Automatic Identification of Pangolin Behavior Using Deep Learning Based on Temporal Relative Attention Mechanism.

With declining populations in the wild, captive rescue and breeding have become one of the most important ways to protect pangolins from extinction. At present, the success rate of artificial breeding is low, due to the insufficient understanding of the breeding behavior characteristics of pangolins. The automatic recognition method based on machine vision not only monitors for 24 h but also reduces the stress response of pangolins. This paper aimed to establish a temporal relation and attention mechanism network (Pangolin breeding attention and transfer network, PBATn) to monitor and recognize pangolin behaviors, including breeding and daily behavior. There were 11,476 videos including breeding behavior and daily behavior that were divided into training, validation, and test sets. For the training set and validation set, the PBATn network model had an accuracy of 98.95% and 96.11%, and a loss function value of 0.1531 and 0.1852. The model is suitable for a 2.40 m × 2.20 m (length × width) pangolin cage area, with a nest box measuring 40 cm × 30 cm × 30 cm (length × width × height) positioned either on the left or right side inside the cage. A spherical night-vision monitoring camera was installed on the cage wall at a height of 2.50 m above the ground. For the test set, the mean Average Precision (mAP), average accuracy, average recall, average specificity, and average F1 score were found to be higher than SlowFast, X3D, TANet, TSN, etc., with values of 97.50%, 99.17%, 97.55%, 99.53%, and 97.48%, respectively. The recognition accuracies of PBATn were 94.00% and 98.50% for the chasing and mounting breeding behaviors, respectively. The results showed that PBATn outperformed the baseline methods in all aspects. This study shows that the deep learning system can accurately observe pangolin breeding behavior and it will be useful for analyzing the behavior of these animals.

The Effect of Genetic Variation on the Sensitivity to Opioid Analgesics in Patients With Postoperative Pain: An Updated Meta-analysis.

BACKGROUND: Responsiveness to opioid analgesics differs among patients with acute postoperative pain. OBJECTIVE: Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids. STUDY DESIGN: An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain. METHODS: PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021. RESULTS: Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human µ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms. LIMITATIONS: Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis. CONCLUSIONS: In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia. KEY WORDS: Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII).

BACKGROUND: Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. METHODS: A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. RESULTS: Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L- T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII­immunized mice. CONCLUSIONS: PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.

Comparison of Venous Blood Gas and Biochemical Parameters in Sunda Pangolin (Manis javanica) and Chinese Pangolin (Manis pentadactyla) before and after Isoflurane Anesthesia.

Venous blood gas analytes are commonly examined in animals, and the results may be important when evaluating the overall health status of an animal. Pangolins are critically endangered mammals, and there is limited information on their physiological reference values in the literature. The aim of this study was to analyze venous blood gas and biochemical parameters before and during isoflurane anesthesia in wild healthy Sunda and Chinese pangolins. The results obtained showed that the blood gas index trends of the two pangolin species before and after isoflurane anesthesia were the same. After anesthesia, the partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), total carbon dioxide (CO2), mean blood bicarbonate (HCO3-), extracellular fluid compartment (BEecf) base excess and the mean blood glucose (Glu) levels of both pangolin species showed a significant increase compared to the pre-anesthesia period. In contrast, the mean blood potassium (K+), lactate (Lac) and mean blood pH levels were significantly lower. No significant differences in the mean blood sodium (Na+) or blood ionized calcium (iCa) levels were observed during anesthesia. This study is important for future comparisons and understanding the health status of this endangered species.

Reprojection Error Analysis and Algorithm Optimization of Hand-Eye Calibration for Manipulator System.

The Euclidean distance error of calibration results cannot be calculated during the hand-eye calibration process of a manipulator because the true values of the hand-eye conversion matrix cannot be obtained. In this study, a new method for error analysis and algorithm optimization is presented. An error analysis of the method is carried out using a priori knowledge that the location of the augmented reality markers is fixed during the calibration process. The coordinates of the AR marker center point are reprojected onto the pixel coordinate system and then compared with the true pixel coordinates of the AR marker center point obtained by corner detection or manual labeling to obtain the Euclidean distance between the two coordinates as the basis for the error analysis. We then fine-tune the results of the hand-eye calibration algorithm to obtain the smallest reprojection error, thereby obtaining higher-precision calibration results. The experimental results show that, compared with the Tsai-Lenz algorithm, the optimized algorithm in this study reduces the average reprojection error by 44.43% and the average visual positioning error by 50.63%. Therefore, the proposed optimization method can significantly improve the accuracy of hand-eye calibration results.

Global Downregulation of Penicillin Resistance and Biofilm Formation by MRSA Is Associated with the Interaction between Kaempferol Rhamnosides and Quercetin.

The rapid development of methicillin-resistant Staphylococcus aureus (MRSA) drug resistance and the formation of biofilms seriously challenge the clinical application of classic antibiotics. Extracts of the traditional herb Chenopodium ambrosioides L. were found to have strong antibiofilm activity against MRSA, but their mechanism of action remains poorly understood. This study was designed to investigate the antibacterial and antibiofilm activities against MRSA of flavonoids identified from C. ambrosioides L. in combination with classic antibiotics, including ceftazidime, erythromycin, levofloxacin, penicillin G, and vancomycin. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the nonvolatile chemical compositions. Reverse transcription (RT)-PCR was used to investigate potential multitargets of flavonoids based on global transcriptional responses of virulence and antibiotic resistance. A synergistic antibacterial and biofilm-inhibiting activity of the alcoholic extract of the ear of C. ambrosioides L. in combination with penicillin G was observed against MRSA, which proved to be closely related to the interaction of the main components of kaempferol rhamnosides with quercetin. In regard to the mechanism, the increased sensitivity of MRSA to penicillin G was shown to be related to the downregulation of penicillinase with SarA as a potential drug target, while the antibiofilm activity was mainly related to downregulation of various virulence factors involved in the initial and mature stages of biofilm development, with SarA and/or σB as drug targets. This study provides a theoretical basis for further exploration of the medicinal activity of kaempferol rhamnosides and quercetin and their application in combination with penicillin G against MRSA biofilm infection. IMPORTANCE In this study, the synergistic antibacterial and antibiofilm effects of the traditional herb C. ambrosioides L. and the classic antibiotic penicillin G on MRSA provide a potential strategy to deal with the rapid development of MRSA antibiotic resistance. This study also provides a theoretical basis for further optimizing the combined effect of kaempferol rhamnosides, quercetin, and penicillin G and exploring anti-MRSA biofilm infection research with SarA and σB as drug targets.

A prognostic analysis of antisynthetase syndrome-related interstitial lung disease.

OBJECTIVE: To analyze prognostic factors of antisynthetase syndrome (ASS)-related interstitial lung disease (ILD). METHODS: We retrospectively collected the data of 77 inpatients with ASS-ILD at our hospital from January 1, 2018, to January 1, 2021. The improvement/stability group and deterioration/death group were defined according to their follow-up outcome. Clinical data of the 2 groups were compared. Univariate analysis was adopted to screen the possible prognostic factors and then logistic regression was used for multivariate analysis. RESULT: After 6 to 42 months of follow-up, 52 patients (67.5%) were classified into the improvement/stability group, and 25 patients (32.5%) were classified into the deterioration/death group. According to the multivariate stepwise logistic regression analysis, respiratory failure (odds ratio [OR] = 6.71, 95% CI: 1.64-27.38, P = .008) and elevated muscle enzymes (OR = 4.31, 95% CI: 1.03-18.05, P = .045) were found to be independent risk factors, while mechanic's hands (OR = 0.06, 95% CI: 0.01-0.37, P = .003) and anti-Jo-1 antibody (OR = 0.24, 95% CI: 0.06-0.93, P = .039) were protective factors. CONCLUSION: The prognostic assessment of ASS-ILD patients should be emphasized. Patients with a poor prognosis should be identified early based on their risk factors to guide clinical management decisions.

Fluorescent Nitrogen-Doped Carbon Dots for Label Live Elder Blood-Stage Plasmodium falciparum through New Permeability Pathways.

To verify the size and emergence time of new permeability pathways (NPPs) in malaria parasites, the permeability of the Plasmodium falciparum-infected erythrocytes was tested with different particle sizes of nanomaterials by flow cytometry assay. The results confirmed the permeability of the host cell membrane increases with parasite maturation for the stage-development evolution of NPPs, and especially found that a particle size of about 50 nm had higher efficiency. As a kind of the novel nanomaterials, nitrogen-doped carbon dots (NCDs) showed no toxicity, specificity binding ability to the malaria parasites, and could label live elder blood-stage P. falciparum through NPPs, indicating the potential application in cell imaging. NPPs and some nanomaterials such as NCDs deserve more attention and exploration for the elimination and prevention of malaria.

High-speed and efficient removal of uranium (VI) from aqueous solution by hydroxyapatite-modified ordered mesoporous carbon (CMK-3).

In recent years, the synthesis and application of green, cost-effective, and sustainable materials for uranium (VI) removal was significant to environmental protection. The ordered mesoporous carbon (CMK-3) supported different mass of hydroxyapatite materials (HAP@CMK-3) were facilely synthesized via hydrothermal method. The resultant materials were characterized by XRD, FT-IR, BET, SEM, TEM mapping, and XPS, and implemented for immobilizing U(VI). Not only the specific surface area of HAP (7.01 m2/g) was increased by the loading on CMK-3 (818.37 m2/g), but also the adsorption capacity of CMK-3 was increased by HAP modification. Impressively, HAP@CMK-3 exhibited highly adsorption capacity of U(VI) with the increase of HAP deposition and was capable of achieving fast reaction. Therein to, the specific surface area of HAP@CMK-3(2:1) was 253.68 m2/g, as well as the adsorption capacity was up to 1072 mg/g (fitted by Langmuir isotherm, at pH=3.0, 298 K) and the adsorption process was completed in 30 min (followed by pseudo-second-order kinetic). The adsorption mechanisms of U(VI) on HAP@CMK-3 involved electrostatic forces, ionic interactions, and chemical complexation. This work offered new avenues to address the limitations of cost and less secondary pollution for the removal of U(IV) from wastewater.

Synergistic Inhibitory Effect of Polymyxin B in Combination with Ceftazidime against Robust Biofilm Formed by Acinetobacter baumannii with Genetic Deficiency in AbaI/AbaR Quorum Sensing.

Carbapenem resistance of Acinetobacter baumannii poses challenges to public health. Biofilm contributes to the persistence of A. baumannii cells. This study was designed to investigate the genetic relationships among carbapenem resistance, polymyxin resistance, multidrug resistance, biofilm formation, and surface-associated motility and evaluate the antibiofilm effect of polymyxin in combination with other antibiotics. A total of 103 clinical A. baumannii strains were used to determine antibiotic susceptibility, biofilm formation capacity, and motility. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting was used to determine the genetic variation among strains. The distribution of 17 genes related to the resistance-nodulation-cell division (RND)-type efflux, autoinducer-receptor (AbaI/AbaR) quorum sensing, oxacillinases (OXA)-23, and insertion sequence of ISAba1 element was investigated. The representative strains were chosen to evaluate the gene transcription and the antibiofilm activity by polymyxin B (PB) in combination with merapenem, levofloxacin, and ceftazidime, respectively. ERIC-PCR-dependent fingerprints were found to be associated with carbapenem resistance and multidrug resistance. The presence of blaOXA-23 was found to correlate with genes involved in ISAba1 insertion, AbaI/AbaR quorum sensing, and AdeABC efflux. Carbapenem resistance was observed to be negatively correlated with biofilm formation and positively correlated with motility. PB in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with deficiency in AbaI/AbaR quorum sensing. Our results not only clarify the genetic correlation among carbapenem resistance, biofilm formation, and pathogenicity in a certain level but also provide a theoretical basis for clinical applications of polymyxin-based combination of antibiotics in antibiofilm therapy. IMPORTANCE Deeper explorations of molecular correlation among antibiotic resistance, biofilm formation, and pathogenicity could provide novel insights that would facilitate the development of therapeutics and prevention against A. baumannii biofilm-related infections. The major finding that polymyxin B in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with genetic deficiency in AbaI/AbaR quorum sensing further provides a theoretical basis for clinical applications of antibiotics in combination with quorum quenching in antibiofilm therapy.

A Nanodrug Coated with Membrane from Brain Microvascular Endothelial Cells Protects against Experimental Cerebral Malaria.

Human malaria is a global life-threatening infectious disease. Cerebral malaria (CM) induced by Plasmodium falciparum parasites accounts for 90% of malaria deaths. Treating CM is challenging due to inadequate treatment options and the development of drug resistance. We describe a nanoparticle formulation of the antimalarial drug dihydroartemisinin that is coated in a biomimetic membrane derived from brain microvascular endothelial cells (BMECs) and test its therapeutic efficacy in a mouse model of experimental cerebral malaria (ECM). The membrane-coated nanoparticle drug has a prolonged drug-release profile and enhanced dual targeting killing efficacy toward parasites residing in red blood cells (iRBCs) and iRBCs obstructed in the BMECs (for both rodent and human). In a mice ECM model, the nanodrug protects the brain, liver, and spleen from infection-induced damage and improves the survival rate of mice. This so-called nanodrug offers new insight into engineering nanoparticle-based therapeutics for malaria and other parasitic pathogen infections.

The Interface between Nanoenergy and Self-Powered Electronics.

In recent decades, nanogenerators based on several techniques such as triboelectric effects, piezoelectric effects, or other mechanisms have experienced great developments. The nanoenergy generated by nanogenerators is supposed to be used to overcome the problem of energy supply problems for portable electronics and to be applied to self-powered microsystems including sensors, actuators, integrated circuits, power sources, and so on. Researchers made many attempts to achieve a good solution and have performed many explorations. Massive efforts have been devoted to developing self-powered electronics, such as self-powered communication devices, self-powered human-machine interfaces, and self-powered sensors. To take full advantage of nanoenergy, we need to review the existing applications, look for similarities and differences, and then explore the ways of achieving various self-powered systems with better performance. In this review, the methods of applying nanogenerators in specific circumstances are studied. The applications of nanogenerators are classified into two categories, direct utilization and indirect utilization, according to whether a treatment process is needed. We expect to offer a line of thought for future research on self-powered electronics.

Optimal Management of the Public and Patients by Pharmacists in the Era of COVID-19: An Evidence-Based Review and Practical Recommendations.

Purpose: Currently, managing the public and patients during the COVID-19 pandemic is constituting a health care challenge worldwide. Patient-oriented management is of crucial importance to promote emergency preparedness and response. This study aims to formulate an integrated pharmacist management strategy of the public and patients and to provide evidence-based and practical references. Methods: Evidence-based review and practical analysis were utilized. First, PubMed, EMBASE and Chinese database were searched. Studies about patient management in major public health emergencies were included. Second, the Chinese experience of patient management was analyzed and identified. Finally, combining evidence-based and practical analysis, the pharmacist management strategy of the public and patients was researched and summarized. Results: Regarding the home quarantine period, pharmacist management services should include medication guidance, guidance on risk monitoring, sanitation measures education, health management guidance and psychological support. Regarding the outpatient visit period, pharmacists should participate in the control of in-hospital infections and provide physician-pharmacist joint clinic services, pharmacy clinic services, medication therapy management, medication consultation services, drug supply guarantee and drug dispensing services. Regarding the hospitalization period, pharmacist management services should include monitoring and evaluating the safety and efficacy of medications, providing strengthened care for special populations and other pharmaceutical care. For non-hospitalized or discharged patients, pharmacist management services should include formulating medication materials and establishing pharmacy management files for discharged patients. Conclusion: An evidence-based, patient-centered and entire-process-integrated pharmacist management strategy of the public and patients is established, which remedies the gaps in the existing patient management and can be implemented to support pharmacists' contributions to COVID-19 pandemic control.

Interictal epileptiform discharges were associated with poorer cognitive performance in adult epileptic patients.

OBJECTIVE: Cognitive impairment is one of the major consequences of epilepsy and has been shown to reduce quality of life. Interictal epileptiform discharges (IEDs) were associated with poorer cognitive performance in children, and the aim of this study was to determine whether there was a similar association in adults. METHODS: A prospective cohort of 167 seizure-free adult patients underwent EEG recording and extensive cognitive evaluations. Global cognition was evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), while sub-dimensions of cognition were evaluated using the Auditory Verbal Learning Test (AVLT), Trial Making Test (TMT)-A and -B, and the 5 constitutive subscales of ACE-R. RESULTS: Performance in ACER, but not AVLT or TMT, was significantly lower in patients with general IEDs. Furthermore, the five subscale scores of ACE-R were significantly lower in patients with general IEDs, and verbal fluency and language scores contributed in a major way to the low scores. Stratified analysis showed that sleep-phase IEDs were also associated with lower performance in ACE-R and its subscales. Finally, non-rapid eye movement (NREM)-IEDs were found to be associated with visuospatial and memory impairment, and IEDs while awake, with poorer performance in TMT-B. SIGNIFICANCE: The results of this study demonstrate that cognitive performance is associated with IEDs in adult epilepsy patients, and could serve as a springboard for further research into reducing IEDs to bring about better cognitive performance.

Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain.

Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.

The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis.

BACKGROUND: Individual response to opioid analgesics varies among patients. OBJECTIVE: This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain. STUDY DESIGN: A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain. SETTING: This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain. METHODS: A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases. RESULTS: Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human µ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms. LIMITATIONS: Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information. CONCLUSION: The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.

A critical role for protein degradation in the nucleus accumbens core in cocaine reward memory.

The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli contribute to cocaine seeking and relapse. Previous studies have shown impairment in cocaine reward memories by manipulating a labile state induced by memory retrieval, but the mechanisms that underlie the destabilization of cocaine reward memory are unknown. In this study, using a Pavlovian cocaine-induced conditioned place preference (CPP) procedure in rats, we tested the contribution of ubiquitin-proteasome system-dependent protein degradation in destabilization of cocaine reward memory. First, we found that polyubiquitinated protein expression levels and polyubiquitinated N-ethylmaleimide-sensitive fusion (NSF) markedly increased 15 min after retrieval while NSF protein levels decreased 1 h after retrieval in the synaptosomal membrane fraction in the nucleus accumbens (NAc) core. We then found that infusion of the proteasome inhibitor lactacystin into the NAc core prevented the impairment of memory reconsolidation induced by the protein synthesis inhibitor anisomycin and reversed the effects of anisomycin on NSF and glutamate receptor 2 (GluR2) protein levels in the synaptosomal membrane fraction in the NAc core. We also found that lactacystin infusion into the NAc core but not into the shell immediately after extinction training sessions inhibited CPP extinction and reversed the extinction training-induced decrease in NSF and GluR2 in the synaptosomal membrane fraction in the NAc core. Finally, infusions of lactacystin by itself into the NAc core immediately after each training session or before the CPP retrieval test had no effect on the consolidation and retrieval of cocaine reward memory. These findings suggest that ubiquitin-proteasome system-dependent protein degradation is critical for retrieval-induced memory destabilization.

Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving.

RATIONALE: Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses). OBJECTIVES: To examine pain responses in abstinent opiate addicts in comparison with healthy controls using a cold-pressor test (CPT) and investigate the correlations of cue-induced drug craving with pain responses. MATERIAL AND METHODS: Fifty-four abstinent OAs and 46 healthy subjects participated in the CPT, and the OAs were also exposed to heroin-related cues the day before the pain test. Outcome measures included pain-tolerance time, VAS ratings of pain intensity and distress, and (in the cue-exposure procedure) VAS ratings of heroin craving and anxiety. RESULTS: In the CPT, abstinent addicts showed shorter pain-tolerance time (85.1 +/- 14.1 s vs. 133.7 +/- 16.7 s, p < 0.05) and higher ratings of pain distress (61 +/- 3.2 vs. 45.6 +/- 3.2, p < 0.01) compared to healthy controls. When we divided the addicts and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by dichotomizing each group in terms of pain-tolerance time, we again found differences between the two PS groups (37.3 +/- 3.5 s vs. 57.4 +/- 5.1 s, p < 0.01 for pain-tolerance time; 66.7 +/- 3.2 vs. 52.4 +/- 3.3, p < 0.01 for distress ratings). For all participants, pain-tolerance time was negatively correlated with VAS ratings for pain intensity and distress. More importantly, the PS addicts reported greater cue-induced craving than the PT addicts (17.8 +/- 2.2 vs. 4.5 +/- 4.2, p < 0.05). For the addict group as a whole, pain distress (the affective aspect of pain) was positively correlated with intensity of cue-induced craving measured on a different day (r = 0.33, p = 0.01). CONCLUSIONS: A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of cue-induced craving. Longitudinal research is needed to clarify the direction of causation between hyperalgesia and opiate addiction.

Diurnal variation in cue-induced responses among protracted abstinent heroin users.

OBJECTIVES: The physiological and psychological responses to drug cue exposure have been assessed in substance abusers. However, there is no study to demonstrate whether the responses to drug cue exposure are diurnal dependence. The present study was to examine whether there was a variation in drug-related cue reactivity across the diurnal cycle among recently abstinent opiate addicts. METHODS: Four groups of 20 abstinent heroin dependent patients (n=80) were exposed to both neutral and drug-related videos at four separate times during the day: 8:00, 12:00, 16:00, and 20:00 h. Physiological and psychological responses, including heart rate, blood pressure, heroin craving, and subjective anxiety were assessed before and after each cue exposure. RESULTS: Drug cue significantly increased craving ratings compared to neutral cues across all the four separate times of day. Drug cue-induced craving was greater in the morning (8:00 am) than noon (12:00 pm), but was similar to evening assessments (8 pm). Drug cues also significantly increased anxiety, which positively correlated with cue-induced craving. Drug cues increased heart rate, systolic and diastolic blood pressures, which were not correlated with cue-induced craving or anxiety. However, no time effects were found on the three physiological measures. CONCLUSIONS: Cue-induced craving could be profoundly affected by the time points of cue exposure, using cue-reactivity paradigm. The relative sensitivity of morning and evening assessments of drug craving suggests a need for replication and further research on mechanisms contributing to these diurnal variations.