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1.
Skin Therapy Lett ; 29(4): 1-4, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38963911

RESUMO

Acne vulgaris is a common, often chronic inflammatory disease that can affect all ages and skin tones. Beyond acute lesions, the sequelae of acne - specifically scarring and dyspigmentation - can be long-lasting, challenging to treat and have substantial psychosocial impact on affected individuals. For acne scarring, treatment modalities include topical, physical, and laser and light therapies, with combination approaches typically yielding optimal outcomes. Trifarotene is a novel fourth generation retinoid with targeted action towards retinoid acid receptor gamma (RAR-γ), the most common isotype found in the epidermis, that has previously been approved for the management of moderate-to-severe facial and truncal acne in individuals over the age of 12 years. Recently, data on trifarotene supports its application in acne scarring. Herein, we provide a succinct review on various treatments for acne scarring and explore how trifarotene and its mechanism of action present an additional topical approach to target atrophic acne scarring.


Assuntos
Acne Vulgar , Cicatriz , Retinoides , Humanos , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Retinoides/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Atrofia , Administração Cutânea
2.
BMJ Open Ophthalmol ; 9(1)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981710

RESUMO

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.


Assuntos
Degeneração Macular , Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Testes de Campo Visual , Humanos , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Estudos Transversais , Degeneração Macular/patologia , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Feminino , Masculino , Idoso , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual/métodos , Acuidade Visual/fisiologia , Idoso de 80 Anos ou mais , Campos Visuais/fisiologia , Oftalmoscopia/métodos , Atrofia/patologia
3.
Alzheimers Res Ther ; 16(1): 153, 2024 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970077

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the 'severity index' generated using a standard classification model trained on patients with AD dementia versus a new model trained on ß-amyloid (Aß) positive patients with amnestic mild cognitive impairment (aMCI). METHODS: We used structural MRI data of 504 patients from the Swedish BioFINDER-1 study cohort (cognitively normal (CN), Aß-negative = 220; SCD, Aß positive and negative = 139; aMCI, Aß-positive = 106; AD dementia = 39). We applied multivariate data analysis to create two predictive models trained to discriminate CN individuals from either individuals with Aß positive aMCI or AD dementia. Models were applied to individuals with SCD to classify their atrophy patterns as either high-risk "disease-like" or low-risk "CN-like". Clinical trajectory and model accuracy were evaluated using 8 years of longitudinal data. RESULTS: In predicting progression from SCD to MCI or dementia, the standard, dementia-based model, reached 100% specificity but only 10.6% sensitivity, while the new, aMCI-based model, reached 72.3% sensitivity and 60.9% specificity. The aMCI-based model was superior in predicting progression from SCD to MCI or dementia, reaching a higher receiver operating characteristic area under curve (AUC = 0.72; P = 0.037) in comparison with the dementia-based model (AUC = 0.57). CONCLUSION: When predicting conversion from SCD to MCI or dementia using structural MRI data, prediction models based on individuals with milder levels of atrophy (i.e. aMCI) may offer superior clinical value compared to standard dementia-based models.


Assuntos
Atrofia , Encéfalo , Disfunção Cognitiva , Demência , Progressão da Doença , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Atrofia/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/diagnóstico , Idoso , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Demência/diagnóstico por imagem , Demência/patologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de Coortes , Testes Neuropsicológicos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia
4.
Zhonghua Nei Ke Za Zhi ; 63(7): 666-673, 2024 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-38951090

RESUMO

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.


Assuntos
Atrofia , Cognição , Disfunção Cognitiva , Substância Cinzenta , Imageamento por Ressonância Magnética , Esclerose Múltipla , Humanos , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Estudos Transversais , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Disfunção Cognitiva/etiologia , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Testes Neuropsicológicos , Masculino , Feminino
5.
BMC Neurol ; 24(1): 235, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969967

RESUMO

BACKGROUND: Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice. METHODS: We investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS). RESULTS: All participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate. CONCLUSION: We demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.


Assuntos
Neuroimagem , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neuroimagem/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Atrofia/patologia , Circulação Cerebrovascular/fisiologia , Espectroscopia de Ressonância Magnética/métodos
6.
Hum Brain Mapp ; 45(10): e26715, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994693

RESUMO

Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.


Assuntos
Atrofia , Demência , Hipocampo , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Atrofia/patologia , Demência/diagnóstico por imagem , Demência/patologia , Masculino , Idoso , Feminino , Processamento de Imagem Assistida por Computador/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
7.
J Headache Pain ; 25(1): 93, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840235

RESUMO

BACKGROUND: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). METHODS: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. RESULTS: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10- 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10- 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10- 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10- 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10- 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. DISCUSSION: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.


Assuntos
Atrofia , Encéfalo , Demência , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos de Enxaqueca , Humanos , Atrofia/patologia , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/patologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Demência/genética , Demência/epidemiologia , Demência/patologia , Demência/etiologia , Feminino , Estudos Longitudinais , Masculino
8.
Medicina (Kaunas) ; 60(6)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38929497

RESUMO

Background and Objectives: Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E is an important antioxidant diminishing the output of reactive oxygen species in the oxidation of fats and the emanation of free radicals, reducing cellular injury and aging. The primary aim of the present study was to assess the positive effects of an ozonide plus a vitamin E acetate-based compound (Ozoile) on genitourinary syndrome symptom relief after a maximum of 20 days of treatment. Materials and Methods: The inclusion criteria for patients' enrollment were women of child-bearing age or in menopause reporting genitourinary syndrome's related symptoms, such as pain, burning, a bad smell, dyspareunia, dryness, itching, bleeding, and nervousness. The exclusion criteria were Sjogren's syndrome and patients administered retinoic acid, an agent that causes mucosal dryness. Participants completed a questionnaire before and after 20 days of treatment. Results: The incidence of pain decreased from 16.7% to 11.8% (p-value < 0.0001). In addition, the mean symptom intensity decreased from 2.10 to 0.87 (p-value < 0.0001). Dryness was the most frequent pre-treatment symptom and decreased from 85.5% to 53.8% (p-value < 0.0001) (mean: 2.21 vs. 0.90; p-value < 0.0001). Conclusions: Ozoile was effective in reducing most gynecologic symptoms related to genitourinary syndrome. However, further studies are needed to compare its effect with other standards of care.


Assuntos
Vitamina E , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Síndrome , Vitamina E/uso terapêutico , Vitamina E/administração & dosagem , Antioxidantes/uso terapêutico , Antioxidantes/administração & dosagem , Doenças Urogenitais Femininas/tratamento farmacológico , Atrofia/tratamento farmacológico , Idoso , Inquéritos e Questionários , Resultado do Tratamento
9.
Neurology ; 103(1): e209561, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38833636

RESUMO

Hand weakness is a frequent chief concern in neurology practice. We report a case of a 55-year-old woman presenting with a chronic, gradually worsening right hand weakness and atrophy, selectively affecting the thenar muscles, without any sensory symptoms. She had a history of carpal tunnel syndrome and previously underwent surgical carpal tunnel release. This case delves into the differential diagnosis of hand weakness and atrophy, emphasizing the significance of myotomal innervation in intrinsic hand muscles. Furthermore, it outlines a systematic approach to diagnosing an uncommon cause for a common clinical presentation, offering a comprehensive differential diagnosis, and exploring various possible causes.


Assuntos
Mãos , Debilidade Muscular , Humanos , Feminino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/diagnóstico , Raciocínio Clínico , Diagnóstico Diferencial , Atrofia Muscular/etiologia , Atrofia Muscular/diagnóstico , Atrofia , Síndrome do Túnel Carpal/diagnóstico
10.
J Aging Stud ; 69: 101226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834246

RESUMO

BACKGROUND: Supporting ageing in place, quality of life and activity engagement are public health priorities for people living with dementia, but little is known about the needs and experiences of community-dwelling people with rarer forms of dementia with lesser known symptoms. Posterior cortical atrophy (PCA) is a rare form of dementia usually caused by Alzheimer's disease but which is characterised by diminished visual processing (rather than a dominant memory problem), which poses challenges for maintaining independence and accessing appropriate support. METHODS: This study used a comparative qualitative design and focussed ethnographic methods to explore experiential differences in activity engagement for 10 people with the most common, memory-led presentation of Alzheimer's disease and 10 people with posterior cortical atrophy within their everyday home environments. RESULTS: While the data collection revealed much rich variation in individual and contextual factors, some tentative high-level differences in the experiences of everyday activities could be drawn out, seemingly attributable to the different diagnoses' differing dominant symptoms. These included people with posterior cortical atrophy being less likely to use environmental cues to initiate activities, and more likely to withhold from asking for support because of preserved insight into the impact of this on carers. This lack of initiation of activities could be misinterpreted as apathy. People with posterior cortical atrophy also were discouraged from engaging in activities by disorientation within the home, and difficulties localising, identifying and manipulating objects. People with the more common, memory-led presentation of Alzheimer's disease exhibited more memory-based difficulties with engaging with activities such as forgetting planned activities, where to locate the items required for an activity and the steps involved. Despite these distinct symptom-led challenges, all participants and their family members demonstrated resourcefulness and resilience in making creative adaptations to support continued engagement in everyday activities, supporting the widely reported management strategies of people with dementia of the Alzheimer's type more generally. CONCLUSIONS: These findings offer helpful insights into some the differing impacts dementia related visual and memory impairments can have on everyday activity engagement, which will be helpful for others navigating these challenges and the health and social care practitioners working with people affected by these conditions. The findings also highlight the vast individual variation in the multitude of individual and contextual factors involved in everyday activity engagement, and suggest important areas for future work utilising methods which are similarly high in ecological validity and accessibility as the home-based focussed ethnographic methods utilised here.


Assuntos
Atividades Cotidianas , Doença de Alzheimer , Antropologia Cultural , Atrofia , Humanos , Doença de Alzheimer/psicologia , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Pesquisa Qualitativa , Qualidade de Vida/psicologia , Córtex Cerebral/patologia , Vida Independente
11.
Int J Rheum Dis ; 27(6): e15210, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837302

RESUMO

INTRODUCTION: The relevance of tubulo-interstitial involvement for kidney prognosis has recently been emphasized, but validated biomarkers for predicting histology are still lacking. The aim of our study was to evaluate different serum and urinary markers of tubular damage in patients with lupus nephritis (LN) and to correlate them with kidney histopathology. METHODS: A single-center retrospective study was conducted from January 2016 to December 2021. Serum and urine samples were collected on the same day of kidney biopsy and correlated with histologic data from a cohort of 15 LN patients. We analyzed the following urinary markers, adjusted for urine creatinine: beta 2-microglobulin, alpha 1-microglobulin, NGAL, uKIM-1, MCP-1, uDKK-3, and uUMOD. The serum markers sKIM-1 and sUMOD were also analyzed. RESULTS: A positive and strong correlation was observed between the degree of interstitial fibrosis (rho = 0.785, p = .001) and tubular atrophy (rho = 0.781, p = .001) and the levels of uDKK3. uUMOD also showed an inverse and moderate correlation with interstitial fibrosis (rho = -0.562, p = .037) and tubular atrophy (rho = -0.694, p = .006). Patients with >10% cortical interstitial inflammation had higher levels of uKIM-1 [4.9 (3.9, 5.5) vs. 0.8 (0.6, 1.5) mcg/mg, p = .001], MCP-1 [3.8 (2. 3, 4.2) vs. 0.7 (0.3, 1.2) mcg/mg, p = .001], sKIM-1 [9.2 (5.9, 32.7) vs. 1.4 (0, 3.5) pg/mL, p = .001], and lower sUMOD [8.7 (0, 39.7) vs. 46.1 (35.7, 53) ng/mL, p = .028]. CONCLUSION: The use of specific urinary and serum biomarkers of tubular dysfunction or injury may help to predict certain histologic parameters in LN patients.


Assuntos
Biomarcadores , Túbulos Renais , Nefrite Lúpica , Humanos , Nefrite Lúpica/urina , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Nefrite Lúpica/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Masculino , Estudos Retrospectivos , Adulto , Túbulos Renais/patologia , Biópsia , Valor Preditivo dos Testes , Pessoa de Meia-Idade , Fibrose , Atrofia , Adulto Jovem
12.
Mult Scler Relat Disord ; 87: 105688, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824793

RESUMO

OBJECTIVES: Gradual expansion of multiple sclerosis lesions over time is known to have a significant impact on disease progression. However, accurately quantifying the volume changes in chronic lesions presents challenges due to their slow rate of progression and the need for longitudinal segmentation. Our study addresses this by estimating the expansion of chronic lesions using data collected over a 1-2 year period and exploring imaging markers that do not require longitudinal lesion segmentation. METHODS: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 42 patients with MS. Lesion expansion, stratified by the severity of tissue damage as measured by mean diffusivity change, was analysed between baseline and 48 months (Progressive Volume/Severity Index, PVSI). Central brain atrophy (CBA) and the degree of tissue loss inside chronic lesions (measured by the change of T1 intensity and mean diffusivity (MD)) were used as surrogate markers. RESULTS: CBA measured after 2 years of follow-up estimated lesion expansion at 4 years with a high degree of accuracy (r = 0.82, p < 0.001, ROC area under the curve 0.92, sensitivity of 94 %, specificity of 85 %). Increased MD within chronic lesions measured over 2 years was strongly associated with future expansion (r = 0.77, p < 0.001, ROC area under the curve 0.87, sensitivity of 81 % and specificity of 81 %). In contrast, change in lesion T1 hypointensity poorly explained future PVSI (best sensitivity and specificity 60 % and 59 % respectively). INTERPRETATION: CBA and, to a lesser extent, the change in MD within chronic MS lesions, measured over a period of 2 years, can provide a reliable and sensitive estimate of the extent and severity of chronic lesion expansion.


Assuntos
Encéfalo , Imagem de Tensor de Difusão , Progressão da Doença , Esclerose Múltipla , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Longitudinais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Imageamento por Ressonância Magnética , Atrofia/patologia , Índice de Gravidade de Doença
13.
J Pharmacol Sci ; 155(4): 121-130, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880546

RESUMO

The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H2S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H2S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.


Assuntos
Sulfeto de Hidrogênio , Miócitos Cardíacos , Sulfetos , Remodelação Ventricular , Animais , Miócitos Cardíacos/metabolismo , Sulfetos/metabolismo , Sulfetos/farmacologia , Sulfeto de Hidrogênio/metabolismo , Células Cultivadas , Trifosfato de Adenosina/metabolismo , Ratos , Atrofia , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Animais Recém-Nascidos , Ratos Sprague-Dawley
14.
Transl Psychiatry ; 14(1): 250, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858380

RESUMO

The etiopathogenesis of late-onset Alzheimer's disease (AD) is increasingly recognized as the result of the combination of the aging process, toxic proteins, brain dysmetabolism, and genetic risks. Although the role of mitochondrial dysfunction in the pathogenesis of AD has been well-appreciated, the interaction between mitochondrial function and genetic variability in promoting dementia is still poorly understood. In this study, by tissue-specific transcriptome-wide association study (TWAS) and further meta-analysis, we examined the genetic association between mitochondrial solute carrier family (SLC25) genes and AD in three independent cohorts and identified three AD-susceptibility genes, including SLC25A10, SLC25A17, and SLC25A22. Integrative analysis using neuroimaging data and hippocampal TWAS-predicted gene expression of the three susceptibility genes showed an inverse correlation of SLC25A22 with hippocampal atrophy rate in AD patients, which outweighed the impacts of sex, age, and apolipoprotein E4 (ApoE4). Furthermore, SLC25A22 downregulation demonstrated an association with AD onset, as compared with the other two transcriptome-wide significant genes. Pathway and network analysis related hippocampal SLC25A22 downregulation to defects in neuronal function and development, echoing the enrichment of SLC25A22 expression in human glutamatergic neurons. The most parsimonious interpretation of the results is that we have identified AD-susceptibility genes in the SLC25 family through the prediction of hippocampal gene expression. Moreover, our findings mechanistically yield insight into the mitochondrial cascade hypothesis of AD and pave the way for the future development of diagnostic tools for the early prevention of AD from a perspective of precision medicine by targeting the mitochondria-related genes.


Assuntos
Doença de Alzheimer , Hipocampo , Transcriptoma , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Masculino , Feminino , Idoso , Predisposição Genética para Doença , Mitocôndrias/metabolismo , Mitocôndrias/genética , Estudo de Associação Genômica Ampla , Idoso de 80 Anos ou mais , Proteínas de Transporte da Membrana Mitocondrial/genética , Atrofia/genética
15.
Neurol Neuroimmunol Neuroinflamm ; 11(5): e200265, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38917380

RESUMO

BACKGROUND AND OBJECTIVES: To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS). METHODS: CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs. RESULTS: The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model. DISCUSSION: These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.


Assuntos
Atrofia , Córtex Cerebral , Esclerose Múltipla Recidivante-Remitente , Osteopontina , Humanos , Osteopontina/líquido cefalorraquidiano , Feminino , Masculino , Adulto , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Atrofia/patologia , Pessoa de Meia-Idade , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Biomarcadores/líquido cefalorraquidiano , Seguimentos , Adulto Jovem , Progressão da Doença
16.
J Biophotonics ; 17(7): e202400095, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850248

RESUMO

Prevention and treatment protocols for taste changes observed during hematopoietic cell transplantation (HCT) are not well-established. The purpose of this study was to assess the efficacy of photobiomodulation (PBM) in relieving taste changes and preventing lingual papillae atrophy. HCT patients received PBM (n = 42) on the tongue dorsum using an InGaAIP laser (660 nm, 100 mW, 1.1 W/cm2, 8.8 J/cm2). During the HCT conditioning (T0), severe neutropenia (T1), and after neutrophil engraftment (T2), taste acuity for sweet, bitter, sour, and salty solutions, and clinical appearance of lingual papillae were compared with those of a placebo group (n = 43). PBM significantly reduced hypogeusia, ageusia, and parageusia at T1 and T2, and also successfully prevented papillae atrophy during all the analyzed HCT periods. In conclusion, PBM enhanced taste acuity during HCT. The decrease in papillae atrophy indicated a potential regenerative effect of this therapy on tongue mucosa.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Terapia com Luz de Baixa Intensidade , Paladar , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Paladar/efeitos da radiação , Língua/efeitos da radiação , Língua/patologia , Atrofia , Distúrbios do Paladar/etiologia , Adulto Jovem , Idoso , Papilas Gustativas/efeitos da radiação
17.
Acta Neuropathol Commun ; 12(1): 109, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943220

RESUMO

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.


Assuntos
Amiloidose , Atrofia , Disfunção Cognitiva , Hipocampo , Humanos , Masculino , Feminino , Idoso , Disfunção Cognitiva/patologia , Disfunção Cognitiva/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Atrofia/patologia , Amiloidose/patologia , Amiloidose/diagnóstico por imagem , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Pessoa de Meia-Idade , Placa Amiloide/patologia , Placa Amiloide/diagnóstico por imagem , Doenças Retinianas/patologia , Doenças Retinianas/diagnóstico por imagem , Vasos Retinianos/patologia , Vasos Retinianos/diagnóstico por imagem , Oftalmoscopia/métodos
18.
Acta Vet Hung ; 72(2): 80-98, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38916958

RESUMO

The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG).The study was performed on 13 mixed breed dogs affected by retinal atrophy (11 males and 2 females that were 1.5-14 years old). Depending on the advancement of RA, SD-OCT examinations identified retinal abnormalities ranging from layer disorganisation to advanced atrophy. The most advanced RA occurred ventral to the optic disc. Total retinal thickness in both eyes (mean ± SD) was lower in dogs with RA compared to controls dorsally (77.7 ± 39.5 µm vs 173.5 ± 13.3 µm), ventrally (33.4 ± 29.9 µm vs 139.5 ± 10.8 µm), nasally (65.0 ± 34.5 µm vs 163.9 ± 11.0 µm) and temporally (61.8 ± 41.7 µm vs 171.9 ± 11.1 µm) to the optic disc. In dogs with locally normal architecture of inner retina, loss of definition of outer retinal layers occurred in many regions. Dark and light-adapted ERGs were reduced in 2 dogs with RA and were unrecordable in 11 dogs. Lesions evident in SD-OCT scans of mixed breed dogs affected with retinal atrophy initially appear ventrally to the optic disc and ventro-dorsally in advanced RA. In all mixed breed dogs with retinal atrophy, clinical signs and SD-OCT results correlate with ERG findings.


Assuntos
Doenças do Cão , Eletrorretinografia , Tomografia de Coerência Óptica , Animais , Cães , Tomografia de Coerência Óptica/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Feminino , Eletrorretinografia/veterinária , Masculino , Retina/diagnóstico por imagem , Retina/patologia , Doenças Retinianas/veterinária , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/patologia , Atrofia/veterinária
19.
Int J Mol Sci ; 25(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38891978

RESUMO

Binge alcohol consumption during adolescence can produce lasting deficits in learning and memory while also increasing the susceptibility to substance use disorders. The adolescent intermittent ethanol (AIE) rodent model mimics human adolescent binge drinking and has identified the nucleus basalis magnocellularis (NbM) as a key site of pathology. The NbM is a critical regulator of prefrontal cortical (PFC) cholinergic function and attention. The cholinergic phenotype is controlled pro/mature neurotrophin receptor activation. We sought to determine if p75NTR activity contributes to the loss of cholinergic phenotype in AIE by using a p75NTR modulator (LM11A-31) to inhibit prodegenerative signaling during ethanol exposure. Male and female rats underwent 5 g/kg ethanol (AIE) or water (CON) exposure following 2-day-on 2-day-off cycles from postnatal day 25-57. A subset of these groups also received a protective dose of LM11A-31 (50 mg/kg) during adolescence. Rats were trained on a sustained attention task (SAT) and behaviorally relevant acetylcholine (ACh) activity was recorded in the PFC with a fluorescent indicator (AChGRAB 3.0). AIE produced learning deficits on the SAT, which were spared with LM11A-31. In addition, PFC ACh activity was blunted by AIE, which LM11A-31 corrected. Investigation of NbM ChAT+ and TrkA+ neuronal expression found that AIE led to a reduction of ChAT+TrkA+ neurons, which again LM11A-31 protected. Taken together, these findings demonstrate the p75NTR activity during AIE treatment is a key regulator of cholinergic degeneration.


Assuntos
Acetilcolina , Neurônios Colinérgicos , Etanol , Córtex Pré-Frontal , Animais , Feminino , Masculino , Ratos , Acetilcolina/metabolismo , Atrofia , Comportamento Animal/efeitos dos fármacos , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/efeitos dos fármacos , Modelos Animais de Doenças , Etanol/toxicidade , Proteínas do Tecido Nervoso , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento , Receptores de Fator de Crescimento Neural/metabolismo
20.
J Neurol Sci ; 462: 123113, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38941706

RESUMO

BACKGROUND: Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). METHODS: Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. RESULTS: The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. CONCLUSIONS: The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.


Assuntos
Doença de Alzheimer , Córtex Cerebral , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Masculino , Feminino , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/etiologia , Idoso , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Idoso de 80 Anos ou mais , Tamanho do Órgão , Seguimentos , Pessoa de Meia-Idade , Progressão da Doença , Atrofia/patologia
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