Persistence of tracer in the application site -a potential confounding factor in nerve regeneration studies

Selective reinnervation of peripheral targets after nerve injury might be assessed by injecting a first tracer in a target before nerve injury to label the original neuronal population, and applying a second tracer after the regeneration period to label the regenerated population. However, altered uptake of tracer, fading, and cell death may interfere with the results. Furthermore, if the first tracer injected remains in the target tissue, available for 're-uptake' by misdirected regenerating axons, which originally innervated another region, then the identification of the original population would be confused. With the aim of studying this problem, the sciatic nerve of adult rats was sectioned and sutured. After 3 days, to allow the distal axon to degenerate avoiding immediate retrograde transport, one of the dyes: Fast Blue (FB), Fluoro-Gold (FG) or Diamidino Yellow (DY), was injected into the tibial branch of the sciatic nerve, or in the skin of one of the denervated digits. Rats survived 2-3 months. The results showed labelled dorsal root ganglion (DRG) cells and motoneurones, indicating that late re-uptake of a first tracer occurs. This phenomenon must be considered when the model of sequential labelling is used for studying the accuracy of peripheral reinnervation.

An enantioselective entry to cis-perhydroisoquinolines

An enantioselective route to cis-perhydroisoquinolines, involving a cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a stereoselective conjugate addition to an unsaturated bicyclic lactam, and the closure of the carbocyclic ring by a ring-closing metathesis as the key steps is reported. This route allows the preparation of 3-cyano derivatives as well as cis-octahydroisoquinolines bearing a quaternary center at the C4-position.

Evaluation of markets for irrigation water in the internal river basins of Catalonia, Spain

Irrigated agriculture has come under close scrutiny in Europe recently because of its high share of total water consumption and its apparent inefficiency. Several water policies have been advocated, in particular the use of economic instruments such as water markets. This paper simulates the impact of a policy based upon water markets on agricultural production in the internal river basins of Catalonia (Spain). This zone presents certain particularities that make it very interesting to study: competition between sectors for the resource (agriculture-urban consumption-recreational uses), recent periods of resource insufficiency and conflicts between irrigators as a result of the measures taken by the hydraulic administration in drought situations. The results show that these markets would guarantee an optimal reassignment of the resource in situations of supply restrictions, and although compared to the situation without markets they would not mean higher economic profits for the irrigators, they could prevent conflicts between them. Nevertheless, doubts exist about their acceptance by irrigators

Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames.

Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.

Entry Regulation Asymmetries and Gasoline Competition in a Mixed Motorway Network

Regulatory and funding asymmetries in the Spanish motorway network produce huge differences in the structure of gasoline markets by motorway type: free or toll. While competition is encouraged among gas stations on free motorways, the regulations for toll motorways allow private concessionaires to auction all gas stations to the same provider, thereby limiting competition and consolidating market power. This paper reports how this regulatory asymmetry results in higher prices and fewer gas stations. Specifically, we show that competition is constrained on toll motorways by the granting of geographical monopolies, resulting in a small number of rivals operating in close proximity to each other, and allowing gas stations to operate as local monopolies. The lack of competition would seem to account for the price differential between toll and free motorways. According to available evidence, deregulation measures affecting toll motorway concessions could help to mitigate price inefficiencies and increase consumer welfare.

Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells.

Store-operated Ca(2+) channels (SOCs) are voltage-independent Ca(2+) channels activated upon depletion of the endoplasmic reticulum Ca(2+) stores. Early studies suggest the contribution of such channels to Ca(2+) homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca(2+) depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca(2+) imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca(2+) entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes.

L'informatique: un outil remarquable pour l'enseignement de la médecine interne générale [The informatics: a remarkable tool for teaching general internal medicine].

INTERMED training implies a three week course, integrated in the "primary care module" for medical students in the first master year at the school of medicine in Lausanne. INTERMED uses an innovative teaching method based on repetitive sequences of e-learning-based individual learning followed by collaborative learning activities in teams, named Team-based learning (TBL). The e-learning takes place in a web-based virtual learning environment using a series of interactive multimedia virtual patients. By using INTERMED students go through a complete medical encounter applying clinical reasoning and choosing the diagnostic and therapeutic approach. INTERMED offers an authentic experience in an engaging and safe environment where errors are allowed and without consequences.

Dix ans de revue de la littérature en médecine interne générale--un premier bilan [Ten years of literature review in general internal medicine--a first assessment].

A group of family physicians in an outpatient clinic in Switzerland prospectively followed scientific literature for ten years. What to remember among the numerous articles retrieved and which paper really changed our practice? If many readings are quickly forgotten, some of them marked our minds and changed our habits. This article is a summary of our efforts to keep the essential tools in clinical practice.

Customer-Related Internal Communication in a Global Matrix Organization

The objective of the thesis was to explore the nature and characteristics of customer-related internal communication in a global industrial matrix organization during a specific customer relationship, and how it could be improved. The theoretical part of the study views the field of the concepts of intra-organizational information and knowledge sharing. The theoretical part also views the internal communications influences to customer relationships, its problematic, and the suggestions to improve internal communication in literature. The empirical part of the study was conducted with the Content Analysis and the Social Network Analysis as research methods. The data was collected by interviews and a questionnaire. Internal communication was observed first generally within the organization from the point of view of a certain business, and secondly, during a specific customer relationship at personal level and at departmental level. The results of the study describe the nature and characteristics of internal communication in the organization. The results give 13 suggestions for improving internal communication in the organization. Although the study has been done in one specific organization, it also offers insights for other organizations as well as managers to improve their internal communication.

Déclaration et traitement des événements indésirables en médecine interne [Incident-reporting electronic-based system in internal medicine].

How to recognize, announce and analyze incidents in internal medicine units is a daily challenge that is taught to all hospital staff. It allows suggesting useful improvements for patients, as well as for the medical department and the institution. Here is presented the assessment made in the CHUV internal medicine department one year after the beginning of the institutional procedure which promotes an open process regarding communication and risk management. The department of internal medicine underlines the importance of feedback to the reporters, ensures the staff of regular follow-up concerning the measures being taken and offers to external reporters such as general practioners the possibility of using this reporting system too.

Challenges to patient-centred care in a general internal medicine context: findings from an exploratory study

Introduction. If we are to promote more patient-centred approaches in care delivery, we have to better characterize the situations in which being patient-centred is difficult to achieve. Data from professionals in health and social care are important because they are the people charged with operationalizing patient-centred care (PCC) in their daily practice. However, empirical accounts from frontline care providers are still lacking, and it is important to gather experiences not only from doctors but also from the other care providers. Indeed, experiences from different professions can help inform our understanding of patient care, which is expected to be both patient-centred and collaborative. Methods. This study was based on the following research question: What factors make the provision of PCC difficult to achieve? Sample and setting. A purposeful sampling technique was used, allowing for a series of choices about the participants and their professional affiliation. Because patient-centredness is the focus, 3 professions appeared to be of special interest: general internists, nurses and social workers. The study was undertaken in the General Internal Medicine Division of a teaching hospital located in a North American context. Data Collection. To answer the research question, a methodological approach based on a theory called phenomenology was chosen. Accordingly, semi-structured interviews were used since they generate understanding of the meanings different individuals have of their lived world. Interviews with 8 physicians, 10 nurses and 10 social workers were eventually conducted. Data analysis. An inductive thematic analysis was employed to make sense of the interview data. Results. The thematic analysis allowed identifying various types of challenges to PCC. Although most of the challenges were perceived by all three groups of professionals, they were perceived to a different degree across the professions, which likely reflected the scope of practice of each profession. The challenges and their distribution across the professions are illustrated in Table 1. Examples of challenges are provided in Table 2. Discussion. There is a tension between what is supposed to be done - what stands in the philosophy of patient -centredness - and what is currently done - the real life with all the challenges to PCC. According to some participants' accounts, PCC clearly risks becoming a mere illusion for health care professionals on which too great pressures are imposed.