Evaluation of Sigma Ligand AZ66 Analgesic Potentiation of Cannabinoids

Sigma receptors have become a popular subject for research the past few decades, but there is still much mystery behind these receptors and how they work. Sigma receptors, like cannabinoid-1 (CB1) receptors, have effects on the human body including appetite regulation, depression, and analgesia. AZ66 is a highly selective sigma receptor ligand that has antagonistic properties. Sigma receptor antagonists have been shown to potentiate the analgesic effects of opiates; however, there are no known literature reports about the interaction between the sigma receptor system and the endocannabinoid system, including CB1 receptors. The purpose of this study is to evaluate AZ66 for potentiation of CB1 related analgesic effects. A tetrad assay was performed for AZ66 using doses 5, 10, and 20 mg/kg (i.p.). The tetrad battery was performed one hour post drug (AZ66) administration. The potentiation study was completed using a 20 mg/kg dose of AZ66 against a 0.3 mg/kg dose of CP 55940. The AZ66 dose was administered one hour before the CP 55940 dose administration, and then the analgesic study was performed 15 minutes post CP 55940 dose administration. The tetrad assay showed that AZ66 exhibited no analgesic effects on its own compared to the control compounds. The potentiation study resulted in significant potentiation of the peripheral analgesic effects of CP 55940 with the addition of AZ66 and insignificant potentiation of central analgesic effects. Future studies will be performed to validate the findings of this study and to further examine the interaction between the sigma receptor system and the cannabinoid system.

Heparin-Peptide Interactions

Heparin is a polydispersed sulfated molecule that is part of the family called glycosaminoglycans found in the extracellular matrix and cell surfaces. This molecule is extremely important for the activation of proteins and protein-receptor interactions that are responsible for downstream cell signaling pathways. Heparin has been isolated from porcine intestine and used as an anticoagulant for the prevention of embolisms, heart thrombosis, and clotting during heart surgeries. This so-called miracle drug was in use until 2008, when isolated batches were found to be contaminated with other glycosaminoglycans similar to heparin. From 2008, there has been a dire need for a more cost-effective purification of heparin in good yield, to remove the contaminants. Heparin has also been used for affinity chromatography to purify heparin-binding proteins. Recombinant protein purification is an important aspect of biotechnology, with a heavy emphasis on developing easy purification systems for large quantities of homogeneously pure therapeutic proteins at low costs. Several affinity tags have been employed to aid in the expression and purification of various proteins. There are, however, various disadvantages, such as interference with the target protein structure, unsuitable elution conditions, multiple-step purification procedures, and many others. In this context, a novel heparin-binding peptide (HB-peptide) was designed based on the heparin-binding region of acidic fibroblast growth factor (FGF-1). The HB-peptide has been shown to bind to heparin with better affinity than other glycosaminoglycans. A one-step Heparin-Sepharose-based purification procedure was developed for various recombinant proteins using mild elution conditions. Using proteolytic cleavage, the affinity tag was removed to obtain a folded protein. Polyclonal antibodies were also grown against the specific sequence of the HB-peptide, which then were used to successfully and specifically bind fusion proteins that only contained the HB-peptide even at the nanogram level. HB-peptide was then coupled onto a solid matrix to be used as an affinity column, in a similar fashion as heparin-Sepharose with HBPs. A mixture of glycosaminoglycans were separated from each other for the most part. In this context, our HB-peptide can be used as a means to separate glycosaminoglycans, yielding pure heparin for future medical use

A survey on the status of acceptance and commitment training in rural Northern California

The interest in acceptance and commitment training (ACT) from within the applied behavior analysis (ABA) community has increased as evidenced by recently published literature addressing the need to examine the acceptability and utilization of ACT within ABA. However, there is limited literature on the perspectives of those working in the field of ABA on the use of ACT. In the present study a survey was conducted of ABA practitioners working in rural northern California to evaluate their level of interest in ACT, their perceptions of ACT being within the scope of practice of ABA, and any perceived challenges in developing their own personal scope of competence in the use of ACT. The results of the survey found that a majority of respondents were interested in research articles and continuing education courses on ACT and indicated a high level of acceptability of ACT as an intervention that is within the scope of practice of ABA. However, when asked about their confidence level in knowledge of ACT procedures and strategies or their confident level in treatment success when incorporating ACT, most reported that their confident level was neither high nor low. Further, a majority of respondents reported that lack of mentorship and training as the main barrier to development of their own personal scope of competence in using ACT in applied settings. Recommendations and suggestions for future research on addressing these barriers to developing one’s scope of competence in ACT are discussed

Entrepreneurship in the Netherlands; Business transfer

This report is the eighth edition of the series 'Entrepreneurship in the Netherlands'. As demonstrated by the name of the series, the reports focus on entrepreneurship but each year a different aspect of entrepreneurship is studied. This eight report deals with business transfer. In the coming years many entrepreneurs in the Netherlands as well as in Europe will retire and cease trading. This will create a large number of enterprises that will be for sale. However at this stage the market for buying and selling such businesses, at least in the Netherlands, is not very well developed and there is a risk that successful enterprises will be closed unnecessarily. In the framework of their entrepreneurship policy, governments as well as the European Commission have developed actions to stimulate a smooth acquisition of these enterprises. In this report, the business transfer case in the Netherlands and the policy developed by the Dutch Government are described.

Career Strategies of Millennial Generation Female Assistant Coaches

The rate of collegiate female coaches is at an all-time low; but there has been limited research on what might help female coaches succeed. The millennial generation, who grew up with increased athletic opportunities provided by Title IX, is entering the profession, and they may have different views of coaching and athletics than previous generations. The purpose of this study was to investigate what factors influenced millennial generation, female assistant coaches’ aspirations to become head coaches and what strategies they believed would help them successfully navigate their careers. The authors interviewed 10 millennial generation, Division I female assistant coaches and found leadership as athletes, appropriate education, and coaching networks, particularly with female coaches, were common strategies for feeling confident in their careers. These findings may help athletic departments create tools, such as women’s only coaching clinics, to help encourage women to become and remain coaches and provide them with the required support

Validation of AD8-Philippines (AD8-P): A brief informant-based questionnaire for dementia screening in the Philippines

Aim: This study was aimed at validating the Filipino version of AD8 (AD8-P). Methods: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. Results: A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. Conclusion: AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline

The upper limbs after stroke: exploring effects of bilateral training and determinants of recovery

Background: Bilateral task training (BT) may improve upper limb (UL) recovery on the affected as well as non-affected side in longstanding stroke however for acute stroke its effects on physical and psychosocial outcomes compared to unilateral training (UT) has not been clearly established. Furthermore, clinical and demographic factors that influence UL training responses and predict UL recovery are also unclear for acute stroke. PrimaryAims: To compare effects of BT and UT on: • ipsilesional and contralesional UL outcomes • anxiety, depression and health related quality of life (HRQOL) Secondary Aims: To investigate: • which clinical and demographic factors influence contralesional training responses • predictors of UL activity limitation over time for the sample as a whole • UL dysfunction as a predictor of HRQOL six months after stroke for the sample as a whole Design: Single-blinded randomised controlled trial, with outcome assessment at baseline (T1), after 6 weeks training (T2), and 18 week follow-up (T3). Participants: 106 in-patients randomised to receive BT (n=56) or UT (n=50) 2 to 4 weeks after stroke onset. Intervention: Supervised BT or UT for 20 minutes on 5 weekdays, over 6 weeks, using a standardised programme developed for the study. Outcome Measures: UL outcomes: Action Research Arm Test (ARAT), Rivermead Motor Assessment (UL scale), Nine-Hole Peg Test (9HPT). Secondary measures: Modified Barthel Index, Hospital Anxiety and Depression Scale, and Nottingham Health Profile. Assessment was conducted by a blinded assessor. Results: Between the two groups, there were no significant differences at T1 or T2 on any contralesional UL measure or on any psychosocial measure (p>0.05). At T3, 9HPT (p=0.03) and ARAT pinch section scores (p=0.04) in the UT group were significantly higher. None of the selected clinical or demographic factors significantly influenced training responses. BT significantly improved ipsilesional dexterity between T1 and T2 (p=0.04). For the sample as a whole, early ARAT and MBI scores significantly predicted contralesional ARAT scores at T2 and T3. Anxiety, depression and UL impairment significantly predicted overall HRQOL at T3. Conclusions: BT was no more effective than UT for the affected arm – in fact UT was more effective for dexterity. BT was more effective than UT, however, for short-term recovery of ipsilesional dexterity. Future studies should determine optimal BT characteristics for contraand ipsilesional recovery in stroke populations with differing levels of severity. Knowledge of predictors of UL activity limitation and HRQOL will enable therapists to target rehabilitation at factors that most influence these important outcomes.sub_phyunpub138_ethesesunpu

Just Brew It!: Coffee\u27s Impact on a Writing and Communication Center Space

Our panel will present results of a semester-long study on coffee\u27s presence in our Writing and Communication Center and argue for the importance of ephemera in understanding how individuals experience their time in the center. Adding on to the existing discussions about space and writing centers, this presentation will address what has been lacking from the ongoing writing center conversation about coffee—until now

Wet air and related metal ion-catalysed oxidation reactions of methylpyridines.

The Wet Air Oxidation process has considerable attractions for the disposal of toxic organic wastes. In this thesis, a fundamental study is made of the mechanism of oxidation under wet air and related conditions of a series of well-defined substances known to occur as components of industrial wastes, and which are known to present difficulties in the Wet Air Oxidation process. In the initial stages, the oxidation of a series of simple alkylpyridines, namely 2-, 3-, and 4-methylpyridines, has been studied under simulated Wet Air Oxidation plant conditions in a laboratory autoclave operating at 250°C and 250 atmospheres. The progress of the oxidation was followed by withdrawing samples at intervals and subjecting these to chromatographic analysis, using Gas Chromatography-Mass Spectrometry and High Performance Liquid Chromatography, so as to establish the nature of the oxidation products. In the autoclave oxidation of 2-, and 4-methylpyridine, a wide range of oxidation products was detected, including a number of compounds which appeared to be derived from the reactions of pyridylalkyl radicals formed from the parent substance, implying that a free radical mechanism was occurring under Wet Air Oxidation conditions. Under these conditions, 3-methylpyridine appeared to be more resistant to oxidation, the only significant oxidation product being the related aldehyde. The literature suggests that the formation of the hydroxyl radical (OH) under Wet Air Oxidation conditions may be responsible for the initiation of the above reactions, and thus the possibility of catalysis of the above systems by reagents known to generate hydroxyl radicals has been explored. The literature suggests that Fenton's reagent, which is a mixture of iron(ll) and hydrogen peroxide, provides a source of hydroxyl radicals. Thus, the oxidation of the methylpyridines using Fenton's reagent at ambient temperature and atmospheric pressure was carried out and it was also used as a catalyst in the autoclave oxidation reactions. The effectiveness of other metal ion/hydrogen peroxide mixtures was explored, e.g. involving iron(lll), copper(ll), copper(l), titanium(lll), and vanadium(IV), as there is considerable evidence from the literature of their involvement in oxidation chemistry. In all of the oxidation reactions investigated, both under autoclave conditions, and at room temperature, evidence of destructive oxidation of the heteroaromatic ring has been gained for all three methylpyridines. However, in addition to ring destruction products, a range of intermediate oxidation products was observed and similarities were found between those products formed in the autoclave and those reactions carried out in the laboratory. However, recent literature has questioned the formation of hydroxyl radicals by Fenton and related reagents, and so the Fenton catalysed oxidation of each of the methylpyridines was explored further. This was done by the incorporation of appropriate radical trapping agents and complexing agents such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and ethylenediaminetetraacetic acid (EDTA) respectively. In each of the oxidation reactions studied, attempts have been made to identify as many as possible of the products observed by comparison with known substances. However, it has been necessary to develop procedures for the preparation of some of these compounds, notably a range of dimeric structures derived from the simple alkylpyridines, e.g. dipyridylethenes, dipyridylethanes, and dipyridylmethanes