Knowledge mapping of job burnout and satisfaction of medical staff and a cross-sectional investigation of county-level hospitals in Southern China.

Background: Job burnout is a worldwide public health problem that has rarely been addressed among rural medical staff, particularly in county-level hospitals. Hence, we conducted a bibliometric study to gain global insights and research trends and a cross-sectional study to assess the current situation among medical staff of county-level hospitals in Southern China. By conducting these studies, we aim to identify factors associated with burnout among medical staff of county-level hospitals in China and provide recommendations for improvement. Methods: Relevant literature on job burnout among medical personnel was searched using the Web of Science Core Collection (WoSCC). CiteSpace was employed for an in-depth cluster analysis to determine research trends and identify the study population. Subsequently, a cross-sectional survey was randomly conducted in three county-level hospitals in Hunan Province of Southern China. Job burnout and satisfaction were assessed using the Maslach Burnout Inventory MBI-Human Services Survey (MBI-HSS) and Job Satisfaction Questionnaire in a total of 362 valid questionnaires collected. The influence factors of the prevalence of job burnout were investigated using logistic regression. Results: In this bibliometric study, 1626 articles were retrieved from 1999 to 2022. China lags behind the United States (US) in both the number and quality of publications in the field of medical staff burnout compared with the US. However, there is a lack of comparative research on job burnout across different job types. County-level medical staff articles are more in line with research hotspots in the field. In total, 362 valid questionnaires were obtained. The total incidence of job burnout among rural medical staff was 27.3 %. Nurses (p < 0.01, OR = 5.95), doctors (p < 0.01, OR = 6.43), and those with administrative jobs (p < 0.01, OR = 7.79) were more likely to experience burnout than those with technical jobs. Medical staff aged 40-49 years (p < 0.01, OR = 0.22) and 50-59 years (p < 0.05, OR = 0.14) were less likely to experience burnout than those aged 20-29 years. Job rewards satisfaction showed a positive correlation with job burnout (p < 0.01, OR = 1.32), but negative correlations with personal development satisfaction (p < 0.05, OR = 0.81) and work internal environment satisfaction (p < 0.05, OR = 0.81). Conclusion: Better working environments, more accessible resources, and higher job rewards contribute to job satisfaction and reduce job burnout among the medical staff of county-level hospitals in China.

Effect of oxycodone combined with ultrasound-guided thoracic paravertebral nerve block on postoperative analgesia in patients with lung cancer undergoing thoracoscopic surgery: protocol for a randomised controlled study.

INTRODUCTION: Postoperative pain is a main component influencing the recovery of patients with lung cancer. The combination of patient-controlled intravenous analgesia (PCIA) and paravertebral nerve block for postoperative analgesia in patients undergoing thoracoscopic lobectomy for lung cancer can achieve a satisfactory analgesic effect and promote early rehabilitation of patients. The objective is to investigate the optimal dose of oxycodone for PCIA combined with paravertebral nerve block, to achieve effective multimodal analgesia management in patients undergoing thoracoscopic lung cancer lobectomy. METHODS AND ANALYSIS: This prospective, double-blind, single-centre, parallel-group, superiority study from 7 April 2023 to 31 December 2024 will include 160 participants scheduled for thoracoscopic lobectomy for lung cancer. Participants will be randomly assigned to four groups in a 1:1:1:1 ratio: OCA group (oxycodone: 0.5 mg/kg), OCB group (oxycodone: 1.0 mg/kg), OCC group (oxycodone: 1.5 mg/kg) and one sufentanil group (sufentanil: 2 µg/kg). Flurbiprofen 50 mg and ondansetron 16 mg are added to each group. All the drugs are diluted with 0.9% saline in a 100 mL volume, with a background infusion rate of 2 mL/hour, a bolus dose of 0.5 mL and a lockout interval of 15 min. The primary outcome is pain scores at rest and dynamic at 24 hours after surgery using a Numeric Rating Scale (NRS). Dynamic NRS scores are defined as NRS when coughing. NRS scores will be assessed at 2, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes include the following variables: (1) NRS score at rest and dynamic at 2, 4, 12 and 48 hours postoperatively; (2) total dose of sufentanil or oxycodone consumption in PCIA; (3) the times of patient-controlled analgesia; (4) Ramsay Sedation Score (RSS) at 2, 4, 12, 24 and 48 hours after the surgery; (5) extubation time; (6) serum C-reactive protein and interleukin six levels; (7) incidence of postoperative nausea and vomiting; (8) incidence of itching; (9) incidence of respiratory depression and (10) gastrointestinal recovery (exhaust time). ETHICS AND DISSEMINATION: The First Affiliated Hospital of Shandong First Medical University's Ethics Committee granted consent for this study (approval number: YXLL-KY-2022(116)). To enable widespread use of the data gathered, we plan to publish the trial's findings in an appropriate scientific journal after it is complete. TRIAL REGISTRATION NUMBER: NCT05742256.

Comparison of dexmedetomidine and dexamethasone as adjuvants to the ultrasound-guided interscalene nerve block in arthroscopic shoulder surgery: a systematic review and Bayesian network meta-analysis of randomized controlled trials.

Introduction: Interscalene block (ISB) is widely regarded as the gold standard treatment for acute pain following arthroscopic shoulder surgery. However, a single injection of a local anesthetic for ISB may not offer sufficient analgesia. Various adjuvants have been demonstrated to prolong the analgesic duration of the block. Hence, this study aimed to assess the relative efficacy of dexamethasone and dexmedetomidine as adjuncts to prolong the analgesic duration for a single- shot ISB. Methods: The efficacy of adjuvants was compared using a network meta-analysis. The methodological quality of the included studies was evaluated using the Cochrane bias risk assessment tool. A comprehensive search of the PubMed, Cochrane, Web of Science, and Embase databases was conducted with a search deadline of March 1, 2023. Various adjuvant prevention randomized controlled trials have been conducted in patients undergoing interscalene brachial plexus block for shoulder arthroscopic surgery. Results: Twenty-five studies enrolling a total of 2,194 patients reported duration of analgesia. Combined dexmedetomidine and dexamethasone (MD = 22.13, 95% CI 16.67, 27.58), dexamethasone administered perineurally (MD = 9.94, 95% CI 7.71, 12.17), high-dose intravenous dexamethasone (MD = 7.47, 95% CI 4.41, 10.53), dexmedetomidine administered perineurally (MD = 6.82, 95% CI 3.43, 10.20), and low-dose intravenous dexamethasone (MD = 6.72, 95% CI 3.74, 9.70) provided significantly longer analgesic effects compared with the control group. Discussion: The combination of intravenous dexamethasone and dexmedetomidine provided the greatest effect in terms of prolonged analgesia, reduced opioid doses, and lower pain scores. Furthermore, peripheral dexamethasone in prolonging the analgesic duration and lowering opioid usage was better than the other adjuvants when used a single medication. All therapies significantly prolonged the analgesic duration and reduced the opioid dose of a single-shot ISB in shoulder arthroscopy compared with the placebo.

Aerobic Exercise in Male Mice Prevents Ventilator-Induced Lung Injury by Inhibiting Mitochondrial Damage from sirt1 Dysregulation.

BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation under general anesthesia. Regular aerobic exercise before surgery improves postoperative recovery and reduces postoperative pulmonary complications, but the mechanism driving this protective effect is unclear. METHODS: To determine how aerobic exercise prevents VILI, we investigated the effects of exercise and mechanical ventilation on the lungs of male mice and the effects of AMPK stimulation (simulating exercise) and cyclic stretching on human lung microvascular endothelial cells (HLMVEC). Sirtuin 1 (Sirt1) knockdown male mice were generated to explore the regulating mechanisms of sirt1 on mitochondrial function in male mice after mechanical ventilation was explored. Western blot, flow cytometry, live cell imaging, and mitochondrial function evaluations were used to determine the protective effects of aerobic exercise in preventing mitochondrial damage in VILI. RESULTS: Mitochondrial function and cell junctions were destroyed by mechanical ventilation in male mice or cyclic stretching in HLMVEC, a model of VILI. However, mitochondrial function and cell junction dysfunction were improved by exercise before mechanical ventilation (male mice) or treatment with AMPK before cyclic stretching (HLMVEC). p66shc, a marker of oxidative stress, was increased, and PINK1, a marker of mitochondrial autophagy, was decreased by mechanical ventilation or cyclic stretching. Sirt1 knockdown increased p66shc and decreased PINK1. Increased sirt1 expression was observed in the exercise and exercise + ventilation groups, suggesting that sirt1 inhibits mitochondrial damage in VILI. CONCLUSIONS: Mechanical ventilation induces mitochondrial damage in lung cells and leads to VILI. Regular aerobic exercise before ventilation may prevent VILI by improving mitochondrial function.

Efficacy and adverse effects of peripheral nerve blocks and local infiltration anesthesia after arthroscopic shoulder surgery: A Bayesian network meta-analysis.

Study objective: To quantitatively assess and compare the efficacy and adverse effects of six different peripheral nerve block techniques after arthroscopic shoulder surgery (ASS). Design: Bayesian network meta-analysis. Methods: The PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure database, Chinese Scientific Journal database, Wan Fang databases were searched to retrieve randomized clinical trials comparing interscalene brachial plexus block, continuous interscalene brachial plexus block, supraclavicular brachial plexus block, suprascapular nerve block, combined suprascapular and axillary nerve block and local infiltration analgesia on postoperative pain, opioid consumption, and adverse effects (defined as Horner's syndrome, dyspnea, hoarseness, vomiting, and nausea) after ASS under general anesthesia (GA). Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Results: A total of 1,348 articles were retrieved initially and 36 randomized clinical trials involving 3,124 patients were included in the final analysis. The network meta-analysis showed that interscalene brachial plexus block was superior in reducing pain and opioid consumption compared to the five other interventions. However, adverse effects were reduced using suprascapular nerve block and combined suprascapular and axillary nerve block compared to interscalene brachial plexus block. Conclusion: Interscalene brachial plexus block was superior in reducing pain and opioid consumption compared to other peripheral nerve blocks but had a higher frequency of adverse events.

Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.

Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes - EHF, TRPM1, FXYD4, CDH15, LHX5, TP73, FBN3, TLX1, C1QL4, COL2A, SEC61G, NEUROD4 and GPR139 - were differentially expressed in recurrent GBM samples; low LHX5 and TLX1 expression predicted poor outcomes. LHX5 and TLX1 expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, LHX5 and TLX1 expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that LHX5 and TLX1 might be involved in GBM recurrence and act as potential biomarkers for this condition.

The Use of Aerosolized Medications in Adult Intensive Care Unit Patients: A Prospective, Multicenter, Observational, Cohort Study.

Background: Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medications in the ICU may contribute to develop appropriate education and improve the quality of aerosol therapy. Methods: A 2-week, prospective, multicenter, observational, cohort study was conducted to record how the aerosolized medications were utilized in the Chinese ICUs, including indications, medications used in solo or combination, dosage, and side-effects in adult patients. Results: A total of 1006 patients from 28 ICUs were enrolled, of which 389 (38.7%) received aerosol therapy. The most common indications for aerosol therapy were difficulty in secretion management (23.1%) and chronic obstructive pulmonary disease exacerbation (18.5%). The combination of inhaled corticosteroids and short-acting muscarinic antagonist was the most commonly used medication (19.5%, 76/389). Ninety-two percent (358/389) of the patients did not have any side effects during aerosol therapy. More patients in the group with mechanical ventilation received bronchodilators than spontaneous breathing patients (81.3% vs. 55.5%, p < 0.001), and more patients who breathed spontaneously through a tracheostomy received mucus-regulating agents than other patients (70% vs. 37.9%, p = 0.004). Conclusion: In mainland China, more than one-third of adult ICU patients received aerosol therapy. Medications utilized during aerosol therapy were variable in patients with different respiratory support. To promote appropriate use of aerosolized medications, high-quality randomized, controlled trials and clinical guidance on aerosolized medication indications and dosing are needed to improve clinical outcomes.

Regulation of Mitochondrial Dynamics by Aerobic Exercise in Cardiovascular Diseases.

Mitochondrial dynamics, including continuous biogenesis, fusion, fission, and autophagy, are crucial to maintain mitochondrial integrity, distribution, size, and function, and play an important role in cardiovascular homeostasis. Cardiovascular health improves with aerobic exercise, a well-recognized non-pharmaceutical intervention for both healthy and ill individuals that reduces overall cardiovascular disease (CVD) mortality. Increasing evidence shows that aerobic exercise can effectively regulate the coordinated circulation of mitochondrial dynamics, thus inhibiting CVD development. This review aims to illustrate the benefits of aerobic exercise in prevention and treatment of cardiovascular disease by modulating mitochondrial function.

Efficacy and safety of ramosetron versus ondansetron for postoperative nausea and vomiting after general anesthesia: a meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative nausea and vomiting is a common side effect of general anesthesia. In this study, we performed a meta-analysis on the efficacy and safety of ramosetron versus ondansetron in the prevention of postoperative nausea and vomiting using the most recently published randomized controlled clinical studies. METHODS: PubMed and EMBASE were searched for randomized controlled clinical trials comparing the efficacy and safety of ramosetron and ondansetron. The meta-analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous outcomes are presented as the relative risk (RR) with a 95% confidence interval (CI). RESULTS: A total of 898 patients from nine selected studies were treated with antiemetics after surgery, including 450 patients who received ondansetron 4 mg and 448 patients who received ramosetron 0.3 mg. The meta-analysis showed no statistically significant difference between the two groups with regard to prevention of postoperative nausea (PON) during different time periods in the 48 hours after surgery. When comparing the efficacy of ramosetron and ondansetron in the prevention of postoperative vomiting (POV), at various time intervals in the 24 hours after surgery, ramosetron was significantly more efficient than ondansetron: 0-6 hours (RR 0.46, 95% CI 0.24-0.92; P=0.03), 0-24 hours (RR 0.72, 95% CI 0.52-1.00; P=0.05), and 6-24 hours (RR 0.51, 95% CI 0.31-0.84; P=0.008). At other time periods between 24 and 48 hours after surgery, ramosetron did not show better efficacy than ondansetron. When comparing the safety profiles of ramosetron and ondansetron, fewer side effects were recorded in the ramosetron group (RR 0.65, 95% CI 0.47-0.91; P=0.01). CONCLUSION: Our meta-analysis demonstrates that ramosetron was more effective than ondansetron in the prevention of early POV (0-24 hours) with fewer recorded side effects. However, our study did not reveal any statistically significant differences in efficacy between ramosetron and ondansetron in the prevention of PON or late POV (at 24-48 hours).

Two crystal modifications of (Pro-Pro-Gly)4-Hyp-Hyp-Gly-(Pro-Pro-Gly)4 reveal the puckering preference of Hyp(X) in the Hyp(X):Hyp(Y) and Hyp(X):Pro(Y) stacking pairs in collagen helices.

Two crystal modifications of a collagen model peptide, (Pro-Pro-Gly)(4)-Hyp-Hyp-Gly-(Pro-Pro-Gly)(4) [where Hyp is (4R,2S)-L-hydroxyproline], showed very similar unit-cell parameters and belonged to the same space group P2(1). Both crystals exhibited pseudo-merohedral twinning. The main difference was in their molecular-packing arrangements. One modification showed pseudo-hexagonal packing, while the other showed pseudo-tetragonal packing. Despite their different packing arrangements, no significant differences were observed in the hydration states of these modifications. The peptide in the pseudo-tetragonal crystal showed a cyclic fluctuation of helical twists with a period of 20 A, while that in the pseudo-hexagonal crystal did not. In these modifications, the puckering conformations of four of the 12 Hyp residues at the X position of the Hyp(X)-Hyp(Y)-Gly sequence were in the opposite conformations to the previous hypothesis that Hyp(X) residues involved in Hyp(X):Hyp(Y) and Hyp(X):Pro(Y) stacking pairs prefer up-puckering and down-puckering conformations, respectively. Detailed investigation of the molecular interactions between Hyp(X) and adjacent molecules revealed that these opposite conformations appeared because the puckering conformation, which follows the hypothesis, is subject to steric hindrance from the adjacent molecule.

High-resolution structures of collagen-like peptides [(Pro-Pro-Gly)4-Xaa-Yaa-Gly-(Pro-Pro-Gly)4]: implications for triple-helix hydration and Hyp(X) puckering.

Structures of (Pro-Pro-Gly)4-Xaa-Yaa-Gly-(Pro-Pro-Gly)4 (ppg9-XYG) where (Xaa, Yaa)=(Pro, Hyp), (Hyp, Pro) or (Hyp, Hyp) were analyzed at high resolution using synchrotron radiation. Molecular and crystal structures of these peptides are very similar to those of the (Pro-Pro-Gly)9 peptide. The results obtained in this study, together with those obtained from related compounds, indicated the puckering propensity of the Hyp in the X position: (1) Hyp(X) residues involved in the Hyp(X):Pro(Y) stacking pairs prefer the down-puckering conformation, as in ppg9-OPG, and ppg9-OOG; (2) Hyp(X) residues involved in the Hyp(X):Hyp(Y) stacking pairs prefer the up-puckering conformation if there is no specific reason to adopt the down-puckering conformation. Water molecules in these peptide crystals are classified into two groups, the 1st and 2nd hydration waters. Water molecules in the 1st hydration group have direct hydrogen bonds with peptide oxygen atoms, whereas those in the 2nd hydration group do not. Compared with globular proteins, the number of water molecules in the 2nd hydration shell of the ppg9-XYG peptides is very large, likely due to the unique rod-like molecular structure of collagen model peptides. In the collagen helix, the amino acid residues in the X and Y positions must protrude outside of the triple helix, which forces even the hydrophobic side chains, such as Pro, to be exposed to the surrounding water molecules. Therefore, most of the waters in the 2nd hydration shell are covering hydrophobic Pro side chains by forming clathrate structures.

Curcumin has potent liver preservation properties in an isolated perfusion model.

BACKGROUND: Curcumin has profound antioxidant and anti-inflammatory properties. This research assessed the effect of curcumin on liver preservation. METHODS: Sprague-Dawley rat livers were flushed with different preservation solutions [Euro-Collins solution (EC), phosphate buffer saline (PBS), University of Wisconsin solution (UW)] with or without curcumin (25-200 microM) and stored at 4 degrees C for 24-48 hours. Livers were then perfused for 120 minutes via the portal vein with oxygenated Krebs-Henseleit bicarbonate buffer solution at a pressure of 18 cm H2O in a perfusion apparatus. The livers in the normal (NL) group were flushed with EC, PBS, or UW, then immediately perfused (zero preservation time). RESULTS: We found that curcumin at 100 microM concentration had the optimal preservation characteristics. Portal flow rates and bile production were significantly higher and liver enzymes (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) were significantly lower in the EC+C livers and PBS+C livers than in the EC or PBS with optimum concentration of 100 microM of curcumin. Comparing UW+C vs. UW livers, at 24 hours there was no difference in these parameters; however, at 36 hours and 48 hours, portal flow rates and bile production were significantly higher in UW+C livers. CONCLUSIONS: We found that curcumin has inherent organ preservation quality as it enhanced liver preservation in PBS. In addition, curcumin enhanced the preservation quality of EC and UW solutions, thereby extending the preservation time while maintaining the organ quality.

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates.

To assess the role of CCL2/MCP-1 in opiate drug abuse and HIV-1 comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild type and CCR2 null mice. Tat and/or morphine additively increased the proportion of CCL2 immunoreactive astroglia. The effects of morphine were prevented by naltrexone. Glial activation was significantly reduced in CCR2-/- versus wild-type mice following Tat or morphine plus Tat exposure. Thus, CCR2 contributes to local glial activation caused by Tat alone or in the presence of opiates, implicating CCR2 signaling in HIV-1 neuropathogenesis in drug abusers and non-abusers.

Helical twists of collagen model peptides.

Average helical twists were calculated by the method of Sugeta and Miyazawa (Biopolymers 1967, 5, 673-679) for all of the collagen model peptides analyzed to date. Calculation of the helical twists of all triplets in each peptide strand provided novel insights for several model peptides. In the (Pro-Pro-Gly)n (n = 9 and 10), the helical twists showed cyclic fluctuations between 40 and 65 degrees with a 20 A period, suggesting that their molecular conformations were close enough to the ideal 7/2-helix to show the helical repeat of 20 A. Rather small helical twists in the guest regions of IBP in complex and T3-785 were attributed to the interaction with Integrin I domain and a relaxed conformation caused by three consecutive triplets lacking imino acid residues, respectively. Although most of the triplets used in this study were imino acid-rich triplets, helical twists were scattered in a wide range from 30 to 70 degrees with an overall average of 52.6 degrees . This distribution of helical twists indicated a strong preference for the 7/2-helical conformation (51.4 degrees ) rather than the 10/3-helical model (36 degrees ).

HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines.

Opiates exacerbate human immunodeficiency virus type 1 (HIV-1) Tat(1-72)-induced release of key proinflammatory cytokines by astrocytes, which may accelerate HIV neuropathogenesis in opiate abusers. The release of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), in particular, is potentiated by opiate-HIV Tat interactions in vitro. Although MCP-1 draws monocytes/macrophages to sites of CNS infection, and activated monocytes/microglia release factors that can damage bystander neurons, the role of MCP-1 in neuro-acquired immunodeficiency syndrome (neuroAIDS) progression in opiate abusers, or nonabusers, is uncertain. Using a chemotaxis assay, N9 microglial cell migration was found to be significantly greater in conditioned medium from mouse striatal astrocytes exposed to morphine and/or Tat(1-72) than in vehicle-, mu-opioid receptor (MOR) antagonist-, or inactive, mutant Tat(delta31-61)-treated controls. Conditioned medium from astrocytes treated with morphine and Tat caused the greatest increase in motility. The response was attenuated using conditioned medium immunoneutralized with MCP-1 antibodies, or medium from MCP-1(-/-) astrocytes. In the presence of morphine (time-release, subcutaneous implant), intrastriatal Tat increased the proportion of neural cells that were astroglia and F4/80+ macrophages at 7 days post-injection. This was not seen after treatment with Tat alone, or with morphine plus inactive Tat(delta31-61) or naltrexone. Glia displayed increased MOR and MCP-1 immunoreactivity after morphine and/or Tat exposure. The findings indicate that MCP-1 underlies most of the response of microglia, suggesting that one way in which opiates exacerbate neuroAIDS is by increasing astroglial-derived proinflammatory chemokines at focal sites of CNS infection and promoting macrophage entry and local microglial activation. Importantly, increased glial expression of MOR can trigger an opiate-driven amplification/positive feedback of MCP-1 production and inflammation.

Crystal structures of collagen model peptides with Pro-Hyp-Gly repeating sequence at 1.26 A resolution: implications for proline ring puckering.

Triple-helical structures of (Pro-Hyp-Gly)n (n = 10, 11) at 100 K and room temperature (RT) were analyzed at 1.26 A resolution by using synchrotron radiation data. Totals of 49 and 42 water molecules per seven triplets in an asymmetric unit were found for the structures at 100 K and RT, respectively. These water molecules were classified into two groups, those in the first and second hydration shells. Although there was no significant difference between water molecules in the first shell at 100 K and those at RT, a significant difference between those in the second shell was observed. That is, the number of water molecules at RT decreased to one half and the average distance from peptide chains at RT became longer by about 0.3 A. On the other hand, of seven triplets in an asymmetric unit, three proline residues at the X position at 100 K clearly showed an up-puckering conformation, as opposed to the recent propensity-based hypothesis for the stabilization and destabilization of triple-helical structures by proline hydroxylation. This puckering was attributed to the interaction between proline rings and the surrounding water molecules at 100 K, which is much weaker at RT, as shown by longer average distance from peptide chains.

Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors.

The present study examined the sex-dependent expression of behavioral sensitization as well as changes of dopamine (DA) transporters and D1, D2, and D3 receptors following repeated intravenous nicotine administration. Male and female Sprague-Dawley rats were implanted with indwelling jugular catheters, equipped with subcutaneous intravenous injection ports. Rats were habituated to activity chambers for 3 days and were subsequently administered 15-s bolus injections of intravenous nicotine (50 microg/kg/ml) 1/day for 21 days. Animals were placed in activity chambers for 60 min immediately after the 1st and 21st nicotine injection. Observational time sampling was also performed. Brains were subsequently removed and frozen for autoradiographic DA transporter/DA receptor analysis on the afternoon females were in proestrus. With one exception, no robust sex differences were observed for locomotor activity or any rearing measures either during baseline or after initial nicotine injection. Females exhibited markedly more behavioral sensitization of locomotor activity, rearing, duration of rearing, and incidence of observed rearing. There were no sex differences in the number of D1 or D2 receptors. Females exhibited an increased number of DA transporters and decreased D3 receptors in the NAcc, relative to males. Multiple regression analyses suggest that D3 receptors and DA transporters in various striatal and NAcc subregions differentially predicted nicotine-induced behaviors for males and females. Collectively, these findings demonstrate that repeated intravenous nicotine produces sex differences in the expression of behavioral sensitization, and suggest that nicotine-induced changes of DA transporters and D3 receptors are partly responsible for increased behavioral sensitization in female rats.

Temporal relationships between HIV-1 Tat-induced neuronal degeneration, OX-42 immunoreactivity, reactive astrocytosis, and protein oxidation in the rat striatum.

HIV-1 transactivating protein Tat is neurotoxic and is believed to play a role in the development of AIDS-associated dementia complex. Neurotoxicity of Tat may be associated with oxidative stress. In this study we examined temporal progression of histopathological changes induced by a single microinjection of Tat 1-72 into the rat striatum. Degenerating neural cells, detected by Fluoro-Jade B staining and increased protein oxidation, determined by protein carbonyl immunostaining, were observed in the striatum as soon as 2 h following the microinjection. Further progression of neuronal degeneration was associated with pronounced infiltration of the area surrounding Tat 1-72 injection site by OX-42 positive macrophages/microglia, which was evident at the 24 h time point. Signs of reactive astrocytosis were found in the striatum of Tat 1-72 injected animals as late as 7 days following the single microinjection. Increased GFAP immunoreactivity and changes in the morphology of astrocytes coincided with a second phase of increased protein carbonyl formation, but not with neuronal degeneration. Control polypeptide, nontoxic Tat delta 31-61, did not cause any cell death, inflammatory reaction or oxidative damage. Results of our study support the hypothesis that oxidative stress may be an early step in the mechanism of Tat neurotoxicity.