From ancient leech to direct thrombin inhibitors and beyond: New from old

Medicinal leeches have been used in health care since before written history, with widely varying popularity over the centuries. Nowadays, medicinal leech therapy is mainly used in plastic and reconstructive microsurgery, with new interesting potential therapeutic applications in many other diseases. The leech's best-known salivary product, hirudin — one of the most powerful natural anticoagulants — was the only remedy to prevent blood clotting until the discovery of heparin. Starting from hirudin, pharmacological research succeeded in developing new anticoagulants, which represent a cornerstone of prevention and treatment of thromboembolic disease. While we are perhaps on the threshold of a new era of anticoagulation, with the development of FXI and XII inhibitors and direct reversible covalent thrombin inhibitors, which promise to achieve effective anticoagulation without bleeding risk. This review retraces the intriguing journey of these drugs in cardiovascular disease, highlighting the fil rouge that links the ancient leech to the current and oncoming antithrombotic therapy. We think that knowledge of the past is key to understanding and appreciating the present and to seize future opportunities

The first 3500 years of aspirin history from its roots - A concise summary

none3Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone - who first described their antipyretic effects - and continued in the 19th century with many researchers involved in their extraction and chemical synthesis. Bayer chemist Felix Hoffmann synthesized aspirin in 1897, and 70 years later the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production. Originally used as an antipyretic and anti-inflammatory drug, aspirin then became, for its antiplatelet properties, a milestone in preventing cardiovascular and cerebrovascular diseases. The aspirin story continues today with the growing evidence of its chemopreventive effect against colorectal and other types of cancer, now awaiting the results of ongoing primary prevention trials in this setting. This concise review revisits the history of aspirin with a focus on its most remote origins.Montinari, Maria Rosa; Minelli, Sergio; De Caterina, RaffaeleMontinari, Maria Rosa; Minelli, Sergio; De Caterina, Raffael

Upstream actuation for bluff-body wake control driven by a genetically inspired optimization

The control of bluff-body wakes for reduced drag and enhanced stability has traditionally relied on the so-called direct-wake control approach. By the use of actuators or passive devices, one can manipulate the aerodynamic loads that act on the rear of the model. An alternative approach for the manipulation of the flow is to move the position of the actuator upstream, hence interacting with an easier-to-manipulate boundary layer. The present paper comprises a bluff-body flow study via large-eddy simulations to investigate the effectiveness of an upstream actuator (positioned at the leading edge) with regard to the manipulation of the wake dynamics and its aerodynamic loads. A rectangular cylinder with rounded leading edges, equipped with actuators positioned at the front curvatures, is simulated at. A genetic algorithm (GA) optimization is performed to find an effective actuation that minimizes drag. It is shown that the GA selects superharmonic frequencies of the natural vortex shedding. Hence, the induced disturbances, penetrating downstream in the wake, significantly reduce drag and lateral instability. A comparison with a side-recirculation-suppression approach is also presented, the latter case being worse in terms of reduced drag (only 8 % drag reduction achieved), despite the total suppression of the side recirculation bubble. In contrast, the GA optimized case contributes to a 20 % drag reduction with respect to the unactuated case. In addition, the large drag reduction is associated with a reduced shedding motion and an improved lateral stability

Robotic versus laparoscopic approach in colonic resections for cancer and Benign diseases. Systematic review and meta-analysis

Objectives The aim of this systematic review and meta-Analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. Materials and Methods A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. Results A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD-0.51, P = 0.003) and the length of hospital stay (MD-0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD-16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD-0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. Conclusions The present meta-Analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections. Copyright: © 2015 Trastulli et al.OBJECTIVES: The aim of this systematic review and meta-analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. MATERIALS AND METHODS: A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. RESULTS: A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD -0.51, P = 0.003) and the length of hospital stay (MD -0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD -16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD -0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. CONCLUSIONS: The present meta-analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections

Multi-frequency aerodynamic control of a yawed bluff body optimized with a genetic algorithm

This experimental work aims to investigate the manipulation of a bluff body flow with a yaw angle of 10\ub0 based on a genetic algorithm optimization. Two loudspeakers are used to generate zero-net mass-flux jets through streamwise slots, which span a large portion of the rounded A-pillars of the bluff body. The actuations produce a maximum drag reduction of 17% and 2% for the leeward and windward side control, respectively. The genetic algorithm has found two typical frequencies to separately drive the actuators on the windward and leeward sides. The drag reduction is 20% under the optimal control law, 3% larger than the 17% attained from the reference single frequency control. In addition, a beneficial effect is observed when considering energy efficiency, which increases by 30% in the optimal control compared to the single frequency control. The drag spectra and velocity mapping in the wake are measured with and without control, and, based on the measurement, the underlying flow mechanism behind the control is proposed

An Atypical Presentation of Primary Hyperparathyroidism in an Adolescent: A Case Report of Hypercalcaemia and Neuropsychiatric Symptoms Due to a Mediastinal Parathyroid Adenoma

Psychiatric disorders are rare clinical manifestations of hypercalcaemia in the pediatric population, are relatively more frequent during adolescence and are often overlooked in cases of severe hypercalcaemia. We described the case of a 17-year-old girl affected by anorexia nervosa, depression and self-harm with incidental detection of moderate hypercalcaemia. Clinical, laboratory and instrumental tests demonstrated that hypercalcaemia was secondary to primary hyperparathyroidism (PHPT) due to a mediastinal parathyroid adenoma in the thymic parenchyma. After parathyroidectomy with robot-assisted surgery, we observed the restoration of calcium and PTH levels in addition to an improvement in psychiatric symptoms. This case demonstrates that serum calcium concentration should be evaluated in adolescents with neurobehavioural symptoms and in cases of hypercalcaemia PHPT should be excluded. Surgery represents the cornerstone of the management of PHPT and may contribute to improving quality of life and psychological function in these patients. However, the complexity of neurological involvement in cases of hypercalcaemia due to PHPT requires further investigations to establish the real impact of this condition on the neurocognitive sphere

Bacterial Faecal Flora in Healthy Women of Different Ages

The composition of the intestinal flora is the result of host physiology, microbial interaction and environmental influences. The possible relationship between faecal flora composition and hormonal modifications in healthy women of different ages was studied. Forty-four normal women were divided into the following groups according to age: group I, 2747 yr; group II, 50-55 yr, 5 yr after menopause. The subjects received no pharmacological treatment. Samples were collected on the 8th and 23rd day of the cycle; two samples were obtained from each postmenopausal woman. Qualitative and quantitative determination of microorganisms was carried out using slightly modified standard methods. In fertile women (group I), the microflora composition was similar for samples collected on the 8th-10th day and during the premenstrual period (23rd day). In postmenopausal women (group III), an increase in fungi, clostridia and aerobic lactobacilli mean concentrations were observed. Escherichia coli mean levels increased and Enterobacteriaceae such as Enterobacter cloacae and Citrobacter freundii were present in 80 per cent of subjects studied. The length of menopause was found to have only a slight influence on flora: the behaviour of the microflora composition in menopausal women in group II may be considered intermediate between groups I and III. This preliminary study demonstrates that there are fluctuations in the composition of the faecal flora in healthy women. The differences observed between premenopausal and postmenopausal women may be a consequence of modifications of the steroid sex hormone pattern.Keywords - Intestinal flora; Age; Premenopausal women; Postmenopausal women; Menopause

A New Set of Chisels for Galactic Archeology: Sc, V, and Zn as Taggers of Accreted Globular Clusters

Chemical tagging is a powerful tool to reveal the origin of stars and globular clusters (GCs), especially when dynamics alone cannot provide robust answers. So far, mostly α-elements and neutron capture elements have been used to distinguish stars born in the Milky Way (MW) from those born in external environments such as that of dwarf galaxies. Here, instead, we use iron-peak element abundances to investigate the origin of a sample of metal-rich GCs. By homogeneously analyzing high-resolution UVES spectra of giant stars belonging to four metal-rich GCs (namely NGC 5927, NGC 6388, NGC 6441, and NGC 6496), we find that while the α-elements Si and Ca have similar abundance ratios for all four GCs, and Ti and neutron capture elements (La, Ba, and Eu) only show a marginal discrepancy, a stark difference is found when considering the abundances of some iron-peak elements (Sc, V, and Zn). In particular, NGC 6388 and NGC 6441 have abundance ratios for these iron-peak elements significantly lower (by ∼0.5 dex) than those measured in NGC 5927 and NGC 6496, which are clearly identified as born in situ MW clusters through an analysis of their orbital properties. These measurements indicate that the environment in which these clusters formed is different, and they provide robust evidence supporting an accreted origin from the same progenitor for NGC 6388 and NGC 6441

A New Set of Chisels for Galactic Archeology:Sc, V, and Zn as Taggers of Accreted Globular Clusters

Chemical tagging is a powerful tool to reveal the origin of stars and globular clusters (GCs), especially when dynamics alone cannot provide robust answers. So far, mostly α-elements and neutron capture elements have been used to distinguish stars born in the Milky Way (MW) from those born in external environments such as that of dwarf galaxies. Here, instead, we use iron-peak element abundances to investigate the origin of a sample of metal-rich GCs. By homogeneously analyzing high-resolution UVES spectra of giant stars belonging to four metal-rich GCs (namely NGC 5927, NGC 6388, NGC 6441, and NGC 6496), we find that while the α-elements Si and Ca have similar abundance ratios for all four GCs, and Ti and neutron capture elements (La, Ba, and Eu) only show a marginal discrepancy, a stark difference is found when considering the abundances of some iron-peak elements (Sc, V, and Zn). In particular, NGC 6388 and NGC 6441 have abundance ratios for these iron-peak elements significantly lower (by ~0.5 dex) than those measured in NGC 5927 and NGC 6496, which are clearly identified as born in situ MW clusters through an analysis of their orbital properties. These measurements indicate that the environment in which these clusters formed is different, and they provide robust evidence supporting an accreted origin from the same progenitor for NGC 6388 and NGC 6441. * Based on observations collected at the ESO-VLT under programs 073.D-0211, 079.B-0721, and 193.D-0232