去甲肾上腺素能系统对埃必定镇痛作用的影响

在大鼠电刺激甩尾测痛模型上,sc或icv埃必定(ipalbidine,Ipa)均具有剂量依赖性的镇痛作用,而脊髓蛛网膜下腔注射Ipa人产生镇痛作用;预先给予利血平可以取消scIpa的镇痛作用,这一作用可被icv补充NE所翻转;电解损毁大鼠叹侧蓝斑,ip二乙基二硫代氨基甲酸钠200mg·kg^-1,酚妥拉明ip10mg·kg^-1或icv150μg和sc哌唑嗪5mg·kg^-1均能使Ipa的镇痛作用明显减弱或消失,而sc育亨宾5mg·kg^-1和ip普萘洛尔10mg·kg^-1对Ipa的镇痛作用无明显影响。上述结果提示Ipa在中枢有镇痛作用,其部位主要在脊髓以上的神经结构,Ipa的镇痛作用可能与去甲肾上腺素能系统的a₁受体有关,而与a₂和β受体无明显关系。     

In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2

The effects of in vivo administration of prostaglandin E2 (PGE2) on several hematologic parameters were investigated in intact mice under both steady-state conditions and in mice hematopoietically rebounding following a sublethal injection of cyclophosphamide. Intravenous injection of native PGE2, or 16,16 dimethyl-PGE2, an enzymatically stable analog of PGE2, resulted in the significant suppression of nucleated bone marrow and splenic cellularity, total resident nucleated peritoneal cells, and the absolute number of detectable granulocyte- macrophage progenitor cells (CFU-GM) per femur or spleen when administered for 3 or 7 consecutive days. The in vivo effects of 16,16 dimethyl-PGE2 were more pronounced on the cyclophosphamide-treated mice. Dose titration analysis of the effects of 16,16 dimethyl-PGE2 revealed significant suppression of hematologic parameters over a concentration range of 10 micrograms-10(-5) micrograms/mouse/day (10(- 5) M-10(-11) M). The reduction in total nucleated marrow, splenic, and peritoneal cellularity observed following PGE2 administration resulted from a selective effect on nonspecific esterase-positive cells. In situ morphological analysis of the progeny of CFU-GM proliferating in cultures established from mice treated with PGE2 in vivo indicated that the reduction in absolute CFU-GM observed resulted from a preferential effect on those colony-forming cells restricted to monocyte-macrophage differentiation. Prostaglandin F2 alpha was without stimulatory or inhibitory effects in vivo on the hematopoietic parameters investigated.     

Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial,randomized, controlled trial

Rationale

The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood.

Objectives

We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.

Methods

In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2?×?2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them.

Results

All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.

Conclusions

tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.     

Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis

Median survival of patients with AL amyloidosis with clinically significant cardiac involvement is 5 months when treated with cyclic melphalan and prednisone. We investigated a regimen of continuous oral melphalan as a single agent for patients with cardiac amyloidosis who were unable to tolerate prednisone or more aggressive chemotherapy. Thirty patients with amyloid cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients, evaluable after 3-4 months of treatment, achieved a partial haematological response and three achieved a complete haematological response; six patients have survived for > 1 year. This regimen appeared to be effective in inducing haematological responses in patients who received total doses of melphalan > 300 mg.     

Effect of brightness in the evaluation of lumbar pedicular screws position: clinical study

Artifact may lead to confusion when evaluating postoperative CT scans of lumbar pedicle screws. The aim of our study was to develop a specific metal artifact reduction image protocol, in order to reduce metal artifact caused by titanium pedicular screw in patients undergoing lumbar pathology by lumbar fusion. Therefore, the reduction in metal artifacts in lumbar pedicle screws allows surgeons to do an accurate diagnosis of the exact placement of inserted pedicle screws, minimizes false reexploration, and maximizes proper and prompt treatment of misplaced screw. In a first step, we performed a retrospective study of 103 titanium alloy pedicle screws in patients undergoing a lumbar instrumented fusion for treatment for degenerative disease. CT scan was performed postoperatively evaluating the possible overdimension caused by artifact. In a second step, a prospective study was performed using a 64-slice multidetector-row computed tomography (MDCT) in 104 titanium alloy pedicle screws in patients undergoing a lumbar instrumented fusion for treatment for degenerative disease. Our results show that on the group of sequential CT scan, mean overdimension (on each side) due to brightness was 1.045 mm (SD 0.45). On the group of 64-slice multichannel CT, mean overdimension (on each side) due to brightness was 0.005 mm at the proximal part of the screw and 0.025 mm at the distal part of the screw. The results observed suggest that beam-hardening artifacts caused by the screw on CT after lumbar fusion are dramatically reduced by using specific metal artifact reduction image protocol in a 64-slice MDCT.     

Applying Computer Adaptive Testing to Optimize Online Assessment of Suicidal Behavior: A Simulation Study

Background

The Internet is used increasingly for both suicide research and prevention. To optimize online assessment of suicidal patients, there is a need for short, good-quality tools to assess elevated risk of future suicidal behavior. Computer adaptive testing (CAT) can be used to reduce response burden and improve accuracy, and make the available pencil-and-paper tools more appropriate for online administration.

Objective

The aim was to test whether an item response–based computer adaptive simulation can be used to reduce the length of the Beck Scale for Suicide Ideation (BSS).

Methods

The data used for our simulation was obtained from a large multicenter trial from The Netherlands: the Professionals in Training to STOP suicide (PITSTOP suicide) study. We applied a principal components analysis (PCA), confirmatory factor analysis (CFA), a graded response model (GRM), and simulated a CAT.

Results

The scores of 505 patients were analyzed. Psychometric analyses showed the questionnaire to be unidimensional with good internal consistency. The computer adaptive simulation showed that for the estimation of elevation of risk of future suicidal behavior 4 items (instead of the full 19) were sufficient, on average.

Conclusions

This study demonstrated that CAT can be applied successfully to reduce the length of the Dutch version of the BSS. We argue that the use of CAT can improve the accuracy and the response burden when assessing the risk of future suicidal behavior online. Because CAT can be daunting for clinicians and applied scientists, we offer a concrete example of our computer adaptive simulation of the Dutch version of the BSS at the end of the paper.     

Punitive laws,key population size estimates,and Global AIDS Response Progress Reports: an ecological study of 154 countries

Introduction : UN global plans on HIV/AIDS have committed to reducing the number of countries with punitive laws criminalizing key populations. This study explores whether punitive laws are associated with countries’ performance on targets set in the global plans. Methods : The study used chi‐square tests of independence to explore associations between legal status, key population size estimates, and HIV service coverage for 193 countries from 2007 to 2014. We used data reported by countries on United Nations Global AIDS Progress Report (GARPR) indicators, and legal data from UNAIDS, UNDP, and civil society organizations. Due to lack of sufficiently reliable legal data, only men who have sex with men (MSM) could be studied. The study utilized public data aggregated at the national level. Correspondence with individual experts in a subset of countries stated the purpose of the study, and all responses were anonymized. Results and Discussion : A significantly larger proportion of countries that criminalize same‐sex sexual behaviour reported implausibly low size estimates or no size estimates for MSM. This is consistent with findings in qualitative research that MSMs are marginalized and reluctant to be studied in countries where same‐sex sexuality is criminalized. Size estimates are often used as the denominators for national HIV service coverage reports. Initially, countries that criminalized same‐sex sexuality appeared to have higher HIV testing coverage among MSM than did countries where it is not criminalized. However, investigation of a subset of countries that have reported 90–100% HIV testing coverage among MSM found that most were based on implausibly low or absent size estimates. Conclusions : Criminalization of same‐sex sexuality is associated with implausibly low or absent MSM size estimates. Low size estimates may contribute to official denial of the existence of MSM; to failure to adequately address their needs; and to inflated HIV service coverage reports that paint a false picture of success. To enable and measure progress in the HIV response, UN agencies should lead a collaborative process to systematically, independently and rigorously gather data on laws and their enforcement.