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1.
J Nanobiotechnology ; 22(1): 180, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622591

ABSTRACT

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.


Subject(s)
Lung Neoplasms , Nanoparticles , Photochemotherapy , Humans , Phototherapy/methods , Indocyanine Green , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Oxygen , Hydrogen-Ion Concentration , Cell Line, Tumor
2.
Perm J ; 28(2): 86-92, 2024 06 14.
Article in English | MEDLINE | ID: mdl-38654626

ABSTRACT

INTRODUCTION: There has been a rapid increase in the utilization of magnetic resonance imaging (MRI) for prostate cancer detection. The objective of this study was to measure the increase in utilization of MRI before prostate biopsy and the effects on the distribution of Prostate Imaging Reporting and Data System (PI-RAD) scores and Gleason grades over a 5-year interval in an integrated health system. METHODS: The authors conducted a retrospective analysis of prostate MRI studies prior to biopsy in the calendar years of 2017 and 2022. Peak PI-RADS score, peak Gleason grade of suspected prostatic lesions, and the number of biopsy cores were collected from radiology reports and pathology reports from patients' electronic health records, respectively. All statistical tests were 2-tailed with a significance level set at p < 0.05. Categorical data analyses were performed using Mann-Whitney tests. Continuous data analyses were performed using t-tests. RESULTS: The total number of prostate MRIs and the number of MRIs with subsequent biopsy respectively increased by 178% and 215% over a 5-year interval (2017-2022). There was a higher proportion of MRI studies with an associated biopsy given a PI-RADS score of ≥ 3 (91%) and a Gleason grade of ≥ 7 (61%) in 2022 than in 2017 (PI-RADS: 75%; Gleason: 28%). CONCLUSIONS: Increased utilization of prostate MRI has been associated with a higher proportion of biopsies with high PI-RADS and Gleason scores consistent with improved patient selection in this integrated health system.


Subject(s)
Magnetic Resonance Imaging , Neoplasm Grading , Patient Selection , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/statistics & numerical data , Magnetic Resonance Imaging/methods , Retrospective Studies , Aged , Middle Aged , Prostate/pathology , Prostate/diagnostic imaging , Biopsy/statistics & numerical data
3.
Acta Neuropsychiatr ; 36(4): 224-231, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38623725

ABSTRACT

OBJECTIVE: Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry. METHODS: Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models. RESULTS: Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls. CONCLUSION: The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.


Subject(s)
Bipolar Disorder , Cerebral Cortex , Creativity , Magnetic Resonance Imaging , Humans , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/pathology , Bipolar Disorder/physiopathology , Male , Female , Adult , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Thinking/physiology , Neuropsychological Tests , Case-Control Studies , Middle Aged
4.
Radiography (Lond) ; 30(3): 889-895, 2024 05.
Article in English | MEDLINE | ID: mdl-38603992

ABSTRACT

INTRODUCTION: Acoustic noise from magnetic resonance imaging (MRI) can cause hearing loss and needs to be mitigated to ensure the safety of patients and personnel. Capturing MR personnel's insights is crucial for guiding the development and future applications of noise-reduction technology. This study aimed to explore how MR radiographers manage acoustic noise in clinical MR settings. METHODS: Using a qualitative design, we conducted semi-structured individual interviews with fifteen MR radiographers from fifteen hospitals around Sweden. We focused on the clinical implications of participants' noise management, using an interpretive description approach. We also identified sociotechnical interactions between People, Environment, Tools, and Tasks (PETT) by adopting a Human Factors/Ergonomics framework. Interview data were analyzed inductively with thematic analysis (Braun and Clarke). RESULTS: The analysis generated three main themes regarding MR radiographers' noise management: (I) Navigating Occupational Noise: Risk Management and Adaptation; (II) Protecting the Patient and Serving the Exam, and (III) Establishing a Safe Healthcare Environment with Organizational Support. CONCLUSION: This study offers insights into radiographers' experiences of managing acoustic noise within MRI, and the associated challenges. Radiographers have adopted multiple strategies to protect patients and themselves from adverse noise-related effects. However, they require tools and support to manage this effectively, suggesting a need for organizations to adopt more proactive, holistic approaches to safety initiatives. IMPLICATIONS FOR PRACTICE: The radiographers stressed the importance of a soundproofed work environment to minimize occupational adverse health effects and preserve work performance. They acknowledge noise as a common contributor to patient distress and discomfort. Providing options like earplugs, headphones, mold putty, software-optimized "quiet" sequences, and patient information were important tools. Fostering a safety culture requires proactive safety efforts and support from colleagues and management.


Subject(s)
Interviews as Topic , Magnetic Resonance Imaging , Noise, Occupational , Qualitative Research , Humans , Sweden , Female , Male , Adult , Middle Aged , Hearing Loss, Noise-Induced/prevention & control , Occupational Exposure/prevention & control , Risk Management
5.
J Bone Miner Res ; 39(7): 855-866, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38648280

ABSTRACT

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system-including subjective feelings of confusion, a reduced ability to focus and think clearly (ie, "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires-the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of magnetic resonance imaging images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus-and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning.


Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog." We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog." Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure.


Subject(s)
Brain , Hypoparathyroidism , Quality of Life , Humans , Hypoparathyroidism/drug therapy , Hypoparathyroidism/pathology , Hypoparathyroidism/physiopathology , Hypoparathyroidism/diagnostic imaging , Male , Female , Middle Aged , Brain/diagnostic imaging , Brain/pathology , Brain/metabolism , Adult , Parathyroid Hormone/blood , Aged , Cross-Sectional Studies , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/pathology , Magnetic Resonance Imaging
6.
J Neuroeng Rehabil ; 21(1): 34, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38443983

ABSTRACT

BACKGROUND: The regulation of gait is critical to many activities of everyday life. When walking, somatosensory information obtained from mechanoreceptors throughout body is delivered to numerous supraspinal networks and used to execute the appropriate motion to meet ever-changing environmental and task demands. Aging and age-related conditions oftentimes alter the supraspinal sensorimotor control of walking, including the responsiveness of the cortical brain regions to the sensorimotor inputs obtained from the peripheral nervous system, resulting in diminished mobility in the older adult population. It is thus important to explicitly characterize such supraspinal sensorimotor elements of walking, providing knowledge informing novel rehabilitative targets. The past efforts majorly relied upon mental imagery or virtual reality to study the supraspinal control of walking. Recent efforts have been made to develop magnetic resonance imaging (MRI)-compatible devices simulating specific somatosensory and/or motor aspects of walking. However, there exists large variance in the design and functionality of these devices, and as such inconsistent functional MRI (fMRI) observations. METHODS: We have therefore completed a systematic review to summarize current achievements in the development of these MRI-compatible devices and synthesize available imaging results emanating from studies that have utilized these devices. RESULTS: The device design, study protocol and neuroimaging observations of 26 studies using 13 types of devices were extracted. Three of these devices can provide somatosensory stimuli, eight motor stimuli, and two both types of stimuli. Our review demonstrated that using these devices, fMRI data of brain activation can be successfully obtained when participants remain motionless and experience sensorimotor stimulation during fMRI acquisition. The activation in multiple cortical (e.g., primary sensorimotor cortex) and subcortical (e.g., cerebellum) regions has been each linked to these types of walking-related sensorimotor stimuli. CONCLUSION: The observations of these publications suggest the promise of implementing these devices to characterize the supraspinal sensorimotor control of walking. Still, the evidence level of these neuroimaging observations was still low due to small sample size and varied study protocols, which thus needs to be confirmed via studies with more rigorous design.


Subject(s)
Magnetic Resonance Imaging , Walking , Humans , Aged , Gait , Neuroimaging , Aging
7.
Hum Brain Mapp ; 45(5): e26584, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38533724

ABSTRACT

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Cross-Sectional Studies , Thalamus , Magnetic Resonance Imaging
8.
J Psychiatr Res ; 172: 351-359, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38447356

ABSTRACT

Cognitive Behavioral Therapy (CBT) is among the gold-standard psychotherapeutic interventions for the treatment of psychiatric disorders, including bipolar disorder (BD). While the clinical response of CBT in patients with BD has been widely investigated, its neural correlates remain poorly explored. Therefore, this scoping review aimed to discuss neuroimaging studies on CBT-based interventions in bipolar populations. Particular attention has been paid to similarities and differences between studies to inform future research. The literature search was conducted on PubMed, PsycINFO, and Web of Science databases in June 2023, identifying 307 de-duplicated records. Six studies fulfilled the inclusion criteria and were reviewed. All of them analyzed functional brain activity data. Four studies showed that the clinical response to CBT was associated with changes in the functional activity and/or connectivity of prefrontal and posterior cingulate cortices, temporal parietal junction, amygdala, precuneus, and insula. In two additional studies, a peculiar pattern of baseline activations in the prefrontal cortex, hippocampus, amygdala, and insula predicted post-treatment improvements in depressive symptoms, emotion dysregulation, and psychosocial functioning, although CBT-specific effects were not shown. These results suggest, at the very preliminary level, the potential of CBT-based interventions in modulating neural activity and connectivity of patients with BD, especially in regions ascribed to emotional processing. Nonetheless, the discrepancies between studies concerning aims, design, sample characteristics, and CBT and fMRI protocols do not allow conclusions to be drawn. Further research using multimodal imaging techniques, better-characterized BD samples, and standardized CBT-based interventions is needed.


Subject(s)
Bipolar Disorder , Cognitive Behavioral Therapy , Humans , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/therapy , Cognitive Behavioral Therapy/methods , Emotions/physiology , Prefrontal Cortex , Gyrus Cinguli , Magnetic Resonance Imaging
9.
Hum Brain Mapp ; 45(4): e26646, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38433705

ABSTRACT

Comprising numerous subnuclei, the thalamus intricately interconnects the cortex and subcortex, orchestrating various facets of brain functions. Extracting personalized parcellation patterns for these subnuclei is crucial, as different thalamic nuclei play varying roles in cognition and serve as therapeutic targets for neuromodulation. However, accurately delineating the thalamic nuclei boundary at the individual level is challenging due to intersubject variability. In this study, we proposed a prior-guided parcellation (PG-par) method to achieve robust individualized thalamic parcellation based on a central-boundary prior. We first constructed probabilistic atlas of thalamic nuclei using high-quality diffusion MRI datasets based on the local diffusion characteristics. Subsequently, high-probability voxels in the probabilistic atlas were utilized as prior guidance to train unique multiple classification models for each subject based on a multilayer perceptron. Finally, we employed the trained model to predict the parcellation labels for thalamic voxels and construct individualized thalamic parcellation. Through a test-retest assessment, the proposed prior-guided individualized thalamic parcellation exhibited excellent reproducibility and the capacity to detect individual variability. Compared with group atlas registration and individual clustering parcellation, the proposed PG-par demonstrated superior parcellation performance under different scanning protocols and clinic settings. Furthermore, the prior-guided individualized parcellation exhibited better correspondence with the histological staining atlas. The proposed prior-guided individualized thalamic parcellation method contributes to the personalized modeling of brain parcellation.


Subject(s)
Thalamic Nuclei , Thalamus , Humans , Reproducibility of Results , Thalamus/diagnostic imaging , Brain , Cerebral Cortex
10.
Sci Rep ; 14(1): 5898, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38467724

ABSTRACT

Early-life adversity covers a range of physical, social and environmental stressors. Acute viral infections in early life are a major source of such adversity and have been associated with a broad spectrum of later-life effects outside the immune system or "off-target". These include an altered hypothalamus-pituitary-adrenal (HPA) axis and metabolic reactions. Here, we used a murine post-natal day 14 (PND 14) Influenza A (H1N1) infection model and applied a semi-holistic approach including phenotypic measurements, gene expression arrays and diffusion neuroimaging techniques to investigate HPA axis dysregulation, energy metabolism and brain connectivity. By PND 56 the H1N1 infection had been resolved, and there was no residual gene expression signature of immune cell infiltration into the liver, adrenal gland or brain tissues examined nor of immune-related signalling. A resolved early-life H1N1 infection had sex-specific effects. We observed retarded growth of males and altered pre-stress (baseline) blood glucose and corticosterone levels at PND42 after the infection was resolved. Cerebral MRI scans identified reduced connectivity in the cortex, midbrain and cerebellum that were accompanied by tissue-specific gene expression signatures. Gene set enrichment analysis confirmed that these were tissue-specific changes with few common pathways. Early-life infection independently affected each of the systems and this was independent of HPA axis or immune perturbations.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Female , Male , Animals , Mice , Humans , Hypothalamo-Hypophyseal System/metabolism , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/genetics , Influenza, Human/metabolism , Transcriptome , Stress, Psychological/metabolism , Pituitary-Adrenal System/metabolism , Brain/diagnostic imaging , Brain/metabolism , Corticosterone
11.
Radiat Oncol ; 19(1): 33, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459584

ABSTRACT

BACKGROUND: Radiotherapy (RT) is an important treatment modality for patients with brain malignancies. Traditionally, computed tomography (CT) images are used for RT treatment planning whereas magnetic resonance imaging (MRI) images are used for tumor delineation. Therefore, MRI and CT need to be registered, which is an error prone process. The purpose of this clinical study is to investigate the clinical feasibility of a deep learning-based MRI-only workflow for brain radiotherapy, that eliminates the registration uncertainty through calculation of a synthetic CT (sCT) from MRI data. METHODS: A total of 54 patients with an indication for radiation treatment of the brain and stereotactic mask immobilization will be recruited. All study patients will receive standard therapy and imaging including both CT and MRI. All patients will receive dedicated RT-MRI scans in treatment position. An sCT will be reconstructed from an acquired MRI DIXON-sequence using a commercially available deep learning solution on which subsequent radiotherapy planning will be performed. Through multiple quality assurance (QA) measures and reviews during the course of the study, the feasibility of an MRI-only workflow and comparative parameters between sCT and standard CT workflow will be investigated holistically. These QA measures include feasibility and quality of image guidance (IGRT) at the linear accelerator using sCT derived digitally reconstructed radiographs in addition to potential dosimetric deviations between the CT and sCT plan. The aim of this clinical study is to establish a brain MRI-only workflow as well as to identify risks and QA mechanisms to ensure a safe integration of deep learning-based sCT into radiotherapy planning and delivery. DISCUSSION: Compared to CT, MRI offers a superior soft tissue contrast without additional radiation dose to the patients. However, up to now, even though the dosimetrical equivalence of CT and sCT has been shown in several retrospective studies, MRI-only workflows have still not been widely adopted. The present study aims to determine feasibility and safety of deep learning-based MRI-only radiotherapy in a holistic manner incorporating the whole radiotherapy workflow. TRIAL REGISTRATION: NCT06106997.


Subject(s)
Brain Neoplasms , Deep Learning , Radiotherapy, Intensity-Modulated , Humans , Feasibility Studies , Retrospective Studies , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Dosage , Magnetic Resonance Imaging/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Brain/diagnostic imaging
12.
Am J Clin Nutr ; 119(5): 1200-1215, 2024 05.
Article in English | MEDLINE | ID: mdl-38452857

ABSTRACT

BACKGROUND: Heat treatments of dairy, including pasteurization and ultra-high temperature (UHT) processing, alter milk macromolecular structures, and ultimately affect digestion. In vitro, animal, and human studies show faster nutrient release or circulating appearance after consuming UHT milk (UHT-M) compared with pasteurized milk (PAST-M), with a faster gastric emptying (GE) rate proposed as a possible mechanism. OBJECTIVES: To investigate the impact of milk heat treatment on GE as a mechanism of faster nutrient appearance in blood. We hypothesized that GE and circulating nutrient delivery following consumption would be faster for UHT-M than PAST-M. METHODS: In this double-blind randomized controlled cross-over trial, healthy female (n = 20; 27.3 ± 1.4 y, mean ± SD) habitual dairy consumers, consumed 500 mL of either homogenized bovine UHT-M or PAST-M (1340 compared with 1320 kJ). Gastric content volume (GCV) emptying half-time (T50) was assessed over 3 h by magnetic resonance imaging subjective digestive symptoms, plasma amino acid, lipid and B vitamin concentrations, and gastric myoelectrical activity were measured over 5 h. RESULTS: Although GCV T50 did not differ (102 ± 7 min compared with 89 ± 8 min, mean ± SEM, UHT-M and PAST-M, respectively; P = 0.051), GCV time to emptying 25% of the volume was 31% longer following UHT-M compared with PAST-M (42 ± 2 compared with 32 ± 4 min, P = 0.004). Although GCV remained larger for a longer duration following UHT-M (treatment × time interaction, P = 0.002), plasma essential amino acid AUC was greater following UHT-M than PAST-M (55,324 ± 3809 compared with 36,598 ± 5673 µmol·min·L-1, P = 0.006). Heat treatment did not impact gastric myoelectrical activity, plasma appetite hormone markers or subjective appetite scores. CONCLUSIONS: Contrary to expectations, GE was slower with UHT-M, yet, as anticipated, aminoacidemia was greater. The larger GCV following UHT-M suggests that gastric volume may poorly predict circulating nutrient appearance from complex food matrices. Dairy heat treatment may be an effective tool to modify nutrient release by impacting digestion kinetics. CLINICAL TRIAL REGISTRY: www.anzctr.org.au (ACTRN12620000172909).


Subject(s)
Cross-Over Studies , Gastric Emptying , Hot Temperature , Milk , Pasteurization , Female , Animals , Humans , Milk/chemistry , Adult , Cattle , Double-Blind Method , Nutrients , Young Adult
13.
Ann Hematol ; 103(7): 2283-2297, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38503936

ABSTRACT

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent ß-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time.


Subject(s)
Blood Transfusion , Iron Overload , beta-Thalassemia , Humans , Female , Iron Overload/mortality , Iron Overload/blood , Iron Overload/etiology , Male , beta-Thalassemia/therapy , beta-Thalassemia/mortality , beta-Thalassemia/blood , beta-Thalassemia/complications , Adult , Retrospective Studies , Adolescent , Ferritins/blood , Young Adult , Middle Aged , Iron/blood , Iron/metabolism , Cohort Studies , Child , Follow-Up Studies , Italy/epidemiology
14.
Small ; 20(32): e2309940, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38534030

ABSTRACT

Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.


Subject(s)
Ferroptosis , Phototherapy , Theranostic Nanomedicine , Humans , Ferroptosis/drug effects , Phototherapy/methods , Animals , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Iron/chemistry , Polyethylene Glycols/chemistry , Mice , Photochemotherapy/methods
15.
Hum Brain Mapp ; 45(2): e26582, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38339904

ABSTRACT

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.


Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Adult , Infant, Newborn , Infant , Humans , Male , Female , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Hypothalamus/diagnostic imaging
16.
Mult Scler ; 30(6): 747-750, 2024 May.
Article in English | MEDLINE | ID: mdl-38372030

ABSTRACT

BACKGROUND: Multiple studies have highlighted elevated rates of depression among individuals with Multiple Sclerosis (MS), with its associated symptoms posing a significant threat to overall well-being. Moreover, existing literature suggests a potential interconnection between depressive manifestations and the decline of physical functionalities in the context of MS. OBJECTIVE: to examine the viability of the Eye Movement Desensitization Reprocessing (EMDR) therapy protocol for the treatment of depressive disorders (DeprEND) for alleviating depression in individuals with MS. METHODS: We conducted a process-outcome study to examine the feasibilty and effectiveness DeprEND enrolling 13 individuals with MS and depressive symtpoms. Psychological and physical assessment pre-, post-intervention and 3-month follow-up were included. Pre- and post-magnetic resonance imaging (MRI) scans were conducted to analyze potential alterations in brain function. RESULTS: The EMDR DeprEND treatment showed a high level of adherence and feasibility. Significant reductions in depressive symptoms were found at post-intervention and at 3 months follow-up. No significant differences were observed in terms of physical symptoms. A significant modulation observed in parietal and premotor areas when examining negative valence stimuli post-treatment was found. CONCLUSION: for The EMDR DeprEND protocol may represent a feasible and cost-effective treatment for reducing depressive symptoms in MS patients and improving their mental well-being.


Subject(s)
Depression , Eye Movement Desensitization Reprocessing , Multiple Sclerosis , Humans , Pilot Projects , Eye Movement Desensitization Reprocessing/methods , Female , Male , Adult , Middle Aged , Multiple Sclerosis/therapy , Multiple Sclerosis/complications , Multiple Sclerosis/physiopathology , Depression/therapy , Depression/etiology , Magnetic Resonance Imaging , Treatment Outcome , Depressive Disorder/therapy
17.
Urol Oncol ; 42(5): 158.e11-158.e16, 2024 May.
Article in English | MEDLINE | ID: mdl-38365461

ABSTRACT

INTRODUCTION: Prostate cancer screening has routinely identified men with very low- or low-risk disease, per the National Comprehensive Cancer Network guidelines. Current literature has demonstrated that the most appropriate management strategy for these patients is active surveillance (AS). The mainstay of AS includes periodic biopsies and biannual prostate-specific antigen tests. However, multiparametric magnetic resonance imaging (mpMRI) is uniquely posed to improve patient surveillance. This study aimed to evaluate the utility of an annual mpMRI in patients on AS, focusing on radiologic upgrading and Prostate Imaging-Reporting and Data System (PI-RADS) trends as indicators of clinically significant disease. METHODS: This prospective, single intuition, study enrolled 208 patients on AS who had at least two biopsies and 1 mpMRI with a median follow-up of 5.03 years. The main outcome variable was time to Gleason grade (GG) reclassification. RESULTS: After delineating patients on their initial PI-RADS score, men with score 3 and 5 lesions at first MRI had comparable GG reclassification-free survival to their counterparts. Conversely, men with initial PI-RADS 4 lesions showed a lower 5-year GG reclassification-free survival compared to those with PI-RADS score 1-2. The cohort was then subset to 70 patients who obtained ≥2 mpMRIs on protocol. Men experiencing uptrending mpMRI scores had an increased risk of GG reclassification, with a 35.4% difference in 5 year GG reclassification-free survival probability on the Kaplan-Meier curve analysis. CONCLUSION: In conclusion, this study demonstrates that for men on AS with stable recapitulated disease, an annual MRI may replace repeat biopsies after confirmatory sampling has been obtained. On the other hand, men who initiate AS with PI-RADS 4 and/or who display uptrending mpMRI scores require periodic biopsies along with repeat imaging. This study highlights the utility of integrating an annual MRI into AS protocols, thus promising a more effective approach to management.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Prostate-Specific Antigen , Prospective Studies , Early Detection of Cancer , Image-Guided Biopsy/methods , Retrospective Studies
18.
Addict Biol ; 29(2): e13381, 2024 02.
Article in English | MEDLINE | ID: mdl-38357782

ABSTRACT

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.


Subject(s)
Cocaine , Substance-Related Disorders , Humans , Transcranial Magnetic Stimulation/methods , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Dorsolateral Prefrontal Cortex , Double-Blind Method , Treatment Outcome
19.
Neuropsychologia ; 196: 108836, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38373518

ABSTRACT

Odour imagery, the ability to experience smell when an appropriate stimulus is absent, has widely been documented as being particularly difficult. However, previous studies have shown the beneficial effect of visual cues (e.g., pictures or words) to facilitate performance in numerous tasks of olfactory nature. Therefore, the use of visual cues to evoke odours seems relevant. In this study, our interest is directed towards non-figurative coloured arrangements, which result from a patented technology and aim at chromatically representing any smell from its chemical composition and sensory description. The aim of this study was to characterise the neural mechanisms of odour imagery facilitated by these non-figurative coloured arrangements. Using functional magnetic resonance imaging, we recorded and compared hemodynamic responses during odour imagery facilitated by non-figurative coloured arrangements and pictures. Our findings reveal that the use of non-figurative coloured arrangements during odour imagery solicits olfactory and non-olfactory brain regions (orbitofrontal cortex, insula, hippocampus, thalamus, dorsolateral prefrontal cortex and supplementary motor area), which are mainly involved in olfactory processing and multimodal integration. Moreover, very similar cortical activity was found between the use of non-figurative coloured arrangements and pictures during odour imagery, with increased activity in the supplementary motor area during the use of coloured arrangements only. Overall, non-figurative coloured arrangements could become a robust tool to visually evoke odours without requiring prior familiarity with the depicted odour. Future studies should use psychometric measures to determine the relationships between brain activation, odour imagery ability and vividness of the generated odour images.


Subject(s)
Cues , Odorants , Humans , Smell/physiology , Imagery, Psychotherapy , Brain/diagnostic imaging
20.
Front Neurol ; 15: 1362704, 2024.
Article in English | MEDLINE | ID: mdl-38419703

ABSTRACT

Chemotherapy and radiotherapy are widely used in the treatment of central nervous system tumors and acute lymphocytic leukemia even in the pediatric population. However, such treatments run the risk of a broad spectrum of cognitive and neurological deficits. Even though the correlation with cognitive decline is still not clear, neuroradiological defects linked to white matter injury and vasculopathies may be identified. Thanks to the use of 7T MRI it is possible to better define the vascular pattern of the brain lesions with the added advantage of identifying their characteristics and anatomical localization, which, however, are not evident with a conventional brain scan. Moreover, the use of Quantitative Susceptibility Mapping (QSM) makes it possible to discriminate between calcium deposits on vessels (chemo-radiation-induced) and hemoglobin deposition in radio-induced cavernomas, speculating, as a result, about the pathophysiology of iatrogenic brain damage. We describe the case of a 9 year-old boy with a T-type acute lymphoid leukemia who had previously been treated with polychemotherapy and high-dose RT. To better define the child's neuroradiological pattern, 7T MRI and QSM were performed in addition to conventional imaging examinations. Our case report suggests the potential usefulness of a QSM study to distinguish radio-induced vascular malformations from mineralizing microangiopathy.

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