Biofabrication for neural tissue engineering applications.

Unlike other tissue types, the nervous tissue extends to a wide and complex environment that provides a plurality of different biochemical and topological stimuli, which in turn defines the advanced functions of that tissue. As a consequence of such complexity, the traditional transplantation therapeutic methods are quite ineffective; therefore, the restoration of peripheral and central nervous system injuries has been a continuous scientific challenge. Tissue engineering and regenerative medicine in the nervous system have provided new alternative medical approaches. These methods use external biomaterial supports, known as scaffolds, to create platforms for the cells to migrate to the injury site and repair the tissue. The challenge in neural tissue engineering (NTE) remains the fabrication of scaffolds with precisely controlled, tunable topography, biochemical cues, and surface energy, capable of directing and controlling the function of neuronal cells toward the recovery from neurological disorders and injuries. At the same time, it has been shown that NTE provides the potential to model neurological diseases in vitro, mainly via lab-on-a-chip systems, especially in cases for which it is difficult to obtain suitable animal models. As a consequence of the intense research activity in the field, a variety of synthetic approaches and 3D fabrication methods have been developed for the fabrication of NTE scaffolds, including soft lithography and self-assembly, as well as subtractive (top-down) and additive (bottom-up) manufacturing. This article aims at reviewing the existing research effort in the rapidly growing field related to the development of biomaterial scaffolds and lab-on-a-chip systems for NTE applications. Besides presenting recent advances achieved by NTE strategies, this work also delineates existing limitations and highlights emerging possibilities and future prospects in this field.

Freshwater vulnerability under high end climate change. A pan-European assessment.

As freshwater availability is crucial for securing a sustainable, lower­carbon future, there is a critical connection between water management and climate policies. Under a rapidly changing climate, it is more important than ever to estimate the degree of future water security. This is a challenging task as it depends on many different variables: the degree of warming and its consequent effects on hydrological resources, the water demand by different sectors, and the possible ameliorations or deteriorations of the effects due to climate change adaptation and mitigation strategies. A simple and transparent conceptual framework has been developed to assess the European vulnerability to freshwater stress under the present hydro-climatic and socioeconomic conditions, in comparison to projections of future vulnerability for different degrees of global warming (1.5°C, 2°C and 4°C), under the high-rate warming scenario (RCP8.5). Different levels of adaptation to climate change are considered in the framework, by employing various relevant pathways of socioeconomic development. A spatially detailed pan-European map of vulnerability to freshwater shortage has been developed at the local administrative level, making this approach extremely useful for supporting regional level policymaking and implementation and strategic planning against future freshwater stress.

"Fast Track" Development and Approval Process for Heart Failure Therapeutics.

Heart failure (HF) is a global epidemic, with a high mortality and morbidity burden. In such diseases, earlier access to lifesaving therapeutic regimens is imperative, and could be accomplished by improving the drug development and approval process, without jeopardizing patient safety. The US Food and Drug Administration (FDA) has already established mechanisms facilitating the latter, but further guidance to enhance and expedite the process holds promise to further improve patient outcomes.

Association between periodontitis and acute myocardial infarction: a case-control study of a nondiabetic population.

BACKGROUND AND OBJECTIVE: Periodontitis and acute myocardial infarction (AMI) are two diseases that share common risk factors. The role of periodontitis as an independent risk factor for cardiovascular disease has been under debate. The aim of this study was to investigate whether an association exists between periodontitis and AMI in a nondiabetic population, using multiple periodontal case definitions. MATERIAL AND METHODS: Periodontal examination was performed in 204 patients with AMI. The control group comprised 102 healthy subjects, without significant coronary disease, confirmed angiographically. Periodontitis was assessed using measurements of clinical attachment loss (CAL), probing depth and number of missing teeth. From these measurements, five different case definitions of periodontitis were generated. RESULTS: Using the continuous forms of periodontal measurements, the odds ratio (95% confidence interval) of the association with incident AMI was 1.74 (1.26-2.50), 1.83 (1.10-3.17) and 1.08 (1.06-1.13) for mean CAL, probing depth and number of missing teeth, respectively. A consistent positive association was observed regardless of the case definition of periodontitis. CONCLUSION: In this nondiabetic population, the association between periodontitis and AMI was consistent across different measurements and/or definitions of periodontitis. The strength of the association increased concomitantly with the robustness of the criteria used to define periodontitis.

First experience of the use of the C-MAC PM videolaryngoscope in a clinical setting by anesthetic nurses: a comparison with anesthetists.

BACKGROUND: The Storz C-MAC videolaryngoscope has been found to facilitate endotracheal intubation and to be easy to use by novice users. However, it has never been studied in those who will probably use it most, anesthetists and anesthetic nurses. The aim of the present study was to identify the number of attempts needed before the participants were able to intubate 2 consecutive patients within 30 seconds. METHODS: Following a didactic session, 22 anesthetists and 21 anesthetic nurses were included in the study and attempted to intubate 184 patients with predicted easy laryngoscopy scheduled to undergo elective surgery. The number of attempts before achieving 2 consecutive successful intubations and time to intubation were recorded for both groups of participants. Perception of ease of use for the device was also recorded. RESULTS: Overall, anesthetic nurses required more attempts before achieving 2 consecutive successful intubations (5.9 +/- 3.24 vs 2.73+/- 1.67, p < 0.0005). They also had significantly more failures until 2 consecutive successful intubations were achieved, compared to anesthetists (4.1 +/- 2.8 vs 1.32 +/- 1.25, p < 0.0005). A significantly higher percentage of anesthetic nurses required more than 3 attempts before achieving 2 consecutive intubations (75% vs 36%, p = 0.016). Regarding the intubation time, no significant differences were recorded between specialties. Anesthetic nurses assessed the C-MAC as easier to use than anesthetists did. CONCLUSIONS: This is the first clinical study assessing the use of the C-MAC videolaryngoscope by inexperienced anesthetists and anesthetic nurses indicating that it is easy to learn and to use in their hands.

Quality of life and pre-operative anxiety level in patients scheduled to undergo thoracic surgery.

PURPOSE: Increased preoperative anxiety levels may lead to adverse outcomes. We aimed at assessing the relationship between quality of life (QoL) and preoperative anxiety level during the 4-week preoperative period in patients scheduled to undergo thoracic surgery and we tried to identify patients who could benefit from preoperative supportive measures. METHODS: One hundred patients comprised the study population (52 men and 48 women) out of the initial 136, who were scheduled to undergo thoracic surgery. Mean age was 56±15 years (±SD). After obtaining informed consent, participants were asked to answer a questionnaire, through a personal interview, 12 to 15 h prior to their scheduled thoracic operation. The questionnaire included questions on demographics and incorporated the State Anxiety Inventory (STAI) and SF-36 scales. RESULTS: Female patients (p=0.023), unemployed patients (p=0.01) and patients that were scheduled for a mediastinoscopy (p=0.001) experienced increased anxiety level. Lower scores in several parameters related to the QoL were found to be associated with increased anxiety level. Limitations in patients' ability to work or to perform other everyday activities as a result of mental health problems (p=0.006), low vitality (p<0.001), bad general mood (p<0.001), deteriorated general health (p<0.001) and general mental health (p<0.001) were associated with preoperative anxiety. No differences were found in anxiety level among lung cancer and non-lung cancer patients. CONCLUSION: This study showed an inverse proportional correlation between preoperative QoL and anxiety during the 4-week period prior to thoracic surgery. Appropriate pharmaceutical and psychological support may improve patients' anxiety level.

Asphyxial cardiac arrest, resuscitation and neurological outcome in a Landrace/Large-White swine model.

The vast majority of laboratory studies on animals have focused on ventricular fibrillation (VF) and not on cardiac arrest (CA) resulting from asphyxia. The aim of this study was to develop a clinically relevant animal model in Landrace/Large-White swine of asphyxial CA resuscitated using the European Resuscitation Council guidelines. Survival and 24 h neurological outcome in terms of functional deficit were also evaluated. Asphyxial arrest was induced by clamping the endotracheal tube (ETT) in 10 Landrace/Large-White piglets. After 4 min of untreated arrest, resuscitation was initiated by unclamping the ETT, 100% oxygen mechanical ventilation, 2 min chest compressions and epinephrine administration. Advanced Life Support algorithm was followed. In case of restoration of spontaneous circulation, the animals were supported for one hour and then observed for 23 h. Coronary perfusion pressure was significantly higher in surviving animals (P < 0.001) during cardiopulmonary resuscitation. End-tidal CO(2) was significantly higher in the animals that survived than in non-surviving animals (P = 0.001). All of the animals were severely neurologically impaired 24 h after CA. This refined model of asphyxia CA is easily reproducible and may be used for pharmacological studies in CA.

Macintosh and Glidescope® performance by Advanced Cardiac Life Support providers: a manikin study.

BACKGROUND: The aim of the present study was to assess whether the use of the Glidescope® would improve the success rates and the duration of intubation attempts during airway management when compared to direct laryngoscopy in Advanced Cardiac Life Support (ACLS) providers with no prior experience in videolaryngoscopy. METHODS: This cross-over randomized study involved 44 ACLS providers. The educational session for the participants included a brief presentation of the equipment and a demonstration of the Glidescope®. All intubations were performed using a 7.5-mm endotracheal tube on an adult manikin. A size 3 Macintosh blade and a standard Glidescope® adult blade were used. Glidescope® videolaryngoscope was used. The primary endpoints were: duration of each endotracheal intubation attempt and success rate for each device. A secondary endpoint was the perception of ease of use with each device. Each participant was asked to assess the ease of use of each device using a visual analogue scale (0=extremely difficult and 10=extremely easy). RESULTS: No statistically significant difference was observed in the time required to successful intubation of the trachea with the Macintosh laryngoscope and the Glidescope®. However, significantly fewer intubation attempts were required with the Glidescope® compared to the Macintosh laryngoscope. In addition, most candidates found that using the videolaryngoscope was easy. CONCLUSION: This study demonstrated that the Glidescope® videolaryngoscopy performed at least as well as conventional laryngoscopy in ACLS providers. Although simpler ventilation techniques should be applied first during critical airway management, this study suggests that, when intubation is needed, videolaryngoscopy cna be helpful.

Levosimendan improves the initial outcome of cardiopulmonary resuscitation in a swine model of cardiac arrest.

BACKGROUND: Cardiac arrest remains the leading cause of death in Western societies. Advanced Life Support guidelines propose epinephrine (adrenaline) for its treatment. The aim of this study was to assess whether a calcium sensitizer agent, such as levosimendan, administered in combination with epinephrine during cardiopulmonary resuscitation, would improve the initial resuscitation success. METHODS: Ventricular fibrillation was induced in 20 Landrace/Large-White piglets, and left untreated for 8 min. Resuscitation was then attempted with precordial compressions, mechanical ventilation and electrical defibrillation. The animals were randomized into two groups (10 animals each): animals in Group A received saline as placebo (10 ml dilution, bolus) + epinephrine (0.02 mg/kg), and animals in Group B received levosimendan (0.012 mg/kg/10 ml dilution, bolus) + epinephrine (0.02 mg/kg) during cardiopulmonary resuscitation. Electrical defibrillation was attempted after 10 min of ventricular fibrillation. RESULTS: Four animals in Group A showed restoration of spontaneous circulation and 10 in Group B (P = 0.011). The coronary perfusion pressure, saturation of peripheral oxygenation and brain regional oxygen saturation were significantly higher during cardiopulmonary resuscitation in Group B. CONCLUSIONS: A calcium sensitizer agent, when administered during cardiopulmonary resuscitation, significantly improves initial resuscitation success and increases coronary perfusion pressure during cardiopulmonary resuscitation.

Comparative study of intravenous amiodarone and procainamide in the treatment of atrial fibrillation of recent onset.

AIM: The aim of the present study was to compare the safety and efficacy of amiodarone and procainamide in the acute cardiology setting. METHODS: The study population consisted of 223 patients with symptomatic atrial fibrillation (AF). After administration of digoxin for ventricular rate control, all patients who failed to restore sinus rhythm (SR) were randomized into 2 groups: group A (113 patients) were administered 300 mg amiodarone intravenously over 30 min and, in case of failure to restore SR, amiodarone of 20 mg/kg/24 h was administered intravenously. Group B (110 patients) were intravenously administered a bolus dose of 1 gm procainamide, at an infusion rate 50/mg/min, and, in case of failure to restore SR, 2 mg/min for the next 24 h. RESULTS: The rate of cardioversion to SR was similar between amiodarone (81.4%) and procainamide (82.7%) (P=NS). Procainamide loading recorded faster cardioversion times than amiodarone loading (P=0.02), but there was no significant difference after that. Amiodarone caused a significant decrease on systolic blood pressure compared to procainamide for the first 18 h (P<0.001), and a significant decrease in the diastolic blood pressure for the first 6 h (P<0.001). Side-effects for either medication were sparse. The only real prognostic factor for successful cardioversion remains the size of left atrium. CONCLUSION: Both drugs were equally effective in restoring SR, though procainamide acts quicker in the loading phase. Both medications are safe and side effects develop only in the maintenance phase.

Experimental isolation and transplantation of hepatocytes with the use of antibody against interleukin-2 receptor (daclizumab) as immunosuppressive agent.

INTRODUCTION: Daclizumab (Dmab) is a genetically engineered humanized IgG1 monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (Tac, CD25, p55) expressed on activated human T lymphocytes. Dmab has been used in a clinical protocol of islet transplantation with satisfactory results. The aim of the present study was to evaluate the use of an antibody against the interleukin-2 receptor (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte allotransplantation (allo-Tx) in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 48 Lewis rats as recipients: four groups of 12 animals each with induction of FHF and 24 hour later hepatocyte Tx--group A: no treatment; group B: cyclosporin (20 mg/kg days 0 to 5 and 10 mg/kg days 6 to 15); group C: Dmab (0.05 mg day of Tx and 0.05 mg day 7); and group D: Dmab and cyclosporine. Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: Statistical analysis showed better survival among groups C (83%, MST = 13) and D (92%, MST = 14.25) compared to groups A (max 72, MST = 1.5) or B (50%, MST = 9). Survival in group D was better but not significantly than group C. Biochemical evaluation and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model showed the safe, effective use of Dmab.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.

The impact of new technology on hepatic resection for malignancy.

HYPOTHESIS: Relatively high morbidity rates remain problematic in hepatic resection for malignant neoplasms. Technological innovations coupled with surgical expertise can ameliorate morbidity and mortality rates. DESIGN: Medical records survey. SETTING: Tertiary care university hospital. PATIENTS: Five hundred one patients underwent liver resection at our hospital from March 1, 1988, through November 30, 1999. Three hundred twenty-one patients (64.1%) had primary carcinoma, whereas 180 (35.9%) had metastatic disease, mainly colorectal secondary disease (83.3%). Morbidity and mortality rates were compared with those of a previous series in the same setting. MAIN OUTCOME MEASURES: Special attention was paid to the impact of new technology (eg, newer imaging techniques, ultrasonic aspiration, intraoperative ultrasonography, argon beam coagulation, and autotransfusion) and improved anesthetic and surgical management on mortality and morbidity rates. RESULTS: Five patients died after liver resection and 93 patients had various complications, representing mortality and morbidity rates of 1.0% and 18.6%, respectively. These results compare favorably with the results of a previous unpublished series (mortality, 5/55 [9.1%]; morbidity, 28/55 [50.9%]). Intraoperative ultrasonography resulted in a change in operative strategy in 7 (17.5%) of a recent group of 40 patients. CONCLUSIONS: Morbidity after major hepatic resection for malignancy can be reduced considerably by applying newer technologies to preoperative and intraoperative decision making. Advanced technology also assists in reducing intraoperative risk by minimizing bleeding during resection of the hepatic parenchyma.

Creation of a neovagina following Williams vaginoplasty and the Creatsas modification in 111 patients with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: Evaluation of the Creatsas modification of Williams vaginoplasty for the creation of neovagina in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome). DESIGN: Record of perioperative and postoperative results and complications. Follow-up evaluations of patients yearly after the operation. SETTING: Division of Pediatric-Adolescent Gynecology and Gynecologic Corrective Surgery, University of Athens (tertiary referral center). PATIENT(S): One hundred eleven patients with MRKH syndrome. INTERVENTION(S): Surgical creation of neovagina using the Williams vaginoplasty technique (group A: 10 patients) or the Creatsas modification of the previous method (group B: 101 patients). MAIN OUTCOME MEASURE(S): Length and width of the neovagina, and the quality of sexual life postoperatively. RESULT(S): A functioning vagina of 10 to 12 cm depth and 5 cm width was created in eight of the patients in group A (80%) and in 98 of those in group B (97.02%). A vagina of 7 to 9 cm depth and 2 to 3 cm width was created in the rest of the patients in both groups. In group A, two wound openings were reported (20%); in two of the patients hemorrhage occurred during the first intercourse, compared to none in group B. A satisfactory sexual life was reported from 94.4% of the patients and an adequate one from 4.16% of them. CONCLUSION(S): The Creatsas modification of Williams vaginoplasty is a simple and effective technique for the creation of a functioning neovagina in young women with vaginal aplasia.

Prevention of postoperative nausea and vomiting after laparoscopic gynaecological surgery. Combined antiemetic treatment with tropisetron and metoclopramide vs. metoclopramide alone.

BACKGROUND AND OBJECTIVE: Female patients undergoing gynaecological procedures, especially laparoscopically, are at high risk of postoperative nausea and vomiting. No available antiemetic is entirely effective. This double-blinded randomized trial examines the efficacy and safety of tropisetron and metoclopramide in combination and compares the results with metoclopramide alone in laparoscopic gynaecological surgery. METHODS: One hundred and twenty female patients scheduled for minor gynaecological laparoscopy, aged 27-43 years, were randomly allocated to receive pretreatment with metoclopramide 10 mg intravenously (n=57) or tropisetron 5 mg with metoclopramide 5 mg (n=63). RESULTS: Fewer patients in the combined treatment group experienced postoperative nausea and vomiting (14% vs. 37%, P=0.008) or needed rescue antiemetic treatment (3% vs. 16%, P=0.038). No significant adverse events were observed. CONCLUSIONS: The combination of the antiemetics was superior, which is probably explained by the fact that the two drugs have different sites of action, thus preventing emesis by blocking different pathways.

Murine ectoplacental cone-derived trophoblast cells express chemokine receptors.

Chemokine receptors (CCRs) have been shown to regulate T cell migration and differentiation as well as the establishment of Th1/Th2 bias. Furthermore, T cells and T cell products are essential to trophoblast development. Thus, postulating that chemokines as well as their receptors may be expressed by trophoblast to move T cells into an interaction with the feto-placental unit, we examined whether CCRs are expressed during the early stages of ectoplacental cone (EPC) formation. For this, murine EPC-derived trophoblast were examined for their ability to express CCRs constitutively or inducible by interferon-gamma (IFN-gamma). Immunofluorescence experiments on EPC-derived trophoblast cells showed that CCR3, CXCR4 and CCR5 are significantly expressed. IFN-gamma accelerated the mobilization of intracellular pools of CCR molecules during early cell culture periods (2-6 h) and, in most cases, increased their expression on EPC-derived trophoblast cells. CCR activity could be detected in the culture supernatants of these cells, inversely proportional to cell surface expression, suggesting the existence of rapid endocytosis and recycling mechanisms. This finding indicates that the level of intracellular CCRs may partly be determined in the extracellular matrix, an event that could play an important role towards neutralization of specific T cell/trophoblast interactions during early stages of pregnancy and protect the fetus against harmful maternal immune responses.