Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways

Accumulation of protein aggregates is the leading cause of cellular dysfunction in neurodegenerative disorders. Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, Prion disease and motor disorders such as amyotrophic lateral sclerosis, present with a similar pattern of progressive neuronal death, nervous system deterioration and cognitive impairment. The common characteristic is an unusual misfolding of proteins which is believed to cause protein deposition and trigger degenerative signals in the neurons. A similar clinical presentation seen in many neurodegenerative disorders suggests the possibility of shared neuronal responses in different disorders. Despite the difference in core elements of deposits in each neurodegenerative disorder, the cascade of neuronal reactions such as activation of glycogen synthase kinase-3 beta, mitogen-activated protein kinases, cell cycle re-entry and oxidative stress leading to a progressive neurodegeneration are surprisingly similar. This review focuses on protein toxicity in two neurodegenerative diseases, AD and PD. We reviewed the activated mechanisms of neurotoxicity in response to misfolded beta-amyloid and α-synuclein, two major toxic proteins in AD and PD, leading to neuronal apoptosis. The interaction between the proteins in producing an overlapping pathological pattern will be also discussed.Shohreh Majd, John H. Power and Hugh J.M. Grantha

The impact of tau hyperphosphorylation at Ser(262) on memory and learning after global brain ischaemia in a rat model of reversible cardiac arrest

An increase in phosphorylated tau (p-tau) is associated with Alzheimer's disease (AD), and brain hypoxia. Investigation of the association of residue-specific tau hyperphosphorylation and changes in cognition, leads to greater understanding of its potential role in the pathology of memory impairment. The aims of this study are to investigate the involvement of the main metabolic kinases, Liver Kinase B1 (LKB1) and Adenosine Monophosphate Kinase Protein Kinase (AMPK), in tau phosphorylation-derived memory impairment, and to study the potential contribution of the other tau kinases and phosphatases including Glycogen Synthase Kinase (GSK-3β), Protein kinase A (PKA) and Protein Phosphatase 2A (PP2A). Spatial memory and learning were tested in a rat global brain ischemic model of reversible cardiac arrest (CA). The phosphorylation levels of LKB1, AMPK, GSK-3β, PP2A, PKA and tau-specific phosphorylation were assessed in rats, subjected to ischaemia/reperfusion and in clinically diagnosed AD and normal human brains. LKB1 and AMPK phosphorylation increased 4 weeks after CA as did AMPK related p-tau (Ser262). The animals showed unchanged levels of GSK-3β specific p-tau (Ser202/Thr205), phospho-PP2A (Tyr307), total GSK-3β, PP2A, phospho-cAMP response element-binding protein (CREB) which is an indicator of PKA activity, and no memory deficits. AD brains had hyperphosphorylated tau in all the residues of Ser262, Ser202 and Thr205, with increased phosphorylation of both AMPK (Thr172) and GSK-3β (Ser9), and reduced PP2A levels. Our data suggests a crucial role for a combined activation of tau kinases and phosphatases in adversely affecting memory and that hyperphosphorylation of tau in more than one specific site may be required to create memory deficits.Shohreh Majd, John H.T.Power, Simon A.Koblar, Hugh J.M.Grantha

Early glycogen synthase kinase-3beta and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation.Shohreh Majd, John H. T. Power, Simon A. Koblar and Hugh J. M. Grantha

Nursing Students' Competencies in Evidence-Based Practice and Its Related Factors

Background: Evidence-Based Practice (EBP) is one of the nursing professional roles that can lead them to provide the best and more effective care. However, no studies are available on nursing students’ competencies in EBP. Objectives: This study aimed to investigate the nursing students’ knowledge, attitude and intention to implement EBP and its related factors in two nursing and midwifery faculties in Tehran, Iran. Materials and Methods: In this cross-sectional study, 170 undergraduate nursing students were selected from two faculties of nursing and midwifery in Tehran, Iran. A census sampling method was applied and they were all before graduation in 2013. The Rubin and Parrish questionnaire was used to assess the students’ knowledge, attitude and intention to implement EBP as well as factors affecting the implementation of EBP. Students completed the instrument through self-report. Descriptive statistics, Independent sample t-test and Pearson correlation coefficient were used to analyze the data. Results: The students mean scores of knowledge, attitude and intention to implement EBP was 31.08 ± 5.77, 50.40 ± 9.58, 36.01 ± 4.64, respectively. The students’ age was inversely correlated with their scores of knowledge, attitude and intention to use EBP (P < 0.05). However, the students’ GPA was in direct association with their knowledge, attitude and intention to implement EBP (P < 0.05). No significant differences were observed between the males and females mean scores in the three subscales. However, significant differences were found between the students mean scores in the two subscales of knowledge and attitudes toward EBP in terms of familiarity with statistics and research methods (P < 0.05). Neither familiarity with research methods nor familiarity with EBP could significantly affect the students’ intention to implement EBP. Conclusions: The present study showed that nursing students have not a high mean score in the three subscales of knowledge, attitude and intention to implement EBP. It is essential for faculties and nurse managers not only to focus on education of EBP, but also to support nurses and nursing students to implement it in the process patient care

Audit of Intrapartum Care Based on the National Guideline for Midwifery and Birth Services

© The Author(s) 2018. Providing high-quality maternity care is a worldwide health concern that necessitates regular assessment of intrapartum practice. In an observational study, we aimed to audit intrapartum care based on the National Guideline for Midwifery and Birth Services. Using quota sampling, a total of 200 pregnant women, admitted for normal vaginal delivery, were recruited from four educational hospitals in Tehran, Iran. An observational checklist was developed based on the national guideline to assess the quality of provided care. Content and face validity of the tool were checked and confirmed. Reliability of the observational checklist and questionnaire was confirmed using concurrent observation (intrarater reliability; r =.93) and test–retest (r =.9) methods, respectively. We found that the compatibility of intrapartum care and the national guideline in different domains were as follows: history taking 88.3%, vital sign measurement 64.6%, performing Leopold’s maneuver 38.5%, initial assessment 83.4%, labor care 22.5%, using pain relief methods 63.5%, labor progress assessment 71.5%, process of delivery 89.5%, and postpartum management 89.5%. The findings indicate that additional attention and monitoring are required to align current intrapartum care practices with the national guidelines

Second Molar Uprighting with Temporary Anchorage Devices: A Finite Element Study

BACKGROUND AND OBJECTIVE: Premature loss of mandibular first molar is a common problem in adults. Mesial tipping of second molar may occur in this situation. Various orthodontic mechanics have been proposed for molar uprighting. The aim of this study was to compare four methods of molar uprighting using Finite Element Analysis(FEM). METHODS: In first model of this finite element study, a 0.019×0.025 inch beta-titanium segmental arch wire with a T-loop was used. In second model a miniscrew was inserted in retromolar space and force was applied using elastomeric chain. The third model was a piece of 0.016×0.022inch beta-titanium wire with a bend which was placed more occlusal than the screw. The fourth model contained a mesially inserted miniscrew with an angle of 70 degrees to bone surface and a 0.018×0.025inch beta-titanium wire with helix. Extrusion, center of rotation and stress distribution in PDL during movement was compared between methods. FINDINGS: Buccal cusp extruded 1.36E-03, 1.13E-03, -9.74E-04 and 1.49E-03 mm in first, second, third and fourth model, respectively. Similarly, in lingual cusp, the amount of vertical displacement was at least in third model (-6.83E-04 mm). This amount in second and first method was 1.12E-03 and 4.05E-04 mm, respectively. The maximum amount of extrusion of lingual cusp occurred in fourth model (9.01E-03 mm). Mesial and distal cusps extruded 2.12E-04 and 1.58E-03 mm in first model, -1.14E-03 and 3.80E-03 mm in second method, -2.37E-03 and 7.04E-04 mm in third design and, 1.88E-03 and 8.57E-03 mm in the fourth model. The center of rotation was located at molar bifurcation in third model. CONCLUSION: The maximum amount of extrusion in both mesiodistal and buccolingual path was seen in fourth model. The best type of movement was found in third model, in which minimum extrusion occurred and center of rotation located at molar bifurcation

Fluoride produces endothelium-dependent relaxation and endothelium-independent contraction in coronary artery

ABSTRACT NaF produced endothelium-dependent relaxation and endothehum-independent contraction in porcine, bovine, canine and human coronary artery rings precontracted with either KCI or prostaglandin F2a