Human macrophages limit oxidation products in low density lipoprotein

This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 ± 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 ± 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 ± 0.5 nmol/mg LDL in cell-free media, and 2.48 ± 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 ± 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 ± 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 ± 59.9 nmol/mg LDL and in cell-free media 242 ± 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation. © 2005 Hultén et al; licensee BioMed Central Ltd

Social correlates of term small for gestational age babies in a Russian arctic setting

BACKGROUND. Small for gestational age (SGA) births have been associated with both short- and long-term adverse health outcomes. Although social risk factors for SGA births have been studied earlier, such data are limited from Northern Russia. OBJECTIVE. We assessed maternal social risk factors for term SGA births based on data from the populationbased Murmansk County Birth Registry (MCBR). DESIGN. Data on term live-born singleton infants born between 2006 and 2011 in Murmansk County were obtained from the MCBR. We applied the 10th percentile for only birth weight (SGAW) or for both birth weight and birth length (SGAWL). Binary logistic regression was used to estimate the effect of independent variables on SGA males and females with adjustment for known risk factors and potential confounders. Both crude and adjusted odds ratios with 95% confidence intervals for the studied risk factors were calculated. RESULTS. The proportions of term SGAW and SGAWL births were 9.7 and 4.1%, respectively. After adjustment for potential confounders, the risk of term SGA births among less educated, unemployed, unmarried, smoking and underweight women was higher compared with women from the reference groups. Evidence of alcohol abuse was also associated with birth of SGAWL and SGAW boys. Maternal overweight and obesity decreased the risk of SGA. CONCLUSIONS. Maternal low education, unemployment, unmarried status, smoking, evidence of alcohol abuse and underweight increased the risk of term SGA births in a Russian Arctic setting. This emphasizes the importance of both social and lifestyle factors for pregnancy outcomes. Public health efforts to reduce smoking, alcohol consumption and underweight of pregnant women may therefore promote a decrease in the prevalence of SGA births.http://www.tandfonline.com/loi/zich20am2017School of Health Systems and Public Health (SHSPH

First-trimester smoking cessation in pregnancy did not increase the risk of preeclampsia/eclampsia : a Murmansk county birth registry study

BACKGROUND : Although prior studies have shown that smoking reduces preeclampsia/eclampsia risk, the consequence of giving up this habit during pregnancy should be assessed. The aims of the current study were threefold: (i) describe maternal characteristics of women with preeclampsia/ eclampsia; (ii) examine a possible association between the number of cigarettes smoked daily during pregnancy and the development of this affliction; and (iii) determine if first-trimester discontinuation of smoking during pregnancy influences the risk. METHODS : A registry-based study was conducted using data from the Murmansk County Birth Registry (MCBR). It included women without pre-existing hypertension, who delivered a singleton infant during 2006±2011 and had attended the first antenatal visit before 12 week of gestation. We adjusted for potential confounders using logistic regression. RESULTS : The prevalence of preeclampsia/eclampsia was 8.3% (95%CI: 8.0±8.6). Preeclampsia/ eclampsia associated with maternal age, education, marital status, parity, excessive weight gain and body mass index at the first antenatal visit. There was a dose-response relationship between the number of smoked cigarettes per day during pregnancy and the risk of preeclampsia/ eclampsia (adjusted OR1-5 cig/day = 0.69 with 95%CI: 0.56±0.87; OR6-10 cig/day = 0.65 with 95%CI: 0.51±0.82; and OR 11 cig/day = 0.49 with 95%CI: 0.30±0.81). There was no difference in this risk among women who smoked before and during pregnancy and those who did so before but not during pregnancy (adjusted OR = 1.10 with 95%CI: 0.91±1.32). CONCLUSIONS : Preeclampsia/eclampsia was associated with maternal age, education, marital status, parity, excessive weight gain, and body mass index at the first antenatal visit. There was a negative dose-response relationship between the number of smoked cigarettes per day during pregnancy and the odds of preeclampsia/eclampsia. However, women who gave up smoking during the first trimester of gestation had the same risk of preeclampsia/eclampsia as those who smoked while pregnant. Consequently, antenatal clinic specialists are advised to take these various observations into account when counselling women on smoking cessation during pregnancy.http://www.plosone.orgam2018School of Health Systems and Public Health (SHSPH

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Anxiety—a sustained state of heightened apprehension in the absence of immediate threat—becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)—achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA—exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA–CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease

Long-term outcome in 324 polytrauma patients: what factors are associated with posttraumatic stress disorder and depressive disorder symptoms?

Background: Physical impairment is well-known to last for many years after a severe injury, and there is a high impact on the quality of the survivor's life. The purpose of this study was to examine if this is also true for psychological impairment with symptoms of posttraumatic stress disorder or depression after polytrauma. Design: Retrospective cohort outcome study. Setting: Level I trauma centre. Population: 637 polytrauma trauma patients who were treated at our Level I trauma centre between 1973 and 1990. Minimum follow-up was 10 years after the injury. Methods: Patients were asked to fill in a questionnaire, including parts of the Posttraumatic Stress Diagnostic Scale, the Impact of Event Scale-Revised and the German Hospital Anxiety and Depression Scale, to evaluate mental health. Clinical outcome was assessed before by standardised scores. Results: Three hundred and twenty-four questionnaires were evaluated. One hundred and forty-nine (45.9%) patients presented with symptoms of mental impairment. Quality of life was significantly higher in the mentally healthy group, while the impaired group achieved a lower rehabilitation status. Conclusions: Mental impairment can be found in multiple trauma victims, even after 10 years or more. Treating physicians should not only focus on early physical rehabilitation but also focus on early mental rehabilitation to prevent long-term problems in both physical and mental disability

Indications for implant removal after fracture healing: a review of the literature

Introduction: The aim of this review was to collect and summarize published data on the indications for implant removal after fracture healing, since these are not well defined and guidelines hardly exist. Methods: A literature search was performed. Results: Though there are several presumed benefits of implant removal, such as functional improvement and pain relief, the surgical procedure can be very challenging and may lead to complications or even worsening of the complaints. Research has focused on the safety of metal implants (e.g., risk of corrosion, allergy, and carcinogenesis). For these reasons, implants have been removed routinely for decades. Along with the introduction of titanium alloy implants, the need for implant removal became a subject of debate in view of potential (dis)advantages since, in general, implants made of titanium alloys are more difficult to remove. Currently, the main indications for removal from both the upper and lower extremity are mostly 'relative' and patient-driven, such as pain, prominent material, or simply the request for removal. True medical indications like infection or intra-articular material are minor reasons. Conclusion: This review illustrates the great variety of view points in the literature, with large differences in opinions and practices about the indications for implant removal after fracture healing. Since some studies have described asymptomatic patients developing complaints after removal, the general advice nowadays is to remove implants after fracture healing only in symptomatic patients and after a proper informed consent. Well-designed prospective studies on this subject are urgently needed in order to form guidelines based on scientific evidence

Reinforcing the role of the conventional C-arm - a novel method for simplified distal interlocking

<p>Abstract</p> <p>Background</p> <p>The common practice for insertion of distal locking screws of intramedullary nails is a freehand technique under fluoroscopic control. The process is technically demanding, time-consuming and afflicted to considerable radiation exposure of the patient and the surgical personnel. A new concept is introduced utilizing information from within conventional radiographic images to help accurately guide the surgeon to place the interlocking bolt into the interlocking hole. The newly developed technique was compared to conventional freehand in an operating room (OR) like setting on human cadaveric lower legs in terms of operating time and radiation exposure.</p> <p>Methods</p> <p>The proposed concept (guided freehand), generally based on the freehand gold standard, additionally guides the surgeon by means of visible landmarks projected into the C-arm image. A computer program plans the correct drilling trajectory by processing the lens-shaped hole projections of the interlocking holes from a single image. Holes can be drilled by visually aligning the drill to the planned trajectory. Besides a conventional C-arm, no additional tracking or navigation equipment is required.</p> <p>Ten fresh frozen human below-knee specimens were instrumented with an Expert Tibial Nail (Synthes GmbH, Switzerland). The implants were distally locked by performing the newly proposed technique as well as the conventional freehand technique on each specimen. An orthopedic resident surgeon inserted four distal screws per procedure. Operating time, number of images and radiation time were recorded and statistically compared between interlocking techniques using non-parametric tests.</p> <p>Results</p> <p>A 58% reduction in number of taken images per screw was found for the guided freehand technique (7.4 ± 3.4) (mean ± SD) compared to the freehand technique (17.6 ± 10.3) (<it>p </it>< 0.001). Total radiation time (all 4 screws) was 55% lower for the guided freehand technique compared to conventional freehand (<it>p </it>= 0.001). Operating time per screw (from first shot to screw tightened) was on average 22% reduced by guided freehand (<it>p </it>= 0.018).</p> <p>Conclusions</p> <p>In an experimental setting, the newly developed guided freehand technique for distal interlocking has proven to markedly reduce radiation exposure when compared to the conventional freehand technique. The method utilizes established clinical workflows and does not require cost intensive add-on devices or extensive training. The underlying principle carries potential to assist implant positioning in numerous other applications within orthopedics and trauma from screw insertions to placement of plates, nails or prostheses.</p