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Long-term inhibition of kappa opioid receptor (KOR) signaling in peripheral pain-sensing neurons is a potential obstacle for development of peripherally-restricted KOR agonists that produce analgesia. Such a long-term inhibitory mechanism is invoked from activation of c-Jun N-terminal kinase (JNK) that follows a single injection of the KOR antagonist norbinaltorphimine (norBNI). This effect requires protein synthesis of an unknown mediator in peripheral pain-sensing neurons. Using 2D difference gel electrophoresis with tandem mass spectrometry, we have identified that the scaffolding protein 14-3-3γ is upregulated in peripheral sensory neurons following activation of JNK with norBNI. Knockdown of 14-3-3γ by siRNA eliminates the long-term reduction in KOR-mediated cAMP signaling by norBNI in peripheral sensory neurons in culture. Similarly, knockdown of 14-3-3γ in the rat hind paw abolished the norBNI-mediated long-term reduction in peripheral KOR-mediated antinociception. Further, overexpression of 14-3-3γ in KOR expressing CHO cells prevented KOR-mediated inhibition of cAMP signaling. These long-term effects are selective for KOR as heterologous regulation of other receptor systems was not observed. These data suggest that 14-3-3γ is both necessary and sufficient for the long-term inhibition of KOR by norBNI in peripheral sensory neurons., Competing Interests: Conflicts of interest Authors report no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pain and pain management in the elderly population is a significant social and medical problem. Pain sensation is a complex phenomenon that typically involves activation of peripheral pain-sensing neurons (nociceptors) which send signals to the spinal cord and brain that are interpreted as pain, an unpleasant sensory experience. In this work, young (4-5 months) and aged (26-27 months) Fischer 344 x Brown Norway (F344xBN) rats were examined for nociceptor sensitivity to activation by thermal (cold and heat) and mechanical stimulation following treatment with inflammatory mediators and activators of transient receptor potential (TRP) channels. Unlike other senses that decrease in sensitivity with age, sensitivity of hindpaw nociceptors to thermal and mechanical stimulation was not different between young and aged F344xBN rats. Intraplantar injection of bradykinin (BK) produced greater thermal and mechanical allodynia in aged versus young rats, whereas only mechanical allodynia was greater in aged rats following injection of prostaglandin E 2 (PGE 2 ). Intraplantar injection of TRP channel activators, capsaicin (TRPV1), mustard oil (TRPA1) and menthol (TRPM8) each resulted in greater mechanical allodynia in aged versus young rats and capsaicin-induced heat allodynia was also greater in aged rats. A treatment-induced allodynia that was greater in young rats was never observed. The anti-allodynic effects of intraplantar injection of kappa and delta opioid receptor agonists, salvinorin-A and D-Pen 2 ,D-Pen 5 ]enkephalin (DPDPE), respectively, were greater in aged than young rats, whereas mu opioid receptor agonists, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) and morphine, were not effective in aged rats. Consistent with these observations, in primary cultures of peripheral sensory neurons, inhibition of cAMP signaling in response to delta and kappa receptor agonists was greater in cultures derived from aged rats. By contrast, mu receptor agonists did not inhibit cAMP signaling in aged rats. Thus, age-related changes in nociceptors generally favor increased pain signaling in aged versus young rats, suggesting that changes in nociceptor sensitivity may play a role in the increased incidence of pain in the elderly population. These results also suggest that development of peripherally-restricted kappa or delta opioid receptor agonists may provide safer and effective pain relief for the elderly., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, novel electrospun nanofibers (NFs) composed of organic polyvinylidine fluoride (PVDF) and inorganic Fe-Mn binary oxide (FMBO) nanoparticles were fabricated using an electrospinning technique for adsorptive decontamination of As(v) from polluted water. The NFs were prepared with doped solutions consisting of different weight ratios of PVDF/FMBO, in a NF matrix, ranging from 0 to 0.5. SEM, XRD, FTIR and TEM then characterized the NFs and FMBO particles. The XRD analysis indicated successful impregnation of FMBO nanoparticles in the NF matrix of the NFs investigated. An As(v) adsorption capacity as high as around 21.32 mg g -1 was obtained using the NF containing the highest amount of FMBO nanoparticles (designated as PVDF/FMBO 0.5). Furthermore, the adsorptive performance of the PVDF/FMBO 0.5 nanofiber could be easily regenerated using diluted alkaline solution (NaOH and NaOCl)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Receptor heteromers often display distinct pharmacological and functional properties compared to the individual receptor constituents. In this study, we compared the properties of the DOP-KOP heteromer agonist, 6'-guanidinonaltrindole (6'-GNTI), with agonists for DOP ([D-Pen2,5]-enkephalin [DPDPE]) and KOP (U50488) in peripheral sensory neurons in culture and in vivo. In primary cultures, all three agonists inhibited PGE 2 -stimulated cAMP accumulation as well as activated extracellular signal-regulated kinase 1/2 (ERK) with similar efficacy. ERK activation by U50488 was Gi-protein mediated but that by DPDPE or 6'-GNTI was Gi-protein independent (i.e., pertussis toxin insensitive). Brief pretreatment with DPDPE or U50488 resulted in loss of cAMP signaling, however, no desensitization occurred with 6'-GNTI pretreatment. In vivo, following intraplantar injection, all three agonists reduced thermal nociception. The dose-response curves for DPDPE and 6'-GNTI were monotonic whereas the curve for U50488 was an inverted U-shape. Inhibition of ERK blocked the downward phase and shifted the curve for U50488 to the right. Following intraplantar injection of carrageenan, antinociceptive responses to either DPDPE or U50488 were transient but could be prolonged with inhibitors of 12/15-lipoxgenases (LOX). By contrast, responsiveness to 6'-GNTI remained for a prolonged time in the absence of LOX inhibitors. Further, pretreatment with the 12/15-LOX metabolites, 12- and 15- hydroxyeicosatetraenoic acid, abolished responses to U50488 and DPDPE but had no effect on 6'-GNTI-mediated responses either in cultures or in vivo. Overall, these results suggest that DOP-KOP heteromers exhibit unique signaling and functional regulation in peripheral sensory neurons and may be a promising therapeutic target for the treatment of pain., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Opioid receptors expressed by peripheral pain-sensing neurons are functionally inactive for antinociceptive signaling under most basal conditions; however, tissue damage or exposure to inflammatory mediators (e.g., bradykinin) converts these receptors from a nonresponsive state to a functionally competent state. Here we tested the hypothesis that the basal, nonresponsive state of the mu- and delta-opioid receptors (MOR and DOR, respectively) is the result of constitutive receptor activity that activates desensitization mechanisms, resulting in MOR and DOR receptor systems that are constitutively desensitized. Consistent with our previous findings, under basal conditions, neither the MOR agonist [d-Ala 2 ,N-MePhe 4 ,Gly-ol 5 ]-enkephalin nor the DOR agonist [d-Pen 2,5 ]-enkephalin, inhibited prostaglandin E 2 (PGE 2 )-stimulated cAMP accumulation in peripheral sensory neurons in culture (ex vivo) or inhibited PGE 2 -stimulated thermal allodynia in the rat hind paw in vivo. Prolonged treatment with naloxone induced MOR and DOR responsiveness both in vivo and ex vivo to a similar magnitude as that produced by bradykinin. Also similar to bradykinin, the effect of naloxone persisted for 60 minutes after washout of the ligand. By contrast, prolonged treatment with 6β-naltrexol, did not induce functional competence of MOR or DOR but blocked the effect of naloxone. Treatment with siRNA for β-arrestin-2, but not β-arrestin-1, also induced MOR and DOR functional competence in cultured peripheral sensory neurons. These data suggest that the lack of responsiveness of MOR and DOR to agonist for antinociceptive signaling in peripheral sensory neurons is due to constitutive desensitization that is likely mediated by β-arrestin-2., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Introduction: Due to the increasing prevalence of arteriosclerosis and the mortality caused by this disease, Coronary Artery Bypass Graft (CABG) has become one of the most common surgical procedures. Utilization of patient education is approved as an effective solution for increasing patient survival and outcomes of treatment. However, failure to consider different aspects of patient education has turned this goal into an unattainable one. The objective of this research was to determine the effect of utilizing the organizational culture improvement model of patient education on CABG patients' anxiety and satisfaction., Methods: The present study is a randomized controlled trial. This study was conducted on eighty CABG patients. The patients were selected from the CCU and Post-CCU wards of a hospital affiliated with Iran University of Medical Sciences in Tehran, Iran, during 2015. Eshpel Burger's Anxiety Inventory and Patients' Satisfaction Questionnaire were used to collect the required information. Levels of anxiety and satisfaction of patients before intervention and at the time of release were measured. The intervention took place after preparing a programmed package based on the organizational culture improvement model for the following dimensions: effective communication, participatory decision-making, goal setting, planning, implementation and recording, supervision and control, and improvement of motivation. After recording the data, it was analyzed in the chi-square test, t-independent and Mann-Whitney U tests. The significance level of tests was assumed to be 0.05. SPSS version 18 was also utilized for data analysis., Results: Research results revealed that variations in the mean scores of situational and personality anxiety of the control and experiment group were descending following the intervention, but the decrease was higher in the experiment group (p≤0.0001). In addition, the variations of the mean scores of patients' satisfaction with education were higher in the experiment group than the control group (p≤0.0001)., Conclusion: Utilization of the organizational culture improvement model of patient education reduces stress in CABG patients and increases their satisfaction with the provided education considering the factors involved in patient education, which were incorporated in the designed model., Competing Interests: There is no conflict of interest to be declared.

A single administration of the κ opioid receptor (KOR) antagonist, norbinaltorphimine (norBNI), produces long-term reduction in KOR function in heterologous expression systems and brain that is mediated by activation of c-Jun N-terminal kinase (JNK). In this study, we examined the long-term effects of norBNI on adult rat peripheral sensory neurons in vivo and ex vivo. Following a single intraplantar (i.pl.) injection of norBNI into the hind paw, peripheral KOR-mediated antinociception in the ipsilateral, but not the contralateral, hindpaw was abolished for at least 9 days. By contrast, the antinociceptive response to mu and delta opioid receptor agonists was unaltered. The long-term inhibitory effect on antinociception produced by pretreatment with norBNI required occupancy of peripheral KOR and was completely blocked by i.pl. injection of the JNK inhibitor, SP600125. In cultures of peripheral sensory neurons, norBNI activated JNK for at least 30 minutes. Furthermore, norBNI blocked KOR-mediated inhibition of adenylyl cyclase activity measured 24 hours later in a JNK-dependent manner, but did not block activation of extracellular signal-regulated kinase (ERK). The long-term inhibitory effect of norBNI on KOR function in vivo and ex vivo was blocked by inhibitors of mRNA translation, cycloheximide and rapamycin. These data suggest that in peripheral sensory neurons norBNI is a KOR-biased ligand for activation of JNK signaling, resulting in long-term blockade of some (antinociception, inhibition of adenylyl cyclase activity), but not all (ERK), KOR signaling. Importantly, norBNI elicits de novo protein synthesis in sensory neuron terminals that produces selective long-term regulation of KOR., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Nursing students, particularly at the time of entering clinical education, experience a great deal of stress and emotion typically related to their educational and clinical competence. Emotional intelligence is known to be one of the required skills to effectively cope with such feelings. The aim of this study was to investigate the effect of training on first-year nursing students' levels of emotional intelligence. This was a quasi-experiment study in which 69 first-year nursing students affiliated with Tehran University of Medical Sciences were assigned to either the control or the experimental groups. The study intervention included of an emotional intelligence educational program offered in eight two-hour sessions for eight subsequent weeks. In total, 66 students completed the study. The study groups did not differ significantly in terms of emotional intelligence scores before and after educational program. Although the educational program did not have an effect on students' emotional intelligence scores, this study finding can be explained. Limited time for exercising the acquired knowledge and skills may explain the non-significant findings. Moreover, our participants were exclusively first-year students who had no clinical experience and hence, might have felt no real need to learn emotional intelligence skills., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Activation of kappa opioid receptors (KORs) expressed by peripheral sensory neurons that respond to noxious stimuli (nociceptors) can reduce neurotransmission of pain stimuli from the periphery to the central nervous system. We have previously shown that the antinociception dose-response curve for peripherally restricted doses of the KOR agonist (-)-(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50488) has an inverted U shape. Here, we found that the downward phase of the U50488 dose-response curve was blocked by an inhibitor of extracellular signal-regulated kinase (ERK) activation U0126. Local administration of the selective KOR agonist salvinorin A (Sal-A), also resulted in an inverted U-shaped curve; however, the downward phase was insensitive to U0126. By contrast, inhibition of c-Jun N-terminal kinase (JNK) partially blocked the downward phase of the dose-response curve to Sal-A, suggesting a role for JNK. In cultures of peripheral sensory neurons, U50488 and Sal-A inhibited adenylyl cyclase activity with similar efficacies; however, their ability to activate ERK and JNK differed. Whereas U50488 activated ERK but not JNK, Sal-A activated JNK but not ERK. Moreover, although both U50488 and Sal-A produced homologous desensitization, desensitization to U50488 was blocked by inhibition of ERK activation, whereas desensitization to Sal-A was blocked by inhibition of JNK. Substitution of an ethoxymethyl ether for the C2 position acetyl group of Sal-A reduced stimulation of JNK, prevented desensitization by ethoxymethyl ether for the C2 position acetyl group of Sal-A, and resulted in a monotonic antinociception dose-response curve. Collectively, these data demonstrate the functional selectivity of KOR ligands for signaling in peripheral sensory neurons, which results in differential effects on behavioral responses in vivo., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Background and Aims: The first step in each systematic review is selection of the most valid database that can provide the highest number of relevant references. This study was carried out to determine the most suitable database for information retrieval in telemedicine field., Methods: Cinhal, PubMed, Web of Science and Scopus databases were searched for telemedicine matched with Education, cost benefit and patient satisfaction. After analysis of the obtained results, the accuracy coefficient, sensitivity, uniqueness and overlap of databases were calculated., Results: The studied databases differed in the number of retrieved articles. PubMed was identified as the most suitable database for retrieving information on the selected topics with the accuracy and sensitivity ratios of 50.7% and 61.4% respectively. The uniqueness percent of retrieved articles ranged from 38% for Pubmed to 3.0% for Cinhal. The highest overlap rate (18.6%) was found between PubMed and Web of Science. Less than 1% of articles have been indexed in all searched databases., Conclusion: PubMed is suggested as the most suitable database for starting search in telemedicine and after PubMed, Scopus and Web of Science can retrieve about 90% of the relevant articles.

Objectives: The purpose of this study was to assess living and workplace safety conditions of construction workers in Tehran, Iran., Methods: This cross-sectional study was conducted among 410 construction sites in a municipal area of Tehran whose municipal building permits were issued in 2011. Data on ventilation, workplace safety and hygiene were collected by direct observation and interviews with site foremen. Noise levels were estimated from 10 sound-level-meter stations in the municipality area., Results: Lack of ventilation in the workers' rooms was abundant. Bathrooms were unhygienic and minimum requirements such as lighting and ventilation did not exist in 80% of the cases. In nearly 50% of large construction sites, sewage and garbage disposal were inappropriate. Elevator safety was poor at all sites and no measures for fall prevention were present in over 88% of active construction sites. This study showed that the mean 24-h equivalent continuous sound level Leq was over 70 dB in 80% of the sites during weekdays., Conclusions: The results of this study revealed poor health and safety living and working conditions of construction workers in Tehran.

Introduction: Complementary and alternative medicines have been used to decrease labor pain for many years. Despite reports that some of these methods reduce pain, increase maternal satisfaction, and improve other obstetric outcomes, they have received limited attention in the US medical literature. The purpose of this study was to evaluate the effects of LI4 acupressure on labor pain in the first stage of labor, on labor duration, and on patient satisfaction., Methods: A single, blind, randomized clinical trial was performed with eligible women (N = 100) who were at the beginning of the active phase of labor (3-4 cm dilatation of cervix with regular uterine contractions). The women in the acupressure group (n = 50) received LI4 acupressure at the onset of the active phase for the duration of each uterine contraction over a period of 20 minutes, and the women in the control group (n = 50) received a touch on this point without massage. Labor pain was measured using a structured questionnaire of a subjective labor pain scale (visual analogue scale) before the intervention, immediately after the intervention, 20 and 60 minutes after the intervention, and then every hour., Results: There were significant differences between the groups in subjective labor pain scores immediately and 20, 60, and 120 minutes after intervention (P ≤ .001). Active phase duration (3-4 cm dilatation to full dilatation) and second stage duration (full dilatation to birth) were shorter in the acupressure group. The women in the acupressure group reported greater satisfaction., Discussion: LI4 acupressure was effective at decreasing pain and duration of labor. The participants were satisfied, and no adverse effects were noted., (© 2012 by the American College of Nurse-Midwives.)