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The current therapy is assuring only symptomatic relief from the disease, and progressive loss of efficacy for these symptomatic treatments warrants the discovery of newer drugs by exploring these novel drug targets. A comprehensive understanding of these therapeutic targets and their neuropathological role in AD is necessary to identify novel molecules for the treatment of AD rationally.Eicosanoids are arachidonic acid (AA) derivatives belonging to a family of lipid signalling mediators that are engaged in both physiological and pathological processes in the brain. Recently, their implication in the prolonged inflammatory response has become a focus of particular interest because, in contrast to acute inflammation, chronic inflammatory processes within the central nervous system (CNS) are crucial for the development of brain pathologies including depression. The synthesis of eicosanoids is catalysed primarily by cyclooxygenases (COX), which are involved in the production of pro-inflammatory AA metabolites, including prostaglandins and thromboxanes. Moreover, eicosanoid synthesis is catalysed by lipoxygenases (LOXs), which generate both leukotrienes and anti-inflammatory derivatives such as lipoxins. Thus, AA metabolites have double- edged pro-inflammatory and anti-inflammatory, pro-resolving properties, and an imbalance between these metabolites has been proposed as a contributor or even the basis for chronic neuroinflammatory effects. This review focuses on important evidence regarding eicosanoid-related pathways (with special emphasis on prostaglandins and lipoxins) that has added a new layer of complexity to the idea of targeting the double-edged AA-derivative pathways for therapeutic benefits in depression. We also sought to explore future research directions that can support a pro-resolving response to control the balance between eicosanoids and thus to reduce the chronic neuroinflammation that underlies at least a portion of depressive disorders.Neurology and associated nanotherapeutics is a complex field in terms of therapeutics and neurological disorder complexity. Brain is an intricate appendage and requires more precise embattled treatment for the particular diseases and hence it's a broad scale for developing more targeted drug deliveries. The brain is one of the most inaccessible tissues of the body due to the existence of the blood-brain barrier (BBB), thus delivery of drugs inside the brain is a striking dare and it is also tricky to treat central nervous system (CNS) complications pharmacologically. The therapeutic aspiration is to accomplish a lowest drug meditation in the brain tissues so as to gain favoured therapeutic results. To devastate this obstacle, nanotechnology is engaged in the field of targeted brain drug delivery and neuropathology targeting. These carriers hold myriad ability as they may augment the drug delivery into the brain by shielding them from degradation and prolonging their transmission in the blood, as well as promoting their transport through the BBB. Nanopharmaceuticals are quickly sprouting as new avenue that is engaged with the drug-loaded nanocarriers to demonstrate unique physicochemical properties and tiny size range for penetrating into the central nervous system. The enchantment behind their therapeutic achievement is the condensed drug dose and inferior toxicity, whereby restricting the therapeutic compound to the specific site. click here Therefore, in this article we have tried to recapitulate the advances the novel scopes for the brain targeted drug delivery for complex neurological disorders.
Hyperandrogenism is a pivotal mediator in the pathogenesis of the polycystic ovary syndrome (PCOS), but the mechanisms of androgen excess in this condition are not fully understood. Angiotensin (Ang)-(1-7) is an active peptide of the renin-angiotensin system (RAS) that stimulates ovarian follicular growth and testosterone release in vitro.
To investigate whether Ang-(1-7), its receptor Mas and angiotensin-converting enzyme 2 (ACE2), the enzyme that converts Ang II into Ang-(1-7), are expressed in rat polycystic ovaries (PCO) and thus if this peptide system might be associated with excess androgen production in PCO.
A rat model that shares some features of PCOS such as disruption of folliculogenesis and multiple ovarian cyst formation was used in the study.
We found reduced levels of Ang-(1-7) and Mas receptor in PCO compared to normal ovaries. Also, ACE2 mRNA expression was reduced in PCO compared to ovaries of control rats (p < 0.05). PCO had high levels of estrogen and testosterone and increased mRNA for upstream enzymes of the steroidogenic cascade, but not of P450 aromatase.
These findings suggest that the ovarian ACE2-Ang-(1-7)-Mas receptor axis is inhibited and therefore may not be a co-factor of excess testosterone production in rat PCO.
These findings suggest that the ovarian ACE2-Ang-(1-7)-Mas receptor axis is inhibited and therefore may not be a co-factor of excess testosterone production in rat PCO.
Utilisation of intervention programmes and services for Persons with Dementia (PWD) has been generally modest despite the growing numbers. One reason has been the lack of knowledge about dementia and information on such services.
We sought to close this gap by providing caregivers with an information session about dementia and the importance and availability of related services. We explored the uptake of intervention programmes and services and reasons for non-uptake thereafter.
Two hundred and seventy-five PWD and caregiver dyads attended the Dyad Education and Empowerment Programme (DEEP). At the DEEP, while caregivers underwent an information session, PWD were assessed by a multidisciplinary team on their need and suitability for programmes and services such as daycare, cognitive engagement programmes and physical rehabilitation. The dyads then received individualized recommendations on the appropriate services, if any. Follow-up through medical records review and phone calls was conducted one month after DEEP to ascertain if the dyads had acted upon the recommendations and if not, what difficulties they encountered.
One hundred and eleven PWD received recommendations, of which 40 (36.0%) agreed and enrolled in the services while 71 (64%) declined. Thematic analysis of the reasons for non-uptake revealed 3 themes PWD-related factors (e.g., refusal, functional improvement or decline), caregiverrelated factors (adequacy of care at home, other care arrangements), and service-related factors (e.g., cost, timing).
Despite adequate information, there are other reasons for non-uptake of dementia- related services, some of which should be addressed to improve service updates and to provide better care for PWD.
Despite adequate information, there are other reasons for non-uptake of dementia- related services, some of which should be addressed to improve service updates and to provide better care for PWD.
The purpose of the study was to evaluate the reliability of our new visual scale for a quick atrophy assessment of parietal lobes on brain Magnetic Resonance Imaging (MRI) among different professionals. A good agreement would justify its use for differential diagnosis of neurodegenerative dementias, especially early-onset Alzheimer's Disease (AD), in clinical settings.
The visual scale named the Parietal Atrophy Score (PAS) is based on a semi-quantitative assessment ranging from 0 (no atrophy) to 2 (prominent atrophy) in three parietal structures (sulcus cingularis posterior, precuneus, parietal gyri) on T1-weighted MRI coronal slices through the whole parietal lobes. We used kappa statistics to evaluate intra-rater and inter-rater agreement among four raters who independently scored parietal atrophy using PAS. Rater 1 was a neuroanatomist (JM), rater 2 was an expert in MRI acquisition and analysis (II), rater 3 was a medical student (OP) and rater 4 was a neurologist (DS) who evaluated parietal atrophy twice in a 3-month interval to assess intra-rater agreement. All raters evaluated the same 50 parietal lobes on brain MRI of 25 cognitively normal individuals with even distribution across all atrophy degrees from none to prominent according to the neurologist's rating.
Intra-rater agreement was almost perfect with the kappa value of 0.90. Inter-rater agreement was moderate to substantial with kappa values ranging from 0.43-0.86.
The Parietal Atrophy Score is the reliable visual scale among raters of different professions for a quick evaluation of parietal lobes on brain MRI within 1-2 minutes. We believe it could be used as an adjunct measure in differential diagnosis of dementias, especially early-onset AD.
The Parietal Atrophy Score is the reliable visual scale among raters of different professions for a quick evaluation of parietal lobes on brain MRI within 1-2 minutes. We believe it could be used as an adjunct measure in differential diagnosis of dementias, especially early-onset AD.
Identifying and classifying individuals with Cognitive Impairment-No Dementia (CIND) has further challenged diagnostic methods, since varying the cutoffs for objective impairment as well as the neuropsychological tests considered can significantly affect diagnosis. Therefore, we investigated the applicability of an actuarial neuropsychological approach for clinical subdivision of CIND and quantified the variability in diagnostic outcomes that results from diverse neuropsychologically derived definition of objective cognitive impairment.
1459 non-demented, clinic-based individuals were recruited from a monocentric memory clinic from 1/1/2016/ to 1/1/2018 and classified as Cognitively Normal (NC), Slight Cognitive Symptom (SCS), SSubtle Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI) via different diagnostic strategies, which varied the composition of objective cognitive assessments involved in the diagnostic process.
We compared two methods of criteria proposed by Jak/Bondi and Petersen/Winblae symptomatic definition for early intervention.Neurodegenerative Diseases (NDD) are the major contributors to age-related causes of mental disability on a global scale. Most NDDs, like Alzheimer's Disease (AD), are complex in nature - implying that they are multi-parametric both in terms of heterogeneous clinical outcomes and underlying molecular paradigms. Emerging evidence from high throughput genomic, transcriptomic and small RNA sequencing experiments hint at the roles of long non-coding RNAs (lncRNAs) in AD. X-inactive Specific Transcript (XIST), a component of the Xic, the X-chromosome inactivation centre, is an RNA gene on the X chromosome of the placental mammals indispensable for the X inactivation process. An extensive literature survey shows that aberrations in Xist expression and in some cases, a disruption of the Xchromosome inactivation as a whole play a significant role in AD. Considering the enormous potential of Xist as an endogenous silencing molecule, the idea of using Xist as a non-conventional chromosome silencer to treat diseases harboring chromosomal alterations is also being implemented. Comprehensive knowledge about how Xist could play such a role in AD is still elusive. In this review, we have collated the available knowledge on the possible Xist involvement and deregulation from the perspective of molecular mechanisms governing NDDs with a primary focus on Alzheimer's disease. Possibilities of XIST mediated therapeutic intervention and linkages between XIC and preferential predisposition of females to AD have also been discussed.
