Antinociceptive and anti-inflammatory activity of extracts and α-pyrones isolated from Cantinoa stricta.

This study evaluated the composition and the antinociceptive and anti-inflammatory activity of the crude extracts and two isolated compounds, anamarine (ANA) and 10-epi-olguine (eOL), obtained from the leaves of Cantinoa stricta (Lamiaceae). Crude ethanolic extract (EEt) and dichloromethane extract (DCM), selected based on NMR data, were submitted to pharmacological tests in male Swiss mice. The oral administration of EEt and DCM significantly reduced the second phase of formalin-induced nociception (60%), lipopolysaccharide (LPS)-induced mechanical hyperalgesia (90%), and carrageenan (Cg)-induced edema (25%). ANA and eOL, the major compounds in EEt and DCM extracts, administered orally or locally (in the paw), also reduced the LPS-induced mechanical hyperalgesia (Oral ID50 1.9 and 3.9 mg/kg; Local ID50 93.4 and 677.3 ng, respectively) without changing the thermal acute nociception or the motor performance of the animals. Local administration of ANA and eOL also reduced Cg-induced edema (40 and 23%, respectively). These isolated compounds did not change the mechanical hyperalgesia induced by tumor necrosis factor-α, interleukin-1ß, prostaglandin E2, dibutyryl cyclic AMP, or forskolin but reversed the hyperalgesia induced by dopamine, epinephrine, and phorbol 12-myristate 13-acetate. The hyperalgesia induced by epinephrine was reversed in male but not in female mice, in which this response is not dependent on protein kinase C (PKC). These results suggest that C. stricta extracts possess antinociceptive and anti-inflammatory activity which is related to the presence of ANA and eOL. Differently from the known analgesics, these substances seem to exert their action mainly interfering with the sympathetic component of pain, possibly with PKC.

Efficacy and safety of hypofractionated radiotherapy versus conventional fractionated radiotherapy in diffuse intrinsic pontine glioma: A systematic review and meta-analysis.

Background: Diffuse intrinsic pontine glioma (DIPG) stands as the predominant type of brainstem glioma. It is characterized by a notably brief median survival period, with the majority of patients experiencing disease progression within six months following radiation therapy. This systematic review and meta-analysis aims to assess the efficacy and safety of hypofractionated radiotherapy (HFRT) compared to conventionally fractionated radiotherapy (CFRT) in DIPG treatment. Materials and methods: A systematic literature search was conducted in four databases, and relevant studies comparing HFRT and CFRT in DIPG were included. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. Statistical analysis was performed using random-effects models with heterogeneity assessment. Results: Five studies met the inclusion criteria, comprising 518 patients. No significant difference in one-year OS was observed between HFRT and CFRT (29% vs. 22%, p = 0.94). The median OS was similar in both treatment groups (9.7 vs. 9.3 months, p = 0.324). Similarly, no significant difference in one-year PFS was found between HFRT and CFRT (19.8% vs. 16.6%, p = 0.82), with comparable median PFS (9.3 vs. 9.4 months, p = 0.20). In meta-regression analysis, there was no association of chemotherapy (p > 0.05) or radiation biologically effective dose (BED) (p > 0.05) regarding OS or PFS outcomes. There were no significant differences in treatment-related toxicities. Conclusions: HFRT yields one-year OS and PFS rates similar to CFRT in DIPG, with no significant differences in treatment-related toxicities. Chemotherapy and BED did not affect OS or PFS.

Assessing Brazilian Medical Student Awareness About Global Surgery: A Survey-Based Study.

BACKGROUND: Global surgery is an interdisciplinary field that advocates for access to equitable, affordable surgical services for all people. Engaging medical students in the field can strengthen the surgical workforce in low- and middle-income countries. We aim to investigate Brazilian medical students' acknowledgment of global surgery and their preferred learning platforms. MATERIALS AND METHODS: We performed a cross-sectional study through an anonymous Portuguese survey on Google Forms, consisting of 30 mixed multiple-choice and five-point Likert scale questions. Students enrolled in a Brazilian medical school from the second to sixth academic year fulfilled inclusion criteria. The association between qualitative variables was assessed using Chi-square, Fisher's exact test, or binary logistic model. RESULTS: We received 1,345 responses from 208 medical schools. Only 20.9% (282/1,345) of participants reported awareness of global surgery, who were predominantly female. 96.5% (1,298/1,345) declared interest in knowing more about global surgery and participants indicated social media (71.6%, 202/282) as the prevalent manner to gain awareness on it, followed by webinars (63.5%, 179/282). Extracurricular classes were the most preferable option among students (61.4%, 827/1,345) to get acquainted with the field, followed by internships (59.4%, 812/1,345), workshops (57%, 767/1,345), and social media (53.4%, 730/1,345). The main obstacles to pursue a global surgery career were lack of national opportunities (32%, 431/1,345) and adequate training (25.4%, 341/1,345). CONCLUSION: We outlined the most strategic pathways to raising awareness on global surgery among Brazilian medical students, providing relevant insights on its education in similar settings.

Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to Metabolism.

Cancer demands precise evaluation and accurate and timely assessment of response to treatment. Imaging must be performed early during therapy to allow adjustments to the course of treatment. For decades, cross-sectional imaging provided these answers, showing responses to the treatment through changes in tumor size. However, with the emergence of immune checkpoint inhibitors, complex immune response patterns were revealed that have quickly highlighted the limitations of this approach. Patterns of response beyond tumor size have been recognized and include cystic degeneration, necrosis, hemorrhage, and cavitation. Furthermore, new unique patterns of response have surfaced, like pseudoprogression and hyperprogression, while other patterns were shown to be deceptive, such as unconfirmed progressive disease. This evolution led to new therapeutic evaluation criteria adapted specifically for immunotherapy. Moreover, inflammatory adverse effects of the immune checkpoint blockade were identified, many of which were life threatening and requiring prompt intervention. Given complex concepts like tumor microenvironment and novel therapeutic modalities in the era of personalized medicine, increasingly sophisticated imaging techniques are required to address the intricate patterns of behavior of different neoplasms. Fluorine 18-fluorodeoxyglucose PET/CT has rapidly emerged as one such technique that spans both molecular biology and immunology. This imaging technique is potentially capable of identifying and tracking prognostic biomarkers owing to its combined use of anatomic and metabolic imaging, which enables it to characterize biologic processes in vivo. This tailored approach may provide whole-body quantification of the metabolic burden of disease, providing enhanced prediction of treatment response and improved detection of adverse events. ©RSNA, 2020.

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Prostate-specific Membrane Antigen PET: Therapy Response Assessment in Metastatic Prostate Cancer.

Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification.© RSNA, 2020See discussion on this article by Barwick and Castellucci.

Can intensive silvicultural management minimize the effects of frost on restoration plantations in subtropical regions?

Temperature is one of the main factors that influence field establishment of forest species. In high-altitude tropical regions and in subtropical regions, the occurrence of frost represents an important restriction in the trajectory and continuity of ecological processes. Thus, we aimed to characterize frost damage in nine native forest species under different silvicultural management schemes in plantations for the restoration of a riparian forest area in southern Brazil. The experiment was carried out in the Quarta Colônia State Park, and seedlings of nine native tree species, representing the Subtropical Seasonal Forest. Frost damage was measured using a visual damage scale based on the frost damage experienced in the winter of 2016. In addition, to evaluate the resilience of the species, height and diameter data were collected over the duration of the experiment. The species Solanum mauritianum was classified as frost resistant; therefore, we propose that it should be recommended for cultivation in regions where frost events usually occur. The other species studied, both the pioneers, S. terebinthifolius, Enterolobium contortisiliquum, Ceiba speciosa, and Inga marginata, as well as the secondary ones, Actinostemon concolor, Trichilia elegans, T. claussenii, and Eugenia rostrifolia, were influenced by the silvicultural management schemes used. Plants managed under intensive silviculture showed lower levels of frost damage and higher survival rates.

Synthesis of Fe2SiO4-Fe7Co3 Nanocomposite Dispersed in the Mesoporous SBA-15: Application as Magnetically Separable Adsorbent.

The mixture containing alloy and oxide with iron-based phases has shown interesting properties compared to the isolated species and the synergy between the phases has shown positive effect on dye adsorption. This paper describes the synthesis of Fe2SiO4-Fe7Co3-based nanocomposite dispersed in Santa Barbara Amorphous (SBA)-15 and its application in dye adsorption followed by magnetic separation. Thus, it was studied the variation of reduction temperature and amount of hydrogen used in synthesis and the effect of these parameters on the physicochemical properties of the iron and cobalt based oxide/alloy mixture, as well as the methylene blue adsorption capacity. The XRD and Mössbauer results, along with the temperature-programmed reduction (TPR) profiles, confirmed the formation of Fe2SiO4-Fe7Co3-based nanocomposites. Low-angle XRD, N2 isotherms, and TEM images show the formation of the SBA-15 based mesoporous support with a high surface area (640 m2/g). Adsorption tests confirmed that the material reduced at 700 °C using 2% of H2 presented the highest adsorption capacity (49 mg/g). The nanocomposites can be easily separated from the dispersion by applying an external magnetic field. The interaction between the dye and the nanocomposite occurs mainly by π-π interactions and the mixture of the Fe2SiO4 and Fe7Co3 leads to a synergistic effect, which favor the adsorption.

Infectious Myelitis.

Myelitis refers to inflammation of the spinal cord which can result in a spectrum of neurologic impairment. Infectious pathogens are an important etiologic category, and can result in myelitis through direct pathogenic effect or through immune-mediated parainfection; this review focuses on the former category. The spectrum of clinical manifestations is summarized and a diagnostic workup provided to aid clinicians in developing an approach to patients presenting with symptoms suggestive of infectious myelitis. This is followed by an overview of the important viral, bacterial, parasitic, and fungal causes of infectious myelitis. The typical presentations, diagnostic modalities, and treatment approaches are outlined for key pathogens culprit in infectious myelitis to allow clinicians to promptly recognize and diagnose specific infectious etiologies of myelitis.

Revisiting Prostate Cancer Recurrence with PSMA PET: Atlas of Typical and Atypical Patterns of Spread.

The introduction of prostate-specific membrane antigen (PSMA) in clinical practice has revolutionized evaluation of biochemical recurrence of prostate cancer after curative-intent treatment. The high expression of this glycoprotein in prostate cancer cells makes PSMA imaging superior to the current conventional staging methods, namely bone scanning and CT. The high capability of PSMA imaging for identifying very small previously undetected lesions has been widely demonstrated in the literature, leading to a rethinking of patient management by oncologists, urologists, and radiation oncologists. The typical and predictable patterns of spread in prostate cancer are still more prevalent, such as spread to pelvic lymph nodes and bone metastasis, but different patterns of disease spread are becoming more commonly recognized with higher reliability because PSMA imaging allows detection of more typical and atypical lesions than conventional imaging. Furthermore, it is important for the reading physician to recognize and understand the typical disease spread and the most prevalent atypical prostate cancer relapses, not only to heighten the relevancy of reports but also to improve imaging consultancy in multispecialty oncologic practice. ©RSNA, 2019.

Reduction of 18F-FDG Dose in Clinical PET/MR Imaging by Using Silicon Photomultiplier Detectors.

Purpose To determine the level of clinically acceptable reduction in injected fluorine 18 (18F) fluorodeoxyglucose (FDG) dose in time-of-flight (TOF)-positron emission tomography(PET)/magnetic resonance (MR) imaging by using silicon photomultiplier (SiPM) detectors compared with TOF-PET/computed tomography (CT) using Lu1.8Y0.2SiO5(Ce), or LYSO, detectors in patients with different body mass indexes (BMIs). Materials and Methods Patients were enrolled in this study as part of a larger prospective study with a different purpose than evaluated in this study (NCT02316431). All patients gave written informed consent prior to inclusion into the study. In this study, 74 patients with different malignant diseases underwent sequential whole-body TOF-PET/CT and TOF-PET/MR imaging. PET images with simulated reduction of injected 18F-FDG doses were generated by unlisting the list-mode data from PET/MR imaging. Two readers rated the image quality of whole-body data sets, as well as the image quality in each body compartment, and evaluated the conspicuity of malignant lesions. Results The image quality with 70% or 60% of the injected dose of 18F-FDG at PET/MR imaging was comparable to that at PET/CT. With 50% of the injected dose, comparable image quality was maintained among patients with a BMI of less than 25 kg/m2. PET images without TOF reconstruction showed higher artifact scores and deteriorated sharpness than those with TOF reconstruction. Conclusion Sixty percent of the usually injected 18F-FDG dose (reduction of up to 40%) in patients with a BMI of more than 25 kg/m2 results in clinically adequate PET image quality in TOF-PET/MR imaging performed by using SiPM detectors. Additionally, in patients with a BMI of less than 25 kg/m2, 50% of the injected dose may safely be used. © RSNA, 2017 Online supplemental material is available for this article.

Effect of Time-of-Flight Information on PET/MR Reconstruction Artifacts: Comparison of Free-breathing versus Breath-hold MR-based Attenuation Correction.

Purpose To evaluate the magnitude and anatomic extent of the artifacts introduced on positron emission tomographic (PET)/magnetic resonance (MR) images by respiratory state mismatch in the attenuation map. Materials and Methods The method was tested on 14 patients referred for an oncologic examination who underwent PET/MR imaging. The acquisition included standard PET and MR series for each patient, and an additional attenuation correction series was acquired by using breath hold. PET data were reconstructed with and without time-of-flight (TOF) information, first by using the standard free-breathing attenuation map and then again by using the additional breath-hold map. Two-tailed paired t testing and linear regression with 0 intercept was performed on TOF versus non-TOF and free-breathing versus breath-hold data for all detected lesions. Results Fluorodeoxyglucose-avid lesions were found in eight of the 14 patients included in the study. The uptake differences (maximum standardized uptake values) between PET reconstructions with free-breathing versus breath-hold attenuation ranged, for non-TOF reconstructions, from -18% to 26%. The corresponding TOF reconstructions yielded differences from -15% to 18%. Conclusion TOF information was shown to reduce the artifacts caused at PET/MR by respiratory mismatch between emission and attenuation data. © RSNA, 2016 Online supplemental material is available for this article.

Naphthoquinones of Sinningia reitzii and Anti-inflammatory/Antinociceptive Activities of 8-Hydroxydehydrodunnione.

Chemical investigation of the tubers of Sinningia reitzii led to the isolation of five new naphthoquinones, 8-hydroxydehydrodunnione (1), 7-hydroxydehydrodunnione (2), 5-hydroxy-6,7-dimethoxy-α-dunnione (3), 5-hydroxy-6,7-dimethoxydunniol (4), and 8-hydroxy-7-methoxy-2-O-methylstreptocarpone (5). Three known naphthoquinones, 7-hydroxy-α-dunnione, 8-hydroxydunnione, and 6,8-dihydroxy-7-methoxy-2-O-methyldunniol, were also identified. When tested for anti-inflammatory activity in a mouse model, compound 1 (50-500 pg/paw) reduced the edema induced by carrageenan in a dose-dependent fashion. The highest dose showed a similar inhibition to that observed for the positive control dexamethasone. At lower doses (5-10 pg/paw), 1 also dose dependently reduced the mechanical hyperalgesia induced by carrageenan. Compound 1 (15 pg/paw) abolished the mechanical hyperalgesia induced by prostaglandin E2 and dopamine, but not that induced by dibutyryl cyclic AMP. Dipyrone (320 µg/paw) completely abolished the hyperalgesia induced by these algogens. Additionally, compound 1 did not alter heat-induced nociception. These results suggest that this new naphthoquinone exhibits important anti-inflammatory and antinociceptive activities, which is dissimilar to that of most known analgesics.

Diagnostic performance of FDG-PET/MRI and WB-DW-MRI in the evaluation of lymphoma: a prospective comparison to standard FDG-PET/CT.

BACKGROUND: Use of FDG-PET/CT for staging and restaging of lymphoma patients is widely incorporated into current practice guidelines. Our aim was to prospectively evaluate the diagnostic performance of FDG-PET/MRI and WB-DW-MRI compared with FDG-FDG-PET/CT using a tri-modality PET/CT-MRI system. METHODS: From 04/12 to 01/14, a total of 82 FDG-PET/CT examinations including an additional scientific MRI on a tri-modality setup were performed in 61 patients. FDG-PET/CT, FDG-PET/MRI, and WB-DW-MRI were independently analyzed. A lesion with a mean ADC below a threshold of 1.2 × 10(-3) mm(2)/s was defined as positive for restricted diffusion. FDG-PET/CT and FDG-PET/MRI were evaluated for the detection of lesions corresponding to lymphoma manifestations according to the German Hodgkin Study Group. Imaging findings were validated by biopsy (n = 21), by follow-up imaging comprising CT, FDG-PET/CT, and/or FDG-PET/MRI (n = 32), or clinically (n = 25) (mean follow-up: 9.1 months). RESULTS: FDG-PET/MRI and FDG-PET/CT accurately detected 188 lesions in 27 patients. Another 54 examinations in 35 patients were negative. WB-DW-MRI detected 524 lesions, of which 125 (66.5% of the aforementioned 188 lesions) were true positive. Among the 188 lesions positive for lymphoma, FDG-PET/MRI detected all 170 instances of nodal disease and also all 18 extranodal lymphoma manifestations; by comparison, WB-DW-MRI characterized 115 (67.6%) and 10 (55.6%) lesions as positive for nodal and extranodal disease, respectively. FDG-PET/MRI was superior to WB-DW-MRI in detecting lymphoma manifestations in patients included for staging (113 vs. 73), for restaging (75 vs. 52), for evaluation of high- (127 vs. 81) and low-grade lymphomas (61 vs. 46), and for definition of Ann Arbor stage (WB-DW-MRI resulted in upstaging in 60 cases, including 45 patients free of disease, and downstaging in 4). CONCLUSION: Our results indicate that FDG-PET/CT and FDG-PET/MRI probably have a similar performance in the clinical work-up of lymphomas. The performance of WB-DW-MRI was generally inferior to that of both FDG-PET-based methods but the technique might be used in specific scenarios, e.g., in low-grade lymphomas and during surveillance.

Combined PET/CT-perfusion in patients with head and neck cancers might predict failure after radio-chemotherapy: a proof of concept study.

BACKGROUND: [18F]FDG-PET/CT imaging is broadly used in head and neck cancer (HNSCC) patients. CT perfusion (CTP) is known to provide information about angiogenesis and blood-flow characteristics in tumors. The aim of this study was to evaluate the potential relationship of FDG-parameters and CTP-parameters in HNSCC preand post-therapy and the potential prognostic value of a combined PET/CT with CTP. METHODS: Thirteen patients with histologic proven HNSCC were prospectively included. All patients underwent a combined PET/CT with integrated CTP before and after therapy. Pre- and post-therapeutic data of CTP and PET of the tumors were compared. Differences were tested using Spearman's rho test and Pearson's correlation. A p-value of p <0.05 was considered statistically significant. Correlations were calculated using Pearson's correlation. Bootstrap confidence intervals were calculated to test for additive confidence intervals. RESULTS: Three patients died due to malignancy recurrence, ten patients were free of recurrence until the end of the follow-up period. Patients with recurrent disease had significantly higher initial CTP-values compared to the recurrence-free patients: BFpre 267.4 (171.2)ml/100 mg/min, BVpre 40.9 (8.4)ml/100 mg and MTTpre 8.2 (6.1)sec. No higher SUVs initially but significantly higher TLG compared to patients without recurrence were found. Post-therapeutic PET-values differed significantly between the two groups: SUVmaxpost 6.0 (3.2), SUVmeanpost 3.6 (2.0) and TLG 21751.7 (29794.0). CONCLUSION: In our proof of concept study, combined PET/CT with integrated CTP might show complementary prognostic data pre- and post chemo-radiotherapy. CTP may be used to predict local tumor recurrence, while FDGPET/CT is still needed for whole-body staging.

Performance of tree-building methods using a morphological dataset and a well-supported Hexapoda phylogeny.

Recently, many studies have addressed the performance of phylogenetic tree-building methods (maximum parsimony, maximum likelihood, and Bayesian inference), focusing primarily on simulated data. However, for discrete morphological data, there is no consensus yet on which methods recover the phylogeny with better performance. To address this lack of consensus, we investigate the performance of different methods using an empirical dataset for hexapods as a model. As an empirical test of performance, we applied normalized indices to effectively measure accuracy (normalized Robinson-Foulds metric, nRF) and precision, which are measured via resolution, one minus Colless' consensus fork index (1-CFI). Additionally, to further explore phylogenetic accuracy and support measures, we calculated other statistics, such as the true positive rate (statistical power) and the false positive rate (type I error), and constructed receiver operating characteristic plots to visualize the relationship between these statistics. We applied the normalized indices to the reconstructed trees from the reanalyses of an empirical discrete morphological dataset from extant Hexapoda using a well-supported phylogenomic tree as a reference. Maximum likelihood and Bayesian inference applying the k-state Markov (Mk) model (without or with a discrete gamma distribution) performed better, showing higher precision (resolution). Additionally, our results suggest that most available tree topology tests are reliable estimators of the performance measures applied in this study. Thus, we suggest that likelihood-based methods and tree topology tests should be used more often in phylogenetic tree studies based on discrete morphological characters. Our study provides a fair indication that morphological datasets have robust phylogenetic signal.

Inguinal lymph node metastases from prostate cancer: clinical, pathology, and multimodality imaging considerations.

Objective: To investigate clinical, pathology, and imaging findings associated with inguinal lymph node (LN) metastases in patients with prostate cancer (PCa). Materials and Methods: This was a retrospective single-center study of patients with PCa who underwent imaging and inguinal LN biopsy between 2000 and 2023. We assessed the following aspects on multimodality imaging: inguinal LN morphology; extrainguinal lymphadenopathy; the extent of primary and recurrent tumors; and non-nodal metastases. Imaging, clinical, and pathology features were compared between patients with and without metastatic inguinal LNs. Results: We evaluated 79 patients, of whom 38 (48.1%) had pathology-proven inguinal LN metastasis. Certain imaging aspects- short-axis diameter, prostate-specific membrane antigen uptake on positron-emission tomography, membranous urethra involvement by the tumor, extra-inguinal lymphadenopathy, and distant metastases-were associated with pathology-proven inguinal LN metastases (p < 0.01 for all). Associations with long-axis diameter, fatty hilum, laterality, and uptake of other tracers on positronemission tomography were not significant (p = 0.09-1.00). The patients with metastatic inguinal LNs had higher prostate-specific antigen levels and more commonly had castration-resistant PCa (p < 0.01), whereas age, histological grade, and treatment type were not significant factors (p = 0.07-0.37). None of the patients had inguinal LN metastasis in the absence of locally advanced disease with membranous urethra involvement or distant metastasis. Conclusion: Several imaging, clinical, and pathology features are associated with inguinal LN metastases in patients with PCa. Isolated metastasis to inguinal LNs is extremely rare and unlikely to occur in the absence of high-risk imaging, clinical, or pathology features.

Objetivo: Investigar achados clinicopatológicos e de imagem associados a metástases linfonodais inguinais em pacientes com câncer de próstata (CaP). Materiais e Métodos: Estudo retrospectivo de uma única instituição de pacientes com CaP submetidos a exames de imagem e biópsia inguinal de linfonodos em 2000­2023. A imagem multimodalidade foi avaliada para morfologia inguinal do linfonodo, linfadenopatia fora da região inguinal, extensão do CaP primário/recorrente e sítios metastáticos não nodais. Características de imagem e clinicopatológicas foram comparadas entre pacientes com e sem linfonodos inguinais metastáticos pela patologia. Resultados: Entre 79 pacientes estudados, 38 (48,1%) apresentaram metástase inguinal de linfonodo comprovada patologicamente. Certos achados de imagem ­ diâmetro do eixo curto, captação do antígeno de membrana prostático específico na tomografia por emissão de pósitrons, envolvimento da uretra membranosa pelo tumor, linfadenopatia fora da região inguinal e metástases a distância ­ foram associados com metástases inguinais no linfonodo pela patologia (p < 0,01). Diâmetro de eixo longo, hilo gorduroso, lateralidade, captação em outros traçadores de tomografia por emissão de pósitrons não foram significativos (p = 0,09­1,00). Clinicopatologicamente, os pacientes com linfonodos inguinais metastáticos apresentaram maior antígeno prostático específico e foram mais resistentes à castração (p < 0,01); idade, grau histológico e tipo de tratamento não foram estatisticamente significantes (p = 0,07­0,37). Nenhum paciente apresentou metástase inguinal isolada no linfonodo na ausência de doença localmente avançada com envolvimento da uretra membranosa ou metástase a distância. Conclusão: Várias características de imagem e clinicopatológicas foram associadas a metástases em LNs inguinais em pacientes com CaP. A metástase isolada para os LNs inguinais é extremamente rara e é improvável que ocorra na ausência de características de imagem e clinicopatológicas de alto risco.

Impact of Muscle Changes Assessed by Ultrasonography on Muscle Strength and Functioning after ICU Discharge: A Systematic Review with Meta-Analysis.

BACKGROUND: Ultrasonography has been used to identify structural, quantitative, and qualitative muscle changes. These changes have been assessed in different muscles during ICU stays; however, it is unclear if it can predict functioning after ICU discharge. OBJECTIVE: To analyze the relationship between muscle changes assessed by ultrasonography and the strength and functioning of ICU survivors. METHODS: A systematic review with a meta-analysis was performed according to the MOOSE guidelines and registered in PROSPERO. Searches of the following databases were performed by two of the authors: PubMed, Cinahl, Embase, Scopus, LILACS, Web of Science, and Science Direct. Qualitative analysis was performed using NOS and AHRQ scales. Meta-analysis was performed using the "R", "metafor" package. Heterogeneity was assessed by I2 and Cochran's Q test. Meta-regression analyses were performed to verify the moderators, and funnel plots and Egger's regression intercept test were used to analyze the publication bias. RESULTS: Sixteen articles were included in the qualitative assessment, and nine were used in the quantitative assessment. There is evidence of correlations between MT and muscle strength (r = 0.20 [0.11; 0.27]; p < 0.0001), and MT (r = 0.35 [0.19; 0.49]; p < 0.0001), CSA (r = 0.30 [0.10; 0.47]; p = 0.0038), EI (r = -0.29 [-0.53; -0.01]; p = 0.043) and mobility. In the subgroup analyses, some evidence of a correlation between specific muscles and strength and mobility were found. CONCLUSIONS: There is evidence for the correlation between muscle characteristics assessed by US and functioning outcomes.

Effects and mechanisms of anterior thalamus nucleus deep brain stimulation for epilepsy: A scoping review of preclinical studies.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a safe and effective intervention for the treatment of certain forms of epilepsy. In preclinical models, electrical stimulation of the ANT has antiepileptogenic effects but its underlying mechanisms remain unclear. In this review, we searched multiple databases for studies that described the effects and mechanisms of ANT low or high frequency stimulation (LFS or HFS) in models of epilepsy. Out of 289 articles identified, 83 were pooled for analysis and 34 were included. Overall, ANT DBS was most commonly delivered at high frequency to rodents injected with kainic acid, pilocarpine, or pentylenetetrazole. In most studies, this therapy increased the latency to the first spontaneous seizure and reduced the frequency of seizures by 20%-80%. Electrophysiology data suggested that DBS reduces the severity of electrographic seizures, decreases the duration and increases the threshold of afterdischarges, reduces the power of low-frequency and increase the power high-frequency bands. Mechanistic studies revealed that ANT DBS leads to a series of short- and long-term changes at multiple levels. Some of its anticonvulsant effects were proposed to occur via the modulation of serotonergic and adenosinergic transmission. The latter seems to be derived from the downregulation of adenosine kinase (ADK). ANT DBS was also shown to increase hippocampal levels of lactate, alter the expression of genes involved in calcium signaling, synaptic glutamate, and the NOD-like receptor signaling pathway. When delivered during status epilepticus or following the injection of convulsant agents, DBS was found to reduce the expression of proinflammatory cytokines and apoptosis. When administered chronically, ANT DBS increased the expression of proteins involved in axonal guidance, changed functional connectivity in limbic circuits, and increased the number of hippocampal cells in epileptic animals, suggesting a neuroprotective effect.