First Constraints from DAMIC-M on Sub-GeV Dark-Matter Particles Interacting with Electrons.

We report constraints on sub-GeV dark matter particles interacting with electrons from the first underground operation of DAMIC-M detectors. The search is performed with an integrated exposure of 85.23 g days, and exploits the subelectron charge resolution and low level of dark current of DAMIC-M charge-coupled devices (CCDs). Dark-matter-induced ionization signals above the detector dark current are searched for in CCD pixels with charge up to 7e^{-}. With this dataset we place limits on dark matter particles of mass between 0.53 and 1000 MeV/c^{2}, excluding unexplored regions of parameter space in the mass ranges [1.6,1000] MeV/c^{2} and [1.5,15.1] MeV/c^{2} for ultralight and heavy mediator interactions, respectively.

B3 agonists or anticholinergics in the treatment of the lower urinary tract dysfunction in patients with multiple sclerosis?-A randomized study.

INTRODUCTION AND OBJECTIVE: Multiple sclerosis (MS) is the most frequent autoimmune demyelinating disease of the central nervous system. MS patients usually present with lower urinary tract dysfunction (LUTD). Objective of this study is to evaluate and compare the efficacy and safety of treating MS patients with LUTD with either a b3 agonist (mirabegron) or anticholinergics. The study's primary outcome is the LUTD symptom improvement. MATERIAL AND METHODS: This is a multi-center, single-blinded, comparative study including 91 MS patients with LUTD. At baseline, patients underwent thorough clinical examination, urine cultivation and abdominal ultrasound and completed urination diaries and specific, validated questionnaires (NBSS, MusiQoL). At second visit, patients were administered either mirabegron or anticholinergics. Treatment was always carried out alongside with MS treatment. Reevaluation was performed 3 months after first visit. Patients underwent the same clinical and imaging tests that were carried out at first visit. RESULTS: We compared several clinical and imaging parameters between the two groups at first visit and month 3 after treatment. Νo statistical difference was noted between the mirabegron group and the anticholinergic group in terms of LUTD improvement. In both groups, improvement from baseline regarding LUTD was recorded. Statistical analysis was performed using the paired and unpaired t test method. No patient discontinued either medication due to side effects. CONCLUSIONS: MS patients receiving either mirabegron or anticholinergic therapy for LUTD showed improvement. Nevertheless, no statistical difference was noted between the two cohorts at 3 months in terms of drug efficacy in all the statistically significant parameters.

Particulate emissions from L-Category vehicles towards Euro 5.

The current experimental study presents particulate emissions from 30 Euro 1-4 L-category vehicles (i.e. 2-, 3- and 4-wheelers such as mopeds, motorcycles, quads and minicars, registered in Europe between 2009 and 2016) tested on a chassis dynamometer. The objectives were to identify those sub-categories with high emissions, to assess whether the measures prescribed in the Euro 5 legislation will effectively control particulate emissions and finally to investigate the need for additional measures. The results showed that 2-stroke (2S) mopeds and diesel minicars comprised the vehicles with the highest particulate mass (PM) and solid particle number above 23 nm (SPN23) emissions (up to 64 mg/km and 4.5 × 1013 km-1, respectively). It is uncertain whether the installation of diesel particulate filters (DPF) is a cost-effective measure for diesel mini-cars in order to comply with Euro 5 standard, while advanced emission controls will be required for 2S mopeds, if such vehicles remain competitive for Euro 5. Regarding 4-stroke mopeds, motorcycles and quads, PM emissions were one order of magnitude lower than 2S ones and already below the Euro 5 limit. Nevertheless, SPN23 emissions from these sub-categories were up to 5 times higher than the Euro 6 passenger cars limit (6 × 1011 km-1). Even recent Euro 4 motorcycles exceeded this limit by up to 3 times. These results indicate that L-category vehicles are a significant contributor to vehicular particulate emissions and should be further monitored during and after the introduction of the Euro 5 step. Moreover, including SPN in the range 10-23 nm increases emission levels by up to 2.4 times compared to SPN23, while volatile and semi-volatile particle numbers were even higher. Finally, cold engine operation was found to be a significant contributor on SPN23 emissions, especially for vehicles with lower overall emission levels. These results indicate that a specific particle number limit may be required for L-category to align emissions with passenger cars.

Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.

Implementation of universal screening for preterm delivery by mid-trimester cervical-length measurement.

OBJECTIVE: To assess the feasibility and results of introducing a policy of universal screening for preterm delivery (PTD) by mid-trimester cervical-length (CL) measurement. METHODS: In this retrospective cross-sectional study of singleton pregnancies, transvaginal sonography for CL measurement was performed at 20-24 weeks of gestation. Vaginal progesterone therapy was offered to women with CL ≤ 15 mm. The incidence of spontaneous PTD (sPTD) according to CL and the distribution of CL measurements were assessed. Rate of PTD before implementation of screening was compared with that after. RESULTS: A total of 10 506 singleton pregnancies were assessed. The decline rate was 1.32%. sPTD < 32 weeks, < 34 weeks and < 37 weeks occurred in 0.51%, 0.82% and 3.90% of pregnancies, respectively. CL measurement was best described by a mixture model distribution comprising a 'short' and a 'long' component. The percentage of the two components varied between subgroups of PTD, with the short component being greater the earlier the birth. CL, history of miscarriage, smoking status and prior PTD were independent predictors in the construction of a model predictive of PTD < 34 weeks (area under the curve = 0.74, P < 0.001). The rate of sPTD < 34 weeks in women with CL ≤ 15 mm receiving progesterone treatment was 20.4%. In the progesterone-treated group, a plateau was observed in the increase in risk for PTD for CL 9-13 mm, whereas below 9 mm the risk increased exponentially. Following the introduction of mid-trimester CL measurement, there was a trend for reduction in the rate of any PTD < 34 weeks of about 20% in comparison with the prescreening period (odds ratio = 0.81; 95% CI, 0.59-1.13). CONCLUSIONS: Universal screening for PTD by transvaginal sonographic measurement of CL at 20-24 weeks is feasible and well accepted by pregnant women. This policy identifies a very high-risk group that may benefit from intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Effects of dietary fat source on lutein, zeaxanthin and total carotenoids content of the egg yolk in laying hens during the early laying period.

1. The study was conducted to investigate the effects of different dietary levels of an unsaturated or saturated fat source and the effects of different dietary energy levels in laying hen diets on the carotenoid content of the egg yolk. 2. Seventy-two ISA Brown laying hens aged 22 weeks old were allocated, for a 10 week period, to three treatments: control diet (HE group) with a 3.4% supplemented fat containing 2.1% soybean and 1.3% palm oil as fat sources and a ratio of unsaturated to saturated fatty acid (u/s) of 3.33; a lowered energy diet with 2.4% supplemented fat containing 1.4% soybean and 1.0% palm oil and u/s of 3.41 (LE+high u/s); a lowered energy diet with 2.4% supplemented fat containing 0.5% soybean and 1.9% palm oil and a u/s of 2.39 (LE+low u/s). A marigold plant extract supplement was used as a source of lutein. 3. Performance parameters (feed consumption, feed conversion, body weight), egg production rate and egg quality parameters were similar between treatments. Dietary fat digestibility at the middle of the study period was not different. Egg yolk total fat content was similar in all treatments at the middle and at the end of the study period. 4. Lutein, zeaxanthin, cis-lutein and total carotenoids content were significantly lower in eggs produced from the LE+low u/s group compared to those from the HE and the LE+high u/s groups (P < 0.01 for all parameters). 5. It was concluded that feeding laying hens with a diet containing 1% less supplemented fat and a lower u/s ratio compared to a control diet and to a diet with 1% less supplemented fat with a higher u/s ratio resulted in a significant reduction of carotenoid expression in the egg yolk at the end of experimental period. Performance and egg quality parameters were not affected by treatments.

Effects of lysolecithin supplementation in low-energy diets on growth performance, nutrient digestibility, viscosity and intestinal morphology of broilers.

1. The study aimed to investigate the effect of lysolecithin supplementation in low-energy diets on growth, nutrient digestibility and intestinal mucosa characteristics of broilers. 2. A total of 800 one-d-old Ross 308 broiler chickens were assigned to 4 dietary treatments consisting of 10 replicates of 20 broilers each. Broilers were fed with 4 different diets: (i) HE: positive control group broilers received a diet with unaltered energy; (ii) LE: negative control group broilers received a diet with lower energy of about 0.27 MJ/kg; (iii) LElys500: broilers received a diet similar to LE supplemented with 500 g/tn lysolecithin product (Lysoforte Booster DryTM); and (iv) LElys300: broilers received a diet similar to LE supplemented with 300 g/tn lysolecithin product. The experimental period was 42 d. 3. Body weight gain in treatments HE was higher than LE during the overall experimental period, while LElys500 and LElys300 had intermediate values. Feed conversion ratio was lower in HE and LElys500 than LE group, while the LElys300 had intermediate values. Fat digestibility was improved in both LElys 500 and LElys300 compared to the HE group. Apparent metabolisable energy (AMEn) was higher in HE, LElys500 and LElys300 than LE. Ileum viscosity at 42 d was also affected, being higher in LE group compared to HE. At 28 d mucosal thickness was lower both in LElys500 and LElys300 compared to HE and LE, while no difference occurred between treatment proliferation patterns of duodenal epithelial cells. 4. These findings indicated that lysolecithin supplementation at 500 g/tn of feed in low-energy diets maintained broiler performance. Supplementation of reformulated low-energy diets induced an increase in digesta viscosity. Lysolecithin supplementation resulted in variable alterations in the duodenum mucosal morphology.

The use of local anesthesia to perform lower limb revascularization in the fragile patient with critical limb ischemia.

Patients with critical limb ischemia are usually compromised, frequently making administration of general or regional anesthesia problematic. We treated 3 fragile patients presenting contraindications to undertake traditional anesthetic techniques for lower limb revascularization, in whom local anesthesia with conscious sedation was used to complete the operation. An axillo-bifemoral, a unilateral axillo-femoral and a femoro-femoral bypass were performed. Procedure was uneventful in all three cases despite the coexistence of specific surgical challenges (distal anastomosis at the profunda in two cases, redo surgery and scarred groin in the third). Surgical revascularization under local anesthesia may be considered in selected high risk patients.

Cardiovascular magnetic resonance evaluation of paediatric patients with systemic lupus erythematosus and cardiac symptoms.

OBJECTIVES: To evaluate the cardiovascular magnetic resonance (CMR) findings in a paediatric population with systemic lupus erythematosus (SLE) and cardiac symptoms. METHODS: Twenty-five SLE children, aged 10.2 ± 2.6 years, with cardiac symptoms and normal routine non-invasive evaluation were examined by CMR, using a 1.5 T system and compared with sex-matched SLE adults. Left ventricular (LV) volumes, ejection fraction, T2 ratio, early (EGE) and late (LGE) gadolinium enhancement were assessed. Acute and chronic lesions were characterised as LGE-positive plus T2 > 2, EGE > 4 or T2 < 2, EGE < 4, respectively. According to LGE, lesions were characterized as: (a) diffuse subendocardial, (b) subepicardial and (c) subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. RESULTS: LV ejection fraction (LVEF) was normal in all SLEs. T2 > 2, EGE > 4 and positive epicardial LGE wall was identified in 5/25 children. Diffuse subendocardial fibrosis was documented in 1/25. No evidence of myocardial infarction was identified in any children. In contrast, in SLE adults, LGE indicative of myocardial infarction was identified in 6/25, myocarditis in 3/25, Libman-Sacks endocarditis in 1/25 and diffuse subendocardial fibrosis in 2/25. The incidence of heart disease in SLE children was lower compared to SLE adults (p < 0.05), with a predominance of myocarditis in children and myocardial infarction in adults. A significant correlation was documented between disease duration and CMR lesions (p < 0.05). CONCLUSION: CMR identifies a predominance of myocarditis in paediatric SLE with cardiac symptoms and normal routine non-invasive evaluation. However, the incidence of cardiac lesions is lower compared to SLE adults, probably due to shorter disease duration. SIGNIFICANCE AND INNOVATION: CMR identifies heart involvement in a significant percentage of SLE children with cardiac symptoms and normal routine noninvasive evaluation.The incidence of heart disease is lower in SLE children compared with SLE adults.Predominance of myocarditis and myocardial infarction is observed in SLE children and SLE adults, respectively.

Cervical length in late second and third trimesters: a mixture model for predicting delivery.

OBJECTIVES: To examine the distribution of cervical length (CL) in the late second and third trimesters of pregnancy and construct survival models for spontaneous delivery. METHODS: This cross-sectional study included 647 women with a singleton pregnancy who had routine CL measurements taken by transvaginal ultrasonography between 24 and 40 weeks' gestation. Only one measurement per patient was included in the analysis. Exploratory data analysis revealed that the distribution of CL measurements was a mixture of two Gaussian distributions, and subsequently a mixture model was applied to describe the distribution of CL. Changes in CL in relation to gestational age were examined by regression analysis and measurements were converted to Z-scores. Survival analysis was applied to the subgroups identified, to describe the probability of delivery throughout gestation. RESULTS: CL was best described by a mixture model of two subgroups with Gaussian distribution, one including women with a long cervix (73.85% of the study population, mean CL of 28.2 ± 4.45 mm) and the other including women with a short cervix (26.15% of the study population, mean CL of 12.3 ± 5.14 mm). CL was dependent on gestational age (GA), therefore conversion to Z-scores was employed in the analysis. Women with a short cervix had a higher probability for spontaneous delivery (hazard ratio (HR), 1.807; P < 0.001) than did women with a long cervix, after adjustment for GA at the time of measurement (GA HR, 1.115; P < 0.001). In both subgroups, the probability of spontaneous delivery was predicted by the GA and CL Z-scores. Survival models for the prediction of spontaneous delivery were constructed separately for the short-cervix subgroup (GA HR, 1.085; P < 0.001 and CL Z-score HR, 0.819; P = 0.003) and the long-cervix subgroup (GA HR, 1.130; P < 0.001 and CL Z-score HR, 0.864; P = 0.005). CONCLUSIONS: CL follows a mixture of two Gaussian distributions, one for a short and one for a long cervix. Late second-trimester/third-trimester CL measurement may be of value in estimating the probability for spontaneous delivery at any given gestational age.

Impact of metabolic syndrome in surgical patients: should we bother?

Clinicians inevitably encounter patients who meet the diagnostic criteria for the metabolic syndrome (MetS); these criteria include central obesity, hypertension, atherogenic dyslipidaemia, and hyperglycaemia. Regardless of the variations in its definition, MetS may be associated with adverse outcomes in patients undergoing both cardiac and non-cardiac surgery. There is a paucity of data concerning the anaesthetic management of patients with MetS, and only a few observational (mainly retrospective) studies have investigated the association of MetS with perioperative outcomes. In this narrative review, we consider the impact of MetS on the occurrence of perioperative adverse events after cardiac and non-cardiac surgery. Metabolic syndrome has been associated with higher rates of cardiovascular, pulmonary, and renal perioperative events and wound infections compared with patients with a non-MetS profile. Metabolic syndrome has also been related to increased health service costs, prolonged hospital stay, and a greater need for posthospitalization care. Therefore, physicians should be able to recognize the MetS in the perioperative period in order to formulate management strategies that may modify any perianaesthetic and surgical risk. However, further research is needed in this field.

Expression profile of the GA733 gene family in colorectal cancer: correlation with clinicopathological parameters.

GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.

Correlation between Central Corneal Thickness and Intraocular Pressure Measured by Goldmann Applanation Tonometry or Pascal Dynamic Contour Tonometry.

PURPOSE: The aim of this study was to investigate the relationship between central corneal thickness and intraocular pressure measured by Goldmann applanation tonometry and Pascal dynamic contour tonometry. PATIENTS AND METHODS: The study included 45 persons (90 eyes), divided into 4 groups: a) 10 normal volunteers (20 eyes); b) 16 patients (32 eyes) with primary open-angle glaucoma; c) 8 patients (16 eyes) with normal-tension glaucoma; and d) 11 patients (22 eyes) with ocular hypertension. Intraocular pressure was measured by Goldmann applanation tonometry and Pascal dynamic contour tonometry, and central corneal thickness was measured by ultrasound pachymetry. The relationship between intraocular pressure and central corneal thickness was evaluated. RESULTS: Intraocular pressure was correlated positively but not strongly enough with central corneal thickness when it was measured by Goldmann applanation tonometry. On the contrary, there was no correlation between intraocular pressure and central corneal thickness when intraocular pressure was measured by Pascal dynamic contour tonometry. CONCLUSION: Central corneal thickness is an important variable in the evaluation of intraocular pressure by Goldmann applanation tonometry. This factor does not interfere with the intraocular pressure measurements taken by Pascal dynamic contour tonometry.

Ocular pulse amplitude measurement using pascal dynamic contour tonometer in glaucoma patients.

AIM: This study aims to measure and compare the ocular pulse amplitude using Pascal dynamic contour tonometry in normal persons and in glaucoma patients. PATIENTS AND METHODS: 20 patients (40 eyes) with primary open angle glaucoma (Group A), 8 patients (16 eyes) with normal tension glaucoma (Group B), and 12 patients (24 eyes) with ocular hypertension (Group C) were included in the study. Control group (Group D) comprised 25 normal volunteers (50 eyes). Intraocular pressure was measured using both Goldmann applanation tonometry in the slit-lamp and Pascal dynamic contour tonometry. Ocular pulse amplitude was evaluated with Pascal dynamic contour tonometry. Statistical evaluation of the differences in ocular pulse amplitude and intraocular pressure among the different groups was performed using Student's t-test. RESULTS: Mean ocular pulse amplitude values expressed in mmHg were 3.66 ± 1.00, 2.46 ± 0.60, 4.04 ± 1.47, and 2.52 ± 0.52, for Groups A, B, C, and D, respectively. The ocular pulse amplitude was significantly higher in Group A (primary open angle glaucoma) and Group C (ocular hypertension) when compared with Group D (control group) and Group B (normal tension glaucoma). No statistically significant difference was detected between Group D (control group) and Group B (normal tension glaucoma). CONCLUSIONS: Although we can measure the intraocular pressure with Goldmann applanation tonometry, no information can be derived regarding the ocular pulse amplitude. The use of Pascal dynamic contour tonometry in intraocular pressure estimation provides useful clinical information also about the magnitude of the ocular pulse amplitude in different types of glaucoma. Pascal dynamic contour tonometry discloses an elevation of ocular pulse amplitude in primary open angle glaucoma and ocular hypertension patients. On the contrary, the ocular pulse amplitude is within normal limits in normal tension glaucoma patients.

Acute inflammation alters adult hippocampal neurogenesis in a multiple sclerosis mouse model.

Neural precursor cells (NPCs) located in the subgranular zone (SGZ) of the dentate gyrus (DG) give rise to thousands of new cells every day, mainly hippocampal neurons, which are integrated into existing neuronal circuits. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of inflammation is somewhat controversial. The present study demonstrates that the inflammatory environment prevailing in the brain of experimental autoimmune encephalomyelitis (EAE) mice enhances the proliferation of NPCs in SGZ of the dorsal DG and alters the proportion between radial glial cells and newborn neuroblasts. The injection protocol of the cell cycle marker bromodeoxyuridine and the immunohistochemical techniques that were employed revealed that the proliferation of NPCs is increased approximately twofold in the SGZ of the dorsal DG of EAE mice, at the acute phase of the disease. However, although EAE animals exhibited significant higher percentage of newborn radial-glia-like NPCs, the mean percentage of newborn neuroblasts rather was decreased, indicating that the robust NPCs proliferation is not followed by a proportional production of newborn neurons. Significant positive correlations were detected between the number of proliferating cells in the SGZ and the clinical score or degree of brain inflammation of diseased animals. Finally, enhanced neuroproliferation in the acute phase of EAE was not found to trigger compensatory apoptotic mechanisms. The possible causes of altered neurogenesis observed in this study emphasize the need to understand more precisely the mechanisms regulating adult neurogenesis under both normal and pathological conditions.

Epidural anaesthesia and analgesia for liver resection.

Although epidural analgesia is routinely used in many institutions for patients undergoing hepatic resection, there are unresolved issues regarding its safety and efficacy in this setting. We performed a review of papers published in the area of anaesthesia and analgesia for liver resection surgery and selected four areas of current controversy for the focus of this review: the safety of epidural catheters with respect to postoperative coagulopathy, a common feature of this type of surgery; analgesic efficacy; associated peri-operative fluid administration; and the role of epidural analgesia in enhanced recovery protocols. In all four areas, issues are raised that question whether epidural anaesthesia is always the best choice for these patients. Unfortunately, the evidence available is insufficient to provide definitive answers, and it is clear that there are a number of areas of controversy that would benefit from high-quality clinical trials.

Clindamycin binding to ribosomes revisited: foot printing and computational detection of two binding sites within the peptidyl transferase center.

Clindamycin is a semi-synthetic lincosamide, active against most Gram-positive bacteria and some protozoa. It binds to the 50S ribosomal subunit and inhibits early peptide chain elongation. By kinetic analysis it has been shown that clindamycin (I) competitively interacts with the A-site of translating ribosomes (C) to form the encounter complex CI, which then slowly isomerizes to a tighter complex, termed C*I. As the final complex is capable of synthesizing peptide bonds with decreased velocity, it was assumed that in C*I complex the drug is fixed near the P-site of the ribosome. In the present study, two series of chemical foot printing experiments were carried out. In the first series, clindamycin and ribosomal complex C were incubated for 1 s and then DMS or kethoxal was added (CI probing). In the second series, complex C was preincubated with clindamycin for 1 min before the addition of DMS or kethoxal (C*I probing). It was found that clindamycin in CI complex protects A2451 and A2602 from chemical probing, both located within the A-site of the catalytic center. In contrast, it strongly protects G2505 in C*I complex, which is a discrete foot print of peptidyl-tRNA bound to the P-site. In both CI and C*I complexes, clindamycin also protects nucleotides A2058 and A2059, located next to the entrance of the exit-tunnel where the nascent peptide leaves the ribosome. Polyamines negatively affect the protection of G2505, but favor the protection of A2451 and A2602 nucleotides. Structure modeling confirms the kinetic and chemical foot printing results and suggests that clindamycin mode of action is more complex than a simple competitive inhibition of peptide bond formation.

Aortic false aneurysm at the distal anastomotic suture line after aortic arch replacement; a case report with review of the literature.

Anastomotic pseudoaneurysm remains one of the main life-threatening complications after surgery on the thoracic aorta. We report a case with a history of ascending and aortic arch replacement and a false aneurysm creation at the anastomotic line found at the 2-year follow-up computed tomography. Either, due to incidental and asymptomatic finding and patient negation to any kind of intervention, it has been followed the medical treatment with blood pressure and heart rate control. In this, we discuss also the ways of treatment and the indication of any interventional therapy. Endovascular stent-grafting is a minimal invasive treatment for thoracic aortic aneurysm. However, its clinical usefulness for anastomotic false aneurysm following thoracic aortic surgery is unclear.

Effect of previous anesthesia experience on patients' knowledge and desire for information about anesthesia and the anesthesiologist: a 500 patients' survey from Greece.

BACKGROUND: This study aimed at assessing the effect of previous anesthesia experience on patients' knowledge of anesthesia and the role of anesthesiologists, on what they would want to know about anesthesia and the way they would like to be informed. METHODS: Questionnaires with fixed questions were distributed to consenting, consecutive surgical patients before the pre-anesthetic visit. Patients were divided into two groups: patients with previous anesthesia experience (Group A) and patients without previous anesthesia experience (Group B). The questionnaires included patients' demographics, questions related to their knowledge about the anesthesiologists' role and about their desire for information. RESULTS: 500 questionnaires were analyzed. The majority of patients (94.2%) know that the anesthesiologist is a specialized doctor and 89.2% believe that the anesthesiologist watches over the patient throughout surgery. These results were similar in both groups. The majority of patients (98.2%) also want to meet the anesthesiologist before surgery and 78% want even more information. Only 65.6% want to be aware of all possible complications, in both groups, while 17.6% do not want to know anything about complications. In general, answers to specific questions regarding what the patients want to know about anesthesia did not differ between groups. The vast majority of patients wish to talk with the anesthesiologist before surgery. CONCLUSION: Previous anesthesia experience did not seem to influence patients' desire for meeting the anesthesiologist and seeking information. A strong desire to personally meet the anesthesiologist is expressed and patients' desire for even more information is noted.

Functional consequences of HLA-DQ8 homozygosity versus heterozygosity for islet autoimmunity in type 1 diabetes.

Human leukocyte antigen (HLA) class II haplotypes are established risk factors in type 1 diabetes (T1D). The heterozygous DQ2/8 genotype confers the highest risk, whereas the DQ6/8 genotype is protective. We hypothesized that DQ2/8 trans-molecules composed of α and ß chains from DQ2 and DQ8 express unique ß-cell epitopes, whereas DQ6 may interfere with peptide binding to DQ8. Here we show that a single insulin epitope (InsB13-21) within the T1D prototype antigenic InsB6-22 peptide can bind to both cis- and trans-dimers, although these molecules display different peptide binding patterns. DQ6 binds a distinct insulin epitope (InsB6-14). The phenotype of DQ8-restricted T cells from a T1D patient changed from proinflammatory to anti-inflammatory in the presence of DQ6. Our data provide new insights into both susceptible and protective mechanism of DQ, where protecting HLA molecules bind autoantigens in a different (competing) binding register leading to 'epitope stealing', thereby inducing a regulatory, rather than a pathogenic immune response.