[Ethical, pedagogical, socio-political and anthropological implications of quaternary prevention]. / Implications éthiques, pédagogiques, sociopolitiques et anthropologiques de la prévention quaternaire.

The concept of quaternary prevention, resulting from a reflection on the doctor-patient relationship, is presented as a renewal of the ageold ethical requirement: first, a doctor must not harm; second, the doctor must control himself/herself. The origin of the concept, its endorsement by the World Organization of Family Doctors (WONCA) and the European Union of General Practitioners (UEMO), its dissemination, and the debates to which it has given rise, are presented by a panel of authors from 12 countries and 3 continents. This collective text deals more specifically with the ethics of prevention, the importance of teaching Quaternary prevention and Evidence Based Medicine, the social and political implications of the concept of quaternary prevention, and its anthropological dimensions.

Le concept de prévention quaternaire, issu d'une réflexion sur la relation médecin-patient, est présenté d'une part comme un renouvellement d'une exigence éthique séculaire ; d'abord ne pas nuire et d'autre part comme un plaidoyer pour un autocontrôle du médecin. L'origine du concept, son approbation par l'Organisation Mondiale des Médecins de Famille (WONCA) et l'Union Européenne des Médecins Omnipraticiens (UEMO), sa diffusion et les débats auxquels il a donné lieu, sont présentés par un panel d'auteurs de 12 pays et trois continents. Ce texte collectif traite plus spécifiquement de l'éthique de la prévention, de l'importance de l'enseignement de la prévention quaternaire et de la médecine factuelle, des implications sociales et politiques du concept de prévention quaternaire et de ses dimensions anthropologiques.

Atomic structure of Mn wires on Si(001) resolved by scanning tunneling microscopy.

At submonolayer coverage, Mn forms atomic wires on the Si(001) surface oriented perpendicular to the underlying Si dimer rows. While many other elements form symmetric dimer wires at room temperature, we show that Mn wires have an asymmetric appearance and pin the Si dimers nearby. We find that an atomic configuration with a Mn trimer unit cell can explain these observations as due to the interplay between the Si dimer buckling phase near the wire and the orientation of the Mn trimer. We study the resulting four wire configurations in detail using high-resolution scanning tunneling microscopy (STM) imaging and compare our findings with the STM images simulated by density functional theory.

Invasive aspergillosis in a putty-nosed monkey (Cercopithecus nictitans) with adrenocortical Cushing's syndrome.

BACKGROUND: An 18-year-old captive female putty-nosed-monkey (Cercopithecus nictitans) with a history of long-term infertility and hyperglucocorticism was euthanized because of perforating thoracic trauma induced by group members and subsequent development of neurological signs. METHODS: Complete necropsy and histopathological examination of formalin-fixed tissue samples was carried out. RESULTS: The monkey showed invasive pulmonary and cerebral infection with Aspergillus fumigatus together with adrenocortical neoplasia and signs of Cushing's syndrome, such as alopecia with atrophic skin changes, evidence for diabetes mellitus and marked immunosuppression. CONCLUSIONS: Spontaneous endocrinopathies are rarely described in non-human primates. Here we report the first case of spontaneous adrenocortical hyperglucocorticism predisposing to systemic aspergillosis in a putty-nosed monkey.

[Future of interprofessional primary care in time of crisis]. / L'avenir des soins primaires interprofessionnels dans un temps de crise.

The world is facing a crisis with several dimensions, economical, moral, social, epidemiological and scientific. This crisis is likely to have an impact on organisation of Primary Care, and on interprofessional collaboration. Several issues are raised by this situation: who will arbitrate rationalisation or rationing of care? Which professions will be called upon to collaborate? How will professionals take side between justice based on redistribution, and justice based on recognition? What will be the cost of reorganizing the work of the various professionals, particularly regarding the modification of the range of skills? How will collaboration among professionals be organized, vertically or horizontally? How will research evolve? This paper tries to reflect on this issues.

[The spirit of community medicine: students learning from students]. / Penser la médecine communautaire s'apprend avec les pairs.

At the University of Lausanne third-year medical students are given the task of spending a month investigating a question of community medicine. In 2009, four students evaluated the legitimacy of health insurers intervening in the management of depression. They found that health insurers put pressure on public authorities during the development of legislation governing the health system and reimbursement for treatment. This fact emerged during the scientific investigation led jointly by the team in the course of the "module of immersion in community medicine." This paper presents each step of their study. The example chosen illustrates the learning objectives covered by the module.

Prevalence of enterococcal groin colonization in patients undergoing cardiac interventions: challenging antimicrobial prophylaxis with cephalosporins in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cephalosporins are recommended for prophylaxis before transcatheter aortic valve replacement (TAVR). Infective endocarditis (IE) after TAVR is caused by enterococci in up to 30% of cases, particularly early after TAVR. Enterococcal colonization in the groin has been postulated as a source of infection, not only because prophylaxis does not cover enterococci but also because most TAVR procedures are performed by transfemoral access. There are few data analysing the groin microbiome to demonstrate the presence of enterococci. AIM: To assess the prevalence of enterococci in the groins of cardiological patients receiving transfemoral interventions. METHODS: This prospective cohort study was undertaken at University Hospital Basel, Switzerland between February and August 2020. Two skin swabs were taken from the groins of consecutive patients undergoing transfemoral cardiac interventions before the administration of antibiotic prophylaxis; for each patient, swabs were taken before and after groin disinfection. Swabs were analysed in the local microbiological laboratory following validated culture methods. FINDINGS: Of 290 included patients, 245 (84.5%) underwent coronary angiography, 31 (10.7%) underwent TAVR, eight (2.8%) underwent right heart catheterization, five (1.7%) underwent closure of patent foramen ovale, and one (0.3%) underwent a MitraClip procedure. Enterococci were detected before disinfection in 48 patients, enterococci were still cultured after disinfection in three patients, and enterococci were detected after disinfection alone (i.e. not detected before disinfection) in one patient. The prevalence of enterococci was 16.6% before disinfection and 1.4% after disinfection. Patients colonized with enterococci had a significantly higher body mass index and were more likely to be diabetic than uncolonized patients. CONCLUSION: Common enterococcal colonization of the groin, coupled with frequent isolation of enterococci from patients with TAVR-associated IE, provides strong evidence that the current recommendation of antimicrobial prophylaxis with cephalosporins before TAVR should be changed to antimicrobial prophylaxis with a compound that is active against enterococci.

Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women.

OBJECTIVE: Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy, normally ovulating women and to correlate these with each other and with the hormones of the gonadal axis. A cycle-dependence of the markers studied would imply an exact timing of the blood sampling for clinical needs. DESIGN: Observational study investigating the two inflammatory markers CRP and leptin in relation to the hormonal pattern of the gonadal axis during the normal cycle. METHODS: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a normal body mass index were evaluated. Serum concentrations of leptin and CRP, as well as of follicle-stimulating hormone, luteinising hormone, 17beta-oestradiol, progesterone, prolactin (PRL) and free testosterone were measured every 1-2 days during one full cycle. RESULTS: Serum levels of leptin and CRP behaved differently during ovulatory cycles, with higher concentrations for leptin only during certain phases. Significant correlations were found in the follicular phase between leptin and PRL and leptin and free testosterone. CONCLUSIONS: Leptin levels change during the menstrual cycle. Leptin levels are more stable on cycle days 1-5 than later in the cycle. For precise cycle-independent measurements, these fluctuations have to be taken into account. There is no similar cyclic pattern for CRP.

[Notes of a family doctor on the follow-up of chronic pain]. / Notes d'un médecin de famille sur le suivi des douleurs chroniques.

From the narrative point of view, illustrating the follow-up of chronic pain suffering patients, some questions are asked by the family doctor, interrogating skills and attitudes. A model of interpersonal continuity of care is here defended.

[Surgical removal of Salzmann's nodules using intraoperative mitomycin C]. / Chirurgische Abtragung von Salzmann-Knoten unter Anwendung von intraoperativem Mitomycin C.

Salzmann's nodules comprise a heterogeneous group of greyish superficial corneal opacities. A substantial percentage is most likely caused by dystrophies. This could explain the recurrences after surgical removal. The Eye Center of the University Hospital Freiburg has been using mitomycin C intraoperatively during surgical removal of Salzmann's nodules since 2007 to prevent recurrences. We recently performed an uncontrolled prospective trial to evaluate this approach and also reviewed the literature. Worldwide, a total of 38 eyes have been treated with mitomycin C during surgery for Salzmann's nodules. No recurrences have been reported so far with follow-up exceeding at least 2 years in almost all eyes. No severe side effects have been observed to date. We therefore think that mitomycin C during surgery for Salzmann's nodules is advisable despite the lack of evidence from a randomized clinical trial. However, all patients must consent to the off label use of mitomycin C.

Regulation of EphB1 expression by dopamine signaling.

The Eph family tyrosine kinase receptors and their ligands have been implicated in axon guidance and neuronal migration during development of the nervous system. In the current study, we aim to characterize the nature of changes in EphB1 receptor expression following increases or decreases in dopamine activity. Neonatal mice (P3) were injected with 6-hydroxydopamine and allowed 13 days to recover. These animals show a profound depletion of dopamine in all areas assayed, with a corresponding dose-dependent decrease in EphB1 expression. Day 3 pups were also injected either chronically (P3-P16) or acutely (P3 only) with cocaine to determine how enhancing dopamine signaling would affect EphB1 signal density. It was found that both treatments significantly increased expression of EphB1 in the cortex, striatum and substantia nigra. Finally, animals were treated prenatally (E15-E17) with cocaine and sacrificed on P7. These animals also showed an increase in EphB1 signal density, but only in the dopaminergic terminal areas in the cortex and striatum. These studies indicate that dopamine activity regulates developmental expression of the tyrosine kinase receptor EphB1.

Altered sensitivity of CD81-deficient mice to neurobehavioral effects of cocaine.

CD81, also known as target of the antiproliferative antibody, is known to be expressed in astrocytes and involved in cell adhesion and, recently, we demonstrated its induction exclusively in the accumbens following cocaine. In the present study, the sensitivity of CD81-deficient mice to behavioral effects of cocaine was evaluated. It was found that CD81-deficient mice exhibited altered sensitivity to cocaine as assessed in the place preference conditioning paradigm and locomotor activity. This deficit in place preference conditioning was not accompanied by a deficit in acquisition or retention of water maze behavior. In addition, CD81 knockout mice exhibited higher levels of nucleus accumbens dopamine as compared to their controls. These observations are discussed in the context of the role of CD81 in cocaine-mediated behaviors.

Neurotoxic effects of amphetamine plus L-DOPA.

1. Male Swiss Webster mice were administered a series of amphetamine injections preceded by either saline or L-DOPA. 2. This injection regimen was performed for either one, two or three consecutive weeks and neurotoxic effects of the drugs were determined one week later. 3. Amphetamine treatment for two weeks produced a greater striata-dopaminergic lesion that treatment for only one week. Three weeks of treatment did not exacerbate the lesion, indicating that the damage had reached maximal levels. 4. L-DOPA pretreatment did not significantly alter any of the toxic effects of the amphetamine. Therefore, some dopaminergic neurons may be resistant to the toxic effects of amphetamine.

Development of an auditory implant manipulator for minimally invasive surgical insertion of implantable hearing devices.

OBJECTIVE: To present the auditory implant manipulator, a navigation-controlled mechanical and electronic system which enables minimally invasive ('keyhole') transmastoid access to the tympanic cavity. MATERIALS AND METHODS: The auditory implant manipulator is a miniaturised robotic system with five axes of movement and an integrated drill. It can be mounted on the operating table. We evaluated the surgical work field provided by the system, and the work sequence involved, using an anatomical whole head specimen. RESULTS: The work field provided by the auditory implant manipulator is considerably greater than required for conventional mastoidectomy. The work sequence for a keyhole procedure included pre-operative planning, arrangement of equipment, the procedure itself and post-operative analysis. CONCLUSION: Although system improvements are necessary, our preliminary results indicate that the auditory implant manipulator has the potential to perform keyhole insertion of implantable hearing devices.

Cocaine-induced expression of the tetraspanin CD81 and its relation to hypothalamic function.

CD81, a tetraspanin transmembrane protein involved in cell adhesion, was found by differential display to be upregulated in the nucleus accumbens of rat brain following acute cocaine treatment (four injections of 30 mg/kg every 2 h followed by 24 h withdrawal). Cocaine-induced expression of CD81 in adult rat brain was confirmed by quantitative real-time RT-PCR. Its expression in neurons and its function in the brain are unknown. In situ hybridization shows a neuron-specific expression pattern in brain regions functionally related to the regulation of cardiovascular function and fluid homeostasis. CD81 displays codistribution to galanin and, to a lesser extent, to vasopressin. These findings add to data that suggest a connection between the brain reward pathway and the centers regulating endocrine and autonomic functions, in relation to neurochemical, behavioral, and somatic consequences of drug abuse.

Specification of distinct dopaminergic neural pathways: roles of the Eph family receptor EphB1 and ligand ephrin-B2.

Dopaminergic neurons in the substantia nigra and ventral tegmental area project to the caudate putamen and nucleus accumbens/olfactory tubercle, respectively, constituting mesostriatal and mesolimbic pathways. The molecular signals that confer target specificity of different dopaminergic neurons are not known. We now report that EphB1 and ephrin-B2, a receptor and ligand of the Eph family, are candidate guidance molecules for the development of these distinct pathways. EphB1 and ephrin-B2 are expressed in complementary patterns in the midbrain dopaminergic neurons and their targets, and the ligand specifically inhibits the growth of neurites and induces the cell loss of substantia nigra, but not ventral tegmental, dopaminergic neurons. These studies suggest that the ligand-receptor pair may contribute to the establishment of distinct neural pathways by selectively inhibiting the neurite outgrowth and cell survival of mistargeted neurons. In addition, we show that ephrin-B2 expression is upregulated by cocaine and amphetamine in adult mice, suggesting that ephrin-B2/EphB1 interaction may play a role in drug-induced plasticity in adults as well.