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1.
Front Immunol ; 15: 1326026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426107

RESUMO

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.


Assuntos
Glomerulonefrite por IGA , MicroRNAs , Humanos , Glomerulonefrite por IGA/patologia , Biomarcadores/urina , Fibrose , MicroRNAs/metabolismo , Atrofia , Colágeno , Luciferases
2.
Int Ophthalmol ; 44(1): 122, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427135

RESUMO

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.


Assuntos
Neovascularização de Coroide , Vasculopatia Polipoidal da Coroide , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Atrofia/complicações , Atrofia/patologia , Corioide/patologia , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/patologia , Corantes , Angiofluoresceinografia/métodos , Verde de Indocianina , Vasculopatia Polipoidal da Coroide/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
3.
PLoS One ; 19(3): e0298208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427650

RESUMO

The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.


Assuntos
Doenças Desmielinizantes , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Substância Branca , Ratos , Humanos , Animais , Ratos Mutantes , 4-Aminopiridina/farmacologia , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/genética , Cerebelo , Gânglios da Base , Potenciais Evocados , Caminhada , Atrofia
4.
Sci Rep ; 14(1): 5079, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429319

RESUMO

The differential diagnosis for optic atrophy can be challenging and requires expensive, time-consuming ancillary testing to determine the cause. While Leber's hereditary optic neuropathy (LHON) and optic neuritis (ON) are both clinically significant causes for optic atrophy, both relatively rare in the general population, contributing to limitations in obtaining large imaging datasets. This study therefore aims to develop a deep learning (DL) model based on small datasets that could distinguish the cause of optic disc atrophy using only fundus photography. We retrospectively reviewed fundus photographs of 120 normal eyes, 30 eyes (15 patients) with genetically-confirmed LHON, and 30 eyes (26 patients) with ON. Images were split into a training dataset and a test dataset and used for model training with ResNet-18. To visualize the critical regions in retinal photographs that are highly associated with disease prediction, Gradient-Weighted Class Activation Map (Grad-CAM) was used to generate image-level attention heat maps and to enhance the interpretability of the DL system. In the 3-class classification of normal, LHON, and ON, the area under the receiver operating characteristic curve (AUROC) was 1.0 for normal, 0.988 for LHON, and 0.990 for ON, clearly differentiating each class from the others with an overall total accuracy of 0.93. Specifically, when distinguishing between normal and disease cases, the precision, recall, and F1 scores were perfect at 1.0. Furthermore, in the differentiation of LHON from other conditions, ON from others, and between LHON and ON, we consistently observed precision, recall, and F1 scores of 0.8. The model performance was maintained until only 10% of the pixel values of the image, identified as important by Grad-CAM, were preserved and the rest were masked, followed by retraining and evaluation.


Assuntos
Aprendizado Profundo , Atrofia Óptica Hereditária de Leber , Disco Óptico , Neurite Óptica , Humanos , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Estudos Retrospectivos , Atrofia Óptica Hereditária de Leber/patologia , Neurite Óptica/patologia , Fotografação , Atrofia/patologia
5.
Nutr J ; 23(1): 34, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38468287

RESUMO

BACKGROUND: The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japanese community-dwelling adults. METHODS: Data with a 2-year follow-up from the sixth wave (July 2008 to July 2010; baseline) to the seventh (July 2010 to July 2012; follow-up) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project were analyzed. Dietary intake was assessed using a 3-day dietary record, and longitudinal volume changes (%) in the total gray matter (TGM), total white matter, and frontal, parietal, occipital, temporal, and insular lobes were assessed using 3-dimensional T1 magnetic resonance imaging scans. Multiple factor analysis and hierarchical clustering revealed sex-specific dietary patterns. Associations between dietary patterns and annual brain-volume changes (%) were evaluated using general linear models adjusted for age, apoprotein E genotype, body mass index, medical history, lifestyle behaviors, socioeconomic factors, and energy intake. RESULTS: Among the 1636 participants (age: 40.3-89.2 years), three dietary patterns were determined for men (n = 815; Western; Vegetable-Fruit-Dairy; and Traditional Japanese diets) and women (n = 821; Western; Grain-Vegetable-Fruit; and Traditional Japanese diets). Compared to women following the Western diet, those on the Traditional Japanese diet had less TGM atrophy. Multivariable-adjusted ß (95% confidence interval) of the annual change (%) of TGM was - 0.145 (-0.287 to -0.002; P = 0.047), which correlated with reduced parietal lobe atrophy. No association between dietary pattern and brain atrophy was observed in men. CONCLUSIONS: Adherence to healthy dietary patterns, with higher consumption of whole grains, seafood, vegetables, fruits, mushrooms, soybean products, and green tea, potentially confers a protective effect against brain atrophy in middle-aged and older Japanese women but not in men. Further research to confirm these results and ascertain the underlying mechanisms is required. This study highlights the importance of sex-specific effects on the relationship between dietary patterns and brain health in diverse populations.


Assuntos
Longevidade , Masculino , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Longitudinais , Vida Independente , Japão , Dieta , Envelhecimento , Verduras , Encéfalo/diagnóstico por imagem , Atrofia
6.
Neurology ; 102(7): e209176, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38471053

RESUMO

BACKGROUND AND OBJECTIVES: Individual brain MRI markers only show at best a modest association with long-term occurrence of dementia. Therefore, it is challenging to accurately identify individuals at increased risk for dementia. We aimed to identify different brain MRI phenotypes by hierarchical clustering analysis based on combined neurovascular and neurodegenerative brain MRI markers and to determine the long-term dementia risk within the brain MRI phenotype subgroups. METHODS: Hierarchical clustering analysis based on 32 combined neurovascular and neurodegenerative brain MRI markers in community-dwelling individuals of the Age-Gene/Environment Susceptibility Reykjavik Study was applied to identify brain MRI phenotypes. A Cox proportional hazards regression model was used to determine the long-term risk for dementia per subgroup. RESULTS: We included 3,056 participants and identified 15 subgroups with distinct brain MRI phenotypes. The phenotypes ranged from limited burden, mostly irregular white matter hyperintensity (WMH) shape and cerebral atrophy, mostly irregularly WMHs and microbleeds, mostly cortical infarcts and atrophy, mostly irregularly shaped WMH and cerebral atrophy to multiburden subgroups. Each subgroup showed different long-term risks for dementia (min-max range hazard ratios [HRs] 1.01-6.18; mean time to follow-up 9.9 ± 2.6 years); especially the brain MRI phenotype with mainly WMHs and atrophy showed a large increased risk (HR 6.18, 95% CI 3.37-11.32). DISCUSSION: Distinct brain MRI phenotypes can be identified in community-dwelling older adults. Our results indicate that distinct brain MRI phenotypes are related to varying long-term risks of developing dementia. Brain MRI phenotypes may in the future assist in an improved understanding of the structural correlates of dementia predisposition.


Assuntos
Demência , Substância Branca , Humanos , Idoso , Encéfalo/patologia , Vida Independente , Imageamento por Ressonância Magnética , Demência/epidemiologia , Fenótipo , Atrofia/patologia , Substância Branca/patologia
7.
Invest Ophthalmol Vis Sci ; 65(3): 18, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38470327

RESUMO

Purpose: To explore the occurrence of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)-associated Type 3 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Importantly, we aimed at describing the existence of separate pathways leading to MA. Methods: We analyzed 41 participants (41 eyes) with treatment-naïve Type 3 MNV who were followed up for a duration of 12 months after beginning the anti-VEGF therapy. At the one-year follow-up visit, optical coherence tomography (OCT) scans were reviewed for the presence of MA. MA regions of interest (ROIs) were selected and traced back to their original dominant baseline lesion (i.e., precursor) through previous serially captured OCT scans. Baseline lesions included precursors associated with the development and exudation of MNV and causes external to the neovascularization itself. Results: At the one-year follow-up visit, MA was graded to be present in 38 (92.7%) out of 41 eyes. These 78 MA ROIs were divided into two subgroups according to the precursor lesion, yielding a group of 53 MA lesions with precursors associated with the development and exudation of MNV (i.e., MA caused by physical harm from Type 3 neovessels, collapse of a serous pigment epithelium detachment, and fibrosis) and 25 MA regions with precursors external to the neovascularization itself (i.e., MA caused by drusen or subretinal drusenoid deposits). Conclusions: Eyes with Type 3 MNV are commonly complicated by MA and precursors of MA include causes associated with the development and exudation of MNV, as well as lesions unrelated to the neovascularization process itself.


Assuntos
Degeneração Macular , Descolamento Retiniano , Humanos , Degeneração Macular/complicações , Degeneração Macular/diagnóstico , Olho , Neovascularização Patológica , Atrofia
8.
BMC Nephrol ; 25(1): 93, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481159

RESUMO

BACKGROUND: Cerebral small vessel disease can be identified using magnetic resonance imaging, and includes white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and brain atrophy. Cerebral small vessel disease and chronic kidney disease share many risk factors, including hypertension. This study aims to explore an association between chronic kidney disease and cerebral small vessel disease, and also to explore the role of hypertension in this relationship. METHODS: With a cross sectional study design, data from 390 older adults was retrieved from the general population study Good Aging in Skåne. Chronic kidney disease was defined as glomerular filtration rate < 60 ml/min/1,73m2. Associations between chronic kidney disease and magnetic resonance imaging markers of cerebral small vessel disease were explored using logistic regression models adjusted for age and sex. In a secondary analysis, the same calculations were performed with the study sample stratified based on hypertension status. RESULTS: In the whole group, adjusted for age and sex, chronic kidney disease was not associated with any markers of cerebral small vessel disease. After stratification by hypertension status and adjusted for age and sex, we observed that chronic kidney disease was associated with cerebral microbleeds (OR 1.93, CI 1.04-3.59, p-value 0.037), as well as with cortical atrophy (OR 2.45, CI 1.34-4.48, p-value 0.004) only in the hypertensive group. In the non-hypertensive group, no associations were observed. CONCLUSIONS: In this exploratory cross-sectional study, we observed that chronic kidney disease was associated with markers of cerebral small vessel disease only in the hypertensive subgroup of a general population of older adults. This might indicate that hypertension is an important link between chronic kidney disease and cerebral small vessel disease. Further studies investigating the relationship between CKD, CSVD, and hypertension are warranted.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Hipertensão , Insuficiência Renal Crônica , Humanos , Idoso , Estudos Transversais , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Hipertensão/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Imageamento por Ressonância Magnética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Atrofia
9.
Neurology ; 102(7): e209172, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38478792

RESUMO

BACKGROUND AND OBJECTIVES: Epilepsy is 1 of the 3 most common neurologic diseases of older adults, but few studies have examined its underlying pathologies in older age. We examined the associations of age-related brain pathologies with epilepsy in older persons. METHODS: Clinical and pathologic data came from 2 ongoing clinical pathologic cohort studies of community-dwelling older adults. Epilepsy was ascertained using Medicare fee-for-service Parts A and B claims data that were linked to data from the cohort studies. The postmortem pathologic assessment collected indices of 9 pathologies including Alzheimer disease, hippocampal sclerosis, macroinfarcts, and cerebral amyloid angiopathy. The fixed brain hemisphere was imaged using 3T MRI scanners before the pathologic assessments in a subgroup of participants. RESULTS: The participants (n = 1,369) were on average 89.3 (6.6) years at death, and 67.0% were women. Epilepsy was identified in 58 (4.2%) participants. Cerebral amyloid angiopathy (odds ratio [OR] = 2.21, 95% CI 1.24-3.95, p = 0.007) and cortical macroinfarcts (OR = 2.74, 95% CI 1.42-5.28, p = 0.003) were associated with a higher odds of epilepsy. Of note, hippocampal sclerosis and Alzheimer disease pathology were not associated with epilepsy (both p's > 0.25), although hippocampal sclerosis was not common and thus hard to examine with the modest number of epilepsy cases here. In 673 participants with MRI data, the association of cerebral amyloid angiopathy and cortical macroinfarcts with epilepsy did not change after controlling for cortical gray matter atrophy, which was independently associated with a higher odds of epilepsy (OR = 1.06, 95% CI 1.02-1.10, p = 0.003). By contrast, hippocampal volume was not associated with epilepsy. DISCUSSION: Cerebrovascular pathologies and cortical atrophy were associated with epilepsy in older persons.


Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Epilepsia , Esclerose Hipocampal , Estados Unidos/epidemiologia , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Medicare , Angiopatia Amiloide Cerebral/patologia , Autopsia , Epilepsia/diagnóstico por imagem , Epilepsia/epidemiologia , Epilepsia/patologia , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
10.
Nat Commun ; 15(1): 2221, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472252

RESUMO

Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication - a necessary step for precise medicine.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Inteligência Artificial , Estudos Transversais , Encéfalo , Hipocampo/patologia , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina , Atrofia/patologia
11.
Int J Med Sci ; 21(4): 674-680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464822

RESUMO

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.


Assuntos
Glomerulonefrite por IGA , Masculino , Humanos , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/complicações , Cistatina C , Nomogramas , Creatinina , Estudos Transversais , Fibrose , Atrofia/complicações , Estudos Retrospectivos , Rim/patologia
12.
Physiol Res ; 73(1): 9-25, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466001

RESUMO

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.


Assuntos
Transplante de Coração , Coração , Feminino , Masculino , Animais , Ratos , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Ventrículos do Coração/patologia , Atrofia/patologia , Hormônios Esteroides Gonadais , Miocárdio/patologia
13.
Transl Vis Sci Technol ; 13(3): 1, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427349

RESUMO

Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression. Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc. Results: The mean follow-up duration was 4.4 ± 1.4 years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association). Conclusions: Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression. Translational Relevance: Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.


Assuntos
Glaucoma , Pressão Intraocular , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Progressão da Doença , Células Ganglionares da Retina/patologia , Glaucoma/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Atrofia/patologia
14.
Sci Rep ; 14(1): 5281, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438548

RESUMO

Although medial temporal atrophy (MTA) and parietal atrophy (Koedam score) have been used to diagnose Alzheimer's disease (AD), early detection of other dementia types remains elusive. The study aims to investigate the association between these brain imaging markers and cognitive function in dementia. This cross-sectional study collected data from the Memory Clinic of Dr. Sardjito General Hospital Yogyakarta, Indonesia from January 2020 until December 2022. The cut-off value of MTA and Koedam score was set with Receiver Operating Curve. Multivariate analysis was performed to investigate the association between MTA and Koedam score with cognitive function. Of 61 patients, 22.95% had probable AD, 59.01% vascular dementia, and 18.03% mixed dementia. Correlation test showed that MTA and Koedam score were negatively associated with Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) score. MTA score ≥ 3 (AUC 0.69) and Koedam score ≥ 2 (AUC 0.67) were independently associated with higher risk of poor cognitive function (OR 13.54, 95% CI 1.77-103.43, p = 0.01 and OR 5.52, 95% CI 1.08-28.19, p = 0.04). Higher MTA and Koedam score indicate worse cognitive function in dementia. Future study is needed to delineate these findings as prognostic markers of dementia severity.


Assuntos
Doença de Alzheimer , Cognição , Humanos , Estudos Transversais , Encéfalo , Doença de Alzheimer/diagnóstico , Atrofia
15.
Compend Contin Educ Dent ; 45(3): 147-150, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460139

RESUMO

The lateralization of the inferior alveolar nerve, or LIAN procedure, may be a surgical consideration for implant-prosthetic rehabilitation in the edentulous mandibular posterior region. This technique can be advantageous in that it does not require a donor site and allows for the immediate placement of an implant, potentially leading to reduced morbidity, healing time, and costs. Although such risks as altered sensory nerve function and weakening of the mandibular body are associated with the LIAN procedure, it is a viable alternative to various regenerative techniques to rehabilitate a patient with an implant-supported fixed prosthesis.


Assuntos
Implantação Dentária Endóssea , Implantes Dentários , Humanos , Implantação Dentária Endóssea/métodos , Mandíbula/cirurgia , Mandíbula/patologia , Nervo Mandibular/cirurgia , Atrofia/patologia
16.
BMJ ; 384: e076981, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453186

Assuntos
Face , Humanos , Atrofia
17.
Lasers Med Sci ; 39(1): 89, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453744

RESUMO

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.


Assuntos
Acne Vulgar , Lasers de Gás , Masculino , Feminino , Humanos , Cicatriz/patologia , Dióxido de Carbono , Resultado do Tratamento , Acne Vulgar/complicações , Eritema/etiologia , Lasers de Gás/uso terapêutico , Atrofia/complicações
18.
Mol Biol Rep ; 51(1): 396, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453810

RESUMO

Vulvar lichen sclerosus (VLS) is a chronic non-neoplastic skin lesion characterized by vulvar itching, pain, atrophy, whitening of the skin and mucous membranes, and gradual atrophy and disappearance of the labia minora, which can eventually lead to vulvar scarring, causing functional impairment and seriously affecting the patient's physical and mental health. VLS can occur at any age, however, its pathogenesis and etiology are not fully understood. Considerable progress has been made in related research on genetic susceptibility factors, autoimmune disorders, collagen metabolism abnormalities, and their triggering factors in disease formation and progression. This article reviews the etiology of vulvar lichen sclerosus.


Assuntos
Doenças Autoimunes , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Atrofia , Dor
19.
J Long Term Eff Med Implants ; 34(3): 27-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505891

RESUMO

Ramus frame dental implants were retrospectively studied in 360 adults with severely atrophic edentulous mandibles. Patient records up to 12 years post-treatment were independently reviewed after a single clinician surgically placed titanium long-arm ("Tatum") ramus frame implants and immediately loaded them with a mandibular overdenture. A total of 11 ramus frames were removed at 19 to 109 months post-treatment, mostly due to supramucosal bar fracture (N = 6) or mobility (N = 3). Kaplan-Meier product-limit analysis revealed the post-treatment survival probability for functional ramus frame implants to be 99.3% at 2 years (266 patients), 98.9% at 3 years (223 patients), 97.9% at 4 years (198 patients), 96.9% at 5 years (160 patients), 96.9% at 6 years (123 patients), 95.0% at 7 years (86 patients), 95.0% at 8 years (67 patients), 93.3% at 9 years (43 patients), and 91.1% at 10 years (25 patients). No statistically significant differences in functional ramus frame implant survival were found relative to patient gender, smoking, presence of natural maxillary teeth, or compliance with semi-annual maintenance care. Fracture of endosseous anterior feet/posterior arms was the most frequent implant-related complication on 29 implants, which were left in place, repaired, or replaced in situ without implant removal. At 5 years, the ramus frame implant functional survival probability without any implant-related biological or mechanical complication was 88.9%. Ramus frame dental implants, immediately loaded with a fully implant-borne mandibular overdenture, exhibited a high degree of long-term functional survival and safety in severely atrophic edentulous human mandibles.


Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários , Adulto , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias , Mandíbula/cirurgia , Atrofia/patologia , Implantação Dentária Endóssea , Planejamento de Prótese Dentária , Resultado do Tratamento , Seguimentos
20.
Neurology ; 102(7): e209183, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38489566

RESUMO

BACKGROUND AND OBJECTIVES: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and clinically impaired older adults who underwent detailed lifetime head trauma characterization. METHODS: This is an observational cohort study of University of California, San Francisco Memory and Aging Center participants (healthy controls [HCs], those with Alzheimer disease or related dementias [ADRDs], subset with traumatic encephalopathy syndrome [TES]). We characterized traumatic brain injury (TBI) and repetitive head impacts (RHI) through contact/collision sports. Study groups were no RHI/TBI, prior TBI only, prior RHI only, and prior RHI + TBI. We additionally looked within TBI (1, 2, or 3+) and RHI (1-4, 5-10, and 11+ years). All underwent baseline MRI, and 67% completed a second MRI (median follow-up = 5.4 years). CSP measures included grade (0-4) and length (millimeters). Groups were compared on likelihood of CSP (logistic regression, odds ratios [ORs]) and whether CSP length discriminated groups (area under the curve [AUC]). RESULTS: Our sample included 266 participants (N = 160 HCs, N = 106 with ADRD or TES; age 66.8 ± 8.2 years, 45.3% female). Overall, 123 (49.8%) participants had no RHI/TBI, 52 (21.1%) had TBI only, 41 (16.6%) had RHI only, 31 (12.6%) had RHI + TBI, and 20 were classified as those with TES (7.5%). Compared with no RHI/TBI, RHI + TBI (OR 3.11 [1.23-7.88]) and TES (OR 11.6 [2.46-54.8]) had greater odds of CSP. Approximately 5-10 years (OR 2.96 [1.13-7.77]) and 11+ years of RHI (OR 3.14 [1.06-9.31]) had higher odds of CSP. CSP length modestly discriminated participants with 5-10 years (AUC 0.63 [0.51-0.75]) and 11+ years of prior RHI (AUC 0.69 [0.55-0.84]) from no RHI/TBI (cut point = 6 mm). Strongest effects were noted in analyses of American football participation. Longitudinally, CSP grade was unchanged in 165 (91.7%), and length was unchanged in 171 (95.5%) participants. DISCUSSION: Among older adults with and without neurodegenerative disease, risk of CSP is driven more by duration (years) of RHI, especially American football, than number of TBI. CSP length (≥6 mm) is relatively specific to individuals who have had substantial prior RHI. Neurodegenerative disease and progressive atrophy do not clearly influence development or worsening of CSP.


Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Traumatismos Craniocerebrais , Futebol Americano , Doenças Neurodegenerativas , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Septo Pelúcido/diagnóstico por imagem , Septo Pelúcido/patologia , Doenças Neurodegenerativas/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Atrofia/patologia
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