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The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates the levels of low-density lipoprotein cholesterol and cardiovascular risk. Potential risks of adverse neurological effects of intensive lipid-lowering treatment have been hypothesized, as cholesterol is a component of the central nervous system. Moreover, several observations suggest that PCSK9 might play a role in neurogenesis, neuronal migration and apoptosis. In rodents, increased expression of PCSK9 has been detected in specific areas of the central nervous system during embryonic development; also, PCSK9 modulates low-density lipoprotein receptor levels in the ischemic brain areas. Despite a putative participation of PCSK9 in nervous system physiology, the absence of PCSK9 in knockout mice or in humans with loss-of-function mutations of PCSK9 gene has not been linked to neurological alterations. In recent years, some concerns have been raised about the potential neurological side effects of cholesterol-lowering treatments and, more specifically of PCSK9 inhibitors. In this review, the evidence regarding the function of PCSK9 in neuron differentiation, apoptosis, and migration and in nervous system development and latest clinical trials evaluating the effects of PCSK9 inhibitors on neurocognitive function will be described.  相似文献   
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Mirafzal  S.  Goujon  A.  Deschamps  R.  Zuber  K.  Sadik  J. C.  Gout  O.  Lecler  Augustin  Savatovsky  J. 《Journal of neurology》2020,267(2):406-414
Journal of Neurology - Spinal imaging in multiple sclerosis remains challenging because of its small size and numerous artifacts. To compare 3D Phase-Sensitive Inversion Recovery (PSIR) to a...  相似文献   
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The high concentrations of free fatty acids as a consequence of obesity and being overweight have become risk factors for the development of different diseases, including neurodegenerative ailments. Free fatty acids are strongly related to inflammatory events, causing cellular and tissue alterations in the brain, including cell death, deficits in neurogenesis and gliogenesis, and cognitive decline. It has been reported that people with a high body mass index have a higher risk of suffering from Alzheimer's disease. Hormones such as oestradiol not only have beneficial effects on brain tissue, but also exert some adverse effects on peripheral tissues, including the ovary and breast. For this reason, some studies have evaluated the protective effect of oestrogen receptor (ER) agonists with more specific tissue activities, such as the neuroactive steroid tibolone. Activation of ERs positively affects the expression of pro‐survival factors and cell signalling pathways, thus promoting cell survival. This review aims to discuss the relationship between lipotoxicity and the development of neurodegenerative diseases. We also elaborate on the cellular and molecular mechanisms involved in neuroprotection induced by oestrogens.  相似文献   
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Phytotherapy is a source of finding new remedies for migraine. Traditional chamomile oil (chamomile extraction in sesame oil) is a formulation in Persian medicine (PM) for pain relief in migraine. An oleogel preparation of reformulated traditional chamomile oil was prepared and then standardized based on chamazulene (as a marker in essential oil) and apigenin via gas chromatography (GC) and high-performance liquid chromatography (HPLC) methods, respectively. A crossover double-blind clinical trial was performed with 100 patients. Each patient took two tubes of drug and two tubes of placebo during the study. Visual analog scale (VAS) questionnaires were filled in by the patients and scores were given, ranging from 0 to 10 (based on the severity of pain) during 24 h. Other complications like nausea, vomiting, photophobia, and phonophobia were also monitored. There was 4.48?±?0.01 μl/ml of chamazulene and 0.233 mg/g of apigenin in the preparation (by correcting the amount with extraction ratio). Thirty-eight patients in the drug-placebo and 34 patients in the placebo-drug groups (a total number of 72 patients as per protocol) completed the process in the randomized controlled trial (RCT). Adapted results from the questionnaires showed that pain, nausea, vomiting, photophobia, and phonophobia significantly (p?<?0.001) decreased by using chamomile oleogel on the patients after 30 min. Results supported the efficacy of chamomile oleogel as a pain relief in migraine without aura.  相似文献   
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The incidence of human immunodeficiency virus(HIV)-infected cases that need total joint replacement(TJR) is generally rising. On the other hand, modern management of HIV-infected cases has enabled them to achieve longevity while increasing the need for arthroplasty procedures due to the augmented degenerative joint disease and fragility fractures, and the risk of osteonecrosis. Although initial investigations on joint replacement in HIV-infected cases showed a high risk of complications, the rec...  相似文献   
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There is a clear clinical need for efficient physiotherapy and rehabilitation programs during and after bone lengthening and reconstruction for gaining the optimal effect and also prevention or treatment of lengthening side effects. Pin tract infection is the most prevalent side effect during lengthening which could be prevented and treated initially via proper wound care. Muscle contractures are typically a consequence of the generated tension on the distracted muscle. It can be managed by physiotherapy initially and surgically in later severe stages. Furthermore, it is essential to avoid muscle contracture development, which is the demonstration of the imbalanced muscle appeals on the joint to inhibit the following subluxation. The knee is the furthermost affected joint by the aforementioned problem due to the inherent lack of ligamentous and bony stability. Joint stiffness is the other possible unfavorable effect of lengthening. It happens because of extensive muscle contractures or may possibly be attributed to rigidity of the joint following the amplified pressure on the joint surface during the process of lengthening. Physiotherapy and occupational therapy including endurance and strength exercise as well as stretching play an important role during the rehabilitation periods for the prevention and also the treatment of muscle contracture and the following deformity and also joint stiffness. Likewise, the effect of mental and physical rehabilitation programs should not be overlooked.  相似文献   
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