Acute aortic dissection determines the fate of initially untreated aortic segments in Marfan syndrome

The aim of the current study was to investigate incidence and causes of surgical interventions in primarily nontreated aortic segments after previous aortic repair in patients with Marfan syndrome.

Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C(-/-) mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C(-/-) mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C(-/-) C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C(-/-) mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3(rd) ventricle in JAM-C(-/-) C57BL/6 mice. Taken together, our study suggests that JAM-C(-/-) C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.

Role of FGFRL1 and other FGF signaling proteins in early kidney development

The mammalian kidney develops from the ureteric bud and the metanephric mesenchyme. In mice, the ureteric bud invades the metanephric mesenchyme at day E10.5 and begins to branch. The tips of the ureteric bud induce the metanephric mesenchyme to condense and form the cap mesenchyme. Some cells of this cap mesenchyme undergo a mesenchymal-to-epithelial transition and differentiate into renal vesicles, which further develop into nephrons. The developing kidney expresses Fibroblast growth factor (Fgf)1, 7, 8, 9, 10, 12 and 20 and Fgf receptors Fgfr1 and Fgfr2. Fgf7 and Fgf10, mainly secreted by the metanephric mesenchyme, bind to Fgfr2b of the ureteric bud and induce branching. Fgfr1 and Fgfr2c are required for formation of the metanephric mesenchyme, however the two receptors can substitute for one another. Fgf8, secreted by renal vesicles, binds to Fgfr1 and supports survival of cells in the nascent nephrons. Fgf9 and Fgf20, expressed in the metanephric mesenchyme, are necessary to maintain survival of progenitor cells in the cortical region of the kidney. FgfrL1 is a novel member of the Fgfr family that lacks the intracellular tyrosine kinase domain. It is expressed in the ureteric bud and all nephrogenic structures. Targeted deletion of FgfrL1 leads to severe kidney dysgenesis due to the lack of renal vesicles. FgfrL1 is known to interact mainly with Fgf8. It is therefore conceivable that FgfrL1 restricts signaling of Fgf8 to the precise location of the nascent nephrons. It might also promote tight adhesion of cells in the condensed metanephric mesenchyme as required for the mesenchymal-to-epithelial transition.

Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron.

Polymyalgia rheumatica in a married couple

The case of a married couple developing polymyalgia rheumatica (PMR) consecutively is presented. The 55-year-old wife complained in June 2010 about pain in her neck. Case history, physical examination, and erythrocyte sedimentation rate (ESR) of 80 mm/hour led to the diagnosis of PMR. In May 2011, her 66-year old husband complained about pain in his neck, shoulders, buttocks, and thighs. Considering anamnesis, physical examination, and ESR of 56 mm/hour, the diagnosis of PMR was made. Both wife and husband responded to steroid treatment. When the steroid dose was gradually reduced, both patients relapsed. In order to lower the cumulative dose of glucocorticoid therapy, 10 mg methotrexate per week was added. In the literature, six cases of polymyalgia rheumatica in married couples have been described to date. In four cases, polymyalgia rheumatica occurred first in the wife. The interval of the diagnosis between the spouses ranged from 0 to 89 months. Although in most of the previous case reports a genetic disposition and an infectious agent have been discussed, this hypothesis must be questioned.

Does surgery improve outcomes for esophageal squamous cell carcinoma? An analysis using the surveillance epidemiology and end results registry from 1998 to 2008

We examined survival associated with locally advanced esophageal squamous cell cancer (SCC) to evaluate if treatment without surgery could be considered adequate.

The role of radiation therapy in resected T2 N0 esophageal cancer: a population-based analysis

The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy.

Negative laparotomy in trauma: are we getting better?

One of the trauma surgeons' daily challenges is the balancing act between negative laparotomy and missed abdominal injury. We opted to characterize the indications that prompted a negative trauma exploratory laparotomy and the rate of missed abdominal injuries in an effort to optimize patient selection for laparotomy. At the Los Angeles County + University of Southern California Medical Center, negative laparotomies and missed injuries are consecutively captured and reviewed at the weekly mortality + morbidity (MM) conferences. All written reports of the MM meetings from January 2003 to December 2008 were reviewed to identify all patients who underwent a negative laparotomy or a laparotomy as a result of an initially missed abdominal injury. Over the 6-year study period, a total of 1871 laparotomies were performed, of which 73 (3.9%) were negative. The rate of missed injuries requiring subsequent laparotomy was 1.3 per cent (25 of 1871). The negative laparotomy rate and the rate of missed injuries did not vary significantly during the study period (2.8 to 4.7%, P = 0.875, and 0.7 to 2.9%, P = 0.689). Penetrating mechanisms accounted for the majority of negative laparotomies (58.9%). The primary indication for negative laparotomy was peritonitis (54.8%) followed by hypotension (28.8%) and suspicious computed tomographic scan findings (27.4%). The complication rate after negative laparotomy was 14.5 per cent, and of these, 10.1 per cent were directly related to the procedure. A low but steady rate of negative laparotomies and missed abdominal injuries after trauma remains. Negative laparotomies and missed abdominal injuries when they occur are still associated with significant complication rates and a prolonged length of stay.

Biochemical profile and outcomes in trauma patients subjected to open cardiopulmonary resuscitation: a prospective observational pilot study

The predictive factors to regain a heartbeat following emergency department resuscitative thoracotomy (EDT) for trauma are poorly understood. The objective of the present study was to prospectively assess the electrolyte profile, coagulation parameters, and acid-base status from intracardiac blood samples in trauma patients subjected to open cardiopulmonary resuscitation (CPR) in the presence of established cardiac arrest.

Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease: A Propensity Score-Adjusted, Population-Based Trend Analysis Involving 10 206 Patients

OBJECTIVE To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING Nationwide Inpatient Sample from 2000 through 2009. PATIENTS A total of 10 206 patients were involved. MAIN OUTCOME MEASURES Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay. RESULTS Overall, 10 206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology

Grigorij Kreidlin (Russia). A Comparative Study of Two Semantic Systems: Body Russian and Russian Phraseology. Mr. Kreidlin teaches in the Department of Theoretical and Applied Linguistics of the State University of Humanities in Moscow and worked on this project from August 1996 to July 1998. The classical approach to non-verbal and verbal oral communication is based on a traditional separation of body and mind. Linguists studied words and phrasemes, the products of mind activities, while gestures, facial expressions, postures and other forms of body language were left to anthropologists, psychologists, physiologists, and indeed to anyone but linguists. Only recently have linguists begun to turn their attention to gestures and semiotic and cognitive paradigms are now appearing that raise the question of designing an integral model for the unified description of non-verbal and verbal communicative behaviour. This project attempted to elaborate lexical and semantic fragments of such a model, producing a co-ordinated semantic description of the main Russian gestures (including gestures proper, postures and facial expressions) and their natural language analogues. The concept of emblematic gestures and gestural phrasemes and of their semantic links permitted an appropriate description of the transformation of a body as a purely physical substance into a body as a carrier of essential attributes of Russian culture - the semiotic process called the culturalisation of the human body. Here the human body embodies a system of cultural values and displays them in a text within the area of phraseology and some other important language domains. The goal of this research was to develop a theory that would account for the fundamental peculiarities of the process. The model proposed is based on the unified lexicographic representation of verbal and non-verbal units in the Dictionary of Russian Gestures, which the Mr. Kreidlin had earlier complied in collaboration with a group of his students. The Dictionary was originally oriented only towards reflecting how the lexical competence of Russian body language is represented in the Russian mind. Now a special type of phraseological zone has been designed to reflect explicitly semantic relationships between the gestures in the entries and phrasemes and to provide the necessary information for a detailed description of these. All the definitions, rules of usage and the established correlations are written in a semantic meta-language. Several classes of Russian gestural phrasemes were identified, including those phrasemes and idioms with semantic definitions close to those of the corresponding gestures, those phraseological units that have lost touch with the related gestures (although etymologically they are derived from gestures that have gone out of use), and phrasemes and idioms which have semantic traces or reflexes inherited from the meaning of the related gestures. The basic assumptions and practical considerations underlying the work were as follows. (1) To compare meanings one has to be able to state them. To state the meaning of a gesture or a phraseological expression, one needs a formal semantic meta-language of propositional character that represents the cognitive and mental aspects of the codes. (2) The semantic contrastive analysis of any semiotic codes used in person-to-person communication also requires a single semantic meta-language, i.e. a formal semantic language of description,. This language must be as linguistically and culturally independent as possible and yet must be open to interpretation through any culture and code. Another possible method of conducting comparative verbal-non-verbal semantic research is to work with different semantic meta-languages and semantic nets and to learn how to combine them, translate from one to another, etc. in order to reach a common basis for the subsequent comparison of units. (3) The practical work in defining phraseological units and organising the phraseological zone in the Dictionary of Russian Gestures unexpectedly showed that semantic links between gestures and gestural phrasemes are reflected not only in common semantic elements and syntactic structure of semantic propositions, but also in general and partial cognitive operations that are made over semantic definitions. (4) In comparative semantic analysis one should take into account different values and roles of inner form and image components in the semantic representation of non-verbal and verbal units. (5) For the most part, gestural phrasemes are direct semantic derivatives of gestures. The cognitive and formal techniques can be regarded as typological features for the future functional-semantic classification of gestural phrasemes: two phrasemes whose meaning can be obtained by the same cognitive or purely syntactic operations (or types of operations) over the meanings of the corresponding gestures, belong by definition to one and the same class. The nature of many cognitive operations has not been studied well so far, but the first steps towards its comprehension and description have been taken. The research identified 25 logically possible classes of relationships between a gesture and a gestural phraseme. The calculation is based on theoretically possible formal (set-theory) correlations between signifiers and signified of the non-verbal and verbal units. However, in order to examine which of them are realised in practice a complete semantic and lexicographic description of all (not only central) everyday emblems and gestural phrasemes is required and this unfortunately does not yet exist. Mr. Kreidlin suggests that the results of the comparative analysis of verbal and non-verbal units could also be used in other research areas such as the lexicography of emotions.

Cascading climate effects and related ecological consequences during past centuries

The interface between climate and ecosystem structure and function is incompletely understood, partly because few ecological records start before the recent warming phase. Here, we analyse an exceptional 100-yr long record of the great tit (Parus major) population in Switzerland in relation to climate and habitat phenology. Using structural equation analysis, we demonstrate an uninterrupted cascade of significant influences of the large-scale atmospheric circulation (North-Atlantic Oscillation, NAO, and North-sea – Caspian Pattern, NCP) on habitat and breeding phenology, and further on fitness-relevant life history traits within great tit populations. We then apply the relationships of this analysis to reconstruct the circulation-driven component of fluctuations in great tit breeding phenology and productivity on the basis of new seasonal NAO and NCP indices back to 1500 AD. According to the structural equation model, the multi-decadal oscillation of the atmospheric circulation likely led to substantial variation in habitat phenology, productivity and consequently, tit population fluctuations with minima during the "Maunder Minimum" (∼ 1650–1720) and the Little Ice Age Type Event I (1810–1850). The warming since 1975 was not only related with a quick shift towards earlier breeding, but also with the highest productivity since 1500, and thus, the impact of the NAO and NCP has contributed to an unprecedented increase of the population. A verification of the structural equation model against two independent data series (1970–2000 and 1750–1900) corroborates that the retrospective model reliably depicts the major long-term NAO/NCP impact on ecosystem parameters. The results suggest a complex cascade of climate effects beginning at a global scale and ending at the level of individual life histories. This sheds light on how large-scale climate conditions substantially affect major life history parameters within a population, and thus influence key ecosystem parameters at the scale of centuries.