Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury

Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortalityrnafter traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be importantrnto elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonularnoccludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anestheticsrnsevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) inrnmurine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression ofrnZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled corticalrnimpact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours afterrnexposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthyrnmice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water contentrnincreased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expressionrnwas significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analysesrnrevealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The studyrndemonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed tornmodulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence thernbarrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Futurernresearch is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema.

Dallo spreco alimentare alla creazione di capitale sociale. Definizione di strumenti metodologici per la valutazione dell'impatto sociale dei progetti di recupero alimentare

Ogni anno in Europa milioni di tonnellate di cibo vengono gettate via. Una stima pubblicata dalla Commissione europea afferma che, nei 27 Stati membri, 89 milioni di tonnellate di cibo, o di 179 kg pro capite, vengono scartati. Lo spreco si verifica lungo tutta la catena di agro alimentare; la riduzione dei rifiuti alimentari è diventata una delle priorità dell'agenda europea. La ricerca si concentra su un caso studio, Last Minute Market, un progetto di recupero di sprechi alimentari. L'impatto di questo progetto dal punto di vista economico e ambientale è già stato calcolato. Quello che verrà analizzato è l'impatto di questa iniziativa sulla comunità e in particolare sul capitale sociale, definito come "l'insieme di norme e reti che consentono l'azione collettiva". Obiettivo del presente lavoro è, quindi, quello di eseguire, attraverso la somministrazione di un questionario a diversi stakeholder del progetto, un’analisi confrontabile con quella del 2009 e di verificare a distanza di cinque anni, se l'iniziativa Last Minute Market abbia prodotto una crescita di capitale sociale nella comunità interessata da questa iniziativa. Per riassumere l’influenza del progetto sul capitale sociale in un indice sintetico, viene calcolato quello che verrà chiamato indice di "affidabilità del progetto" (definito in statistica, la "capacità di un prodotto, un sistema o un servizio di fornire le prestazioni richieste, per un certo periodo di tempo in condizioni predeterminate").

Die Rolle der IFN-gamma Signalübertragung und von MyD88 in der Angiotensin-II-induzierten vaskulären Dysfunkion, Inflammation und arteriellen Hypertonie

Im Rahmen dieser Arbeit wurde die Rolle von myelomonozytären Zellen, IFN-gamma (Interferon gamma), MyD88 (myeloid differentiation factor 88) und zugrundeliegenden Signalwege in der Angiotensin II (ATII)-induzierten vaskulären Inflammation, Dysfunktion und arteriellen Hypertonie untersucht. Wie bereits veröffentlichte Vordaten aus meiner Arbeitsgruppe zeigten, schützt die Depletion von Lysozym M (LysM)+ myelomonozytären Zellen (Diphteriatoxin-vermittelt in Mäusen, die transgen für den humanen Diphtheriatoxin-Rezeptor sind, LysMiDTR Mäuse) vor der ATII-induzierten vaskulären Dysfunktion und arterieller Hypertonie, und kann durch adoptiven Zelltransfer von Wildtyp Monozyten wiederhergestellt werden. In meiner Arbeit konnte ich zeigen, dass die Rekonstitution von Monozyten-depletierten LysMiDTR Mäusen mit Wildtyp Monozyten den Phänotyp der vaskulären Dysfunktion wiederherstellen kann, die Rekonstitution mit gp91phox-/y oder Agtr1-/- Monozyten jedoch nicht. Die Hypertonus-mediierenden Effekte dieser infiltrierenden Monozyten scheinen demnach von der intakten ATII und NADPH Oxidase Signalübertragung in diesen Zellen abhängig zu sein. Vermutlich ebenfalls für die Aktivierung der Monozyten funktionell wichtig sind IFN-gamma, produziert durch NK-Zellen, und der Transkriptionsfaktor T-bet (T-box expressed in T cells), exprimiert von NK-Zellen und Monozyten. IFN-gamma-/- Mäuse waren partiell geschützt vor der ATII-induzierten vaskulären Dysfunktion und charakterisiert durch reduzierte Level an Superoxid im Gefäß im Vergleich zu ATII-infundierten Wildtyp Mäusen. IFN-gamma-/- und T-bet defiziente Tbx21-/- Mäuse zeichneten sich ferner durch eine reduzierte ATII-mediierte Rekrutierung von NK1.1+ NK-Zellen, als ein Hautproduzent von IFN-gamma, sowie CD11b+GR-1low Interleukin-12 (IL-12) kompetenten Monozyten aus. Durch Depletions- und adoptive Transferexperimente konnte ich in dieser Arbeit NK-Zellen als essentielle Mitstreiter in der vaskulären Dysfunktion identifizieren und stellte fest, dass T-bet+LysM+ myelomonozytäre Zellen für die NK-Zellrekrutierung in die Gefäßwand und lokale IFN-gamma Produktion benötigt werden. Damit wurde erstmals NK-Zellen eine essentielle Rolle in der ATII-induzierten vaskulären Dysfunktion zugeschrieben. Außerdem wurde der T-bet-IFN-gamma Signalweg und die gegenseitige Monozyten-NK-Zellaktivierung als ein potentielles therapeutisches Ziel in kardiovaskulären Erkrankungen aufgedeckt. Des Weiteren identifizierte ich in meiner Arbeit MyD88 als ein zentrales Signalmolekül in der ATII-getriebenen Inflammation und vaskulären Gefäßschädigung. MyD88 Defizienz reduzierte den ATII-induzierten Anstieg des systolischen Blutdrucks und die endotheliale und glattmuskuläre vaskuläre Dysfunktion. Zusätzlich waren die vaskuläre Superoxid-Bildung sowie die Expressionslevel der NADPH Oxidase, der wichtigsten Quelle für oxidativem Stress im Gefäß, in ATII-infundierten MyD88-/- Mäusen im Vergleich zum Wildtyp reduziert. Mit Hilfe von durchflusszytometrischen Analysen deckte ich zudem auf, dass die ATII-induzierte Einwanderung von CD45+ Leukozyten, insbesondere CD11b+Ly6G-Ly6Chigh inflammatorischen Monozyten in MyD88-/- Mäusen signifikant abgeschwächt war. Diese Resultate wurden durch immunhistochemische Untersuchung von Aortengewebe auf CD68+, F4/80+ und Nox2+ Makrophagen/Phagozyten sowie Expressionsanalysen von Inflammationsmarkern untermauert. Analysen der mRNA Expression in Aortengewebe zeigten ferner eine in Wildtyp Mäusen nach ATII Infusion tendenziell gesteigerte Expression von inflammatorischen Monozytenmakern sowie eine abnehmende Expression von reparativen Monozytenmarken, während dieser Shift zu einem proinflammatorsichen Phänotyp in MyD88-/- blockiert zu sein schien. Dies zeigt eine Rolle von MyD88 in der terminalen Differenzierung von myelomonozytären Zellen an. Um dies weitergehend zu untersuchen und aufzudecken, ob die MyD88 Effekte abhängig sind von Zellen der hämatopoetischen Linie oder Gewebszellen, wurden Knochenmarktransferexperimente durchgeführt. MyD88 Defizienz in Knochenmark-abstammende Zellen reduzierte die ATII-induzierte vaskuläre Dysfunktion und Infiltration der Gefäßwand mit CD45+ Leukozyten und inflammatorischen myelomonozytären Zellen. Die protektiven Effekte der MyD88 Defizienz in der Angiotensin II-induzierten Inflammation konnten nicht auf Signalwege über die Toll-like Rezeptoren TLR2, -7 oder -9 zurückgeführt werden, wie die Untersuchung der vaskulären Reaktivität entsprechender Knockout Mäuse zeigte. Zusammenfassend konnte ich in meiner Arbeit zeigen, dass die Infiltration der Gefäßwand mit Nox2+AT1R+T-bet+MyD88+ myelomonozytären Zellen und die Wechselwirkung und gegenseitige Aktivierung dieser Zellen mit IFN-gamma produzierenden NK-Zellen eine zentrale Bedeutung in der Pathogenese der Angiotensin II (ATII)-induzierten vaskulären Dysfunktion, Inflammation und arteriellen Hypertonie einnehmen.

Portare la tecnologia in cabina: le nuove tecnologie a servizio dell'interprete e il caso della simultanea con testo

The digital revolution has affected all aspects of human life, and interpreting is no exception. This study will provide an overview of the technology tools available to the interpreter, but it will focus more on simultaneous interpretation, particularly on the “simultaneous interpretation with text” method. The decision to analyse this particular method arose after a two-day experience at the Court of Justice of the European Union (CJEU), during research for my previous Master’s dissertation. During those days, I noticed that interpreters were using "simultaneous interpretation with text" on a daily basis. Owing to the efforts and processes this method entails, this dissertation will aim at discovering whether technology can help interpreters, and if so, how. The first part of the study will describe the “simultaneous with text” approach, and how it is used at the CJEU; the data provided by a survey for professional interpreters will describe its use in other interpreting situations. The study will then describe Computer-Assisted Language Learning technologies (CALL) and technologies for interpreters. The second part of the study will focus on the interpreting booth, which represents the first application of the technology in the interpreting field, as well as on the technologies that can be used inside the booth: programs, tablets and apps. The dissertation will then analyse the programs which might best help the interpreter in "simultaneous with text" mode, before providing some proposals for further software upgrades. In order to give a practical description of the possible upgrades, the domain of “judicial cooperation in criminal matters” will be taken as an example. Finally, after a brief overview of other applications of technology in the interpreting field (i.e. videoconferencing, remote interpreting), the conclusions will summarize the results provided by the study and offer some final reflections on the teaching of interpreting.

The Effect of Weight on the Perception of Political Candidates

Chris Christie recently visited the famous “Wailing Wall” in Jerusalem, Israel, during his first trip abroad as governor of New Jersey. The New York Post reported on his trip with the headline “The Whale at the Wall” (Campanile 2012). Given headlines like this, it is easy to see anecdotal evidence of the stigmatization that surrounds obesity within contemporary American society. What’s more important is that these social stigmas that Americans are faced with every day are not merely surface level jokes bantered about for a cheap laugh. They are often prejudices that permeate every aspect of human life. Whether it comes to finding a date, looking for a job, or trying to be taken serious by one’s peers, weight is always a topic of concern. In an effort to understand how far entrenched these biases are in society, this thesis studies the ramifications of obesity in politics. In this thesis, I attempt to understand to what extent, if any, obesity matters in regard to candidate appearance, voters' choices, and political behavior.

Capuchin Monkeys (Cebus apella) Fail to Be Equitable in an Ultimatum Game

The ultimatum game is a commonly used economics game testing humans' sense of fairness. In the game, a "proposer" is given a sum of money and is told they can split it however they want with another human partner. The partner can then either accept the division and both proposer and responder receive the proposed amounts, or the responder can reject the offer and neither player will get anything. Human subjects from most western cultures typically share almost half of an allotted amount, but it remains unknown whether our close primate relatives share this generosity. Recent attempts to present chimpanzees with the ultimatum game have provided inconclusive results, with some studies finding the animals share humans' disposition to behave 'fairly' and others concluding that chimpanzees act selfishly to maximize their own rewards. Capuchin monkeys are known to share many human and chimpanzee social and cooperative behaviors, and this study was the first to present capuchin monkeys with a version of the ultimatum game. Subjects were presented with two differently colored tokens representing different qualitative reward contingencies, one equitable and the other inequitable in favor of the subject proposer. Subjects could select and place one of the tokens in a transfer container. The capuchins were first tested with a "dictator game" where, after the subject monkey selected a token, the rewards (equitable or inequitable) were distributed to the subject and a nearby partner monkey that was not an active participant. The capuchins were then tested on an ultimatum game in which after the subject selected and placed a token in the container, the container was moved to the partner. The partner needed to remove the token and transfer it back to the experimenter for the rewards to be distributed. As such, the partner could reject the subject's offer by refusing to participate and neither would receive a reward. The experiment was conducted to determine if the subject monkey would select the equitable reward option rather than the selfish option in order to maintain the partner's cooperation in the task. Capuchin subjects behaved selfishly and selected the inequitable token significantly more often than the equitable token in both the dictator and ultimatum game with no significant difference in preference between the two games. Interestingly, despite the occasional occurrence of rejection by the partner monkeys (resulting in no reward for the subject), subjects never altered their strategy, continuing to prefer the selfish token. The study may indicate that capuchin monkeys have an inability to judge the effect of their behavior on a conspecific's reward outcome, or an indifference to the outcome if there is an individual cost associated with behaving prosocially.

Investigation of Rudimentary Meta-Cognition in Lion-Tailed Macaques and Tufted Capuchins

Meta-cognition, or "thinking about thinking," has been studied extensively in humans, but very little is known about the process in animals. Although great apes and rhesus macaques (Macaca mulatta) have demonstrated multiple apparently meta-cognitive abilities, other species have either been largely ignored or failed to convincingly display meta-cognitive traits. Recent work by Marsh, however, raised the possibility that some species may possess rudimentary or partial forms of meta-cognition. This thesis sought to further investigate this possibility by running multiple comparative experiments. The goal of the first study was to examine whether lion-tailed macaques, a species that may have a rudimentary form of meta-cognition, are able to use an uncertainty response adaptively, and if so, whether they could use the response flexibly when the stimuli for which the subjects should be uncertain changed. The macaques' acquisition of the initial discrimination task is ongoing, and as such there were not yet data to support a conclusion either way. In the second study, tufted capuchins were required to locate a food reward hidden beneath inverted cups that sat on a Plexiglas tray. In some conditions the capuchins were shown where the food was hidden, in others they could infer its location, and in yet others they were not given information about the location of the food. On all trials, however, capuchins could optionally seek additional information by looking up through the Plexiglas into the cups. In general, capuchins did this less often when they were shown the food reward, but not when they could infer the reward's location. These data suggest capuchins only meta-cognitively control their information seeking in some conditions, and thus, add support to the potential for a rudimentary form of meta-cognition. In convergence with other studies, these results may represent early models for rudimentary meta-cognition, although viable alternative explanations still remain.

The Constitutional-Judicial Control of the Legislative and Executive Powers in Central and Eastern European Countries

This project looked at the nature, contents, methods, means and legal and political effects of the influence that constitutional courts exercise upon the legislative and executive powers in the newly established democracies of Central and Eastern Europe. The basic hypothesis was that these courts work to provide a limitation of political power within the framework of the principal constitutional values and that they force the legislature and executive to exercise their powers and duties in strict accordance with the constitution. Following a study of the documentary sources, including primarily the relevant constitutional and statutory provisions and decisions of constitutional courts, Mr. Cvetkovski prepared a questionnaire on various aspects of the topics researched and sent it to the respective constitutional courts. A series of direct interviews with court officials in six of the ten countries then served to clarify a large number of questions relating to differences in procedures etc. that arose from the questionnaires. As a final stage, the findings were compared with those described in recent publications on constitutional control in general and in Central and Eastern Europe in particular. The study began by considering the constitutional and political environment of the constitutional courts' activities in controlling legislative and executive powers, which in all countries studied are based on the principles of the rule of law and the separation of powers. All courts are separate bodies with special status in terms of constitutional law and are independent of other political and judicial institutions. The range of matters within their jurisdiction is set by the constitution of the country in question but in all cases can be exercised only with the framework of procedural rules. This gives considerable significance to the question of who sets these rules and different countries have dealt with it in different ways. In some there is a special constitutional law with the same legal force as the constitution itself (Croatia), the majority of countries allow for regulation by an ordinary law, Macedonia gives the court the autonomy to create and change its own rules of procedure, while in Hungary the parliament fixes the rules on procedure at the suggestion of the constitutional court. The question of the appointment of constitutional judges was also considered and of the mechanisms for ensuring their impartiality and immunity. In the area of the courts' scope for providing normative control, considerable differences were found between the different countries. In some cases the courts' jurisdiction is limited to the normative acts of the respective parliaments, and there is generally no provision for challenging unconstitutional omissions by legislation and the executive. There are, however, some situations in which they may indirectly evaluate the constitutionality of legislative omissions, as when the constitution contains provision for a time limit on enacting legislation, when the parliament has made an omission in drafting a law which violates the constitutional provisions, or when a law grants favours to certain groups while excluding others, thereby violating the equal protection clause of the constitution. The control of constitutionality of normative acts can be either preventive or repressive, depending on whether it is implemented before or after the promulgation of the law or other enactment being challenged. In most countries in the region the constitutional courts provide only repressive control, although in Hungary and Poland the courts are competent to perform both preventive and repressive norm control, while in Romania the court's jurisdiction is limited to preventive norm control. Most countries are wary of vesting constitutional courts with preventive norm control because of the danger of their becoming too involved in the day-to-day political debate, but Mr. Cvetkovski points out certain advantages of such control. If combined with a short time limit it can provide early clarification of a constitutional issue, secondly it avoids the problems arising if a law that has been in force for some years is declared to be unconstitutional, and thirdly it may help preserve the prestige of the legislation. Its disadvantages include the difficulty of ascertaining the actual and potential consequences of a norm without the empirical experience of the administration and enforcement of the law, the desirability of a certain distance from the day-to-day arguments surrounding the political process of legislation, the possible effects of changing social and economic conditions, and the danger of placing obstacles in the way of rapid reactions to acute situations. In the case of repressive norm control, this can be either abstract or concrete. The former is initiated by the supreme state organs in order to protect abstract constitutional order and the latter is initiated by ordinary courts, administrative authorities or by individuals. Constitutional courts cannot directly oblige the legislature and executive to pass a new law and this remains a matter of legislative and executive political responsibility. In the case of Poland, the parliament even has the power to dismiss a constitutional court decision by a special majority of votes, which means that the last word lies with the legislature. As the current constitutions of Central and Eastern European countries are newly adopted and differ significantly from the previous ones, the courts' interpretative functions should ensure a degree of unification in the application of the constitution. Some countries (Bulgaria, Hungary, Poland, Slovakia and Russia) provide for the constitutional courts' decisions to have a binding role on the constitutions. While their decisions inevitably have an influence on the actions of public bodies, they do not set criteria for political behaviour, which depends rather on the overall political culture and traditions of the society. All constitutions except that of Belarus, provide for the courts to have jurisdiction over conflicts arising from the distribution of responsibilities between different organs and levels in the country, as well for impeachment procedures against the head of state, and for determining the constitutionality of political parties (except in Belarus, Hungary, Russia and Slovakia). All the constitutions studied guarantee individual rights and freedoms and most courts have jurisdiction over complaints of violation of these rights by the constitution. All courts also have some jurisdiction over international agreements and treaties, either directly (Belarus, Bulgaria and Hungary) before the treaty is ratified, or indirectly (Croatia, Czech Republic, Macedonia, Romania, Russia and Yugoslavia). In each country the question of who may initiate proceedings of norm control is of central importance and is usually regulated by the constitution itself. There are three main possibilities: statutory organs, normal courts and private individuals and the limitations on each of these is discussed in the report. Most courts are limited in their rights to institute ex officio a full-scale review of a point of law, and such rights as they do have rarely been used. In most countries courts' decisions do not have any binding force but must be approved by parliament or impose on parliament the obligation to bring the relevant law into conformity within a certain period. As a result, the courts' position is generally weaker than in other countries in Europe, with parliament remaining the supreme body. In the case of preventive norm control a finding of unconstitutionality may act to suspend the law and or to refer it back to the legislature, where in countries such as Romania it may even be overturned by a two-thirds majority. In repressive norm control a finding of unconstitutionality generally serves to take the relevant law out of legal force from the day of publication of the decision or from another date fixed by the court. If the law is annulled retrospectively this may or may not bring decisions of criminal courts under review, depending on the provisions laid down in the relevant constitution. In cases relating to conflicts of competencies the courts' decisions tend to be declaratory and so have a binding effect inter partes. In the case of a review of an individual act, decisions generally become effective primarily inter partes but is the individual act has been based on an unconstitutional generally binding normative act of the legislature or executive, the findings has quasi-legal effect as it automatically initiates special proceedings in which the law or other regulation is to be annulled or abrogated with effect erga omnes. This wards off further application of the law and thus further violations of individual constitutional rights, but also discourages further constitutional complaints against the same law. Thus the success of one individual's complaint extends to everyone else whose rights have equally been or might have been violated by the respective law. As the body whose act is repealed is obliged to adopt another act and in doing so is bound by the legal position of the constitutional court on the violation of constitutionally guaranteed freedoms and rights of the complainant, in this situation the decision of the constitutional court has the force of a precedent.

Management of Patients Presenting with Acute Subdural Hematoma due to Ruptured Intracranial Aneurysm

Acute subdural hematoma is a rare presentation of ruptured aneurysms. The rarity of the disease makes it difficult to establish reliable clinical guidelines. Many patients present comatose and differential diagnosis is complicated due to aneurysm rupture results in or mimics traumatic brain injury. Fast decision-making is required to treat this life-threatening condition. Determining initial diagnostic studies, as well as making treatment decisions, can be complicated by rapid deterioration of the patient, and the mixture of symptoms due to the subarachnoid hemorrhage or mass effect of the hematoma. This paper reviews initial clinical and radiological findings, diagnostic approaches, treatment modalities, and outcome of patients presenting with aneurysmal subarachnoid hemorrhage complicated by acute subdural hematoma. Clinical strategies used by several authors over the past 20 years are discussed and summarized in a proposed treatment flowchart.

Sensitivity of Nd isotopic composition in seawater to changes in Nd sources and paleoceanographic implications

It has been argued that past changes in the sources of Nd could hamper the use of the Nd isotopic composition (ϵNd) as a proxy for past changes in the overturning of deep water masses. Here we reconsider uncertainties associated with ϵNd in seawater due to potential regional to global scale changes in the sources of Nd by applying a modeling approach. For illustrative purposes we describe rather extreme changes in the magnitude of source fluxes, their isotopic composition or both. We find that the largest effects on ϵNd result from changes in the boundary source. Considerable changes also result from variations in the magnitude or ϵNd of dust and rivers but are largely constrained to depths shallower than 1 km, except if they occur in or upstream of regions where deep water masses are formed. From these results we conclude that changes in Nd sources have the potential to affect ϵNd. However, substantial changes are required to generate large-scale changes inϵNd in deep water that are similar in magnitude to those that have been reconstructed from sediment cores or result from changes in meridional overturning circulation in model experiments. Hence, it appears that a shift in ϵNdcomparable to glacial-interglacial variations is difficult to obtain by changes in Nd sources alone, but that more subtle variations can be caused by such changes and must be interpreted with caution.

Alternate or additional findings to stone disease on unenhanced computerized tomography for acute flank pain can impact management

PURPOSE: We evaluated the incidence and clinical relevance of alternate or additional findings on unenhanced CT in patients with acute flank pain and suspected urinary calculi. MATERIALS AND METHODS: A consecutive series of 1,500 patients underwent unenhanced CT due to acute flank pain. The absence or presence of urinary tract calculi and their localization were recorded. Alternate or additional CT findings were classified according to whether they required immediate or deferred treatment, or were of little or no clinical importance. RESULTS: Of the 1,500 patients 1,035 (69%) had urinary tract calculi, including 309 (30%) with nephrolithiasis, 377 (36%) with ureterolithiasis and 349 (34%) with the 2 conditions. Urolithiasis alone was found in 331 of these patients (32%) and additional pathological conditions were noted in 704 (68%). Of all patients 1,064 (71%) had other or additional CT findings. Of all patients 207 (14%) had nonstone related CT findings requiring immediate or deferred treatment, 464 (31%) had pathological conditions of little clinical importance and 393 (26%) had pathological conditions of no clinical relevance. CT was normal in 105 of all patients (7%). CONCLUSIONS: Unenhanced CT in patients with acute flank pain allows the accurate diagnosis of urinary stone disease and it can also provide further important information leading to emergency or deferred treatment in a substantial number of patients.

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or 2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a fast arterial Po(2) probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group (P < 0.001), and mixed venous saturation was consistently greater in the high RR group (P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage

Stem cell regeneration of damaged tissue has recently been reported in many different organs. Since the loss of retinal pigment epithelium (RPE) in the eye is associated with a major cause of visual loss - specifically, age-related macular degeneration - we investigated whether hematopoietic stem cells (HSC) given systemically can home to the damaged subretinal space and express markers of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were used in a sodium iodate (NaIO(3)) model of RPE damage in the mouse. The optimal time for adoptive transfer of bone marrow-derived stem cells relative to the time of injury and the optimal cell type [whole bone marrow, mobilized peripheral blood, HSC, facilitating cells (FC)] were determined by counting the number of GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65. The time at which bone marrow-derived cells were adoptively transferred relative to the time of NaIO(3) injection did not significantly influence the number of cells that homed to the subretinal space. At both one and two weeks after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were observed in the damaged subretinal space, at sites of RPE loss, but not in the normal subretinal space. The combined transplantation of HSC+FC cells appeared to favor the survival of the homed stem cells at two weeks, and RPE-65 was expressed by adoptively transferred HSC by four weeks. We have shown that systemically injected HSC homed to the subretinal space in the presence of RPE damage and that FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65 was expressed on adoptively transferred HSC in the denuded areas.

The horse genome project - sequence based insights into male reproductive mechanisms

The growing knowledge on physiology, cell biology and biochemistry of the reproductive organs has provided many insights into molecular mechanisms that are required for successful reproduction. Research directed at the investigation of reproduction physiology in domestic animals was hampered in the past by a lack of species-specific genomic information. The genome sequences of dog, cattle and horse have become publicly available in 2005, 2006 and 2007 respectively. Although the gene content of mammalian genomes is generally very similar, genes involved in reproduction tend to be less conserved than the average mammalian gene. The availability of genome sequences provides a valuable resource to check whether any protein that may be known from human or mouse research is present in cattle and/or horse as well. Currently there are more than 200 genes known that are involved in the production of fertile sperm cells. Great progress has been made in the understanding of genetic aberrations that lead to male infertility. Additionally, the first genetic mechanisms are being discovered that contribute to the quantitative variation of fertility traits in fertile male animals. Here, I will review some selected aspects of genetic research in male fertility and offer some perspectives for the use of genomic sequence information.

Cost-effectiveness of pharmacogenetic testing to predict treatment response to angiotensin-converting enzyme inhibitor

OBJECTIVE: This study aimed to assess the potential cost-effectiveness of testing patients with nephropathies for the I/D polymorphism before starting angiotensin-converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a healthcare perspective. METHODS: We used a combination of a decision analysis and Markov modeling technique to evaluate the potential economic value of this pharmacogenetic test by preventing unfavorable treatment in patients with nephropathies. The estimation of the predictive value of the I/D polymorphism is based on a systematic review showing that DD carriers tend to respond well to ACE inhibitors, while II carriers seem not to benefit adequately from this treatment. Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients with end-stage renal disease (ESRD) prevented and the differences in the incremental costs and incremental effect expressed as life-years free of ESRD. A probabilistic sensitivity analysis was conducted to determine the robustness of the results. RESULTS: Compared with unselective treatment, testing patients for their ACE genotype could save 12 patients per 1000 from developing ESRD during the 3 years covered by the model. As the mean net cost savings was euro 356,000 per 1000 patient-years, and 9 life-years free of ESRD were gained, selective treatment seems to be dominant. CONCLUSION: The study suggests that genetic testing of the I/D polymorphism in patients with nephropathy before initiating ACE therapy will most likely be cost-effective, even if the risk for II carriers to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD carriers. Further studies, however, are required to corroborate the difference in treatment response between ACE genotypes, before genetic testing can be justified in clinical practice.