliances

RESUMEN Objetivo : Evaluar la preferencia y aceptabilidad sobre seis diferentes diseños de aparatos ortodónticos fijos en adolescentes peruanos de dos colegios de Lima. Material y Métodos : Se realizó un estudio descriptivo y transversal en un total de 140 adolescentes con edades entre 10 y 16 años, que completaron una ficha de registro en donde se evaluó la preferencia, aceptabilidad, orden de preferencia y aceptabilidad al uso sobre seis diferentes diseños de aparatos fijos visualizados en un álbum de fotografías. Resultados : Los datos fueron analizados con el paquete estadístico SPSS versión 24.0. Se utilizó un nivel de significancia de 5% con un intervalo de confianza de 95%. Debido a la naturaleza de las variables se utilizó la prueba de Chi cuadrado Los adolescentes prefirieron los brackets metálicos con módulos elásticos de colores y arco de acero (24,3%, n=34); y la aceptabilidad fue de 92,1%. Para el orden de preferencia, se encontró la siguiente jerarquía de primer a sexto lugar: brackets metálicos con módulos elásticos de colores y arco de acero > brackets de zafiro con módulos elásticos transparentes y arco estético > brackets metálicos con módulos elásticos transparentes y arco de acero > brackets de zafiro con módulos elásticos transparentes y arco de acero > brackets de zafiro con módulos elásticos de colores y arco de acero > brackets metálicos autoligantes y arco de acero/brackets de zafiro con módulos elásticos de colores y arco de acero. Se encontró una asociación estadísticamente significativa para algunas preguntas sobre la aceptabilidad al uso en relación al grupo de edad, sexo e institución educativa. Conclusiones : Los adolescentes prefirieron los brackets metálicos con módulos elásticos de colores y arco de acero. Los brackets metálicos autoligantes con arco de acero y los brackets de zafiro con módulos elásticos de colores y arco de acero, presentaron menos preferencia.

ABSTRACT Objective : To evaluate the preference and acceptability of six different orthodontic fixed appliance designs in Peruvian adolescents from two schools in Lima. Material and Methods : A descriptive cross-sectional study was executed. A total of 140 adolescents aged between 10 and 16 years completed a registration form in which the preference, acceptability, order of preference and acceptability to use were evaluated on six different designs of fixed orthodontic appliances displayed in a photo album. Results : Data analysis was performed using the SPSS program version 24.0. A p-value of less than 0.05 was considered as a level for significance. Due to the nature of the variables the Chi square test was used. Adolescents preferred metal brackets with colored elastomeric modules and steel arch (24.3%, n= 34); and the acceptability was 92.1%. For the order of preference, the following hierarchy was found from the first to the sixth place: metal brackes with colored elastomeric modules and steel archwire > sapphire brackets with transparent elastomeric modules and aesthetic archwire > metal brackets with transparent elastomeric modules and steel archwire > sapphire brackets with transparent elastomeric modules and steel archwire > sapphire brackets with colored elastomeric modules and steel archwire > self-ligating metal brackets and steel archwire/sapphire brackets with colored elastomeric modules and steel archwire. A statistically significant association was found for some questions about acceptability to use in relation to the age group, sex and educational institution. Conclusions : Adolescents preferred metallic brackets with colored elastomeric modules and steel arches. The less preferred appliances were the self-ligating metallic brackets with steel archwire and the sapphire brackets with colored elastomeric modules and steel archwire.

Suicidal behaviour after first-episode psychosis: results from a 1-year longitudinal study in Portugal.

BACKGROUND: Suicide is one of the main causes of excess of premature death in psychotic patients. Published studies found that suicide risk begins in ultra-high risk of psychosis and continues in early years of the disease. Previous studies identifying predictive and risk factors associated with suicidality in first-episode psychosis (FEP) are highly inconsistent. Also, there are relatively few longitudinal studies on suicidal behaviour in FEP. The aim of this study was to examine prevalence, evolution and predictors of suicidal behaviour at baseline and the 12-month follow-up in patients presenting with FEP. METHODS: One hundred and eighteen patients presenting with FEP were recruited from two early psychosis units in Portugal. A comprehensive assessment examining socio-demographic and clinical characteristics was administered at baseline and the 12-month follow-up. Odds ratio were calculated using logistic regression analyses. McNemar test was used to evaluate the evolution of suicidal behaviour and depression prevalence from baseline to 12 months of follow-up. RESULTS: Follow-up data were available for 60 participants from the 118 recruited. Approximately 25.4% of the patients had suicidal behaviour at the baseline evaluation, with a significant reduction during the follow-up period to 13.3% (p = 0.035). A multivariate binary logistic regression showed that a history of suicidal behaviour and depression at baseline independently predicted suicidal behaviour at baseline, and a history of suicidal behaviour and low levels of total cholesterol predicted suicidal behaviour at the 12-month follow-up. A significant proportion of patients also had depression at the baseline evaluation (43.3%), with the last month of suicidal behaviour at baseline independently predicting depression at this time. CONCLUSIONS: The findings of our study indicate that suicidal behaviour was prevalent on the year after FEP. Patients with a history of suicidal behaviour, depression at baseline and low levels of cholesterol should undergo close evaluation, monitoring and possible intervention in order to reduce suicide risk in the early phases of psychosis.

GMP-Automated Purification of Copper-61 Produced in Cyclotron Liquid Targets: Methodological Aspects.

BACKGROUND: Expanding the range of metal-based PET radiopharmaceuticals that can be produced by the widely available network of biomedical cyclotrons is a major priority. Copper- 61 is a positron emitter with very favourable physical (61.5% ß+, 1.22 MeV max.) and chemical properties, which emerged as a promising PET imaging agent. OBJECTIVES: This work aimed to develop and optimise a GMP-automated purification method for copper-61 produced in a cyclotron using a natural zinc liquid target. METHODS: The automated purification process was performed using a commercially available Synthera ® Extension module (IBA, Louvain-la-Neuve, Belgium) using a three-column method: two extraction chromatographic resins and a strong anion exchange resin. The final product was evaluated using HPGe and ICP-MS analysis, to assess the radionuclidic and chemical purity of the final copper- 61 solution. RESULTS: The automated purification process was completed within 1 h of processing time, with an average yield of 63.0 ± 15.0%, in a maximum volume of 5 mL. The radionuclidic purity of copper- 61 in the final solution was over 95% for 7 h after EOB. ICP-MS analysis revealed 4.8 ± 2.4 µg of natural zinc in the final purified sample, and the copper-61 molar activity was 230.5 ± 139.3 GBq/µmol. CONCLUSION: The described purification process allows for the production of a highly radionuclidically and chemically pure, GMP compliant copper-61 solution, ready to be used for the development of copper-61 based radiopharmaceuticals for routine clinical use.

Copper-64 Chloride Exhibits Therapeutic Potential in Three-Dimensional Cellular Models of Prostate Cancer.

Prostate cancer (PCa) is the second most common cancer type in men, and in advanced metastatic stages is considerable incurable. This justifies the need for efficient early diagnostic methods and novel therapies, particularly radiopharmaceuticals with the potential for simultaneous diagnosis and therapy (theranostics). We have previously demonstrated, using monolayer-cultured cells, that copper-64 chloride, a promising theranostic agent for PCa, has the potential to induce significant damage in cancer cells while having minimal side effects in healthy tissues. Here, we further explored this compound for its theranostic applications using more advanced PCa cellular models, specifically multicellular spheroids. Namely, we evaluated the cellular uptake of 64CuCl2 in three human PCa spheroids (derived from 22RV1, DU145, and LNCaP cells), and characterized the growth profile and viability of those spheroids as well as the clonogenic capacity of spheroid-derived cells after exposure to 64CuCl2. Furthermore, the populations of cancer stem cells (CSCs), known to be important for cancer resistance and recurrence, present in the spheroid models were also evaluated using two different markers (CD44 and CD117). 64CuCl2 was found to have significant detrimental effects in spheroids and spheroid-derived cells, being able to reduce their growth and impair the viability and reproductive ability of spheroids from both castration-resistant (22RV1 and DU145) and hormone-naïve PCa (LNCaP). Interestingly, resistance to 64CuCl2 treatment seemed to be related with the presence of a CSC population, since the most resistant spheroids, derived from the DU145 cell line, had the highest initial percentage of CSCs among the three cell lines under study. Altogether, these results clearly highlight the theranostic potential of 64CuCl2.

PROFIP: A Portuguese early intervention programme for first-episode psychosis in Lisbon.

AIM: There is currently no national plan for early intervention in first-episode psychosis in Portugal. Consequently, there is some heterogeneity in the evaluation and treatment of first-episode psychosis across the country. The aim of this article is to provide a complete description of the early intervention programme Programa de Intervenção nas Fases Iniciais da Psicose (PROFIP) in Lisbon, a pioneering team in Portugal for treating first-episode psychosis (FEP) patients. We also describe the baseline socio-demographic and clinical data obtained from new patients over a 1-year period. PROFIP programme accepts all cases of FEP, taking a transdiagnostic approach. METHODS: Description of PROFIP programme and baseline socio-demographic and clinical data obtained from new patients over a 1-year period. RESULTS: The team was constituted to provide early detection, treatment and support to people aged 16 to 35 years with affective and non-affective FEP. Over a 1-year period, 39 patients were included in the PROFIP programme. The majority of patients were young male patients with a diagnosis of non-affective psychosis, and with 56% of patients reporting cannabis use. Patients received pharmacological and psychosocial interventions based on evidence and individual needs. CONCLUSIONS: Our team allowed young people with early psychosis to receive effective care. We do need improvements, namely in referrals and the education of health professionals. More teams in our country should be constituted, allowing larger numbers of patients with early psychosis to be treated by specialized teams.