Glucose derived carbon nanosphere (CSP) conjugated TTK21, an activator of the histone acetyltransferases CBP/p300, ameliorates amyloid-beta 1-42 induced deficits in plasticity and associativity in hippocampal CA1 pyramidal neurons.

The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer's disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small-molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aß-impaired long-term potentiation (LTP) induced by high-frequency stimulation, theta burst stimulation, and synaptic tagging/capture (STC). This functional rescue was correlated with CSP-TTK21-induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity- and memory-related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small-molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD.

What evidence do economic evaluations in dental care provide? A scoping review.

OBJECTIVE: To collate the body of evidence in economic studies of different dental interventions. METHODS: Eligible English studies after 1980 were sourced from MEDLINE using MeSH terms and reviewed independently by 4 teams. Studies were grouped according to the type of dental intervention and their quality appraised using Drummond's Checklist. RESULTS: The number of dental economic studies increased from 1980 to 2016. A total of 91 studies were identified following the search strategy. Most studies were conducted in the United States (n=23), followed by Germany (n=14), Australia (n=10) and the United Kingdom (n=9). Preventative dental interventions comprised 37% of included studies (n=34), followed by restorative (n=14), prosthodontic (n=13) and periodontal interventions (n=12). Cost effectiveness analyses (n=68) comprise 75% of full economic evaluation (EE) studies, followed by cost-utility (n=17) and cost-benefit (n=6). Quality assessment checklists identified 60 studies as good, 23 as moderate and 8 as poor. Common methodological limitations were identified in EE studies. Comparison of studies identified trends and common findings within each dental intervention. CONCLUSION: High quality economic studies are important in directing resources and funding by policy makers. Standardisation of reporting outcome measures will improve the potential for interpretation and comparison between studies. Research adhering to recommended quality assessment checklists will improve the overall quality of evidence to better identify cost-effective treatments for different dental interventions.

ß-aminobutyric acid mediated drought stress alleviation in maize (Zea mays L.).

The present study highlights the role of ß-aminobutyric acid (BABA) in alleviating drought stress effects in maize (Zea mays L.). Chemical priming was imposed by pretreating 1-week-old plants with 600 µM BABA prior to applying drought stress. Specific activities of key antioxidant enzymes and metabolites (ascorbate and glutathione) levels of ascorbate-glutathione cycle were studied to unravel the priming-induced modulation of plant defense system. Furthermore, changes in endogenous ABA and JA concentrations as well as mRNA expressions of key genes involved in their respective biosynthesis pathways were monitored in BABA-primed (BABA+) and non-primed (BABA-) leaves of drought-challenged plants to better understand the mechanistic insights into the BABA-induced hormonal regulation of plant response to water-deficit stress. Accelerated stomatal closure, high relative water content, and less membrane damage were observed in BABA-primed leaves under water-deficit condition. Elevated APX and SOD activity in non-primed leaves found to be insufficient to scavenge all H2O2 and O2 (·-) resulting in oxidative burst as evident after histochemical staining with NBT and DAB. A higher proline accumulation in non-primed leaves also does not give much protection against drought stress. Increased GR activity supported with the enhanced mRNA and protein expressions might help the BABA-primed plants to maintain a high GSH pool essential for sustaining balanced redox status to counter drought-induced oxidative stress damages. Hormonal analysis suggests that in maize, BABA-potentiated drought tolerance is primarily mediated through JA-dependent pathway by the activation of antioxidant defense systems while ABA biosynthesis pathway also plays an important role in fine-tuning of drought stress response.

Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.

The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P < 0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P < 0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.

Atomistic origin of an ordered superstructure induced superconductivity in layered chalcogenides.

Interplay among various collective electronic states such as charge density wave and superconductivity is of tremendous significance in low-dimensional electron systems. However, the atomistic and physical nature of the electronic structures underlying the interplay of exotic states, which is critical to clarifying its effect on remarkable properties of the electron systems, remains elusive, limiting our understanding of the superconducting mechanism. Here, we show evidence that an ordering of selenium and sulphur atoms surrounding tantalum within star-of-David clusters can boost superconductivity in a layered chalcogenide 1T-TaS2-xSex, which undergoes a superconducting transition in the nearly commensurate charge density wave phase. Advanced electron microscopy investigations reveal that such an ordered superstructure forms only in the x area, where the superconductivity manifests, and is destructible to the occurrence of the Mott metal-insulator transition. The present findings provide a novel dimension in understanding the relationship between lattice and electronic degrees of freedom.

Real-space coexistence of the melted Mott state and superconductivity in Fe-substituted 1T-TaS2.

We have performed high-resolution angle-resolved photoemission spectroscopy of layered chalcogenide 1T-Fe(x)Ta(1-x)S(2) which undergoes a superconducting transition in the nearly commensurate charge-density-wave phase (melted Mott phase). We found a single electron pocket at the Brillouin-zone center in the melted Mott phase, which is created by the backfolding of bands due to the superlattice potential of charge-density-wave. This electron pocket appears in the x region where the samples show superconductivity, and is destroyed by the Mott- and Anderson-gap opening. Present results suggest that the melted Mott state and the superconductivity coexist in real space, providing a new insight into the interplay between electron correlation, charge order, and superconductivity.

A randomized study of the efficacy and safety of intravenous acetaminophen vs. intravenous placebo for the treatment of fever.

This randomized, double-blind, placebo-controlled study evaluated the antipyretic effect and safety of intravenous (i.v.) acetaminophen using an endotoxin-induced fever model. Subjects exhibiting sufficient fever response following administration of reference standard endotoxin (RSE) were randomly assigned to receive i.v. acetaminophen 1,000 mg (n = 31) or matching placebo (n = 29). The primary efficacy end point was the weighted sum of temperature differences from baseline through 6 h. Relative to placebo, i.v. acetaminophen administration produced a rapid decrease in temperature that persisted throughout the 6-h study period. The primary end point favored i.v. acetaminophen over placebo (P < 0.001). Temperature differences from baseline reached statistical significance at T30 min after endotoxin administration (15 min after completing the study medication infusion). Acetaminophen administered i.v. was well tolerated, and the frequency of adverse events was comparable to that after administration of i.v. placebo. This study shows that i.v. acetaminophen in a single 1,000-mg dose is safe and effective in reducing fever.

Randomised, double-blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis.

OBJECTIVE: This study aimed to determine whether a new glyceryl trinitrate patch preparation is effective in treating chronic lateral epicondylosis. DESIGN: Randomised double-blind controlled clinical trial. SETTING: Private practice PATIENTS: 154 adult patients with chronic lateral epicondylosis were recruited, with 136 patients completing the trial. INTERVENTIONS: 8 weeks of glyceryl trinitrate patch application (dosages of 72 mg/24 h, 1.44 mg/24 h, and 3.6 mg/24 h), or placebo patch application. MAIN OUTCOME MEASURES: Subjective global assessment of change in elbow symptoms, patient-rated tennis elbow evaluation, visual analogue pain at rest, visual analogue pain with activity, visual analogue pain intensity, grip strength, and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System. RESULTS: At 8 weeks there was a significant decrease in elbow pain with activity in the glyceryl trinitrate 0.72 mg/24 h group compared with placebo (p = 0.04). There were no other significant differences. CONCLUSIONS: Continuous 1.25 mg/24 h topical glyceryl trinitrate treatment, when combined with daily exercise rehabilitation, has previously demonstrated efficacy in treating chronic lateral epicondylosis. There was significantly decreased elbow pain with activity at 8 weeks in the glyceryl trinitrate 0.72 mg/24 h group (p = 0.04). This short-term dose-ranging study did not demonstrate a treatment effect of a new topical glyceryl trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h, which conflicts with previous studies on topical glyceryl trinitrate treatment. TRIAL REGISTRATION NUMBER: NCT00447928.

Effects of cognitive-behavioural therapy on anxiety for children with high-functioning autistic spectrum disorders.

INTRODUCTION: Children with autistic spectrum disorders (ASD) often exhibit one or more comorbid disorders, including anxiety, disruptive behaviour, mental retardation, and depression. Various studies have documented the effectiveness of cognitive-behavioural therapy (CBT) in treating children with anxiety. Although studies have indicated a high prevalence of anxiety in individuals with ASD, there is a lack of systematic studies substantiating the effectiveness of cognitive-behavioural interventions among children with high-functioning autism. METHODS: This pilot study investigated the effects of a 16-session CBT programme on six high-functioning children diagnosed with ASD (mean age 11.50 years, standard deviation 0.84 years). These children were diagnosed with ASD or Asperger's syndrome by the DSM-IV criteria. Measures on levels of child's anxiety, parental and teacher stress were administered at pre- and post-treatment. RESULTS: Children showed lower levels of anxiety at post-treatment. Parents and teachers also reported lower levels of stress following the CBT programme. CONCLUSION: Findings from the present study provided some evidence of the effects of CBT for high-functioning autistic children in reducing anxiety, parental and teacher stress. Interpretation of the findings, recommendations for future research and implications of the present study are presented.

Identification of immunodominant VP1 linear epitope of enterovirus 71 (EV71) using synthetic peptides for detecting human anti-EV71 IgG antibodies in Western blots.

A major IgG-specific immunodominant VP1 linear epitope of enterovirus 71 (EV71) strain 41 (5865/SIN/00009), defined by the core sequence LEGTTNPNG, was identified by Pepscan analysis. Oligonucleotides corresponding to the amino-acid sequence of synthetic peptide SP32 were cloned and over-expressed in Escherichia coli as a recombinant glutathione-S-transferase (GST)-SP32 fusion protein. In ELISAs, this protein did not react with human anti-EV71 IgG antibodies, but there was significant immunoreactivity according to western blot analysis. The amino-acid sequence of SP32 was highly specific for detecting EV71 strains in western blot analysis, and showed no immunoreactivity with monoclonal antibodies raised against other enteroviruses, e.g., CA9 and Echo 6.

Gadolinium use in spine procedures for patients with allergy to iodinated contrast--experience of 127 procedures.

BACKGROUND AND PURPOSE: To review the safety and efficacy of gadolinium as a contrast agent in spine pain management procedures in patients who are at high risk for a contrast reaction and are therefore unacceptable candidates for the use of standard nonionic contrast. METHODS: We reviewed our records over a 4-year period of interlaminar and foraminal epidural steroid injections, nerve blocks, facet injections, intercostal blocks, and diskograms in the lumbar, thoracic, and cervical spine for cases in which patients had allergies that made them unsuitable candidates for standard nonionic contrast and where gadolinium was used to confirm needle tip placement before injection of medication. RESULTS: Ninety-two patients underwent 127 procedures. A spinal needle was used in all but 7 procedures. All patients were outpatients and all were discharged without complication after 20 to 45 minutes with follow-up instructions. No delayed complications were reported. Gadolinium was visualized by using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. For epidural steroid injection, the gadolinium dose ranged from 1 to 5 mL, nerve blocks from 0.2 to 1 mL per level, facet injections from 0.2 to 0.5 mL per level, intercostal blocks used 0.5 mL, and diskograms from 1.5 to 7.5 mL per level. The highest dose received by 1 patient was an intradiskal 15.83 mL during a 3-level diskogram. CONCLUSION: Gadolinium seems to be a safe alternative to standard nonionic contrast in spine pain management procedures in those patients considered to be at high risk for a contrast reaction.

COX inhibitors and breast cancer.

There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Preclinical evidence favours an antitumour role for COX inhibitors in breast cancer. However, the epidemiological evidence for an association is conflicting. Trials are being conducted to study the use of COX inhibitors alone and in combination with other agents in the chemoprevention of breast cancer, and in the neo-adjuvant, adjuvant, and metastatic treatment settings. In evaluating the potential use of these agents particularly in cancer chemoprophylaxis, the safety profile is as important as their efficacy. Concern over the cardiovascular safety of both selective and nonselective COX-inhibitors has recently been highlighted.

Dry eye after refractive surgery.

Photorefractive keratectomy and laser in situ keratomileusis can induce or exacerbate dry eye after surgery. This manifests as an increase in degree and frequency of symptoms, corneal findings, such as superficial punctate keratopathy, and abnormal results of dry eye tests, such as the Schirmer test and tear break-up time. The cause mainly involves decreased corneal sensation, resulting in decreased feedback to the lacrimal gland and reduced tear production. Other causes may include increased evaporation, inflammation, or toxicity of medications. Dry eye may result infrequently in impaired wound healing and decreased optical quality of the cornea, but it is transient, lasting from a few weeks up to 1 year. Patients should be warned about this distressing complication. During a period of dry eye, artificial tears and punctal plugs are helpful in preventing or alleviating patient discomfort.

Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy.

Laser epithelial keratomileusis (LASEK) is a surgical technique that may be performed in patients with low myopia who are considering conventional photorefractive keratectomy (PRK), in patients with thin corneas, and in patients with professions or lifestyles that predispose them to trauma. Ethanol (18%) is applied for 25 seconds and a hinged epithelial flap is created. After laser ablation, the flap is repositioned over the ablated stroma. Our data showed that epithelial defects occurred in 63% eyes on Day 1. Postoperative pain was absent in 47%. Uncorrected visual acuity of 20/40 or better was achieved in all patients at 1 week. Data from several studies suggest that LASEK may reduce postoperative pain and corneal haze associated with PRK. LASEK offers the potential advantage of avoiding flap-related complications associated with laser in situ keratomileusis and decreasing postoperative pain and corneal scarring associated with PRK. Long-term studies are needed to confirm these potential advantages and to determine the safety, efficacy, and predictability of this surgical technique.

Effect of different endotracheal suctioning systems on cardiorespiratory parameters of ventilated patients.

INTRODUCTION: We conducted this prospective randomised cross-over study to evaluate the effect of closed system (CS) versus open system (OS) endotracheal suctioning on heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), oxygen saturation (SpO2) and electrocardiogram (ECG) rhythm of patients on mechanical ventilation. MATERIALS AND METHODS: Fourteen adult patients were randomly allocated to receive either CS or OS suctioning in the first instance. For the subsequent suctioning, they were crossed over to the alternate suctioning system. The various cardiorespiratory parameters were recorded at BL1 (baseline 1), S1 (first suction pass), BL2 (baseline 2, i.e. immediately post first suction pass), S2 (second suction pass), T2 (2 minutes post suction) and T5 (5 minutes post suction). RESULTS: Compared to CS, OS suctioning was found to result in higher HR at S1 (P < or = 0.05) and S2 (P < or = 0.05); higher MAP at BL2 (P < or = 0.05); lower SpO2 at BL2 (P < or = 0.01) and S2 (P < or = 0.01). There was no significant difference in RR between the two suctioning systems. OS suctioning was also noted to result in a significantly higher incidence of arrhythmia (P < = or 0.05). CONCLUSION: Our study shows that OS suctioning results in more adverse changes in cardiorespiratory parameters compared to CS suctioning.

Brimonidine 0.2% versus apraclonidine 0.5% for prevention of intraocular pressure elevations after anterior segment laser surgery.

OBJECTIVE: To compare the efficacy of brimonidine 0.2% with apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. DESIGN: Double-masked, randomized clinical trial. PARTICIPANTS: Sixty-six patients underwent either laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:yttrium-aluminum-garnet laser capsulotomy. INTERVENTION: Eyes received either one drop of brimonidine 0.2% or apraclonidine 0.5% before laser surgery. MAIN OUTCOME MEASURES: Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. RESULTS: Before the laser treatment, 33 patients (50.0%) received brimonidine 0.2% and 33 patients (50.0%) received apraclonidine 0.5%. Eight of 33 patients (24.2%) in the brimonidine-treated group and 9 of 33 patients (27.3%) in the apraclonidine group had postoperative IOP increases of 5 mmHg or more. This was not statistically different (P = 0.80). By the time of last follow-up examination, 3 of 33 patients (9.1%) in the brimonidine-treated group and 3 of 33 patients (9.1%) in the apraclonidine group had IOP increases of 10 mmHg or more. This was also not statistically different (P > or = 0.95). The mean IOP reduction from baseline in the brimonidine group (-2.8 +/- 2.8 mmHg) was not statistically different (P = 0.55) compared with the mean IOP reduction in the apraclonidine group (-3.6 +/- 3.3 mmHg). There were no statistically significant changes in mean heart rate or blood pressure in either group except for a slight reduction in diastolic blood pressure at 1 hour (P = 0.005) in the brimonidine group (-5.2 +/- 7.4 mmHg) compared with the apraclonidine group (-0.2 +/- 6.4 mmHg). There were no clinically significant side effects noted in either group. CONCLUSIONS: A single preoperative drop of brimonidine 0.2% is as effective as apraclonidine 0.5% in preventing IOP elevation immediately after anterior segment laser surgery.

Managing autonomic dysreflexia through the use of clinical practice guidelines.

One of the goals listed in the American Association of Spinal Cord Injury Nurses (AASCIN) strategic plan 1993-1998, is to provide strategic vision to advance professional practice in spinal cord injury (SCI) nursing. In this quest, along with the development of Standards of Spinal Cord Injury Nursing Practice, the AASCIN Clinical Practice Committee is developing Clinical Practice Guidelines to describe a suggested course of action to address specific clinical conditions or needs of individuals with spinal cord injury. The first Clinical Practice Guideline to be completed is Autonomic Dysreflexia (AD) (Kuric & Hixon, 1996). The purpose of this article is to review the pathophysiology of AD and then describe the symptoms, assessment parameters and nursing interventions suggested in the Clinical Practice Guidelines.

Interdisciplinary professional practice leadership within a program model: BC Rehab's experience.

In restructuring from a departmental to a program management model, BC Rehab successfully developed the role of professional practice leader to address clinical standards of practice and other concerns related to individual disciplines. A review of the role of professional practice leader is presented. Practice leaders are in a unique position to promote interdisciplinary, client-focused service. Because practice leaders' mandates cross program boundaries, they are able to keep the broad scope and goals of rehabilitation in the forefront, offering a balance to the program-specific perspective. It is imperative for practice leaders to maintain connections to operational and clinical issues to avoid isolation.