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By identifying and overcoming challenges to the conduct and reporting of scoping reviews, reviewers may better ensure that scoping reviews are effective in meeting the objectives of scoping reviews.

By identifying and overcoming challenges to the conduct and reporting of scoping reviews, reviewers may better ensure that scoping reviews are effective in meeting the objectives of scoping reviews.Alzheimer's disease is a multifactorial neurodegenerative condition manifested through acute cognitive decline, amyloid plaque deposits and neurofibrillary tangles. Complete cure for this disease remains elusive as the conventional drugs address only a single molecular target while Alzheimer's disease involves a complex interplay of different sets of molecular targets and signaling networks. In this context, the possibility of employing multi-drug combinations to rescue neurons from the dysregulated metabolic changes is being actively investigated. The present work investigates a poly-herbal formulation, Brahmi Nei that has been traditionally used for anxiolytic disorders and immunomodulatory effects, for its efficiency in ameliorating cognitive decline through a combination of behavioral, biochemical, histopathological, gene and protein expression analyses. Our results reveal that the formulation shows excellent neuroregenerative properties, rescues neurons from inflammatory damage, reduces neuritic plaque deposits and improves working memory in rodent models with scopolamine-induced dementia. The microarray analysis shows that the formulation induces the expression of pro-survival pathways and positively modulates genes involved in memory consolidation, axonal growth and proliferation in a concentration-dependent manner with therapeutic concentrations restoring the normal conditions in the brain of the diseased animals. The neuritic spine morphology confirms the long-term memory potentiation through improved mushroom spine density, increased dendritic length and connectivity. Taken together, our study provides mechanistic evidence to prove that the traditional formulation can be a superior therapeutic strategy to treat cognitive decline when compared to the conventional mono-drug treatment.GABAA and glycine receptors mediate fast synaptic inhibitory neurotransmission. CAY10585 mouse Despite studies showing that activation of cerebral glycine receptors could be a potential strategy in the treatment of epilepsy, few studies have assessed the effects of existing anticonvulsant therapies on recombinant or native glycine receptors. We, therefore, evaluated the actions of a series of anticonvulsants at recombinant human homo-oligomeric glycine receptor α1, α2 and α3 subtypes expressed in Xenopus oocytes using two-electrode voltage-clamp methods, and then assessed the most effective drug at native glycine receptors from entorhinal cortex neurons using whole-cell voltage-clamp recordings. Ganaxolone, tiagabine and zonisamide positively modulated glycine induced currents at recombinant homomeric glycine receptors. Of these, zonisamide was the most efficacious and exhibited an EC50 value ranging between 450 and 560 μM at α1, α2 and α3 subtypes. These values were not significantly different indicating a non-selective modulation of glycine receptors. Using a therapeutic concentration of zonisamide (100 μM), the potency of glycine was significantly shifted from 106 to 56 μM at α1, 185 to 112 μM at α2, and 245 to 91 μM at α3 receptors. Furthermore, zonisamide (100 μM) potentiated exogenous homomeric and heteromeric glycine mediated currents from layer II pyramidal cells of the lateral or medial entorhinal cortex. As therapeutic concentrations of zonisamide positively modulate recombinant and native glycine receptors, we propose that the anticonvulsant effects of zonisamide may, at least in part, be mediated via this action.Depression is a common mental illness and leading cause of disability. link2 Most current antidepressants are associated with significant limitations, and in particular, a delayed onset and low rate of efficacy. Consequently, there remains an ongoing need for antidepressants that are either more effective or better tolerated than existing standards. We previously identified ZY-1408 as a drug with a novel chemical structure and potential anti-depressant-like activity. Specifically, ZY-1408 is a novel serotonin 2C (5-HT2C) receptor antagonist and serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. In this study, we further investigated the antidepressant-like efficacy of ZY-1408 using in vitro and in vivo behavioral tests. ZY-1408 showed 5-HT2C receptor antagonist and 5-HT/NE reuptake inhibitor properties in vitro. Meanwhile, ZY-1408 decreased immobility in vivo in a dose-dependent manner in rats (via the forced-swim test) and mice (via the tail-suspension test). The behavioral test results do not appear to result from stimulation of locomotor activity. In chronically stressed rats, repeated ZY-1408 treatment significantly reversed depressive-like behavior, including reduced sucrose preference, decreased locomotor activity, and prolonged time to begin eating. Furthermore, in vivo microdialysis showed that administration of ZY-1408 significantly increased extracellular concentrations of 5-HT and NE in the hippocampus of freely moving rats. Thus, ZY-1408 is a potent and orally active 5-HT2C receptor antagonist and 5-HT/NE reuptake inhibitor with antidepressant-like activity in rodents.Mitochondria are essential for neuronal survival and function, and mitochondrial dysfunction plays a critical role in the pathological development of Parkinson's disease (PD). Mitochondrial quality control is known to contribute to the survival of dopaminergic (DA) neurons, with mitophagy being a key regulator of the quality control system. In this study, we show that mitophagy is impaired in the substantia nigrapars compacta (SNc) of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with the sigma-1 receptor (Sig 1R) agonist 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) reduced loss of DA neurons, restored motor ability andMPTP-induced damage to mitophagy activity in the SNc of PD-like mice. Additionally, knockdown of Sig 1R in SH-SY5Y DA cells inhibited mitophagy and enhanced 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity, whereas application of the Sig 1R selective agonist SKF10047 promoted clearance of damaged mitochondria. Moreover, knockdown of Sig 1R in SH-SY5Y cells resulted in decreased levels of p-ULK1 (Unc-51 Like Autophagy Activating Kinase 1) (Ser555), p-TBK1 (TANK Binding Kinase 1) (Ser172), p-ubiquitin (Ub) (Ser65), Parkin recruitment, and stabilization of PTEN-induced putative kinase 1 (PINK1) in mitochondria. The present data provide the first evidence for potential roles of PINK1/Parkin in Sig 1R-modulated mitophagy in DA neurons.This study shows a clinical case report of a kidney transplant patient who traveled from Mexico to The Netherlands and ate green vegetables in an international food restaurant. After 5 days, he started having diarrhea, nausea, colic, and a physical feeling of malaise. The patient only received symptomatic treatment after showing the characteristic symptoms of traveler's diarrhea. When he returned to Mexico, the clinical picture worsened, and he was hospitalized. Clinical analyses indicated dehydration and acute kidney injury stage II. Coproparasitoscopic study showed the presence of Cyclospora cayetanensis. Parenteral solutions, gastric mucosal protector, ciprofloxacin, and a soft diet were administrated as treatment. The patient was discharged 72 h later with an improvement of the kidney function.

Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment.

This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging.

A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatmetwork activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

Soft markers are nonspecific findings detected by ultrasonography during the second trimester that are often transient and nonpathologic but may imply an increased risk of underlying fetal aneuploidy. However, large-scale prospectively stratified studies focusing on the prevalence of chromosomal aberrations, including copy number variants, in fetuses with different types of isolated soft markers have rarely been published in the literature.

This study aimed to investigate clinical outcomes in fetuses with isolated soft markers by single nucleotide polymorphism array with long-term follow-up and to propose a diagnostic algorithm based on specific types of soft markers.

The prevalence of fetal isolated soft markers was 13.2% (7869 of 59,503). A total of 2466 fetuses with ultrasonographic soft markers during the second trimester, which were subjected to single nucleotide polymorphism array with long-term follow-up, were selected in this prospective study over a 5-year period. Soft markers were categorized rate in fetuses without chromosomal aberrations was 91.7%; however, it was significantly lower in the mild ventriculomegaly (86.2% vs 93.0%; P<.0001) and short femur length groups (71.4% vs 93.6%; P<.0001).

The potential chromosomal aberrations and clinical prognoses varied widely among different types of isolated soft markers. Pathogenic copy number variants are more often present in specific softmarkers, especially when multiple soft markers are found. Thus, a specific soft marker type-based prenatal genetic testing algorithm was proposed.

The potential chromosomal aberrations and clinical prognoses varied widely among different types of isolated soft markers. Pathogenic copy number variants are more often present in specific soft markers, especially when multiple soft markers are found. Thus, a specific soft marker type-based prenatal genetic testing algorithm was proposed.Oxygen supply implies higher production cost and reduction of maximum theoretical yields. Thus, generation of fermentation products is more cost-effective. Aiming to find a key piece for the production of (poly)-3-hydroxybutyrate (PHB) as a fermentation product, here we characterize an acetoacetyl-CoA reductase, isolated from a Candidatus Accumulibacter phosphatis-enriched mixed culture, showing a (kcatNADH/KMNADH)/(kcatNADPH/KMNADPH)>500. Further kinetic analyses indicate that, at physiological concentrations, this enzyme clearly prefers NADH, presenting the strongest NADH preference so far observed among the acetoacetyl-CoA reductases. Structural and kinetic analyses indicate that residues between E37 and P41 have an important role for the observed NADH preference. Moreover, an operon was assembled combining the phaCA genes from Cupriavidus necator and the gene encoding for this NADH-preferring acetoacetyl-CoA reductase. link3 Escherichia coli cells expressing that assembled operon showed continuous accumulation of PHB under oxygen limiting conditions and PHB titer increased when decreasing the specific oxygen consumption rate.