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The hematopoietic stem cell engraftment depends on adequate cell numbers, their homing, and the subsequent short and long-term engraftment of these cells in the niche. We performed a systematic review of the methods employed to track hematopoietic reconstitution using molecular imaging. We searched articles indexed, published prior to January 2020, in PubMed, Cochrane, and Scopus with the following keyword sequences: (Hematopoietic Stem Cell OR Hematopoietic Progenitor Cell) AND (Tracking OR Homing) AND (Transplantation). Of 2191 articles identified, only 21 articles were included in this review, after screening and eligibility assessment. The cell source was in the majority of bone marrow from mice (43%), followed by the umbilical cord from humans (33%). The labeling agent had the follow distribution between the selected studies: 14% nanoparticle, 29% radioisotope, 19% fluorophore, 19% luciferase, and 19% animal transgenic. The type of graft used in the studies was 57% allogeneic, 38% xenogeneic, and 5% autologous, being the HSC receptor: 57% mice, 9% rat, 19% fish, 5% for dog, porcine and salamander. The imaging technique used in the HSC tracking had the following distribution between studies: Positron emission tomography/single-photon emission computed tomography 29%, bioluminescence 33%, fluorescence 19%, magnetic resonance imaging 14%, and near-infrared fluorescence imaging 5%. The efficiency of the graft was evaluated in 61% of the selected studies, and before one month of implantation, the cell renewal was very low (less than 20%), but after three months, the efficiency was more than 50%, mainly in the allogeneic graft. In conclusion, our review showed an increase in using noninvasive imaging techniques in HSC tracking using the bone marrow transplant model. However, successful transplantation depends on the formation of engraftment, and the functionality of cells after the graft, aspects that are poorly explored and that have high relevance for clinical analysis.

Fibroblastic reticular cells (FRCs), usually found and isolated from the T cell zone of lymph nodes, have recently been described as much more than simple structural cells. Originally, these cells were described to form a conduit system called the “reticular fiber network” and for being responsible for transferring the lymph fluid drained from tissues through afferent lymphatic vessels to the T cell zone. However, nowadays, these cells are described as being capable of secreting several cytokines and chemokines and possessing the ability to interfere with the immune response, improving it, and also controlling lymphocyte proliferation. Here, we performed a systematic review of the several methods employed to investigate the mechanisms used by fibroblastic reticular cells to control the immune response, as well as their ability in determining the fate of T cells. We searched articles indexed and published in the last five years, between 2016 and 2020, in PubMed, Scopus, and Cochrane, following the PRISMA guidelines. We found 175 articles published in the literature using our searching strategies, but only 24 articles fulfilled our inclusion criteria and are discussed here. Other articles important in the built knowledge of FRCs were included in the introduction and discussion. The studies selected for this review used different strategies in order to access the contribution of FRCs to different mechanisms involved in the immune response: 21% evaluated viral infection in this context, 13% used a model of autoimmunity, 8% used a model of GvHD or cancer, 4% used a model of Ischemic-reperfusion injury (IRI). Another four studies just targeted a particular signaling pathway, such as MHC II expression, FRC microvesicles, FRC secretion of IL-15, FRC network, or ablation of the lysophosphatidic acid (LPA)-producing ectoenzyme autotaxin. In conclusion, our review shows the strategies used by several studies to isolate and culture fibroblastic reticular cells, the models chosen by each one, and dissects their main findings and implications in homeostasis and disease.

The main objective of this cross-sectional study was to compare the self-reported depressive symptoms and physical activity (PA) levels among participants who performed self- nonexercising (NE), guided exercise (SGE), remotely supervised exercise (RSE), and face-to-face supervised exercise (FFE) during social distancing. Three hundred and forty-four individuals (≥18 years and 67% women) answered a self-reported online survey that included questions related to the physical exercise practice (e.g., supervised and remote) during social distancing and questions about perceptions of depressive symptoms (Montgomery-Asberg Depression Rating Scale-Self Rated [MADRS-S] scores) and metabolic equivalent task minutes per week (METs min•wk-1) of moderate- and vigorous-intensity PA, and total PA scores (International Physical Activity Questionnaire-Short Form) before and during social distancing. The RSE group (n=45) showed higher METs of vigorous-intensity PA than the SGE (n=146) and NE (n=109) groups. The RSE and FFE (n=44) groups showed higher METs of the total PA scores than the SGE and NE groups. The NE group showed higher MADRS-S scores than the other groups. Lower MADRS-S scores depend on the exercise practice and higher METs of vigorous-intensity PA depend on the supervised exercise practice. Thus, telehealth interventions can be implemented during the pandemic to enhance vigorous PA.

Highlights • High hemodynamic response in the AI and SMA in the FoG when an APA was required. • Connectivity between the right and left insulae was correlated with severity of FoG. • Both groups showed different brain network organizations between SMA and bilateral AI. • SMA was found to be a hub in patients with FoG when an APA was required., Specific impairments of anticipatory postural adjustment (APA) during step initiation have been reported in patients with Parkinson’s disease (PD) and freezing of gait (FoG). Although APA disruption has been associated with FoG, there is scarce knowledge about its neural correlates. We sought to better understand the neural networks involved with APA in patients with FoG by assessing the level of hemodynamic response of specific brain regions and the functional connectivity during the leg lifting task. In the current investigation, APAs of patients with PD, with and without (nFoG) freezing were assessed during a leg lifting task in an event-related, functional magnetic resonance imaging (er-fMRI) protocol. Results identified a high hemodynamic response in the right anterior insula (AI) and supplementary motor area (SMA) in the FoG group when an APA was required. The nFoG had stronger connectivity between the right and left insulae than the FoG group. The strength of this connectivity was negatively correlated with the severity of FoG. Both groups showed different brain network organizations comprising the SMA and the bilateral AI. The SMA was found to be a hub in patients with FoG when an APA was required for the task. Our findings suggest that both groups used compensatory mechanism comprising the insulae during APA. Neither group used the entire network comprised of the insulae and SMA to accomplish the task. The FoG group relied more on SMA as a hub than as part of a broader network to exchange information during the APA.

Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered in angiogenesis have been developed to reach and modulate different phases of this process. We performed a systematic review with the search criterion (Glioblastoma OR Glioma) AND (Therapy OR Therapeutic) AND (Nanoparticle) AND (Antiangiogenic OR Angiogenesis OR Anti-angiogenic) in Pubmed, Scopus, and Cochrane databases, in which 312 articles were identified; of these, only 27 articles were included after selection and analysis of eligibility according to the inclusion and exclusion criteria. The data of the articles were analyzed in five contexts: the characteristics of the tumor cells; the animal models used to induce GBM for antiangiogenic treatment; the composition of nanoformulations and their physical and chemical characteristics; the therapeutic anti-angiogenic process; and methods for assessing the effects on antiangiogenic markers caused by therapies. The articles included in the review were heterogeneous and varied in practically all aspects related to nanoformulations and models. However, there was slight variance in the antiangiogenic effect analysis. CD31 was extensively used as a marker, which does not provide a view of the effects on the most diverse aspects involved in angiogenesis. Therefore, the present review highlighted the need for standardization between the different approaches of antiangiogenic therapy for the GBM model that allows a more effective meta-analysis and that helps in future translational studies.

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.

During the 16th century and at the beginning of the 17th century the age-old competition between scholarly doctors and folk healers became more and more serious, creating a division between the two categories entrusted with treating population diseases. On one side there were the representatives who practiced medicine in an official capacity, and on the other, the "others", that is, the charlatans, the acrobats and female healers. Two representatives of these contrasting approaches of practicing medicine within the health profession during that historical period were two Italian doctors, Domenico Lanzoni and Giuseppe Rosaccio. Together, with their ties to the city of Bologna and the bolognese Carracci family of painters, they were able to describe in complete detail these two types of practices as medical sciences of the sixteenth and early seventeenth century.

To describe cerebral (structural and functional MRI) and neuropsychological long term changes in moderate drowning victim's compared to healthy volunteers in working memory and motor domains. We studied 15 adult drowning victim's in chronic stage (DV - out of 157 eligible cases of sea water rescues with moderate drowning classification) paired to 18 healthy controls (HC). All participants were investigated using intelligence, memory, and attention neuropsychological standard tests and underwent functional (motor and working memory tasks) and structural magnetic resonance imaging (MRI) in a 3 T system. All images were preprocessed for head movement correction and quantitative analysis was performed using FSL and freesurfer software packages. We found no between group differences in neuropsychological assessments. No MRI brain lesion was observed in patients, neither difference on morphometric parameters in any cortical or subcortical brain structure. In constrast, functional MRI revealed that patients showed increased brain response in the motor (left putamen and insula) and memory (left cuneus and lingual gyrus - not the classical memory network) tasks. Functional brain changes in motor and visual brain regions in victims of moderate drowning may indicate reduced brain reserve, despite the lack of structural and behavior alterations. More attention should be given to investigate ageing effects in this nonfatal drowning group.

Saccades were assessed in 21 adults (age 24 years, SD = 4) and 15 children (age 11 years, SD = 1), using combined functional magnetic resonance imaging (fMRI) and eye-tracking. Subjects visually tracked a point on a horizontal line in four conditions: time and position predictable task (PRED), position predictable (pPRED), time predictable (tPRED) and visually guided saccades (SAC). Both groups in the PRED but not in pPRED, tPRED and SAC produced predictive saccades with latency below 80 ms. In task versus group comparisons, children's showed less efficient learning compared to adults for predictive saccades (adults = 48%, children = 34%, p = 0.05). In adults brain activation was found in the frontal and occipital regions in the PRED, in the intraparietal sulcus in pPRED and in the frontal eye field, posterior intraparietal sulcus and medial regions in the tPRED task. Group-task interaction was found in the supplementary eye field and visual cortex in the PRED task, and the frontal cortex including the right frontal eye field and left frontal pole, in the pPRED condition. These results indicate that, the basic visuomotor circuitry is present in both adults and children, but fine-tuning of the activation according to the task temporal and spatial demand mature late in child development.

Drowning is a serious and frequently neglected public health threat. Primary respiratory impairment after submersion often leads to brain dysfunction. Depending on the period of global hypoxia (respiratory failure), clinical aspects of neurological dysfunction are evident on the first evaluation after the water rescue. Nowadays, many neuropsychological assessments after drowning are inconclusive, with some studies reporting only minor neurological or cognitive impairments. The aim of this study is to identify measures in neuropsychological tests that most contribute to classify volunteers as moderate drowning subjects or healthy controls. To the best of our knowledge, this study is the first neuropsychological prospective case-control study of moderate drowning in a country with large coastal cities.Fifteen moderate drowning patients (DP), who met the inclusion criteria, were compared with 18 healthy controls (HC). All subjects were assessed on memory, learning, visual spatial ability, executive function, attention, and general intellectual functioning and underwent structural magnetic resonance (MR) imaging of the brain at 3.0 T, in order to exclude subjects with anatomic abnormalities.Neuropsychological tests assessing learning, execution function, and verbal fluency-Rey Auditory Verbal Learning Test (RAVLT) general learning ability, Digit Span total, Phonological Verbal Fluency (total FAS correct), and Brief Visuospatial Memory Test Revised (BVMT) correct recognition-have the strongest discriminating ability, using predictive models via the partial least squares (PLS) approach for data classification, while the other tests have shown similar predictive values between groups.Learning, execution function, and verbal fluency domains were the most critically affected domains. Serious impairments in the same domains have already been reported in severe drowning cases, and we hypothesize that subtle alterations found in moderate drowning cases, although not sufficient to be detected in daily routine, may possibly have a negative impact on cognitive reserve.

Static body equilibrium is an essential requisite for human daily life. It is known that visual and vestibular systems must work together to support equilibrium. However, the relationship between these two systems is not fully understood. In this work, we present the results of a study which identify the interaction of brain areas that are involved with concurrent visual and vestibular inputs. The visual and the vestibular systems were individually and simultaneously stimulated, using flickering checkerboard (without movement stimulus) and galvanic current, during experiments of functional magnetic resonance imaging. Twenty-four right-handed and non-symptomatic subjects participated in this study. Single visual stimulation shows positive blood-oxygen-level-dependent (BOLD) responses (PBR) in the primary and associative visual cortices. Single vestibular stimulation shows PBR in the parieto-insular vestibular cortex, inferior parietal lobe, superior temporal gyrus, precentral gyrus and lobules V and VI of the cerebellar hemisphere. Simultaneous stimulation shows PBR in the middle and inferior frontal gyri and in the precentral gyrus. Vestibular- and somatosensory-related areas show negative BOLD responses (NBR) during simultaneous stimulation. NBR areas were also observed in the calcarine gyrus, lingual gyrus, cuneus and precuneus during simultaneous and single visual stimulations. For static visual and galvanic vestibular simultaneous stimulation, the reciprocal inhibitory visual-vestibular interaction pattern is observed in our results. The experimental results revealed interactions in frontal areas during concurrent visual-vestibular stimuli, which are affected by intermodal association areas in occipital, parietal, and temporal lobes.

The hippocampus is one of the earliest sites involved in the pathology of Alzheimer's disease (AD). Therefore, we specifically investigated the sensitivity and specificity of hippocampal volume and glucose metabolism in patients being evaluated for AD, using automated quantitative tools (NeuroQuant – magnetic resonance imaging [MRI] and Scenium – positron emission tomography [PET]) and clinical evaluation. This retrospective study included adult patients over the age of 45 years with suspected AD, who had undergone fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) and MRI. FDG-PET-CT images were analyzed both qualitatively and quantitatively. In quantitative volumetric MRI analysis, the percentage of the total intracranial volume of each brain region, as well as the total hippocampal volume, were considered in comparison to an age-adjusted percentile. The remaining brain regions were compared between groups according to the final diagnosis. Thirty-eight patients were included in this study. After a mean follow-up period of 23 ± 11 months, the final diagnosis for 16 patients was AD or high-risk mild cognitive impairment (MCI). Out of the 16 patients, 8 patients were women, and the average age of all patients was 69.38 ± 10.98 years. Among the remaining 22 patients enrolled in the study, 14 were women, and the average age was 67.50 ± 11.60 years; a diagnosis of AD was initially excluded, but the patients may have low-risk MCI. Qualitative FDG-PET-CT analysis showed greater accuracy (0.87), sensitivity (0.76), and negative predictive value (0.77), when compared to quantitative PET analysis, hippocampal MRI volumetry, and specificity. The positive predictive value of FDG-PET-CT was similar to the MRI value. The performance of FDG-PET-CT qualitative analysis was significantly more effective compared to MRI volumetry. At least in part, this observation could corroborate the sequential hypothesis of AD pathophysiology, which posits that functional changes (synaptic dysfunction) precede structural changes (atrophy).

Introduction Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy. Method We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. In addition, trim and fill were used to assess publication bias. Results The search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models. Conclusion This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.

The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

To assess the reproducibility of brain-activation and eye-movement patterns in a saccade paradigm when comparing subjects, tasks, and magnetic resonance (MR) systems.Forty-five healthy adults at two different sites (n = 45) performed saccade tasks with varying levels of target predictability: predictable (PRED), position predictable (pPRED), time predictable (tPRED), and prosaccade (SAC). Eye-movement pattern was tested with a repeated-measures analysis of variance. Activation maps reproducibility were estimated with the cluster overlap Jaccard index and signal variance coefficient of determination for within-subjects test-retest data, and for between-subjects data from the same and different sites.In all groups latencies increased with decreasing target predictability: PREDpPREDtPREDSAC (P0,001). Activation overlap was good to fair (0.40) in all tasks in the within-subjects test-retest comparisons and poor (0.40) in the tPRED for different subjects. The overlap of the different tasks for within-groups data was higher (0.40-0.68) than for the between-groups data (0.30-0.50). Activation consistency was 60-85% in the same subjects, 50-79% in different subjects, and 50-80% in different sites. In SAC, the activation found in the same and in different subjects was more consistent than in other tasks (50-80%).The predictive saccade tasks produced evidence for brain-activation and eye-movement reproducibility.

To report Magnetic Resonance Imaging (MRI) and/or Magnetic Resonance Spectroscopy (MRS) findings in subjects with hypoxic encephalopathy caused by drowning in recent literature and to compare them with non-specific hypoxic encephalopathy.Systematic review of the Medline Database for bibliographic citations from 1996 to 2008.The studies included in this review described a total of 68 victims of drowning. From those, 58 performed MRS with a decrease of N-Acetyl-Aspartate/Creatine ratio in 75.86% (n = 44), and presence of lactate in 65.52% (n = 38) of the cases. MRI data was available in 46 cases. The main finding was brain edema in 78.26% (n = 36) and abnormalities of MRI signal in basal ganglia in 75% (n = 27) of the cases. Worse clinical outcomes were reported in conjunction with degree of MRI and MRS alterations. The findings were more consistent in the latter. Comparing these results with literature from non-specific hypoxic brain injury, the drowning process is apparently more variable.We found a trend to a more variable pattern of brain injury as seen by MRI/MRS in victims of drowning, which may reflect the nature of the aggression. Possibly there are different mechanisms involved in aquatic submersion, such as temperature, not present in pure hypoxic injury.

Tatiana T Sibov,1,2 Lorena F Pavon,1 Liza A Miyaki,1 Javier B Mamani,1 Leopoldo P Nucci,1,2 Larissa T Alvarim,1,3 Paulo H Silveira,1 Luciana C Marti,1 LF Gamarra1–31Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Departamento de Neurologia e Neurociências, Universidade Federal de São Paulo, São Paulo, Brazil; 3Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, BrazilAbstract: Here we describe multimodal iron oxide nanoparticles conjugated to Rhodamine-B (MION-Rh), their stability in culture medium, and subsequent validation of an in vitro protocol to label mesenchymal stem cells from umbilical cord blood (UC-MSC) with MION-Rh. These cells showed robust labeling in vitro without impairment of their functional properties, the viability of which were evaluated by proliferation kinetic and ultrastructural analyzes. Thus, labeled cells were infused into striatum of adult male rats of animal model that mimic late onset of Parkinson's disease and, after 15 days, it was observed that cells migrated along the medial forebrain bundle to the substantia nigra as hypointense spots in T2 magnetic resonance imaging. These data were supported by short-term magnetic resonance imaging. Studies were performed in vivo, which showed that about 5 × 105 cells could be efficiently detected in the short term following infusion. Our results indicate that these labeled cells can be efficiently tracked in a neurodegenerative disease model.Keywords: mesenchymal stem cells, multimodal iron oxide nanoparticles, Rhodamine, magnetic resonance imaging, Parkinson's disease

Forty-eight children aged from 4 to 11 months, affected by Congenital Nasolacrimal Duct Obstruction (CNDO), treated successfully by local hydrostatic massage, were retrospectively included in two groups: Group A treated by massage and antibiotic eye drops, Group B treated by massage only. The comparison shows a quicker resolution of the CNDO when antibiotic eye drops are administered. The Author stresses the utility of topical antibiotic therapy regardless of the presence of mucopurulent discharge.

The pathogenesis of diabetic retinopathy (DR) consists of a complex patch-work of factors correlated and independent on one another at the same time. It is therefore difficult to find pharmaceuticals able to produce different, or even mutually contrasting effects. Another difficulty are the intrinsic characteristics of the disease which after developing to a "critical" stage, evolves with independent mechanism to the most advanced stages. In spite of that, a great deal of medicaments has been suggested so far, all providing therapeutical logic to interfere with one or more pathogenetical stages of the lesions. Although several clinical trials have been performed, survey and follow-up are still limited and insufficient to draw conclusion on the effectiveness of medical therapy. In recent times new types of medicaments such as aldose-reductase inhibitors and carbonic anhydrase-inhibitors have been suggested. The preliminary results present encouraging perspectives for their use, although caution, until long-term results are available with greater surveys and longer follow-up periods, is advised.

The comparative efficiency of sonography and computerised axial tomography on the diagnosis of retinoblastoma was assessed in 8 consecutive cases. Ocular echography revealed a 100% sensitivity whereas CT scans gave false negatives in 2 out of the 8 cases (80% sensitivity). The value of ultrasound scanning as the diagnostic test of first choice for suspected retinoblastoma is therefore emphasised.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).