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Background and Objectives: Leishmaniasis is a protozoan parasitic disease which is transmitted by the female Phlebotomus sand fly and is prevalent in four continents. The first-choice treatment for the leishmaniasis is pentavalent antimonials, which are potentially toxic and often ineffective and use of them exhibit therapeutic failure. These pharmaceutical problems point towards the need to develop novel chemotherapeutic agents. Seaweeds are considered as source of bioactive metabolites characterized by a broad spectrum of biological activities. Materials and Methods: In this experimental study, cold and hot water crude extracts of four species of green, brown and red marine algae "Caulerpa sertularioides, Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" collected along the Bushehr coast of the Persian Gulf (southwest of Iran), prepared and their in vitro activities against Leishmania major promastigote were evaluated by using the MTT assay test. Results: The cold and hot water crude extracts of four algae species exhibited different anti-Leishmanial activities. The minimum inhibitory concentration of hot water extracts calculated as IC50 was as follows: Caulerpa sertularioides (IC50 ≤ 85 µg/ml), Gracilaria corticata (IC50 ≤ 38 µg/ml), Gracillaria salicornia (IC50 ≤ 46 µg/ml) and Sargassum oligocystum (IC509 ≤ 78 µg/ml, while these values for cold water extracts were (IC50 >125 µg/ml) for Caulerpa Sertularioides (IC50 >65 µg/ml) for Gracilaria corticata (IC50 >74 µg/ml) for Gracilaria salicornia and (IC50 >105 µg/ml) for Sargassum oligocystum, IC50 values for reference drug (Amphotericin B) was (0.16-0.2 µg/ml). Discussion: According to the results, inhibitory effects of the crude extracts from these four species algae specially hot water crude extracts from "Gracilaria corticata, Gracillaria salicornia and Sargassum oligocystum" are significant and in accordance with other studies that has been done on different algae species. So these results are sufficiently promising to be followed with further studies on isolation and characterization of pure compounds from these algae species as well as in vivo experiments, a work that is already under way in our laboratory. [ABSTRACT FROM AUTHOR]

Recently, it was stated that the proliferative activity (P) of a cell population could be indirectly calculated by multiplying the MIB-1 immunopositivity and silver-stainable nucleolar organizer region (AgNOR) features extracted exclusively in MIB-1 positive (pos.) nuclei: P=MIB-1×AgNORMIB-1pos.. To study the prognostic significance of this hypothesis, MIB-1 immunohistochemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MIB-1mean) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis system AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chosen tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR countMIB-1pos., AgNOR areaMIB-1pos.). AgNOR count and AgNOR countMIB-1pos. showed a different data distribution [2.7±0.7 (mean±SD) vs 3.9±1.1; r=0.315, P=0.014]. Similar results were obtained for AgNOR area and AgNOR areaMIB-1pos. (5.1±2.1 µm2 vs 7.5±2.4 µm2; r=0.501, P<0.001). Kaplan–Meier survival curves revealed significant differences for MIB-1mean ( P=0.0018) and AgNOR areaMIB-1pos. ( P=0.0340). In Cox models, both parameters provided independent prognostic information. Using their combination, the P, three groups of patients with statistically different survival could be separated ( P=0.0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measurements in MIB-1 positive nuclei appears to be more useful in breast cancer prognosis than the exclusive application of one of the two methods. By this combined application, probably effects of tumor biology are represented more precisely. [ABSTRACT FROM AUTHOR]

Care Management for Polytrauma Patients in a Level-1 Trauma Centre Abstract. In our level-1 trauma institution, polytrauma patients with an Injury Severity Score of 16 or higher are facing waiting times for transfer to a rehabilitation facility, causing a negative financial outcome for our institution. The purpose of this study is to stimulate rapid transfer to a rehabilitation facility. In a single-centre case study, care management for (poly)trauma patients was started to ensure time-directed treatment for trauma patients related to Diagnosis-Related Groups (DRG). In the period of 2013-2018 there was an increase in trauma admissions up to 14 % (n = 16 157) with a mean length of hospital stay of 6.4 days, together with a reduction in the number of trauma bed capacity from 50 to 42. In relation to the DRGs, regular trauma patients who were not in need of a stationary rehabilitation facility stayed in line with the expected time of hospital stay. But (poly)trauma patients (n = 1831) with the need of a stationary stay in a rehabilitation centre were faced with waiting times before they could be transferred. The average excess waiting time in relation to DRG for polytrauma patients was 5.1 days. Trauma patients for a rehabilitation centre have a higher Case Mix Index (CMI) compared to those who do not require inpatient rehabilitation (4.22 versus 1.04, p <0.0001). With about 280 trauma patients annually waiting an extra 5.1 days for transfer to a rehabilitation facility, the financial burden for our department amounts to Swiss francs 885,360 without reimbursement. Since no extra bed capacities in rehabilitation facilities are available in our area, it may be advised to set up an early in-hospital trauma rehabilitation program in a level-1 trauma centre in order to reduce financial loss.

Background: To assess whether circadian patterns of temperature correlate with further values of intracranial pressure (ICP) in severe brain injury treated with hypothermia., Methods: We retrospectively analyzed temperature values in subarachnoid hemorrhage patients treated with hypothermia by endovascular cooling. The circadian patterns of temperature were correlated with the mean ICP across the following day (ICP 24 )., Results: We analyzed data from 17 days of monitoring of three subarachnoid hemorrhage patients that underwent aneurysm coiling, sedation and hypothermia due to refractory intracranial hypertension and/or cerebral vasospasm. ICP 24 ranged from 11.5 ± 3.1 to 24.2 ± 6.2 mmHg. The ratio between the coefficient of variation of temperature during the nocturnal period (18:00-6:00) and the preceding diurnal period (6:00-18:00) [temperature variability (TV)] ranged from 0.274 to 1.97. Regression analysis showed that TV correlated with ICP 24 (Pearson correlation = -0.861, adjusted R square = 0.725, p < 0.001), and that ICP 24  = 6 (4-TV) mmHg or, for 80% prediction interval, [Formula: see text] mmHg. The results indicate that the occurrence of ICP 24 higher than 20 mmHg is unlikely after a day with TV ≥1.0., Conclusions: TV correlates with further ICP during hypothermia regardless the strict range that temperature is maintained. Further studies with larger series could clarify whether intracranial hypertension in severe brain injury can be predicted by analysis of oscillation patterns of autonomic parameters across a period of 24 h or its harmonics.

In this study, we assessed the potential role of the TT genotype of the gene of the methylenetetrahydrofolate reductase for the manifestation of thrombotic microangiopathies, enrolling 40 affected patients (mean age [+/- standard deviation] 35 +/- 11 years). As a result, the methylenetetrahydrofolate reductase 677TT genotype was more prevalent in patients with thrombotic microangiopathies compared with controls (adjusted odds ratio = 2.58, 95% confidence interval = 1.2-5.7, P = .018), particularly in those suffering from the hemolytic uremic syndrome. A hemolytic more severe clinical course of thrombotic microangiopathies in carriers of the methylenetetrahydrofolate reductase 677TT genotype was not observed. In summary, our findings suggest a significant influence of the methylenetetrahydrofolate reductase genotype on the manifestation of thrombotic microangiopathies. The 677 TT genotype of this polymorphism appears to be a risk factor for manifestation of these rare thrombotic disorders, possibly explained by endothelial activation and increased oxidative stress.

The 34 Leu (100T) variant of the factor XIII Val34Leu (G100T-) polymorphism slows down fibrinolysis and has been proposed as a thrombotic risk factor. In this pilot study, we enrolled 40 patients (mean age +/- SD = 38 +/- 11 years) and 728 controls to assess the role of this genetic variant for the manifestation of thrombotic microangiopathies. From the genotype prevalences, an increased manifestation risk for carriers of the TT genotype (homozygous Leu variant) of the factor XIII Val34Leu (G100T-) polymorphism was calculated (odds ratio [OR] = 2.44; 95% confidence interval [CI] = 0.8-7.6; P = .11). This association was statistically significant for patients with thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome (TTP-HUS) (OR = 6.6; 95% CI = 1.7-25.9; P = .006). Our data suggest a role of the homozygous Leu variant of the factor XIII Val34Leu polymorphism in the manifestation of thrombotic microangiopathies. Decreased fibrinolysis in the presence of this genetic variant provides a plausible explanation for this association.

Unlabelled: After achieving a reduction of pain scores for 10 h with a single dose wound infiltration after shoulder surgery, we examined in a prospective, placebo-controlled and double-blinded study the analgesic effects of continuous wound infiltration with different concentrations of ropivacaine. Forty-five patients undergoing shoulder surgery were randomly assigned into three groups to receive single dose wound infiltration with 30 mL saline (group S) or ropivacaine 7.5 mg/mL (groups R2 and R3.75) after skin closure. Postoperatively, patients received a continuous wound infiltration with saline (group S), ropivacaine 2 mg/mL (group R2) or ropivacaine 3.75 mg/mL (group R3.75) for 48 h. Supplemental pain relief was provided by IV patient-controlled analgesia with the opioid piritramide. At 1, 2, 3, 4, 24, and 48 h postoperatively visual analogue scale (VAS) values (0-100 mm), piritramide requirements and side effects were registered. Plasma levels of ropivacaine were measured preoperatively and at 24 h and 48 h after surgery. Until 48 h VAS values were smaller in group R3.75 compared with group S (group R3.75, 8 +/- 9 mm; group S, 31 +/- 14 mm; P < 0.005), whereas 4 h and 48 h postoperatively VAS values were even smaller in group R3.75 compared with group R2 (P < 0.05). Cumulative piritramide consumption was always smaller in groups R2 and R3.75 compared with group S (1-24 h, P < 0.005; 48 h, P < 0.05). Plasma ropivacaine levels remained less than the toxic threshold. We conclude that continuous postoperative wound infiltration with ropivacaine, especially using 3.75 mg/mL, provides smaller VAS values and opioid requirement in comparison with saline after shoulder surgery., Implications: The continuous postoperative wound infiltration after shoulder surgery with different concentrations of ropivacaine, 2 mg/mL and 3.75 mg/mL, results in lower pain scores and opioid requirement compared with infiltration with placebo. Plasma levels of ropivacaine remained less than the toxic threshold.

Recently, it was stated that the proliferative activity (P) of a cell population could be indirectly calculated by multiplying the MIB-1 immunopositivity and silver-stainable nucleolar organizer region (AgNOR) features extracted exclusively in MIB-1 positive (pos.) nuclei: P=MIB-1 x AgNOR(MIB-1pos.). To study the prognostic significance of this hypothesis, MIB- immunohistochemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MIB-1mean) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis system AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chosen tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR countMIB-1pos., AgNOR areaMIB-1pos.). AgNOR count and AgNOR countMIB-1pos. showed a different data distribution [2.7+/-0.7 (mean+/-SD) vs 3.9+/-1.1; r=0.315, P=0.014]. Similar results were obtained for AgNOR area and AgNOR areaMIB-1pos. (5.1+/-2.1 microm2 vs 7.5+/-2.4 microm2; r=0.501, P<0.001). Kaplan-Meier survival curves revealed significant differences for MIB-1mean (P=0.0018) and AgNOR areaMIB-1pos. (P=0.0340). In Cox models, both parameters provided independent prognostic information. Using their combination, the P, three groups of patients with statistically different survival could be separated (P=0.0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measurements in MIB-1 positive nuclei appears to be more useful in breast cancer prognosis than the exclusive application of one of the two methods. By this combined application, probably effects of tumor biology are represented more precisely.