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1.
Ann Surg Oncol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971953

ABSTRACT

BACKGROUND: In cT4b esophageal cancer, accurate assessment of tracheobronchial tree invasion after definitive chemoradiotherapy (dCRT) aids in the selection of patients for whom an oncologic radical esophagectomy can be achieved. The current report aimed to determine the accuracy of endobronchial ultrasound in assessing tumor invasion in the tracheobronchial tree after dCRT in patients with cT4b esophageal cancer. METHODS: Esophageal cancer patients with suspicion of tracheobronchial tree invasion on the diagnostic contrast-enhanced computed tomography (CT) who underwent a staging endobronchial ultrasonography (EBUS) were eligible for inclusion in this study. To assess the accuracy of the EBUS in assessing tumor ingrowth in the tracheobronchial tree after dCRT, patients who had an EBUS during restaging and underwent surgery were included in the final analysis. RESULTS: The final analysis included 26 patients. For 18 (90%) of 20 patients in whom the anatomy of the tracheobronchial tree was restored on the restaging EBUS and tumor invasion was considered to be absent, a radical esophagectomy was achieved. In six patients, persistent ingrowth was observed during the restaging EBUS. For these patients, the EBUS was repeated after a median of 9 weeks. Tumor invasion was considered to be absent in four patients, and a radical resection was achieved in three of these patients. CONCLUSION: The EBUS provides valuable information on the assessment of tracheobronchial tree invasion in cT4b esophageal cancer patients after dCRT. This information could aid in the proper selection of patients who benefit from a curative but highly invasive esophagectomy.

2.
Alzheimers Res Ther ; 16(1): 148, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961512

ABSTRACT

BACKGROUND: Leveraging Alzheimer's disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. METHODS: We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aß, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). RESULTS: The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. CONCLUSION: These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity.


Subject(s)
Magnetic Resonance Imaging , Positron-Emission Tomography , tau Proteins , Humans , Female , Male , Aged , tau Proteins/metabolism , Longitudinal Studies , Cross-Sectional Studies , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Alzheimer Disease/psychology , Alzheimer Disease/metabolism , Brain/diagnostic imaging , Brain/pathology , Brain/metabolism , Amyloid beta-Peptides/metabolism , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/metabolism , Cognition/physiology , Middle Aged , Cognitive Reserve/physiology , Biomarkers , Neuroimaging/methods
3.
Nat Commun ; 15(1): 5716, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977681

ABSTRACT

Quantum links can interconnect qubit registers and are therefore essential in networked quantum computing. Semiconductor quantum dot qubits have seen significant progress in the high-fidelity operation of small qubit registers but establishing a compelling quantum link remains a challenge. Here, we show that a spin qubit can be shuttled through multiple quantum dots while preserving its quantum information. Remarkably, we achieve these results using hole spin qubits in germanium, despite the presence of strong spin-orbit interaction. In a minimal quantum dot chain, we accomplish the shuttling of spin basis states over effective lengths beyond 300 microns and demonstrate the coherent shuttling of superposition states over effective lengths corresponding to 9 microns, which we can extend to 49 microns by incorporating dynamical decoupling. These findings indicate qubit shuttling as an effective approach to route qubits within registers and to establish quantum links between registers.

4.
Alzheimers Dement ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38988055

ABSTRACT

INTRODUCTION: Spatial extent-based measures of how far amyloid beta (Aß) has spread throughout the neocortex may be more sensitive than traditional Aß-positron emission tomography (PET) measures of Aß level for detecting early Aß deposits in preclinical Alzheimer's disease (AD) and improve understanding of Aß's association with tau proliferation and cognitive decline. METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aß level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+. RESULTS: EXT enabled earlier detection of Aß deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aß+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL. DISCUSSION: These findings indicate EXT may be more sensitive to Aß's role in preclinical AD than level and improve targeting of individuals for AD prevention trials. HIGHLIGHTS: Aß spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aß EXT improved detection of Aß below traditional PET thresholds. Early regional Aß deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aß EXT than Aß level. Neocortical tau onset aligned with reaching widespread neocortical Aß.

5.
Ann Neurol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007398

ABSTRACT

OBJECTIVE: Elevated entorhinal cortex (EC) tau in low beta-amyloid individuals can predict accumulation of pathology and cognitive decline. We compared the accuracy of magnetic resonance imaging (MRI)-derived locus coeruleus integrity, neocortical beta-amyloid burden by positron emission tomography (PET), and hippocampal volume in identifying elevated entorhinal tau signal in asymptomatic individuals who are considered beta-amyloid PET-negative. METHODS: We included 188 asymptomatic individuals (70.78 ± 11.51 years, 58% female) who underwent 3T-MRI of the locus coeruleus, Pittsburgh compound-B (PiB), and Flortaucipir (FTP) PET. Associations between elevated EC tau and neocortical PiB, hippocampal volume, or locus coeruleus integrity were evaluated and compared using logistic regression and receiver operating characteristic analyses in the PiB- sample with a clinical dementia rating (CDR) of 0. Associations with clinical progression (CDR-sum-of-boxes) over a time span of 6 years were evaluated with Cox proportional hazard models. RESULTS: We identified 26 (21%) individuals with high EC FTP in the CDR = 0/PiB- sample. Locus coeruleus integrity was a significantly more sensitive and specific predictor of elevated EC FTP (area under the curve [AUC] = 85%) compared with PiB (AUC = 77%) or hippocampal volume (AUC = 76%). Based on the Youden-index, locus coeruleus integrity obtained a sensitivity of 77% and 85% specificity. Using the resulting locus coeruleus Youden cut-off, lower locus coeruleus integrity was associated with a two-fold increase in clinical progression, including mild cognitive impairment. INTERPRETATION: Locus coeruleus integrity has promise as a low-cost, non-invasive screening instrument to detect early cortical tau deposition and associated clinical progression in asymptomatic, low beta-amyloid individuals. ANN NEUROL 2024.

6.
Nat Commun ; 15(1): 5124, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879504

ABSTRACT

Large Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). However, there is still no consensus on the role volcanism played as a trigger, or its source - previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.

7.
Article in English | MEDLINE | ID: mdl-38848027

ABSTRACT

PURPOSE: To describe the prevalence and the variables associated with TDIs in schoolchildren aged 8 to 14 years in Estância Velha city in southern Brazil, placing emphasis on molar incisor hypomineralization. METHODS: Students enrolled in public schools of a medium-sized city in the southern Brazil were selected using cluster random sampling. Clinical examinations assessed molar incisor hypomineralization-MIH (European Academy of Pediatric Dentistry criteria), dental caries (DMFT index), and TDIs (O'Brien's criteria). Socioeconomic and demographic variables were assessed using a standardized questionnaire. Prevalence ratios were estimated using Poisson regression (p < 0.05). RESULTS: 513 students (54.8% female), with a mean age of 11.6 (± 1.9) years, participated in the study. The prevalence of TDIs was 11.3%, with enamel fracture representing 90.4%. The high prevalence of traumatic dental injuries was associated with MIH (PR: 2.22 CI: 1.27; 3.87; p < 0.01) and overjet > 3 mm (PR: 2.03 CI 1.19; 3.45; p < 0.01). CONCLUSION: The sample of schoolchildren from southern Brazil had a low prevalence of traumatic dental injuries. Molar incisor hypomineralization and increased overjet were associated with the higher prevalence of traumatic dental injuries.

8.
Article in English | MEDLINE | ID: mdl-38894618

ABSTRACT

BACKGROUND: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk. METHODS: In this prospective cohort study, we used data from the population-based HUNT Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP and estimated cardiorespiratory fitness across three surveys (HUNT1, 1984-86 - HUNT3, 2006-08). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-19. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia. RESULTS: In total, 7594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1062 (14.0%) participants. We identified two multidimensional trajectories throughout adulthood within three age groups: one with higher SBP and DBP, and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, APOE ε4 status, education, marital status and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% CI 0.51, 0.78) with corresponding RD of -0.07 (95% CI -0.10, -0.04). CONCLUSIONS: Having a beneficial multidimensional trajectory of SBP, DBP and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk.

9.
Med Image Anal ; 97: 103222, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38936222

ABSTRACT

Since the rise of deep learning, new medical segmentation methods have rapidly been proposed with extremely promising results, often reporting marginal improvements on the previous state-of-the-art (SOTA) method. However, on visual inspection errors are often revealed, such as topological mistakes (e.g. holes or folds), that are not detected using traditional evaluation metrics. Incorrect topology can often lead to errors in clinically required downstream image processing tasks. Therefore, there is a need for new methods to focus on ensuring segmentations are topologically correct. In this work, we present TEDS-Net: a segmentation network that preserves anatomical topology whilst maintaining segmentation performance that is competitive with SOTA baselines. Further, we show how current SOTA segmentation methods can introduce problematic topological errors. TEDS-Net achieves anatomically plausible segmentation by using learnt topology-preserving fields to deform a prior. Traditionally, topology-preserving fields are described in the continuous domain and begin to break down when working in the discrete domain. Here, we introduce additional modifications that more strictly enforce topology preservation. We illustrate our method on an open-source medical heart dataset, performing both single and multi-structure segmentation, and show that the generated fields contain no folding voxels, which corresponds to full topology preservation on individual structures whilst vastly outperforming the other baselines on overall scene topology. The code is available at: https://github.com/mwyburd/TEDS-Net.

10.
Adv Gerontol ; 37(1-2): 40-45, 2024.
Article in Russian | MEDLINE | ID: mdl-38944771

ABSTRACT

The aim of the study was to investigate the peculiarities of morphometric parameters of peripheral blood lymphocytes in chronic pyelonephritis in elderly patients in comparison with young and middle-aged patients. A total of 81 patients with chronic pyelonephritis in the exacerbation phase were examined. All patients were divided into three age groups according to WHO recommendations: the 1st - 42patients of young age (18-44 years); the 2nd - 17 patients of middle age (45-59 years); the 3rd - 22 elderly patients (60-74 years). Computer morphometry of lymphocytes was performed in all examined patients. In elderly patients with chronic pyelonephritis the size and сytoplasmic-nuclear ratio of lymphocytes increase. This indicates the preservation of lymphocyte defense responses at this age. In male patients with chronic pyelonephritis in the 1st and 2nd age groups the size of lymphocytes increases, and in female patients - decreases. The сytoplasmic-nuclear ratio increases in males of these age groups, while it remains unchanged or decreases in females. Indirect indications of reduced immunity in young and middle-aged women with chronic inflammation in the kidneys have been obtained.


Subject(s)
Lymphocytes , Pyelonephritis , Humans , Pyelonephritis/blood , Pyelonephritis/diagnosis , Middle Aged , Female , Male , Lymphocytes/immunology , Lymphocytes/pathology , Aged , Adult , Chronic Disease , Age Factors
11.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38904081

ABSTRACT

The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation. Using ultra-high field diffusion magnetic resonance imaging, we examined whether microstructural properties (neurite density index and orientation dispersion index) in the locus coeruleus were related to those in cortical and subcortical regions, and whether this was modulated by plasma glial fibrillary acidic protein levels, as a proxy of astrocyte reactivity. In our cohort of 60 healthy individuals (30 to 85 yr, 50% female), higher glial fibrillary acidic protein correlated with lower neurite density index in frontal cortical regions, the hippocampus, and the amygdala. Furthermore, under higher levels of glial fibrillary acidic protein (above ~ 150 pg/mL for cortical and ~ 145 pg/mL for subcortical regions), lower locus coeruleus orientation dispersion index was associated with lower orientation dispersion index in frontotemporal cortical regions and in subcortical regions. Interestingly, individuals with higher locus coeruleus orientation dispersion index exhibited higher orientation dispersion index in these (sub)cortical regions, despite having higher glial fibrillary acidic protein levels. Together, these results suggest that the interaction between locus coeruleus-norepinephrine cells and astrocytes can signal a detrimental or neuroprotective pathway for brain integrity and support the importance of maintaining locus coeruleus neuronal health in aging and in the prevention of age-related neurodegenerative diseases.


Subject(s)
Astrocytes , Glial Fibrillary Acidic Protein , Locus Coeruleus , Humans , Female , Male , Locus Coeruleus/diagnostic imaging , Astrocytes/physiology , Aged , Middle Aged , Adult , Aged, 80 and over , Glial Fibrillary Acidic Protein/metabolism , Magnetic Resonance Imaging/methods , Cerebral Cortex/diagnostic imaging , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Neurites/physiology
12.
Alzheimers Res Ther ; 16(1): 119, 2024 05 31.
Article in English | MEDLINE | ID: mdl-38822365

ABSTRACT

BACKGROUND: Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aß)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology. METHODS: 142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aß)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates. RESULTS: At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity. CONCLUSIONS: Our findings demonstrate that the LC can provide resilience against Aß-related attention decline. However, when Aß accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aß-related cognitive decline.


Subject(s)
Alzheimer Disease , Locus Coeruleus , Magnetic Resonance Imaging , Parietal Lobe , Humans , Female , Male , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Alzheimer Disease/physiopathology , Aged , Locus Coeruleus/diagnostic imaging , Locus Coeruleus/pathology , Magnetic Resonance Imaging/methods , Parietal Lobe/diagnostic imaging , Aged, 80 and over , Attention/physiology , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Positron-Emission Tomography , Cross-Sectional Studies , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Neuropsychological Tests
13.
Alzheimers Res Ther ; 16(1): 129, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886798

ABSTRACT

BACKGROUND: Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer's disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine's neuroprotective effects, potentially compromising the neuronal integrity of LC's cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness. METHODS: A total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample. RESULTS: Across the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP. CONCLUSIONS: Our findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Locus Coeruleus , Magnetic Resonance Imaging , Positron-Emission Tomography , tau Proteins , Humans , Locus Coeruleus/diagnostic imaging , Locus Coeruleus/pathology , Female , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Male , Aged , tau Proteins/metabolism , Aged, 80 and over , Cohort Studies , Amyloid beta-Peptides/metabolism , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Carbolines , Thiazoles , Aniline Compounds , Brain Cortical Thickness
14.
Front Vet Sci ; 11: 1403174, 2024.
Article in English | MEDLINE | ID: mdl-38840629

ABSTRACT

Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3's lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3's lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms.

15.
Nat Commun ; 15(1): 4809, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844444

ABSTRACT

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.


Subject(s)
Aging , Alzheimer Disease , Olfactory Perception , Positron-Emission Tomography , tau Proteins , Humans , Female , tau Proteins/metabolism , tau Proteins/genetics , Male , Aged , Olfactory Perception/physiology , Aging/physiology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/physiopathology , Aged, 80 and over , Olfactory Pathways/metabolism , Olfactory Pathways/diagnostic imaging , Smell/physiology , Brain/metabolism , Brain/diagnostic imaging , Temporal Lobe/metabolism , Temporal Lobe/diagnostic imaging , Middle Aged
16.
RSC Med Chem ; 15(5): 1652-1663, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38784460

ABSTRACT

MANIO is an efficient p53-activating anticancer agent with remarkable selectivity to the p53 pathway and promising antitumor activity against colorectal cancer (CRC). Herein, a library of novel MANIO derivatives, including hydroxymethyl- and bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles, was synthesized by rational structural modulation. The antiproliferative activity of twenty derivatives was evaluated in a panel of human CRC cells with different p53 status. From this library, five compounds with R- and S-configuration and with aromatic or heteroaromatic groups at position 3, including the enantiomer of MANIO, were identified as selective towards p53-expressing cancer cells. On the other hand, two compounds with S-configuration, 6-hydroxymethyl- and 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazoles, showed high cytotoxicity against WTp53-expressing HCT116 colon cells but, unlike MANIO, exhibited p53-independent inhibitory activity in CRC. The results described provide relevant structural and pharmacophoric data for the design of new p53-activating agents for precision therapy of CRC or other p53-related cancers harboring both wild-type or mutated p53 forms.

17.
West Afr J Med ; 41(3): 333-341, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38788218

ABSTRACT

BACKGROUND: Accelerated orthodontic teeth movement are procedures carried out to increase the rate of tooth movement thereby reducing treatment time. There are numerous techniques currently available to accelerate orthodontic treatment time, but evidence is still needed to determine the degree to which orthodontists accept and practice accelerated orthodontics. The present study is aimed at assessing the knowledge of Orthodontists on the practice of accelerated orthodontics; as well as their willingness to adopt it as a treatment option for their patients. METHODOLOGY: Ethical approval was obtained before the commencement of the study. The study population comprised all orthodontists practicing in Nigeria. Questionnaires were administered physically to the orthodontists at their annual general meeting. E-mails were further used to distribute the questionnaire to the orthodontists who were absent from the annual meeting. The questionnaire obtained information on respondents' biodata, knowledge, attitude, and practice of accelerated orthodontic treatment procedures.Statistical analysis was performed using IBM SPSS software version 27. The level of significance was 0.05 for all statistical analysis. RESULTS: The study participants comprised 60 respondents, with a mean age of 34.18 years and a male-to-female ratio of 1.3:1. A Majority of them were satisfied with treatment time/duration (61.7%), they had a good knowledge of accelerated orthodontics (83.3%) with piezocision (75%) and micro-osteoperforation (63.3%) being the most popular. All orthodontists were interested in accelerated orthodontics, if it offered up to 30% reduction in treatment time. Major limitations to the practice included unavailability of technique materials (50%), insufficient knowledge (41.7%) and cost (35%). CONCLUSION: Most orthodontists did not routinely practice accelerated orthodontics despite adequate knowledge. They were willing to offer accelerated orthodontic treatment (AOT) if patients were willing to pay an additional fee. The less invasive methods were more accepted.


CONTEXTE: Les mouvements dentaires orthodontiques accélérés sont des procédures réalisées pour augmenter la vitesse de déplacement des dents, réduisant ainsi le temps de traitement. Il existe de nombreuses techniques actuellement disponibles pour accélérer le temps de traitement orthodontique, mais des preuves sont encore nécessaires pour déterminer dans quelle mesure les orthodontistes acceptent et pratiquent l'orthodontie accélérée. La présente étude vise à évaluer les connaissances des orthodontistes sur la pratique de l'orthodontie accélérée, ainsi que leur volonté de l'adopter comme option de traitement pour leurs patients. MÉTHODOLOGIE: L'approbation éthique a été obtenue avant le début de l'étude. La population étudiée comprenait tous les orthodontistes exerçant au Nigeria. Des questionnaires ont été administrés physiquement aux orthodontistes lors de leur assemblée générale annuelle. Des courriels ont ensuite été utilisés pour distribuer le questionnaire aux orthodontistes absents de l'assemblée annuelle. Le questionnaire a recueilli des informations sur les données biographiques des répondants, ainsi que sur leurs connaissances, attitudes et pratiques en matière de traitement orthodontique accéléré. L'analyse statistique a été réalisée à l'aide du logiciel IBM SPSS version 27. Le niveau de signification était de 0,05 pour toutes les analyses statistiques. RÉSULTATS: Les participants à l'étude étaient au nombre de 60, avec un âge moyen de 34,18 ans et un ratio hommes-femmes de 1,3:1. La majorité d'entre eux étaient satisfaits du temps/durée du traitement (61,7 %), ils avaient de bonnes connaissances en orthodontie accélérée (83,3 %) avec la piezocision (75 %) et la micro-ostéoperforation (63,3 %) étant les plus populaires. Tous les orthodontistes étaient intéressés par l'orthodontie accélérée, si elle offrait une réduction allant jusqu'à 30 % du temps de traitement. Les principales limitations à la pratique comprenaient l'indisponibilité des matériaux de technique (50 %), le manque de connaissances (41,7 %) et le coût (35 %). CONCLUSION: La plupart des orthodontistes ne pratiquaient pas systématiquement l'orthodontie accélérée malgré des connaissances adéquates. Ils étaient prêts à proposer un traitement orthodontique accéléré (TOA) si les patients étaient prêts à payer des frais supplémentaires. Les méthodes moins invasives étaient plus acceptées. MOTS-CLÉS: Orthodontie accélérée, orthodontiste, temps de traitement, piezocision.


Subject(s)
Health Knowledge, Attitudes, Practice , Orthodontists , Humans , Male , Female , Adult , Surveys and Questionnaires , Nigeria , Attitude of Health Personnel , Orthodontics, Corrective/methods , Orthodontics/methods , Practice Patterns, Dentists'/statistics & numerical data , Middle Aged
18.
Bull Exp Biol Med ; 176(5): 612-616, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38730106

ABSTRACT

We experimentally demonstrated that chronic social stress during the development of a depression-like state enhances lung metastasis and modifies the expression of many carcinogenesis- and apoptosis-related genes in the hypothalamus of mice, including genes involved in lung cancer pathogenesis in humans. Analysis of the expression of genes encoding the major clinical markers of lung cancer in the hypothalamus of mice with depression-like behavior revealed increased expression of the Eno2 gene encoding neuron-specific enolase, a blood marker of lung cancer progression in humans. It was shown that the expression of this gene in the hypothalamus correlated with the expression of many carcinogenesis- and apoptosis-related genes. The discovered phenomenon may have a fundamental significance and requires further studies.


Subject(s)
Biomarkers, Tumor , Depression , Hypothalamus , Lung Neoplasms , Phosphopyruvate Hydratase , Animals , Male , Mice , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinogenesis , Depression/genetics , Depression/metabolism , Depression/pathology , Gene Expression Regulation, Neoplastic , Hypothalamus/metabolism , Hypothalamus/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Phosphopyruvate Hydratase/analysis , Phosphopyruvate Hydratase/genetics , Stress, Psychological/genetics , Stress, Psychological/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism
19.
Animal ; 18(6): 101157, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744228

ABSTRACT

The comb is an ornament involved in signalling condition in domestic fowl. We hypothesised that comb size, comb shape complexity (i.e., rugosity, the comb perimeter jaggedness), and comb laterality of laying hens would be influenced by the degree of environmental enrichment experienced during juvenile development in the form of resource choice. We conducted a 2 × 2 factorial crossover experiment with pullets reared in pens containing four perches of equal length and four litter areas of equal size. Pullets were exposed to a single choice vs multiple choices of perch and litter types (i.e., all the same vs all different) during Weeks 1-4 (Period 1) and/or Weeks 5-15 (Period 2) of rearing (n = 4 pens/treatment combination) prior to transfer to standard adult laying pens for Weeks 16-27 (Period 3). In Week 27, combs were photographed, and comb laterality (hanging on left or right side) was noted. Using a custom-made image analysis programme, we captured comb area (mm2), perimeter length (mm), and rugosity ((perimeter length - horizontal length) / horizontal length) from comb photographs of 6-7 randomly selected hens/pen. We predicted that hens reared in the multi-choice environment during Periods 1 and 2 would have larger, more complex, and left-side-biased combs than those in the other treatment groups, reflecting lower allostatic load. The predicted comb side bias was based on a possible bias in head posture/movements associated with greater right eye/ear use and left-brain hemispheric dominance. Contrary to our predictions, we detected an overall right-side bias in comb laterality, and no associations between resource choice treatment in Period 1 or Period 2 and comb area, perimeter length, rugosity, or laterality of the adult hens. Thus, variation in allostatic load resulting from the rearing treatments was insufficient to modify the trajectory of comb morphological development, possibly due to a ceiling effect when comparing environmental treatments on the positive end of the welfare spectrum. We found that left-lopping combs had shorter perimeters than right-lopping combs. However, among hens with left-lopping combs, those with larger combs were heavier and had less feather damage, while among hens with right-lopping combs, those with longer-perimeter combs were heavier and tended to have less comb damage. In conclusion, comb characteristics were related to physical condition at the individual level but did not serve as sensitive integrated indicators of hen welfare in response to basic vs enhanced resource choice during rearing.


Subject(s)
Chickens , Animals , Chickens/physiology , Chickens/anatomy & histology , Chickens/growth & development , Female , Comb and Wattles/anatomy & histology , Comb and Wattles/physiology , Housing, Animal , Functional Laterality/physiology , Environment , Animal Husbandry/methods , Cross-Over Studies
20.
Article in English | MEDLINE | ID: mdl-38763835

ABSTRACT

OBJECTIVE: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established. METHODS: Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory-6 item version [STAI]), and cerebral amyloid-beta (Aß; 18F-florbetapir) PET and a subset underwent tau (18F-flortaucipir) PET. Linear regressions estimated associations of Aß in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite). RESULTS: Greater Aß deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aß with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score. CONCLUSION: Greater worry was associated with Aß but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD.

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