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1.
World J Orthop ; 12(10): 751-759, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34754831

RESUMO

BACKGROUND: From February 2020 onwards, our country has been hit by the coronavirus severe acute respiratory syndrome-2 (SARS-CoV-2) infection. At a glance, hospitals became overrun and had to reformulate all the assistance guidelines, focusing on the coronavirus disease 2019. One year after the start of the pandemic, we present the results of a morbimortality study. AIM: To analyze how our department was affected by the outbreak in terms of morbimortality, and to analyze demographic data, admission to hospital-related data, and subgroups analyses for patients with hip fractures and polytrauma. METHODS: We designed a study comparing data from patients who were admitted to our unit due to a lower limb fracture or a high energy trauma during the pandemic (from March to April 2020) to those admitted during the same period in 2019 before the pandemic. during the pandemic situation. Both cohorts completed a minimum of 6 mo of follow-up. RESULTS: The number of patients admitted to hospital in 2020 was nearly half of those in 2019. Hip fractures in the elderly represented 52 out of 73 of the admitted patients. Twenty patients had a positive test result for SARS-CoV-2 infection. Patients with SARS-CoV-2 infection were admitted to the hospital for a longer time than the non-infected (P < 0.001), and had a higher mortality rate during hospitalization and follow-up (P = 0.02). Patients with a hip fracture associated with a severe respiratory syndrome were mostly selected for conservative treatment (P = 0.03). CONCLUSION: Mortality and readmission rates were higher in the 2020 cohort and during follow-up, in comparison with the cohort in 2019.

2.
Sci Rep ; 11(1): 20928, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686732

RESUMO

Gender significantly influences sociodemographic, medical, psychiatric and addiction variables in cocaine outpatients. Educational level may be a protective factor showing less severe addictive disorders, longer abstinence periods, and better cognitive performance. The aim was to estimate gender-based differences and the influence of educational level on the clinical variables associated with cocaine use disorder (CUD). A total of 300 cocaine-consuming patients undergoing treatments were recruited and assessed using the Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Women developed CUD later but exhibited more consumption of anxiolytics, prevalence of anxiety disorders, eating disorders, and major depressive disorders. Alcohol and cannabis use disorders were more frequent in men. A predictive model was created and identified three psychiatric variables with good prognosis for distinguishing between women and men. Principal component analysis helped to describe the different profile types of men and women who had sought treatment. Low educational levels seemed to be a risk factor for the onset, development, and duration of CUD in both genders. Women and men exhibited different clinical characteristics that should be taken into account when designing therapeutic policies. The educational level plays a protective/risk role in the onset, development and progression of CUD, thus prolonging the years of compulsory education and implementing cognitive rehabilitation programmes could be useful.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34695542

RESUMO

BACKGROUND: Stressful episodes and high alcohol consumption during adolescence are considered major risk factors for the development of psychiatric disorders in adulthood. Identification of mechanisms underlying these early events, which enhanced vulnerability to mental illness, is essential for both their prevention and treatment. METHODS: Male Wistar rats were used to investigate the long-term effects of early restraint stress and intermittent alcohol exposure (intragastric administration of 3 g/kg ethanol; 4 days/week for 4 weeks during adolescence) on anxiety-like behavior and the expression of signaling systems associated with emotional behaviors [e.g., corticosterone, fatty acid-derived molecules and endocannabinoid enzymes, glutamate receptor subunits, corticotropin releasing hormone receptors (CRHR1 and CRHR2) and neuropeptide Y receptors (NPY1R and NPYR2)] in the blood and amygdala. RESULTS: Overall, both stress and alcohol exposure during adolescence induced anxiogenic-like behaviors, increased plasma levels of corticosterone and increases in the amygdalar expression of the cannabinoid CB2 receptor and certain subunits of glutamate receptors (i.e., mGluR1, mGluR5 and NMDAR1) in young adult rats. In addition, there were specific main effects of alcohol exposure on the expression of the cannabinoid CB1 receptor, monoacylglycerol lipase (MAGL) and NPY2R in the amygdala, and significant increases were observed in rats exposed to alcohol. Interestingly, there were significant interaction effects between restraint stress and alcohol exposure on the expression of plasma 2-arachidonoyl glycerol (2-AG), and both CRHR1,2 and NPY1R in the amygdala. Thus, the restraint stress was associated with increased 2-AG levels, which was not observed in rats exposed to alcohol. The alcohol exposure was associated with an increased expression of CRHR1,2 but the restraint stress prevented these increases (stress alcohol rats). In contrast, NPY1R was only increased in rats exposed to stress and alcohol. Finally, we did not observe any potentiation of the behavioral and molecular effects by the combination of stress and alcohol, which is concordant with an overall ceiling effect on some of the variables. CONCLUSION: Separate and combined early stress and alcohol induced a common anxious phenotype with increased corticosterone in adulthood. However, there were differences in the amygdalar expression of signaling systems involved in maladaptive changes in emotional behavior. Therefore, our results suggest the existence of partially different mechanisms for stress and alcohol exposures.

4.
Biomedicines ; 9(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34572393

RESUMO

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid and a bioactive lipid that is synthesized by the enzyme autotaxin (ATX). The ATX-LPA axis has been associated with cognitive dysfunction and inflammatory diseases, mainly in a range of nonalcoholic liver diseases. Recently, preclinical and clinical evidence has suggested a role of LPA signaling in alcohol use disorder (AUD) and AUD-related cognitive function. However, the ATX-LPA axis has not been sufficiently investigated in alcoholic liver diseases. An exploratory study was conducted in 136 participants, 66 abstinent patients with AUD seeking treatment for alcohol (alcohol group), and 70 healthy control subjects (control group). The alcohol group was divided according to the presence of comorbid liver diseases (i.e., fatty liver/steatosis, alcoholic steatohepatitis, or cirrhosis). All participants were clinically evaluated, and plasma concentrations of total LPA and ATX were measured using enzyme-linked immunosorbent assays. Data were primarily analyzed using analysis of covariance (ANCOVA) while controlling for age, body mass index, and sex. Logistic regression models were created to assess the association of the ATX-LPA axis and AUD or liver disease. LPA and ATX were log10-transformed to fit the assumptions of parametric testing.The main results were as follows: total LPA and ATX concentrations were dysregulated in the alcohol group, and patients with AUD had significantly lower LPA (F(1,131) = 10.677, p = 0.001) and higher ATX (F(1,131) = 8.327, p = 0.005) concentrations than control subjects; patients with AUD and liver disease had significantly higher ATX concentrations (post hoc test, p < 0.05) than patients with AUD but not liver disease; significant correlations between AUD-related variables and concentrations of LPA and ATX were only found in the non-liver disease subgroup (the duration of alcohol abstinence with LPA and ATX (r = +0.33, p < 0.05); and the severity of AUD with ATX (rho = -0.33, p < 0.05)); and a logistic regression model with LPA, ATX, and AUD-related variables showed an excellent discriminative power (area under the curve (AUC) = 0.915, p < 0.001) for distinguishing patients with AUD and comorbid liver disease. In conclusion, our data show that the ATX-LPA axis is dysregulated in AUD and suggest this lipid signaling, in combination with relevant AUD-related variables, as a reliable biomarker of alcoholic liver diseases.

5.
Interv Neuroradiol ; : 15910199211040279, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516326

RESUMO

PURPOSE: Wide-neck bifurcation aneurysms remain challenging for the neurointerventionist and/or neurosurgeon despite many recent advances. The pCONus (Phenox, Bochum, Germany) is an emerging device for endovascular neck protection, we report the first long-term results of this device. METHODS: We performed a retrospective analysis of all consecutive intracranial wide-neck bifurcation aneurysms treated with the pCONus. Patients' characteristics were reviewed, procedural complications, angiographic (Roy-Raymond scale) and clinical outcomes were documented. RESULTS: Between January 2016 and September 2019, 43 patients (74% female, median age 56 [49-66] years) with 43 wide-neck bifurcation aneurysms (mean width of 6.8 ± 2.1 mm, dome/neck ratio of 1.3 ± 0.2 and neck of 5.2 ± 1.3 mm) were included. A procedural angiographic complication was reported in five patients (12%), no patient presented a post-operative neurological deficit or long-term complication, mortality rate was 0%. At last follow-up (median of 46.5 months [38.3-51.7]), an adequate occlusion (complete and neck remnant) was observed in 37/43 patients (86%) and an aneurysm remnant in 6/43 (14%). Four patients (9%) needed retreatment. No in-stent stenosis or branch occlusion was depicted. CONCLUSION: pCONus device provides a safe and efficient alternative for endovascular wide-neck bifurcation aneurysms management, with long-term stability.

6.
Hip Int ; : 11207000211036320, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554849

RESUMO

BACKGROUND: The purpose of this study was to determine patient-reported outcome measures (PROMs) changes in: (1) pain, function and global health; and (2) predictors of PROMs in patients undergoing aseptic revision total hip arthroplasty (rTHA) using a multilevel model with patients nested within surgeon. METHODS: A prospective cohort of 216 patients with baseline and 1-year PROMs who underwent aseptic rTHA between January 2016 and December 2017 were analysed. The most common indication for rTHA was aseptic loosening, instability, and implant failure. The PROMs included in this study were HOOS Pain and HOOS Physical Function Short-form (PS), Veterans RAND-12 Physical Component Score (VR-12 PCS), and VR-12 Mental Component Score (MCS). Multivariable linear regression models were constructed for predicting 1-year PROMs. RESULTS: Mean 1-year PROMs improvement for aseptic revisions were 30.4 points for HOOS Pain and 22.1 points for HOOS PS. Predictors of better pain relief were patients with higher baseline pain scores. Predictors of better 1-year function were patients with higher baseline function and patients with a posterolateral hip surgical approach during revision. Although VR-12 PCS scores had an overall improvement, nearly 50% of patients saw no improvement or had worse physical component scores. Only 30.7% of patients reported improvements in VR-12 MCS. CONCLUSIONS: Overall, patients undergoing aseptic rTHA improved in pain and function PROMs at 1 year. Although global health assessment improved overall, nearly half of aseptic rTHA patients reported no change in physical/mental health status. The associations highlighted in this study can help guide the shared decision-making process by setting expectations before aseptic revision THA.

7.
Front Mol Biosci ; 8: 718301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490351

RESUMO

Proteins bearing prion-like domains (PrLDs) are essential players in stress granules (SG) assembly. Analysis of data on heat stress-induced recruitment of yeast PrLDs to SG suggests that this propensity might be connected with three defined protein biophysical features: aggregation propensity, net charge, and the presence of free cysteines. These three properties can be read directly in the PrLDs sequences, and their combination allows to predict protein recruitment to SG under heat stress. On this basis, we implemented SGnn, an online predictor of SG recruitment that exploits a feed-forward neural network for high accuracy classification of the assembly behavior of PrLDs. The simplicity and precision of our strategy should allow its implementation to identify heat stress-induced SG-forming proteins in complete proteomes.

8.
Interv Neuroradiol ; : 15910199211039926, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516332

RESUMO

PURPOSE: To evaluate the safety and efficacy of the Tigertriever 13 (Rapid Medical, Yoqneam, Israel) stent retriever in acute ischemic stroke (AIS) patients with primary or secondary distal, medium vessel occlusions (DMVO). METHODS: We performed a retrospective analysis of all consecutive AIS patients who underwent thrombectomy with the Tigertriever13 for DMVO. Patients' characteristics were reviewed, procedural complications, angiographic (modified thrombolysis in cerebral infarction score [mTICI]) and clinical (modified Rankin Scale [mRS]) outcomes were documented. RESULTS: Between November 2019 and November 2020, 16 patients with 17 DMVO were included (40% female, median age 60 [50-65] years). The Tigertriever13 was used in 11/17 (65%, median NIHSS of 8 [6-15]) primary DMVO and in 6/17 (35%, median NIHSS of 20 [13-24]) cases of secondary DMVO after a proximal thrombectomy. The successful reperfusion rate (mTICI 2b, 2c, 3) was 94% (16/17) for the dedicated vessel. At day 1, CT imaging showed a subarachnoid hemorrhage in 29% of the cases and a parenchymal hematoma in 12%. At 3 months, 65% of the patients (11/17) had a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the Tigertriever13 appears to be safe and effective for DMVO. Clinical and anatomical results are in line with those of patients with proximal occlusions.

9.
Int. j. med. surg. sci. (Print) ; 8(3): 1-7, sept. 2021. ilus
Artigo em Inglês | LILACS | ID: biblio-1292580

RESUMO

Hip femoral head fractures are extremely uncommon, but likely associated with traumatic hip dislocations. Both lesions require emergent treatment to avoid further complications.19-year-old male patient was received after a high-energy motor vehicle accident with severe brain and thoraco-abdominal trauma and a displaced femoral head fracture with posterior hip dislocation with no acetabular fracture. An emergent open reduction and internal fixation with 2 headless screws was performed, as well as posterior capsule repair. After 1 month as an inpatient in Intensive Care Unit, he sustained a new episode of posterior hip dislocation. Consequently, a second successful surgical reduction was obtained, and hip stability was achieved by posterior reconstruction with iliac crest autograft fixed with cannulated screw and posterior structure repair. Two years later, he was able to walk independently and he does not present any signs of degenerative joint disease nor avascular necrosis.


Las fracturas de la cabeza femoral son extremadamente raras y están asociadas comúnmente con una luxación de cadera traumática. Ambas lesiones requieren tratamiento urgente con el objetivo de evitar complicaciones posteriores. Un paciente varón de 19 años fue trasladado tras un accidente de tráfico de alta energía en el que sufrió un traumatismo craneoencefálico y toracoabdominal grave, además de una fractura de cabeza femoral desplazada junto a una luxación posterior de cadera sin afectación acetabular. De manera urgente, fue intervenido mediante una reducción abierta y fijación interna de la fractura con dos tornillos canulados sin cabeza y reparación de la cápsula articular posterior. Tras un mes de ingreso en la unidad de cuidados intensivos, sufrió un nuevo episodio de luxación posterior de cadera. Debido a ello, se realiza una segunda intervención quirúrgica con reducción abierta y en la que se obtiene una adecuada estabilidad de la cadera mediante reconstrucción posterior con la adición de autoinjerto tricortical de cresta ilíaca y reparación capsular posterior. Después de dos años de seguimiento, el paciente deambula de manera independiente, sin dolor y sin signos degenerativos ni de necrosis avascular en las pruebas de imagen.


Assuntos
Humanos , Masculino , Adulto Jovem , Transplante Autólogo/métodos , Fraturas do Fêmur/cirurgia , Cabeça do Fêmur/lesões , Luxações Articulares/complicações , Ílio/cirurgia
10.
Sci Rep ; 11(1): 15583, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341419

RESUMO

Cognitive reserve (CR) is the capability of an individual to cope with a brain pathology through compensatory mechanisms developed through cognitive stimulation by mental and physical activity. Recently, it has been suggested that CR has a protective role against the initiation of substance use, substance consumption patterns and cognitive decline and can improve responses to treatment. However, CR has never been linked to cognitive function and neurotrophic factors in the context of alcohol consumption. The present cross-sectional study aims to evaluate the association between CR (evaluated by educational level), cognitive impairment (assessed using a frontal and memory loss assessment battery) and circulating levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in patients with alcohol use disorder (AUD). Our results indicated that lower educational levels were accompanied by earlier onset of alcohol consumption and earlier development of alcohol dependence, as well as impaired frontal cognitive function. They also suggest that CR, NT-3 and BDNF may act as compensatory mechanisms for cognitive decline in the early stages of AUD, but not in later phases. These parameters allow the identification of patients with AUD who are at risk of cognitive deterioration and the implementation of personalized interventions to preserve cognitive function.


Assuntos
Alcoolismo/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/sangue , Escolaridade , Neurotrofina 3/sangue , Abstinência de Álcool/psicologia , Consumo de Bebidas Alcoólicas/sangue , Alcoolismo/psicologia , Disfunção Cognitiva/psicologia , Reserva Cognitiva , Comorbidade , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Componente Principal , Curva ROC
11.
Brain Struct Funct ; 226(7): 2243-2264, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236532

RESUMO

Preclinical studies on the effects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication often prescribed in alcohol use disorder (AUD) patients with depression, results in alcohol consumption escalation after resuming drinking. However, a potential neuroinflammatory component on this escalation remains unexplored despite the immunomodulatory role of serotonin. Here, we utilized a rat model of 14-daily administration of the SSRI fluoxetine (10 mg/kg/day) along alcohol self-administration deprivation to study the effects of fluoxetine cessation on neuroinflammation after resuming alcohol drinking. Microglial morphology and inflammatory gene expression were analyzed in prelimbic cortex, striatum, basolateral amygdala and dorsal hippocampus. Results indicated that alcohol drinking reinstatement increased microglial IBA1 immunoreactivity and altered morphometric features of activated microglia (fractal dimension, lacunarity, density, roughness, and cell area, perimeter and circularity). Despite alcohol reinstatement, fluoxetine cessation modified microglial morphology in a brain region-specific manner, resulting in hyper-ramified (spatial complexity of branching), reactive (lower heterogeneity and circularity)-like microglia. We also found that microglial cell area correlated with changes in mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1ß, IL6, IL10) and the innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifically, TLR4 correlated with microglial spatial complexity assessed by fractal dimension in striatum, suggesting a role in process branching. These findings suggest that alcohol drinking reinstatement after fluoxetine treatment cessation disturbs microglial morphology and reactive phenotype associated with a TLR4/inflammatory response to alcohol in a brain region-specific manner, facts that might contribute to alcohol-induced damage through the promotion of escalation of alcohol drinking behavior.

12.
EFSA J ; 19(7): e06689, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34257732

RESUMO

The qualified presumption of safety (QPS) approach was developed to provide a regularly updated generic pre-evaluation of the safety of biological agents, intended for addition to food or feed, to support the work of EFSA's Scientific Panels. The QPS approach is based on an assessment of published data for each agent, with respect to its taxonomic identity, the body of relevant knowledge, safety concerns and occurrence of antimicrobial resistance. Safety concerns identified for a taxonomic unit (TU) are, where possible, confirmed at the species/strain or product level and reflected by 'qualifications'. In the period covered by this statement, no new information was found that would change the status of previously recommended QPS TUs. Schizochytrium limacinum, which is a synonym for Aurantiochytrium limacinum, was added to the QPS list. Of the 78 microorganisms notified to EFSA between October 2020 and March 2021, 71 were excluded; 16 filamentous fungi, 1 Dyella spp., 1 Enterococcus faecium, 7 Escherichia coli, 1 Streptomyces spp., 1 Schizochytrium spp. and 44 TUs that had been previously evaluated. Seven TUs were evaluated: Corynebacterium stationis and Kodamaea ohmeri were re-assessed because an update was requested for the current mandate. Anoxybacillus caldiproteolyticus, Bacillus paralicheniformis, Enterobacter hormaechei, Eremothecium ashbyi and Lactococcus garvieae were assessed for the first time. The following TUs were not recommended for QPS status: A. caldiproteolyticus due to the lack of a body of knowledge in relation to its use in the food or feed chain, E. hormaechei, L. garvieae and K. ohmeri due to their pathogenic potential, E. ashbyi and C. stationis due to a lack of body of knowledge on their occurrence in the food and feed chain and to their pathogenic potential. B. paralicheniformis was recommended for the QPS status with the qualification 'absence of toxigenic activity' and 'absence of genetic information to synthesize bacitracin'.

13.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208173

RESUMO

Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.


Assuntos
Astrócitos/metabolismo , Restrição Calórica , Endocanabinoides/metabolismo , Hipotálamo/metabolismo , Metabolismo dos Lipídeos , Transdução de Sinais , Animais , Animais Recém-Nascidos , Peso Corporal , Encéfalo/patologia , Feminino , Regulação da Expressão Gênica , Gliose/genética , Gliose/patologia , Inflamação/genética , Inflamação/patologia , Metabolismo dos Lipídeos/genética , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais/genética
14.
Parkinsonism Relat Disord ; 88: 3-9, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34090180

RESUMO

BACKGROUND: The enzyme ATP13A2 holds promise as biomarker in Parkinson's disease (PD). No study has examined the content of ATP13A2 in serum and cerebrospinal fluid (CSF) in idiopathic PD cohorts, or how ATP13A2 relates to the clinical features of the disease. METHODS: ATP13A2 concentration was evaluated with ELISA and immunoblotting. Correlations of serum and CSF ATP13A2 with clinical parameters were examined. The antiparkinsonian medication regimen was expressed as levodopa equivalent dose (LED, mg/day). RESULTS: Serum ATP13A2 concentration was similar in patients and controls, and it correlated with LED and MDS-UPDRS part-IV score (p < .0001), a scale which allows evaluating motor complications. LED also correlated with MDS-UPDRS part-IV score (p < .0001). Serum ATP13A2 concentration and LED were higher in patients with motor complications than in patients without motor complications (p < .0001). The ratio of serum ATP13A2 concentration versus LED was calculated, and mean value was similar in patients with or without motor complications. ATP13A2 concentration in the CSF was undetectable in many subjects because the ELISA assay was hampered by its detection limit. Immunoblotting indicated that CSF ATP13A2 content was higher in patients relative to controls (p = .0002), and no clinical correlations were found. CONCLUSIONS: Increasing LED enhanced serum ATP13A2 concentration and facilitated the development of motor complications. There is a direct relationship between serum ATP13A2 level and the dose intensity of the antiparkinsonian dopaminergic medication. The associations between serum ATP13A2 and LED suggest that serum ATP13A2 content might be a marker of dopamine replacement therapy.

15.
Antioxidants (Basel) ; 10(5)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062880

RESUMO

Background. Salivary α-synuclein (aSyn) and its nitrated form, or 3-nitrotyrosine-α-synuclein (3-NT-αSyn), hold promise as biomarkers for idiopathic Parkinson's disease (IPD). Nitrative stress that is characterized by an excess of 3-nitrotyrosine proteins (3-NT-proteins) has been proposed as a pathogenic mechanism in IPD. The objective is to study the pathological role of native αSyn, 3-NT-αSyn, and 3-NT-proteins in the saliva and submandibulary glands of patients with IPD. Methods. The salivary and serum αSyn and 3-NT-proteins concentration is evaluated with ELISA in patients and controls. Correlations of αSyn and 3-NT-proteins content with clinical features of the disease are examined. Immunohistochemical 3-NT-αSyn expression in submandibulary gland sections is analyzed. Results. (a) Salivary concentration and saliva/serum ratios of native αSyn and 3-NT-proteins are similar in patients and controls; (b) salivary αSyn and 3-NT-proteins do not correlate with any clinical feature; and (c) three patterns of 3-NT-αSyn-positive inclusions are observed on histological sections: rounded "Lewy-type" aggregates of 10-25 µm in diameter, coarse deposits with varied morphology, and spheroid inclusions or bodies of 3-5 µm in diameter. "Lewy-type" and coarse inclusions are observed in the interlobular connective tissue of the gland, and small-sized bodies are located within the cytoplasm of duct cells. "Lewy-type" inclusions are only observed in patients, and the remaining patterns of inclusions are observed in both the patients and controls. Conclusions. The patients' saliva presents a similar concentration of native αSyn and 3-nitrotyrosine-proteins than that of the controls, and no correlations with clinical features are found. These findings preclude the utility of native αSyn in the saliva as a biomarker, and they indicate the absence of nitrative stress in the saliva and serum of patients. As regards nitrated αSyn, "Lewy-type" inclusions expressing 3-NT-αSyn are observed in the patients, not the controls-a novel finding that suggests that a biopsy of the submandibulary gland, if proven safe, could be a useful technique for diagnosing IPD. Finally, to our knowledge, this is also the first description of 3-NT-αSyn-immunoreactive intracytoplasmic bodies in cells that are located outside the nervous system. These intracytoplasmic bodies are present in duct cells of submandibulary gland sections from all subjects regardless of their pathology, and they can represent an aging or involutional change. Further immunostaining studies with different antibodies and larger samples are needed to validate the data.

16.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065168

RESUMO

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aß) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aß plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1ß in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.


Assuntos
Doença de Alzheimer/metabolismo , Metabolismo Energético/fisiologia , Hipotálamo/metabolismo , Doenças Metabólicas/metabolismo , Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismo , Resistina/metabolismo
17.
Sci Rep ; 11(1): 10512, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006966

RESUMO

In this study, we measured diurnal patterns of sap flow (Vs) in cacao trees growing in three types of agroforestry systems (AFs) that differ in the incident solar radiation they receive. We modeled the relationship of Vs with several microclimatic characteristics of the AFs using mixed linear models. We characterized microclimatic variables that may have an effect on diurnal patterns of sap flow: air relative humidity, air temperature, photosynthetically active radiation and vapor pressure deficit. Overall, our model predicted the differences between cacao Vs in the three different AFs, with cacao plants with dense Musaceae plantation and high mean diurnal incident radiation (HPAR) displaying the highest differences compared to the other agroforestry arrangements. The model was also able to predict situations such as nocturnal transpiration in HPAR and inverse nocturnal sap flows indicative of hydraulic redistribution in the other AFs receiving less incident radiation. Overall, the model we present here can be a useful and cost-effective tool for predicting transpiration and water use in cacao trees, as well as for managing cacao agroforestry systems in the Amazon rainforest.

18.
Injury ; 52 Suppl 4: S71-S75, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33992422

RESUMO

INTRODUCTION: the frequency of distal femur fractures in the elderly is rapidly increasing. A study of these fractures was conducted in our center in order to evaluate the comorbidities and the mortality associated with this entity. MATERIAL AND METHODS: all the distal femur fractures by low energy in patients over 65 years old at a tertiary center were included, between January 2010 and December 2016. Baseline characteristics, the type of fracture, comorbidities, and functional status before admission, were collected. The relationship of each of these variables to the final functional class, immediate and late complications and mortality during the follow-up. Fifty-nine patients were included, with a median age of 85.3 years (IQR 78.6-91.6). Fifty-one patients were women. In 10 patients, the fractures were atraumatic (postural change mainly in non-walking patients), and in 54 of the cases were treated surgically (6 with retrograde intramedullary nailing and 48 with lateral locking plate). The median time to surgery was 4.5 days (IQR 2-6) and 14 patients were operated within 48 hours. The median follow-up was 26.3 months. RESULTS: fourteen patients died during the first year of follow-up. Factors independently associated with death during the first year after the fracture were: conservative treatment, and the inability to ambulate before the episode. The absence of certain comorbidities, such as chronic heart disease, and cancer, and an age under 80 years, behaved as protective factors. CONCLUSION: low-energy distal femur fractures comprise a severe injury in the elderly and are associated with high mortality. Surgical treatment showed better outcomes in terms of survival, with no significant differences depending on the type of fracture, the type of implant or the median time to surgery.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Comorbidade , Feminino , Fraturas do Fêmur/cirurgia , Fêmur , Fixação Interna de Fraturas , Humanos
19.
Arch Bone Jt Surg ; 9(2): 152-157, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34026931

RESUMO

Background: Soft tissue injury associated with fractures of the distal tibia is a predictive factor for a poor prognosis. The purpose of this study was to investigate factors associated with the need for a flap coverage after distal tibial fracture, and whether there was a difference in functional outcomes between patients with flap coverage or no flap coverage for a distal tibial fracture. Methods: All fractures of the distal tibia treated in our department between 2010 and 2017 were reviewed. The functional result was assessed using the SF-36 Quality of Life Questionnaire, the Visual Analog Scale (VAS) when walking and the AOFAS scale (American Orthopedic Foot and Ankle Society). Results: 132 distal tibia fractures were reviewed, of which 51 required soft tissue flap reconstruction, which was associated with open fractures (P<0.001, OR 5.25), high energy trauma (P<0.001, OR 1.7)), the use of external fixation (p <0.001, OR 12.5) and the presence of vascular alterations on the Angio-CT scan (P<0.001). No significant differences were found in any of the scales that assessed the functional results between the group of patients who required soft tissue flap reconstruction and the group of patients who did not. Conclusion: We found that the need for a soft tissue flap was associated with the following parameters: open fracture, high energy of trauma, presence of skin necrosis, the use of external fixation and the existence of vascular injury. In relation to functional results, differences were not found between the group that needed coverage with a flap and the one that did not.

20.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919113

RESUMO

Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5'-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.


Assuntos
Fosfatase Alcalina/genética , Calcinose/complicações , Hipofosfatasia/patologia , Mutação , Terapia de Reposição de Enzimas/métodos , Humanos , Hipofosfatasia/enzimologia , Hipofosfatasia/etiologia , Hipofosfatasia/terapia
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