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1.
Medicina (Kaunas) ; 60(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39064518

ABSTRACT

Background and Objectives: Radiofrequency catheter ablation (RFCA) is a highly successful intervention. By comparing the lesion changes in prostate parenchymal and striated muscle tissues after RFCA with and without cooling, it was possible to assess the correlation between the shape regularity, area, and perimeter of the thermal lesion, and to predict the geometric shape changes of the lesions. Materials and Methods: A standard prostate and striated muscle RFCA procedure was performed on 13 non-purebred dogs in two sessions: no cooling and cooling with 0.1% NaCl solution. Microtome-cut 2-3 µm sections of tissue samples were stained with haematoxylin and eosin and further examined. The quotient formula was employed to evaluate the geometric shape of the damage zones at the ablation site. Results: The extent of injury following RFCA in striated muscle tissue was comparable to that in prostate parenchymal tissue. Regression analysis indicated a strong and positive relationship between area and perimeter in all experimental groups. In the experimental groups of parenchymal tissues with and without cooling, an increase in the area or perimeter of the damage zone corresponded to an increase in the quotient value. A similar tendency was observed in the striated muscle group with cooling. However, in the striated muscle group without cooling, an increase in lesion area or perimeter lowered the quotient value. Standardised regression coefficients demonstrated that in the striated muscle with cooling, the damage zone shape was more determined by area than perimeter. However, in the parenchymal tissue, the perimeter had a more substantial impact on the damage zone shape than the area. Conclusions: The damage area and perimeter have predictive power on the overall shape regularity of damage zone geometry in both striated muscles and parenchymal tissue. This approach is employed to achieve a balance between the need for tumour eradication and the minimisation of ablation-induced complications to healthy tissue.


Subject(s)
Catheter Ablation , Muscle, Striated , Animals , Male , Catheter Ablation/methods , Catheter Ablation/adverse effects , Dogs , Parenchymal Tissue , Prostate/surgery , Prostate/pathology , Muscle, Skeletal/injuries
2.
Hum Brain Mapp ; 45(9): e26761, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38895882

ABSTRACT

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.


Subject(s)
Brain , Humans , Female , Male , Adult , Middle Aged , Brain/diagnostic imaging , Brain/pathology , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Diffusion Magnetic Resonance Imaging/methods , Water , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Parenchymal Tissue/diagnostic imaging , Parenchymal Tissue/pathology , White Matter/diagnostic imaging , White Matter/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Processing Speed
3.
PLoS Comput Biol ; 20(5): e1011973, 2024 May.
Article in English | MEDLINE | ID: mdl-38781253

ABSTRACT

Recent progresses in intravital imaging have enabled highly-resolved measurements of periarteriolar oxygen gradients (POGs) within the brain parenchyma. POGs are increasingly used as proxies to estimate the local baseline oxygen consumption, which is a hallmark of cell activity. However, the oxygen profile around a given arteriole arises from an interplay between oxygen consumption and delivery, not only by this arteriole but also by distant capillaries. Integrating such interactions across scales while accounting for the complex architecture of the microvascular network remains a challenge from a modelling perspective. This limits our ability to interpret the experimental oxygen maps and constitutes a key bottleneck toward the inverse determination of metabolic rates of oxygen. We revisit the problem of parenchymal oxygen transport and metabolism and introduce a simple, conservative, accurate and scalable direct numerical method going beyond canonical Krogh-type models and their associated geometrical simplifications. We focus on a two-dimensional formulation, and introduce the concepts needed to combine an operator-splitting and a Green's function approach. Oxygen concentration is decomposed into a slowly-varying contribution, discretized by Finite Volumes over a coarse cartesian grid, and a rapidly-varying contribution, approximated analytically in grid-cells surrounding each vessel. Starting with simple test cases, we thoroughly analyze the resulting errors by comparison with highly-resolved simulations of the original transport problem, showing considerable improvement of the computational-cost/accuracy balance compared to previous work. We then demonstrate the model ability to flexibly generate synthetic data reproducing the spatial dynamics of oxygen in the brain parenchyma, with sub-grid resolution. Based on these synthetic data, we show that capillaries distant from the arteriole cannot be overlooked when interpreting POGs, thus reconciling recent measurements of POGs across cortical layers with the fundamental idea that variations of vascular density within the depth of the cortex may reveal underlying differences in neuronal organization and metabolic load.


Subject(s)
Brain , Oxygen Consumption , Oxygen , Oxygen/metabolism , Brain/metabolism , Brain/blood supply , Oxygen Consumption/physiology , Animals , Humans , Models, Neurological , Computer Simulation , Computational Biology/methods , Parenchymal Tissue/metabolism
4.
Eur J Radiol ; 175: 111447, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677039

ABSTRACT

OBJECTIVES: Robustness of radiomic features in physiological tissue is an important prerequisite for quantitative analysis of tumor biology and response assessment. In contrast to previous studies which focused on different tumors with mostly short scan-re-scan intervals, this study aimed to evaluate the robustness of radiomic features in cancer-free patients and over a clinically encountered inter-scan interval. MATERIALS AND METHODS: Patients without visible tumor burden who underwent at least two portal-venous phase dual energy CT examinations of the abdomen between May 2016 and January 2020 were included, while macroscopic tumor burden was excluded based upon follow-up imaging for all patients (≥3 months). Further, patients were excluded if no follow-up imaging was available, or if the CT protocol showed deviations between repeated examinations. Circular regions of interest were placed and proofread by two board-certified radiologists (4 years and 5 years experience) within the liver (segments 3 and 6), the psoas muscle (left and right), the pancreatic head, and the spleen to obtain radiomic features from normal-appearing organ parenchyma using PyRadiomics. Radiomic feature robustness was tested using the concordance correlation coefficient with a threshold of 0.75 considered indicative for deeming a feature robust. RESULTS: In total, 160 patients with 480 repeated abdominal CT examinations (range: 2-4 per patient) were retrospectively included in this single-center, IRB-approved study. Considering all organs and feature categories, only 4.58 % (25/546) of all features were robust with the highest rate being found in the first order feature category (20.37 %, 22/108). Other feature categories (grey level co-occurrence matrix, grey level dependence matrix, grey level run length matrix, grey level size zone matrix, and neighborhood gray-tone difference matrix) yielded an overall low percentage of robust features (range: 0.00 %-1.19 %). A subgroup analysis revealed the reconstructed field of view and the X-ray tube current as determinants of feature robustness (significant differences in subgroups for all organs, p < 0.001) as well as the size of the region of interest (no significant difference for the pancreatic head with p = 0.135, significant difference with p < 0.001 for all other organs). CONCLUSION: Radiomic feature robustness obtained from cancer-free subjects with repeated examinations using a consistent protocol and CT scanner was limited, with first order features yielding the highest proportion of robust features.


Subject(s)
Radiography, Dual-Energy Scanned Projection , Tomography, X-Ray Computed , Humans , Male , Female , Tomography, X-Ray Computed/methods , Middle Aged , Radiography, Dual-Energy Scanned Projection/methods , Aged , Adult , Retrospective Studies , Pancreas/diagnostic imaging , Liver/diagnostic imaging , Radiography, Abdominal/methods , Aged, 80 and over , Spleen/diagnostic imaging , Parenchymal Tissue/diagnostic imaging , Psoas Muscles/diagnostic imaging , Radiomics
5.
BJU Int ; 134(2): 219-228, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38355293

ABSTRACT

OBJECTIVE: To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software-based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP. PATIENTS AND METHODS: A total of 894 PN patients with available studies (2011-2014) were evaluated. The PPVP was measured from cross-sectional imaging at ≤3 months before and 3-12 months after PN using semi-automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative-importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP. RESULTS: The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2, and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71-88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76-92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05). CONCLUSIONS: A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour-related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys.


Subject(s)
Glomerular Filtration Rate , Kidney Neoplasms , Kidney , Nephrectomy , Organ Sparing Treatments , Humans , Nephrectomy/methods , Female , Male , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Middle Aged , Aged , Kidney/blood supply , Organ Sparing Treatments/methods , Organ Size , Retrospective Studies , Parenchymal Tissue , Tumor Burden
6.
Nature ; 626(8001): 1108-1115, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38326622

ABSTRACT

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.


Subject(s)
Depressive Disorder, Major , Matrix Metalloproteinase 8 , Monocytes , Stress, Psychological , Animals , Humans , Mice , Depressive Disorder, Major/blood , Depressive Disorder, Major/enzymology , Depressive Disorder, Major/genetics , Depressive Disorder, Major/metabolism , Extracellular Space/metabolism , Matrix Metalloproteinase 8/blood , Matrix Metalloproteinase 8/deficiency , Matrix Metalloproteinase 8/genetics , Matrix Metalloproteinase 8/metabolism , Mice, Inbred C57BL , Monocytes/chemistry , Monocytes/immunology , Monocytes/metabolism , Nucleus Accumbens/metabolism , Nucleus Accumbens/pathology , Parenchymal Tissue/metabolism , Single-Cell Gene Expression Analysis , Social Behavior , Social Isolation , Stress, Psychological/blood , Stress, Psychological/genetics , Stress, Psychological/immunology , Stress, Psychological/metabolism
7.
Nature ; 627(8002): 157-164, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38418877

ABSTRACT

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow1,2 through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.


Subject(s)
Brain , Cerebrospinal Fluid , Extracellular Fluid , Neurons , Action Potentials , Brain/cytology , Brain/metabolism , Brain Waves/physiology , Cerebrospinal Fluid/metabolism , Extracellular Fluid/metabolism , Glymphatic System/metabolism , Kinetics , Nerve Net/physiology , Neurons/metabolism , Optogenetics , Parenchymal Tissue/metabolism , Ions/metabolism
8.
Rev. int. androl. (Internet) ; 21(4): 1-8, oct.-dic. 2023. ilus, tab
Article in English | IBECS | ID: ibc-226002

ABSTRACT

Purpose: The aim of this study is to evaluate the anatomical factors influencing elasticity values of normal testicular parenchyma using shear wave elastography (SWE). Methods: This study examined 68 healthy male volunteers (117 testes in which standard transverse axis ultrasonography views could be obtained) via conventional scrotal ultrasonography and SWE. Both the mean (EMean) and standard deviation (ESD) elasticity values were acquired. Results: In the standard transverse axis view of the rete testis at the mid-lateral edge of the testes, the EMean values in 2mm the testicular parenchyma from the rete testis and the testicular capsule at the same level as the rete testis were all significantly larger than in the central zone (P<0.001, P<0.001, respectively). The EMean value in the testicular parenchyma 2mm from the testicular capsule on the line formed approximately 45° below the horizontal line of the rete testis was significantly larger than in the rete testis approximately 45° above the horizontal line (P<0.001). In two standard transverse axis views, the ESD values in other regions were significantly larger than those in the central zones (all P<0.001). Also, the EMean values in the transmediastinal arteries were larger than those of the surrounding normal testicular parenchyma (P<0.001). Conclusion: Based on SWE, factors including the testicular capsule, the density of testicular fibrous septa, the depth of the Q-Box™, and the transmediastinal artery may influence the testes elasticity measurement. (AU)


Subject(s)
Humans , Male , Young Adult , Adult , Middle Aged , Elasticity , Parenchymal Tissue , Testis/diagnostic imaging , Testis/anatomy & histology , Elasticity Imaging Techniques/methods , Ultrasonography
9.
Nature ; 622(7981): 164-172, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37674082

ABSTRACT

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2-7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations.


Subject(s)
Self Tolerance , T-Lymphocytes , Thymus Gland , Animals , Mice , Cell Differentiation , Epithelial Cells/cytology , Epithelial Cells/metabolism , Self Tolerance/immunology , Self Tolerance/physiology , T-Lymphocytes/classification , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Thymus Gland/cytology , Thymus Gland/immunology , Parenchymal Tissue , Muscle Cells , Endocrine Cells , Chromatin , Transcription, Genetic , Ghrelin
10.
Biomech Model Mechanobiol ; 22(6): 2083-2096, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37535253

ABSTRACT

Automobile crashes and blunt trauma often lead to life-threatening thoracic injuries, especially to the lung tissues. These injuries can be simulated using finite element-based human body models that need dynamic material properties of lung tissue. The strain-rate-dependent material parameters of human parenchymal tissues were determined in this study using uniaxial quasi-static (1 mm/s) and dynamic (1.6, 3, and 5 m/s) compression tests. A bilinear material model was used to capture the nonlinear behavior of the lung tissue, which was implemented using a user-defined material in LS-DYNA. Inverse mapping using genetic algorithm-based optimization of all experimental data with the corresponding FE models yielded a set of strain-rate-dependent material parameters. The bilinear material parameters are obtained for the strain rates of 0.1, 100, 300, and 500 s-1. The estimated elastic modulus increased from 43 to 153 kPa, while the toe strain reduced from 0.39 to 0.29 when the strain rate was increased from 0.1 to 500 s-1. The optimized bilinear material properties of parenchymal tissue exhibit a piecewise linear relationship with the strain rate.


Subject(s)
Lung , Parenchymal Tissue , Humans , Stress, Mechanical , Finite Element Analysis , Elastic Modulus , Models, Biological
11.
J Mammary Gland Biol Neoplasia ; 28(1): 11, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37249685

ABSTRACT

Many studies on bovine mammary glands focus on one stage of development. Often missing in those studies are repeated measures of development from the same animals. As milk production is directly affected by amount of parenchymal tissue within the udder, understanding mammary gland growth along with visualization of its structures during development is essential. Therefore, analysis of ultrasound and histology data from the same animals would result in better understanding of mammary development over time. Thus, this research aimed to describe mammary gland development using non-invasive and invasive tools to delineate growth rate of glandular tissue responsible for potential future milk production. Mammary gland ultrasound images, biopsy samples, and blood samples were collected from 36 heifer dairy calves beginning at 10 weeks of age, and evaluated at 26, 39, and 52 weeks. Parenchyma was quantified at 10 weeks of age using ultrasound imaging and histological evaluation, and average echogenicity was utilized to quantify parenchyma at later stages of development. A significant negative correlation was detected between average echogenicity of parenchyma at 10 weeks and total adipose as a percent of histological whole tissue at 52 weeks. Additionally, a negative correlation between average daily gain at 10 and 26 weeks and maximum echogenicity at 52 weeks was present. These results suggest average daily gain and mammary gland development prior to 39 weeks of age is associated with development of the mammary gland after 39 weeks. These findings could be predictors of future milk production, however this must be further explored.


Subject(s)
Diet , Obesity , Cattle , Animals , Female , Mammary Glands, Animal/diagnostic imaging , Parenchymal Tissue , Milk/chemistry
12.
Medicina (Kaunas) ; 59(4)2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37109660

ABSTRACT

Background and Objectives: Prostate cancer is on the rise in the European Union, and radiofrequency ablation (RFA) is one of the minimally invasive treatment options used for its treatment. Therefore, the aim of this study was to investigate and analyze the effects of RFA on prostate tissues. Materials and Methods: A standard prostate RFA procedure was performed on 13 non-purebred dogs in three sessions: no cooling (NC), cooling with a 0.1% NaCl solution (C.01), and cooling using a 0.9% NaCl solution (C.09). Microtome-cut 2-3 µm sections of prostate samples were stained with hematoxylin and eosin and further examined. Results: A histopathologic evaluation identified four zones of exposure: direct, application, necrosis, and transitional, as the damage on tissues decreased going further from the ablation site. The areas and perimeters of these zones were calculated, and geometric shapes of ablative lesions were evaluated using the quotient formula. Areas and perimeters of prostate tissue lesions in the NC and C.09 sessions were of similar size, whereas those found in C.01 were statistically significantly smaller. Lesions observed in session C.01 were of the most regular geometric shape, while the most irregular ones were found in session C.09. The shapes of lesions closest to the ablation electrode were the most irregular, becoming more regular the further away from the electrode they were. Conclusions: Prostate RFA leads to tissue damage with distinct morphological zones. Notably, the prostate lesions were the smallest and the most regular in shape after RFA procedures using the 0.1% NaCl cooling solution. It can be argued that smaller ablation sites may result in smaller scars, thus allowing for faster tissue healing if the blood flow and innervation at the ablation site are not compromised.


Subject(s)
Catheter Ablation , Radiofrequency Ablation , Male , Animals , Dogs , Catheter Ablation/adverse effects , Catheter Ablation/methods , Sodium Chloride , Parenchymal Tissue , Necrosis , Saline Solution
13.
BMC Genomics ; 24(1): 40, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36694114

ABSTRACT

BACKGROUND: Gilts experiencing sustained hyperprolactinemia from d 90 to 109 of gestation showed an early onset of lactogenesis coupled with premature mammary involution. To better understand the molecular mechanisms underlying the premature mammary involution observed in these gilts, a transcriptomic analysis was undertaken. Therefore, this study aimed to explore the effect of hyperprolactinemia on the global transcriptome in the mammary tissue of late gestating gilts and identify the molecular pathways involved in triggering premature mammary involution. METHODS: On d 90 of gestation, gilts received daily injections of (1) canola oil until d 109 ± 1 of gestation (CTL, n = 18); (2) domperidone (to induce hyperprolactinemia) until d 96 ± 1 of gestation (T7, n = 17) or; (3) domperidone (until d 109 ± 1 of gestation (T20, n = 17). Mammary tissue was collected on d 110 of gestation and total RNA was isolated from six CTL and six T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array was used for hybridization. Functional enrichment analyses were performed to explore the biological significance of differentially expressed genes, using the DAVID bioinformatics resource. RESULTS: The expression of 335 genes was up-regulated and that of 505 genes down-regulated in the mammary tissue of T20 vs CTL gilts. Biological process GO terms and KEGG pathways enriched in T20 vs CTL gilts reflected the concurrent premature lactogenesis and mammary involution. When looking at individual genes, it appears that mammary cells from T20 gilts can simultaneously upregulate the transcription of milk proteins such as WAP, CSN1S2 and LALBA, and genes triggering mammary involution such as STAT3, OSMR and IL6R. The down-regulation of PRLR expression and up-regulation of genes known to inactivate the JAK-STAT5 pathway (CISH, PTPN6) suggest the presence of a negative feedback loop trying to counteract the effects of hyperprolactinemia. CONCLUSIONS: Genes and pathways identified in this study suggest that sustained hyperprolactinemia during late-pregnancy, in the absence of suckling piglets, sends conflicting pro-survival and cell death signals to mammary epithelial cells. Reception of these signals results in a mammary gland that can simultaneously synthesize milk proteins and initiate mammary involution.


Subject(s)
Hyperprolactinemia , Pregnancy , Swine , Animals , Female , Hyperprolactinemia/chemically induced , Hyperprolactinemia/genetics , Hyperprolactinemia/metabolism , Transcriptome , Domperidone/metabolism , Domperidone/pharmacology , Parenchymal Tissue , Mammary Glands, Animal/metabolism , Sus scrofa , Lactation
14.
São Paulo; s.n; 2023. 23 p.
Thesis in Portuguese | Coleciona SUS, Sec. Munic. Saúde SP, HSPM-Producao, Sec. Munic. Saúde SP | ID: biblio-1532801

ABSTRACT

A pneumonia adquirida na comunidade (PAC) é a infecção aguda do parênquima pulmonar que ocorre no meio comunitário. A PAC representa a maior causa de morbidade e mortalidade em todo o mundo em crianças abaixo de cinco anos. Nesta faixa etária, a etiologia viral é a mais comum; porém, dentre as causas bacterianas, o Streptoccocus pneumoniae é o mais prevalente. As manifestações clínicas variam de acordo com o patógeno, hospedeiro e da gravidade da doença, sendo geralmente descrita com tosse, febre e desconforto respiratório. A PAC complicada é a pneumonia que, apesar do uso de antibióticos, evolui com complicações locais ou sistêmicas. Nos pacientes hospitalizados, as hemoculturas devem ser consideradas para auxiliar no diagnóstico etiológico e planejamento terapêutico. O tratamento inicial deve ser iniciado empiricamente com antibióticos. Caso haja necessidade de hospitalização, hemoculturas devem ser consideradas para auxiliar na propedêutica. Após implementação das vacinas pneumocócicas, principalmente após introdução da vacina pneumocócica 13 valente (PCV 13), houve redução significativa dos casos de pneumonia bacteriana e também da necessidade hospitalização. Diante de tal realidade, a elaboração do trabalho possui como objetivo a melhora dos procedimentos e a padronização dos atendimentos da população pediátrica com um quadro clínico sugestivo pneumonia adquirida na comunidade, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), ao construir um protocolo clínico de atendimento específico para a doença. O presente trabalho objetiva elaborar um protocolo clínico de atendimento de pneumonia adquirida na comunidade no Hospital do Servidor Público Municipal de São Paulo, contribuindo na assistência médica dos pacientes pediátricos. Apesar do grande avanço com a introdução das vacinas pneumocócicas, a PAC ainda representa uma importante causa de mortalidade na população infantil, sendo fundamental a elaboração de protocolos clínicos para abordar corretamente os pacientes que recorrem a um Pronto Socorro Infantil. Protocolos clínicos são diretrizes fundamentadas nas melhores práticas para a abordagem e tratamento de determinadas doenças, baseadas em evidência científica. O presente trabalho objetiva a melhora dos procedimentos e a uniformização dos atendimentos da população pediátrica com pneumonia, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), com a construção de um protocolo clínico de atendimento específico para a doença, a partir da revisão de literatura atualizada, cujo período de vigência seguirá os progressos científicos sobre o tema. Palavras-chave: Pneumonia Adquirida da Comunidade. Protocolos clínicos. Pediatria. Serviços Médicos de Emergência. Vacinas Pneumocócicas


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Pediatrics/standards , Pneumonia/complications , Pneumonia/mortality , Pneumonia, Pneumococcal/diagnosis , Respiratory Syncytial Viruses/pathogenicity , Respiratory Tract Diseases/diagnosis , Clinical Protocols/standards , Pneumonia, Bacterial/drug therapy , Cough/diagnosis , Pneumococcal Vaccines/therapeutic use , Parenchymal Tissue/physiopathology , Medical Assistance/standards , Anti-Bacterial Agents/administration & dosage , Noxae/analysis
15.
Revista Digital de Postgrado ; 11(3): 348, dic. 2022. ilus
Article in Spanish | LILACS, LIVECS | ID: biblio-1416665

ABSTRACT

Introducción: La fístula salival es la comunicaciónde la glándula salival o el conducto parotídeo hacia la piel,debido a una lesión traumática del parénquima o del conducto deexcreción; no suele ser una complicación frecuente en parotiditisaguda. El objetivo de este trabajo es destacar la presentaciónatípica de un caso de parotiditis bacteriana asociado a fistulasalival hacia el conducto auditivo externo y cavidad oral, y aparálisis facial periférica. Caso clínico: Paciente masculino de15 años de edad, quien consulta por otalgia y otorrea derechaasociado a aumento de volumen en región parotídea ipsilateralde 5 días de evolución. Al examen físico se evidencia, caraasimétrica con desviación de comisura labial hacia la izquierda ycierre palpebral completo sin esfuerzo, con aumento de volumende parótida derecha con signos de flogosis, otorrea purulentaderecha . solución de continuidad en tercio medio de pisode conducto auditivo externo. Ecosonograma de piel y partesblandas, reveló cambios inflamatorios en glándula parótida concolección de 112 cc., Los hallazgos tomográficos de oído medioy mastoides corroboraron hallazgos del ecosonograma. se realizódrenaje quirúrgico del absceso y se trató con Clindamicina600 mg vía endovenosa cada 6 horas y Penicilina Cristalina200 mg/kg/ peso cada 6 horas y su evolución fue satisfactoria.Conclusión:Los abscesos parotídeos pueden presentarse demanera atípica o en raras ocasiones con drenaje a través delconducto auditivo externo(AU)


Introduction: Salivary fistula is the communicationof the salivary glands or the parotid duct to the skin, due toa traumatic injury to the parenchyma or the excretion duct; Itis not usually a frequent complication in acute parotitis. the eobjective of this work is to highlight the atypical presentation of acase of bacterial parotitis associated with salivary fistula towardsthe external auditory canal and oral cavity, and peripheralfacial paralysis. Clinical case: A 15-year-old male patient, whoconsulted due to otalgia and right otorrhea associated with anincrease in volume in the ipsilateral parotid region of 5 days ofevolution. On physical examination, an asymmetrical face withdeviation of the lip corner to the leth and complete palpebralclosure without effort, with increased volume of the rightparotid gland with signs of phlogosis, right purulent otorrhea and continuity solution in the middle third of the external auditory canal are evident. Ultrasound of the skin and so the tissues revealed inflammatory changes in the parotid glands with a collection of 112 cc. yhe tomographic findings of the middle ear and mastoids corroborated the findings of the echosonogram; Surgical drainage of the abscess was performed and he was treated with clindamycin 600 mg intravenously every 6 hours and crystalline penicillin 200 mg/kg/weight every 6 hours, and his evolution was satisfactory. Conclusion: Parotid abscesses can present atypically or rarely with drainage through the external auditory canal(AU)


Subject(s)
Humans , Male , Adolescent , Parotitis , Salivary Gland Fistula , Ear Canal , Parotid Gland , Physical Examination , Clindamycin , Abscess , Ear , Parenchymal Tissue
16.
Nature ; 611(7936): 585-593, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36352225

ABSTRACT

Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1+ PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer's disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD.


Subject(s)
Central Nervous System , Cerebrospinal Fluid , Macrophages , Parenchymal Tissue , Animals , Mice , Alzheimer Disease/metabolism , Brain/metabolism , Central Nervous System/cytology , Central Nervous System/metabolism , Cerebrospinal Fluid/metabolism , Macrophages/physiology , Meninges/cytology , Rheology , Extracellular Matrix Proteins/metabolism , Aging/metabolism , Phagocytosis , Endocytosis , Interferon-gamma/metabolism , Parenchymal Tissue/cytology , Humans
17.
Radiología (Madr., Ed. impr.) ; 64(5): 456-463, Sep.-Oct. 2022. ilus
Article in Spanish | IBECS | ID: ibc-209921

ABSTRACT

Objetivo: Las calcificaciones torácicas se encuentran con frecuencia en las radiografías y TC de tórax, en una gran variedad de trastornos. Si bien la mayoría de las calcificaciones son secuelas benignas de una enfermedad anterior, aportan información importante para establecer el diagnóstico. En este artículo se analizan los diferentes tipos de lesiones calcificadas halladas en el tórax, prestando especial atención a las que se sitúan fuera del parénquima pulmonar. Se utiliza un enfoque basado en la localización para el diagnóstico diferencial, a la vez que se proporcionan al lector perlas diagnósticas y se analiza la importancia clínica de los diferentes tipos de calcificaciones. Conclusión: Las calcificaciones torácicas son un hallazgo frecuente en las pruebas de imagen habituales. El conocimiento de las diferentes etiologías y manifestaciones radiológicas proporciona al radiólogo las herramientas necesarias para elaborar un diagnóstico diferencial, así como para diferenciar correctamente los hallazgos que necesitan un mayor estudio de los que pueden ser descartados.(AU)


Objective: Thoracic calcifications are frequently found in chest radiographs and CTs, occurring in a wide variety of disorders. Although most calcifications are harmless sequelae of previous disease, they provide important information to establish the diagnosis. This article reviews the different types of calcified lesions found in the chest, focusing on lesions outside the lung parenchyma. A location-based approach to the differential diagnosis is used, while providing the reader with diagnostic pearls and discussing the clinical importance of the different types of calcifications. Conclusion: Chest calcifications are a common finding in routine chest imaging. Understanding the different etiologies and radiologic manifestations provide the radiologist with the necessary tools to elaborate a differential diagnosis, as well as to correctly differentiate the findings that need further work-up from the ones that can be dismissed.(AU)


Subject(s)
Humans , Parenchymal Tissue , Radiography, Thoracic , Radiography , Diagnosis, Differential , Diagnostic Imaging , Tomography, X-Ray Computed , Calcium , Radiology
18.
Am J Physiol Lung Cell Mol Physiol ; 322(6): L882-L889, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35537098

ABSTRACT

Lung resistance (RL) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in RL, but the mechanism is not entirely clear. The first step toward understanding the effect of DI is to determine how each of the resistance components is affected by DI. In the present study, we measured RL and apparent airway resistance (RAW, which combines the effects of airway resistance and airway heterogeneity) simultaneously before and after a DI in acetylcholine (ACh)-challenged ex vivo sheep lungs. We found that at normal breathing frequency (0.25 Hz) ACh-challenge led to a doubling of RL, 80.3% of that increase was caused by an increase in RAW; the increase in apparent tissue resistance (RT) was insignificant. 57.7% of the increase in RAW was abolished by a single DI. After subtracting RAW from RL, the remaining RT was mostly independent of ACh-challenge and its reduction after a DI came mostly from the change in the mechanical properties of lung parenchyma. We conclude that at normal breathing frequency, RL in an unchallenged lung is mostly composed of RT, and the increase in RL due to ACh-challenge stems mostly from the increase in RAW and that both RAW and RT can be greatly reduced by a DI, likely due to a reduction in true airway resistance and heterogeneity, as well as parenchymal tissue hysteresis post DI.


Subject(s)
Airway Resistance , Parenchymal Tissue , Animals , Inhalation , Lung , Respiratory Function Tests , Sheep
19.
Rev. patol. respir ; 25(2): 54-56, Abri - Jun 2022. ilus
Article in Spanish | IBECS | ID: ibc-207326

ABSTRACT

El secuestro pulmonar es una rara enfermedad congénita del tracto respiratorio, en la cual existe un parénquima pulmonar no funcionante que presenta una circulación arterial aberrante. Puede acompañarse de otras alteraciones torácicas como enfisema lobar, el síndrome de la cimitarra o malformaciones adenomatoides quísticas. El diagnóstico en la edad adulta suele ser incidental, aunque también puede presentarse en un menor número de pacientes como infecciones respiratorias de repetición.(AU)


Pulmonary sequestration is a rare congenital disease of the respiratory tract, in which there is a non-functioning lung parenchyma that presents an aberrant arterial circulation. It can be accompanied by other thoracic alterations such as lobar emphysema, scimitar syndrome or cystic adenomatoid malformations. Diagnosis in adulthood is usually incidental, although it can also present in a smaller number of patients as recurrent respiratory infections.(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Bronchopulmonary Sequestration , Respiratory System , Congenital Abnormalities , Parenchymal Tissue , Respiratory Tract Diseases/complications , Respiratory Tract Diseases/diagnosis
20.
Eur J Med Res ; 27(1): 42, 2022 Mar 19.
Article in English | MEDLINE | ID: mdl-35305692

ABSTRACT

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/physiopathology , Diagnosis, Differential , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/physiopathology , Immunoglobulin G4-Related Disease/surgery , Parenchymal Tissue/physiopathology , Aged , Humans , Male
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