Time Points T1 Research Articles

Self-confidence and level of knowledge after cardiopulmonary resuscitation training in 14 to 18-year-old schoolchildren: A randomised-interventional controlled study in secondary schools in Germany.

Education of schoolchildren in cardiopulmonary resuscitation (CPR) is a strategic goal for improvement of bystander CPR in society. The primary objective was to analyse the impact of CPR training on the resuscitation knowledge and self-confidence of secondary schoolchildren. In addition, independent predictors of improved CPR knowledge and self-confidence were investigated. Randomised-interventional controlled study. Four secondary schools in Germany. Four hundred and twenty-four schoolchildren aged from 14 to 18 years were included into the study. Fifty-one percent were female, and 33% had an immigrant background. The intervention group received a 90-min CPR training session, whereas controls had no intervention. Levels of knowledge and self-confidence in initiating CPR were analysed by a study questionnaire before (t0), 90 min after (t1) and 6 months after training (t2). Based on the evaluation of study questionnaires, the primary endpoint was to determine the development of resuscitation knowledge and self-confidence in initiating cardiopulmonary resuscitation at survey time-points t0, t1 and t2. Schoolchildren in the intervention group (n=207) showed a significantly higher level of knowledge (P < 0.001) and self-confidence (P < 0.001) at t1 and t2 compared with controls (n=217). Age was a predictor for long-term self-confidence [odds ratio (OR), 1.20; 95% confidence interval (95% CI), 1.02 to 1.41; P = 0.032]. The long-term benefit in the level of knowledge and self-confidence were significantly higher in native compared with immigrant schoolchildren: (OR, 1.79; 95% CI, 1.14 to 2.82; P = 0.011) and (OR, 1.67; 95% CI, 1.07 to 2.60; P = 0.024), respectively. Guideline compliant (90 min) theoretical and practical CPR training improves the level of knowledge and self-confidence in 14 to 18-year-old schoolchildren. Older schoolchildren are more likely to have increased self-confidence with respect to initiating CPR. Schoolchildren with an immigrant background showed a significantly lower increase in their level of knowledge and self-confidence compared with native children. Adaptation and simplification of teaching materials and further research on educational methods for CPR are urgently needed to enable a sustainable approach to teaching CPR, which also produces a long-lasting effect in the entire population.

Multi-temporal polarimetry in land-cover classification

ABSTRACTThis study uses time-series Sentinel-1(S-1) synthetic aperture radar images to evaluate the impact of multi-temporal polarimetric processing on land-cover classification. Various polarimetric processing methods are applied to multi-temporal S-1 data set in order to obtain several inputs parameters for land-cover classification: e.g. time-series coherence matrices from dual-polarization data (shows coherence among polarizations in matrix for separated time points t1, t2, to tn); scatter zone time series; multi-temporal single and dual-polarization coherence matrices (reveal coherences among time points for one or two polarizations); and parameters from the H/α decomposition. Then, the classification potential of each polarimetric data set is compared to a reference classification, which was derived from time series of dual-polarization backscatter (σ0) images. We evaluate if polarimetric processing of dual-polarization images brings better classification results than alone classification of backscatter image. Finally, we evaluate the impact of segment size and the classifier on classification accuracy.The classification based on polarimetric data sets is consistently better than that of backscatter time series. A maximum overall accuracy of 93.2% was achieved for the classification of four basic land-cover classes (urban, agriculture, forest, and water) using a composite data set made up time series of scatter zone derived from the H/α plane and scatter zone temporal stability maps. This accuracy was 4.5% better compared to our reference classification based on σ0 time series. Similar trends were observed for more detailed land-cover classes. Classification accuracy is heavily influenced by segment size and can drop by about 15% for very small segments. The most suitable classifier proved to be the Support Vector Machine, which performed up to 12% better than the worst one. This study demonstrates the suitability of multi-temporal polarimetry processing for land--cover classification.

Intestinal Inflammation in Chilean Infants Fed With Bovine Formula vs. Breast Milk and Its Association With Their Gut Microbiota

Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation.Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1β genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs).Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1β genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium.Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.

The Effect of Anaesthetic Techniques on Maternal and Cord Blood Brain-Derived Neurotrophic Factor Levels.

Brain-derived neurotrophic factor (BDNF), a member of neurotrophins, plays a critical role in neuronal tissue. In this study, the effects of spinal or general anaesthesia on cord and maternal peripheral blood BDNF and malondialdehyde (MDA) levels were investigated in patients undergoing elective caesarean section. Eighty patients with term pregnancy were included. General anaesthesia was induced with intravenous (IV) propofol 2 mg kg-1 in the general anaesthesia group (n=36). In the spinal anaesthesia group (n=35), hyperbaric bupivacaine 0.5%, 9 mg (1.8 mL) was injected intrathecally. Maternal blood samples were taken immediately after positioning the patient on the operating table (T1), before clamping the umbilical cord (T2) and 24 hours after the first sample was obtained (T3). Cord blood samples were drawn from the umbilical artery (T4). Maternal BDNF levels (pg mL-1) measured at T2 time point were higher in the general anaesthesia group compared to the spinal anaesthesia group (p<0.001). Cord blood BDNF levels were higher in the general anaesthesia group compared to the spinal anaesthesia group (p<0.001). In both groups, cord blood BDNF levels were significantly lower compared to the maternal blood samples collected at any time point (p<0.001, for all). There was a negative association between both maternal and cord blood BDNF levels with maternal MDA and cord blood MDA levels, respectively (r=-0.379, p<0.001; r=-0.375, p=0.001, respectively). The anaesthetic technique may have an influence on maternal peripheral and cord blood BDNF levels.

Influence of Photobiomodulation Therapy on Gingivitis Induced by Multi-Bracket Appliances: A Split-Mouth Randomized Controlled Trial.

The objective of this split-mouth trial was to investigate the influence of photobiomodulation therapy (PBMT) on adjuvant treatment of gingivitis induced by multi-bracket appliances, after bracket debonding and professional tooth cleaning. Thirteen patients (mean age 16.15 years; standard deviation ±2.12 years) who had completed active orthodontic treatment with fixed orthodontic appliances in an orthodontic clinic were included on a randomized basis. At time point T0, after bracket debonding and professional tooth cleaning, the papilla bleeding index (PBI) and bleeding on probing (BOP) were assessed in the upper jaw by the blinded investigator (M.S.), who was not aware at any time of which quadrant received PBMT. The study was based on a patient-blinded split-mouth design. In each patient, PBMT was administered by a practitioner (S.S.) in one upper quadrant (wavelength: 660 nm; Power: 100 mW; Power density: 100 mW/cm2; Energy density per application point = 2 J/cm2; Energy per application point = 2 J; Total dose = 52 J/cm2; Total energy = 52 J; Irradiation time: 26 × 20 sec), while the other upper quadrant received a simulated laser application with the laser system turned off. Randomized equal allocation of the sides was accomplished. The second PBI and BOP assessment followed 4-6 days after laser irradiation (T1) by M.S. No statistical differences were observed between the sides with regard to PBI and BOP values at T0 (p > 0.05). The PBI and BOP values decreased significantly between T0 and T1 on both sides (p < 0.05). At T1, the PBI and BOP values were significantly lower in the laser side in comparison with the control side (p < 0.05). On the basis of these results and study parameters, adjuvant PBMT is able to accelerate the healing process in patients with gingivitis induced by multi-bracket appliances.

Long-term impact of a six-month telemedical care programme on mortality, heart failure readmissions and healthcare costs in patients with chronic heart failure

Aims The TElemonitoring in the MAnagement of Heart Failure (TEMA-HF) 1 long-term follow-up study assessed whether an initial six-month telemonitoring (TM) programme compared with usual care (UC) would result in reduced all-cause mortality, heart failure admissions and healthcare costs in chronic heart failure (CHF) patients at long-term follow-up. Methods Of the 160 patients included in the multi-centre, randomised controlled telemonitoring trial (TEMA-HF 1, time point t0); 142 CHF patients (65% male; age: 76 ± 10 years; EF: 36 ± 15%) were alive and entered the follow-up study (time point: t1) with a final evaluation at 79 months (time point: t2). Both TM and UC group patients received standard heart failure care during the follow-up study (time points: t1 –t2). The primary endpoint was all-cause mortality. Secondary outcomes included days lost due to heart failure readmissions and readmission/patient follow-up related healthcare costs. Results Compared with usual care, the initial six-month TM programme had no significant effect on all-cause mortality (hazard ratio: 0.83; 95% confidence interval, 0.57 to 1.20; p = 0.32). The number of days lost due to heart failure readmissions was significantly lower in the TM group (p = 0.04). Healthcare costs did not differ significantly between the TM (€ 9140 ± 10580) and UC group (€ 12495 ± 22433) (p = 0.87). Discussion An initial six-month telemonitoring programme was not associated with reduced all-cause mortality in CHF patients at long-term follow-up but resulted in a reduction in the number of days lost due to heart failure readmissions. This study is registered in the ClinicalTrials.gov registry (NCT03171038) (URL: https://clinicaltrials.gov/ct2/show/NCT03171038).

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background:Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome.Methods:176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4–8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR.Results:Plasma levels of TERT were significantly lower at T2 (P<0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73–0.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10–4.11)-fold and 4.55 (95% CI 1.48–13.95)-fold higher, respectively, than those with undetectable plasma TERT levels.Conclusions:Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy.

Features of MRI stromal enhancement with neoadjuvant chemotherapy: a subgroup analysis of the ACRIN 6657/I-SPY TRIAL.

.Although the role of cancer-activated stroma in malignant progression has been well investigated, the influence of an activated stroma in therapy response is not well understood. Using retrospective pilot cohorts, we previously observed that MRI detected stromal contrast enhancement was associated with proximity to the tumor and was predictive for relapse-free survival in patients with breast cancer receiving neoadjuvant chemotherapy. Here, to evaluate the association of stromal contrast enhancement to therapy, we applied an advanced tissue mapping technique to evaluate stromal enhancement patterns within 71 patients enrolled in the I-SPY 1 neoadjuvant breast cancer trial. We correlated MR stromal measurements with stromal protein levels involved in tumor progression processes. We found that stromal percent enhancement values decrease with distance from the tumor edge with the estimated mean change ranging to () for time points T2 through T4. While not statistically significant, we found a decreasing trend in global stromal signal enhancement ratio values with the use of chemotherapy. There were no statistically significant differences between MR enhancement measurements and stromal protein levels. Findings from this study indicate that stromal features characterized by MRI are impacted by chemotherapy and may have predictive value in a larger study.

Predicting Treatment Response of Breast Cancer to Neoadjuvant Chemotherapy Using Ultrasound-Guided Diffuse Optical Tomography

PURPOSE: To prospectively investigate ultrasound-guided diffuse optical tomography (US-guided DOT) in predicting breast cancer response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Eighty-eight breast cancer patients, with a total of 93 lesions, were included in our study. Pre– and post–last chemotherapy, size and total hemoglobin concentration (THC) of each lesion were measured by conventional US and US-guided DOT 1 day before biopsy (time point t0, THC THC0, SIZE S0) and 1 to 2 days before surgery (time point tL, THCL, SL). The relative changes in THC and SIZE of lesions after the first and last NAC cycles were considered as the variables ΔTHC and ΔSIZE. Receiver operating characteristic curve was performed to calculate ΔTHC and ΔSIZE cutoff values to evaluate pathologic response of 93 breast cancers to NAC, which were then prospectively used to predicate response of 61 breast cancers to NAC. RESULTS: The cutoff values of ΔTHC and ΔSIZE for evaluation of breast cancers NAC treatment response were 23.9% and 42.6%. At ΔTHC 23.9%, the predicted treatment response in 61 breast lesions for the time points t1 to t3 was calculated by area under the curve (AUC), which were AUC1 0.534 (P=.6668), AUC2 0.604 (P=.1893), and AUC3 0.674(P =. 0.027), respectively; for ΔSIZE 42.6%, at time points t1 to t3, AUC1 0.505 (P=.9121), AUC2 0.645 (P=.0115), and AUC3 0.719 (P=.0018). CONCLUSION: US-guided DOT ΔTHC 23.9% and US ΔSIZE 42.6% can be used for the response evaluation and earlier prediction of the pathological response after three rounds of chemotherapy.

Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2%–3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12 ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant (PWex < 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12 ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis

Comparison of the effects of different doses of oxycodone on endotracheal intubation during general anesthesia induction period

Objective To compare the clinical effect of different doses of oxycodone on endotracheal intubation during general anesthesia induction period. Methods Ninety-five patients with endotracheal intubation general anesthesia were selected as the research subjects, and the patients were randomly divided into group A, group B and group C. 31 patients in group A received intravenous administration of oxycodone 0.20mg/kg, 32 patients in group B received intravenous administration of oxycodone 0.25mg/kg, and 32 patients in group C received intravenous administration of oxycodone 0.30mg/kg.The adrenaline, norepinephrine, dopamine concentration, as well as mean arterial pressure and heart rate at different time points were compared among the three groups. Results The mean arterial pressure and heart rate at T0 time point were decreased to varying extent compared with those at T1 time point(t=23.618, 7.412; 22.928, 9.063; 32.636, 9.422, P=0.000, 0.000; 0.000, 0.000; 0.000, 0.000). The heart rate, mean arterial pressure at T2, T3 and T4 time points in group A were increased compared with T0 time point(t=13.834, 6.506, 7.015; 17.604, 14.796, 16.323, P=0.000, 0.000, 0.000; 0.000, 0.000, 0.000). The adrenaline, norepinephrine and dopamine at T2, T3 and T4 time points in group A were increased compared with T0 time point(t=121.662, 64.533, 15.687; 31.498, 16.933, 9.286; 39.712, 116.049, 147.102, P=0.000, 0.000, 0.000; 0.000, 0.000, 0.000; 0.000, 0.000, 0.000). The heart rate, mean arterial pressure, adrenaline, norepinephrine and dopamine at T2, T3 and T4 time points in group B and group C were decreased significantly compared with those in group A(t=19.586, 31.972, 16.844, 27.087; 14.046, 14.822, 15.377, 23.826; 7.756, 14.396, 13.268, 23.342, 100.573, 104.010, 37.612, 38.892, 107.377, 117.969; 56.135, 56.757, 24.223, 25.300, 95.057, 82.088; 22.878, 25.731, 5.532, 5.934, 134.763, 83.628, P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000; 0.000, 0.000, 0.000, 0.000, 0.000, 0.000; 0.000, 0.000, 0.000, 0.000, 0.000, 0.000; 0.000, 0.000, 0.000, 0.000; 0.000, 0.000, 0.000, 0.000; 0.000, 0.000, 0.000, 0.000), and the differences were statistically significant(all P<0.05). Conclusion During the induction of general anesthesia, the appropriate dose of oxycodone in patients with endotracheal intubation was 0.25mg/kg, which could effectively maintain the hemodynamic stability, such as mean arterial pressure, and could reduce the stress response. Key words: Anesthesia, intratracheal; Dose-response relationship, drug; Oxycodone

Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program

BackgroundExposure to polychlorinated biphenyls (PCBs) is associated with depressive symptomatology. A cause of depressive symptoms is a disturbance in the neurotransmitter system of dopamine (DA). Animal as well as human studies report that PCBs can influence the DA system. This study examined whether PCB-related depressive symptoms are affected by DA metabolites in humans with high PCB body burden.MethodsThis study is part of the German HELPcB surveillance program (Health Effects in high Level exposure to PCB) for occupationally exposed workers and their relatives. Data was collected from 178 participants on two measurement time points (t1 and t2) with a one-year time lag in between the two time points. PCBs were analyzed in plasma via human biomonitoring and a validated questionnaire was used to identify existence and severity of depressive symptoms. As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test whether the association between PCB exposure and severity of depressive symptoms is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation was tested with the SPSS macro MEDIATE.ResultsWe found a significant mediation over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The positive association between PCB exposure with severity of depressive symptoms was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was associated with lower concentration in urinary HVA. A reduced HVA concentration at t1 was correlated with increased depressive symptoms severity at t2. No meditations were found for VMA.ConclusionsThis work indicates that the association of PCB exposure and an increase of depressive symptoms after one year is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps towards finding an explanation for an underlying neurochemical pathomechanism of PCB-related depressive symptomatology.

Bacterial Contamination of Endodontic Materials before and after Clinical Storage

IntroductionThe aim of this study was to evaluate the bacterial contamination in endodontic consumables (gutta-percha points, rubber dams, paper mixing pads, caulking agents, and endodontic instrument sponges [EISs]) before and after clinical use and storage. MethodsMaterials were randomly sampled in triplicates at 3 time points (t0, at package opening; t1, at 7 days; and t2, at 14 days) during their clinical usage. The gutta-percha points and caulking agent (25 mg) were added to 1 mL phosphate-buffered saline (PBS). The rubber dam, paper mixing pad, and EIS were added to 25 mL PBS. After vortexing, centrifuging, and removing the supernatant, the pellet was resuspended in 1 mL PBS, plated on fastidious anaerobic agar, and incubated aerobically and anaerobically. The grown colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The total bacterial load was calculated in the remaining volume (800 μL) from each sample by quantitative polymerase chain reaction after DNA extraction. ResultsAll tested materials showed a varied number of contaminated samples at the 3 time points (except EIS at t0) using MALDI-TOF MS. The most isolated genera were Propionibacterium (42%) and Staphylococcus (32%). By using non–culture-based approaches, all tested materials at the 3 time points (except gutta-percha at t0 and the caulking agent at t0, t1, and t2) carried bacterial DNA. ConclusionsThe majority of the tested materials harbored bacteria in their samples before and after clinical storage. Nosocomial infection derived from commonly used consumables could have an impact on the outcome of endodontic treatment.

Cardiac telerehabilitation: A novel cost-efficient care delivery strategy that can induce long-term health benefits.

Background Finding innovative and cost-efficient care strategies that induce long-term health benefits in cardiac patients constitutes a big challenge today. The aim of this Telerehab III follow-up study was to assess whether a 6-month additional cardiac telerehabilitation programme could induce long-term health benefits and remain cost-efficient after the tele-intervention ended. Methods and results A total of 126 cardiac patients first completed the multicentre, randomised controlled telerehabilitation trial (Telerehab III, time points t0 to t1). They consequently entered the follow-up study (t1) with evaluations 2 years later (t2). A quantitative analysis of peak aerobic capacity (VO2 peak, primary endpoint), international physical activity questionnaire self-reported physical activity and HeartQoL quality of life (secondary endpoints) was performed. The incremental cost-effectiveness ratio was calculated. Even though a decline in VO2 peak (24 ± 8 ml/[min*kg] at t1 and 22 ± 6 ml/[min*kg] at t2; P ≤ 0.001) was observed within the tele-intervention group patients; overall they did better than the no tele-intervention group ( P = 0.032). Dividing the incremental cost (-€878/patient) by the differential incremental quality-adjusted life years (QALYs) (0.22 QALYs) yielded an incremental cost-effectiveness ratio of -€3993/QALY. Conclusions A combined telerehabilitation and centre-based programme, followed by transitional telerehabilitation induced persistent health benefits and remained cost-efficient up to 2 years after the end of the intervention. A partial decline of the benefits originally achieved did occur once the tele-intervention ended. Healthcare professionals should reflect on how innovative cost-efficient care models could be implemented in standard care. Future research should focus on key behaviour change techniques in technology-based interventions that enable full persistence of long-term behaviour change and health benefits. This study is registered in the ISRCTN registry (ISRCTN29243064).

The influence of ketamine on KCC2 in spinal cord of rat in remifentanil-induced hyperalgesia

Objective To explore the effect of pre-treatment of subcutaneous injection of ketamine on remifentanil induced hyperalgesia and K+ /Cl-cotransporter 2, KCC2) expression on spinal cord of rats. Methods 60 male adult SD rats were randomly divided into five groups(n=12 in each group): control group (group C), the incision group(group I), the incision plus remifentanil group(group I+ R), the incision plus ketamine group(group I+ K) and the incision plus remifentanil and ketamine group(group I+ R+ K). Mechanical withdrawal threshold (MWT) was evaluated at 24 hours before incision(T0), 2 hours, 6 hours, 24 hours and 48 hours after incision(T1~T4). The lumbar spinal cords of rats were taken out at T4 time point and the KCC2 detected was detected by immunofluorescence analysis and western blot analysis. Results Compared with group C(T1(14.5±1.7)g, T2(14.2±1.1)g, T3(13.9±1.8)g, T4(14.2±1.1)g), MWT of other groups at T1 (I(5.6±0.8)g, I+ R(3.2±1.0)g, I+ K(6.8±1.7)g, I+ R+ K(5.1±1.6)g), T2 (I(6.9±1.0)g, I+ R(4.3±1.2)g, I+ K(8.0±1.4)g, I+ R+ K(6.2±1.5)g), T3 (I(7.6±0.9)g, I+ R(5.4±1.1)g, I+ K(10.3±1.2)g, I+ R+ K(7.1±1.1)g), T4 (I(8.9±1.1)g, I+ R(7.5±1.4)g, I+ K(11.3±1.2)g, I+ R+ K(8.3±1.2)g)and the expression of KCC2 at T4 decreased (P<0.05). Compared with group I(T1(5.6±0.8)g, T2(6.9±1.0)g, T3(7.6±0.9)g, T4(8.9±1.1)g), MWT of group I+ R (T1(3.2±1.0)g, T2(4.3±1.2)g, T3(5.4±1.1)g, T4(7.5±1.4)g) decreased at all time points after incision (T1~T4)(P<0.05) and the expression of KCC2 at T4 decreased significantly (P<0.05). Compared with group I(T1(5.6±0.8)g, T2(6.9±1.0)g, T3(7.6±0.9)g, T4(8.9±1.1)g), MWT of group I+ K (T1(6.8±1.7)g, T2(8.0±1.4)g, T3(10.3±1.2)g, T4(11.3±1.2)g) increased at all time points after incision (T1~T4)(P<0.05) and the expression of KCC2 at T4 increased (P<0.05). Compared with group I+ R(T1(3.2±1.0)g, T2(4.3±1.2)g, T3(5.4±1.1)g, T4(7.5±1.4)g), MWT of group I+ R+ K (T1(5.1±1.6)g, T2(6.2±1.5)g, T3(7.1±1.1)g, T4(8.3±1.2)g) increased at all time points after incision (T1~T4)(P<0.05) and the expression of KCC2 at T4 increased (P<0.05). Conclusion Pre-treatment of subcutaneous injection of ketamine can reduce the hyperalgesia of rats induced by remifentanil and reduce the inhibition of KCC2 expression on dorsal horn of spinal cord. Key words: Remifentanil; Hyperalgesia; Ketamine; KCC2

Evaluation of the use of shock index in identifying acute blood loss in healthy blood donor dogs.

To determine if shock index (SI) would increase following blood donation and if it would be a more sensitive assessment of acute blood loss as compared with heart rate (HR), blood pressure, and plasma lactate. Prospective study. University teaching hospital. Twenty client-owned clinically normal dogs. Peripheral venous blood measurements and blood donation. Data were collected at 3 time points: prior to donation (Tpre ), immediately after donation (T0 ), and 10 minutes following completion of donation (T10 ). HR and systolic blood pressure (SBP) were recorded and used to calculate SI at time points Tpre , T0 , and T10 . Packed cell volume (PCV), total plasma protein (TPP), and plasma lactate were evaluated from a peripheral venous blood sample at Tpre and T10. The mean SI was significantly increased at both time points following blood donation as compared to baseline (SIpre = 0.88±0.19 vs SI0 = 1.17±0.21 vs SI10 = 1.12±0.25 (P = 0.0002 and 0.0003, respectively). Following blood donation, the mean SBP was significantly lower (SBPpre = 149±24 mm Hg, SBP0 = 118±20 mm Hg; P = 0.0001, SBP10 = 133±21 mm Hg; P = 0.011). The mean HR was not significantly different at T0 but was significantly increased at T10 (HRpre = 128±21/min, HR0 = 136±25/min, P = 0.193; HR10 = 146±29/min, P = 0.003). There was no significant difference in mean PCV (PCVpre = 50±4%, PCV10 = 48±4%, P = 0.08). The mean TPP and plasma lactate were significantly different following donation but still within the reference interval (TPPpre = 6.8±0.4 g/dL, TPP10 = 6.4±0.4 g/dL, P = 0.0014; Lacpre = 1.7±0.7mmol/L, Lac10 = 1.9±0.8 mmol/L, P = 0.04). A receiver operating characteristic (ROC) analysis comparing area under the curve (AUC) for SI, HR, and SBP at T0 and T10 compared to Tpre found that SI (AUC at T0 : 0.858, CI: 0.730, 0.984 AUC at T10 : 0.769 CI: 0.617, 0.921) was a better indicator of blood loss than SBP at both T0 (AUC 0.165, CI: 0.0384, 0.292, P<0.0001) and T10 (AUC 0.288, CI: 0.124, 0.451, P<0.001) and better than HR at T0 (AUC 0.574, CI: 0.392, 0.756, P<0.001). An SI cut-off of 1.064 was 80% specific and 85% sensitive at T0 for detecting blood loss. An SI>1.0 is a sensitive and specific tool for detecting acute small volume blood loss in healthy dogs.

Retinoids, anxiety and peripartum depressive symptoms among Chinese women: a prospective cohort study

BackgroundThe current study aimed to investigate whether serum RBP levels can be a key predictor of peripartum depression (PPD).MethodsThis was a prospective cohort study, conducted at a general teaching hospital in South China. Research participants were evaluated at three time points: the third trimester of pregnancy (T1), after delivery at week one (T2), and after delivery week six (T3) using a set of self-reported questionnaires and blood sample assays.ResultsA total of 156 subjects were included for data analysis. The prevalence of anxiety symptoms ranged from 32.69% to 36.53%. The prevalence of PPD was also high and ranged from 27.56% to 35.89%. In the third trimester, significant predictors of depressive symptoms include serum retinol-binding protein (RBP) concentrations and estradiol levels (P = 0.008 and 0.033, respectively). At one week after delivery, serum concentrations of RBP at T2 were still significant predictors of depressive symptoms (P = 0.020, and serum estradiol concentrations at T1 were a significant predictor (P = 0.010). The most stable predictor of depressive symptoms at T3 was anxiety symptoms, especially at T3 time point (P < 0.001). Serum RBP concentrations at T1 and T2 were still significant predictors of depressive symptoms at T3.ConclusionA high prevalence of anxiety and depressive symptoms tended to persist in Chinese women during the peripartum period. This study, which found the potential contribution of RBP to the occurrence of PPD, requires that large sample studies be conducted in future with a longer-term follow-up period, in order to confirm its results.

Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats.

Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from hippocampus and entorhinal cortices by Percoll density gradient centrifugation. Cells were labeled with microglia surface antigens and analyzed by flow cytometry. Consistent with prior studies, isolated cells yielded a highly enriched population of brain macrophages/microglia (>95% pure), evidenced by staining for the macrophage/microglia antigen CD11b. Polarization states of CD11b+CD45low microglia were evaluated by expression of M1 surface markers, major histocompatibility complex (MHC) II, CD32, CD86, and M2 surface marker, CD206 (mannose receptor). Ethanol-treated animals begin to show increased expression of M1 and M2 markers at T0 (p=n.s.), with significant changes at the T2 time point. At T2, expression of M1 markers, MHC-II, CD86, and CD32 were increased (p<0.05) in hippocampus and entorhinal cortices, while M2 marker, CD206, was increased significantly only in entorhinal cortices (p<0.05). All effects resolved to control levels by T4. In summary, four-day binge alcohol exposure produces a transient increase in both M1 (MHC-II, CD32, and CD86) and M2 (CD206) populations of microglia isolated from the entorhinal cortex and hippocampus. Thus, these findings that both pro-inflammatory and potentially beneficial, recovery-promoting microglia phenotypes can be observed after a damaging exposure of alcohol are critically important to our understanding of the role of microglia in the pathogenesis of AUDs.

Effect of Alprazolam on Redox Status in Renal Transplantation Donors and Recipients.

BACKGROUND Benzodiazepines are the most popular premedication drugs thought to act through the GABA/benzodiazepine receptor complex and alprazolam is one of the most potent benzodiazepines that have a quick onset. While there is a growing body of evidence supporting alprazolam in the amelioration of redox status in animals, no study has been performed concerning its antioxidant activity in humans. The purpose of this investigation was to determine the effect of alprazolam on redox status. MATERIAL AND METHODS This study was a four-group randomized controlled trial. Participants were recruited from Acibadem University Acibadem International Hospital and included a convenience sample of 82 donors and recipients undergoing renal transplantation. Patients were randomly divided into four groups. While donors and recipients in experimental groups (G1 and G3) were administered alprazolam 0.5 mg orally one hour before the operation, those in control groups (G2 and G4) were not. Serum advanced oxidative protein products, total thiol, free hemoglobin, ischemic modified albumin, and sialic acid levels at different time points were measured to evaluate the redox status. RESULTS All oxidative stress parameters were higher in the alprazolam premedication groups (G1, G3) at all time points than in the control groups (G2, G4). Basal values of oxidative parameters (at time point T1) in patients with CKD (G3, G4) were lower than in healthy donors (G1, G2). CONCLUSIONS Alprazolam premedication in donors and end-stage renal failure patients undergoing renal transplantation does not improve redox homeostasis but further experimental studies are needed.

Integrating transcriptomics and metabolomics for the analysis of the aroma profiles of Saccharomyces cerevisiae strains from diverse origins

BackgroundDuring must fermentation thousands of volatile aroma compounds are formed, with higher alcohols, acetate esters and ethyl esters being the main aromatic compounds contributing to floral and fruity aromas. The action of yeast, in particular Saccharomyces cerevisiae, on the must components will build the architecture of the wine flavour and its fermentation bouquet. The objective of the present work was to better understand the molecular and metabolic bases of aroma production during a fermentation process. For such, comparative transcriptomic and metabolic analysis was performed at two time points (5 and 50 g/L of CO2 released) in fermentations conducted by four yeast strains from different origins and/or technological applications (cachaça, sake, wine, and laboratory), and multivariate factorial analyses were used to rationally identify new targets for improving aroma production.ResultsResults showed that strains from cachaça, sake and wine produced higher amounts of acetate esters, ethyl esters, acids and higher alcohols, in comparison with the laboratory strain. At fermentation time T1 (5 g/L CO2 released), comparative transcriptomics of the three S. cerevisiae strains from different fermentative environments in comparison with the laboratory yeast S288c, showed an increased expression of genes related with tetracyclic and pentacyclic triterpenes metabolism, involved in sterol synthesis. Sake strain also showed upregulation of genes ADH7 and AAD6, involved in the formation of higher alcohols in the Ehrlich pathway. For fermentation time point T2 (50 g/L CO2 released), again sake strain, but also VL1 strain, showed an increased expression of genes involved in formation of higher alcohols in the Ehrlich pathway, namely ADH7, ADH6 and AAD6, which is in accordance with the higher levels of methionol, isobutanol, isoamyl alcohol and phenylethanol observed.ConclusionsOur approach revealed successful to integrate data from several technologies (HPLC, GC-MS, microarrays) and using different data analysis methods (PCA, MFA). The results obtained increased our knowledge on the production of wine aroma and flavour, identifying new gene in association to the formation of flavour active compounds, mainly in the production of fatty acids, and ethyl and acetate esters.