A gating mutation in the internal pore of ASIC1a.

Using a substituted cysteine accessibility scan, we have investigated the structures that form the internal pore of the acid-sensing ion channel 1a. We have identified the amino acid residues Ala-22, Ile-33, and Phe-34 in the amino terminus and Arg-43 in the first transmembrane helix, which when mutated into cysteine, were modified by intracellular application of MTSET, resulting in channel inhibition. The inhibition of the R43C mutant by internal MTSET requires opening of the channel. In addition, binding of Cd2+ ions to R43C slows the channel inactivation. This indicates that the first transmembrane helix undergoes conformational changes during channel inactivation. The effect of Cd2+ on R43C can be obtained with Cd2+ applied at either the extracellular or the intracellular side, indicating that R43C is located in the channel pore. The block of the A22C, I33C, and F34C mutants by MTSET suggests that these residues in the amino terminus of the channel also participate to the internal pore.

Relève en médecine interne générale: enjeux et perspectives [Perspectives and challenges to guarantee training and renewal in general internal medicine]

Training new doctors in general internal medicine represents a challenge. This requires to define future needs, which result from interest that are not necessarily convergent between patients, doctors, insurers and politicians. Problems related to medical demography in Switzerland, with the ageing of the population, the increase in health care costs and the place of Switzerland within the European Community require the implementation of specific objectives to train new physicians in general internal medicine. The success of these opportunities depends on social factors, political choices and choices from physician's association. In this article we will approach these challenges by formulating some proposals--nonexhaustive--in order to guarantee sufficient renewal in general internal medicine.

The Four Different Types of Internal Hernia Occurring After Laparascopic Roux-en-Y Gastric Bypass Performed for Morbid Obesity: Are There Any Multidetector Computed Tomography (MDCT) Features Permitting Their Distinction?

BACKGROUND: Four different types of internal hernias (IH) are known to occur after laparoscopic Roux-en-Y gastric bypass (LRYGBP) performed for morbid obesity. We evaluate multidetector row helical computed tomography (MDCT) features for their differentiation. METHODS: From a prospectively collected database including 349 patients with LRYGBP, 34 acutely symptomatic patients (28 women, mean age 32.6), operated on for IH immediately after undergoing MDCT, were selected. Surgery confirmed 4 (11.6%) patients with transmesocolic, 10 (29.4%) with Petersen's, 15 (44.2%) with mesojejunal, and 5 (14.8%) with jejunojejunal IH. In consensus, 2 radiologists analyzed 13 MDCT features to distinguish the four types of IH. Statistical significance was calculated (p < 0.05, Fisher's exact test, chi-square test). RESULTS: MDCT features of small bowel obstruction (SBO) (n = 25, 73.5%), volvulus (n = 22, 64.7%), or a cluster of small bowel loops (SBL) (n = 27, 79.4%) were inconsistently present and overlapped between the four IH. The following features allowed for IH differentiation: left upper quadrant clustered small bowel loops (p < 0.0001) and a mesocolic hernial orifice (p = 0.0003) suggested transmesocolic IH. SBL abutting onto the left abdominal wall (p = 0.0021) and left abdominal shift of the superior mesenteric vessels (SMV) (p = 0.0045) suggested Petersen's hernia. The SMV predominantly shifted towards the right anterior abdominal wall in mesojejunal hernia (p = 0.0033). Location of the hernial orifice near the distal anastomosis (p = 0.0431) and jejunojejunal suture widening (p = 0.0005) indicated jejunojejunal hernia. CONCLUSIONS: None of the four IH seems associated with a higher risk of SBO. Certain MDCT features, such as the position of clustered SBL and hernial orifice, help distinguish between the four IH and may permit straightforward surgery.

Evolutionary and biomedical consequences of internal melanins.

The adaptive function of melanin located in the integument is well known. Although pigments are also deposited in various internal organs, their function is unclear. A review of the literature revealed that 'internal melanin' protects against parasites, pollutants, low temperature, oxidative stress, hypoxemia and UV light, and is involved in the development and function of organs. Importantly, several studies have shown that the amount of melanin deposited on the external body surface is correlated with the amount located inside the body. This finding raises the possibility that internal melanin plays more important physiological roles in dark than light-colored individuals. Internal melanin and coloration may therefore not evolve independently. This further emphasizes the major role played by indirect selection in evolutionary processes.

Advantages of a modified gastroscope for video-assisted internal mammary artery harvesting.

Instead of standard rigid thoracoscopes, we used a modified gastroscope for video assistance during 12 minimally invasive left internal mammary harvesting. Flexibility and remote control of its last centimeters give to the gastroscope a total freedom of movements, and perfect positioning in every direction. The scope is equipped with cold light, a suction canal and an irrigation canal, which allow for in situ washing without needing to remove it from the thoracic cavity. Thanks to these advantages, vision and lighting are always perfect.

Membership and internal democracy. Immigrant organisations in the city of Oslo

Immigrant organisations in the City of Oslo receive support from the government for their daily operation. In order to receive such support, each organisation must be membership-based and have internal democratic procedures. This paper raises the question of how we can understand this combination of support for ethnic based organisations and requirements of membership and internal democracy. It explores the usefulness of two partly overlapping ways of understanding this policy and discusses their interrelationship. Firstly, within the context of the crisis of multiculturalism, the paper discusses whether this combination is based on the aim of strengthening the organisations’ procedural commitment to liberal-democratic principles. Secondly, the paper analyses whether requirements of membership and internal democracy can mainly be understood within the framework of the Nordic model of voluntary organisation. By comparing the policy at three empirical levels, the paper concludes that this combination can mainly be understood within the framework of the traditional historical Nordic model, but that there is an ambiguity in this policy related to minority rights.

Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns.

BACKGROUND: Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. METHODS: We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay. RESULTS: Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. CONCLUSIONS: IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Intraoral open reduction and internal fixation of displaced mandibular angle fractures using a specific ad hoc reduction-compression forceps: a preliminary study

OBJECTIVES: To preliminarily evaluate prospectively the accuracy and reliability of a specific ad hoc reduction-compression forceps in intraoral open reduction of transverse and displaced mandibular angle fractures. STUDY DESIGN: We analyzed the clinical and radiologic data of 7 patients with 7 single transverse and displaced angle fractures. An intraoral approach was performed in all of the patients without using perioperative intermaxillary fixation. A single Arbeitsgemeinschaft Osteosynthese (AO) unilock reconstruction plate was fixed to each stable fragment with 3 locking screws (2.0 mm in 5 patients and 2.4 mm in 2 patients) at the basilar border of the mandible, according to AO/American Society of Internal Fixation (ASIF) principles. Follow-up was at 1, 3, 6, and 12 months, and we noted the status of healing and complications, if any. RESULTS: All of the patients had satisfactory fracture reduction as well as a successful treatment outcome without complications. CONCLUSION: This preliminary study demonstrated that the intraoral reduction of transverse and displaced angle fractures using a specific ad hoc reduction-forceps results in a high rate of success.

Discovery of Dogger in the internal limestone dorsale to the S of Tetouan (Northern Rif, Morocco) - Paleogeographic consequences

The Dogger (Bajocian-Lower Bathonian) has been dated for the first time in the internal Limestone Dorsale of the Rif by means of ammonites and radiolarians. It shows radiolarian and nodular limestone facies. It is concluded, then, that radiolarian sedimentation began during the Dogger in this realm, and that a drowning of the `'Ghomaride margin'' occurred at that time.

Aging and the lateralization of oscillatory activities related to external and internal motor preparation

Selection of action may rely on external guidance or be motivated internally, engaging partially distinct cerebral networks. With age, there is an increased allocation of sensorimotor processing resources, accompanied by a reduced differentiation between the two networks of action selection. The present study examines the age effects on the motor-related oscillatory patterns related to the preparation of externally and internally guided movements. Thirty-two older and 30 younger adults underwent three delayed motor tasks with S1 as preparatory and S2 as imperative cue: Full, laterality instructed by S1 (external guidance); Free, laterality freely selected (internal guidance); None, laterality instructed by S2 (no preparation). Electroencephalogram (EEG) was recorded using 64 surface electrodes. Motor-Related Amplitude Asymmetries (MRAA), indexing the lateralization of oscillatory activities, were analyzed within the S1-S2 interval in the mu (9-12 Hz) and low beta (15-20 Hz) motor-related frequency bands. Reaction times to S2 were slower in older than younger subjects, and slower in the Free than in the Full condition in older subjects only. In the Full condition, there were significant mu MRAA in both age groups, and significant low beta MRAA only in older adults. The Free condition was associated with large mu MRAA in younger adults and limited low beta MRAA in older adults. In younger subjects, the lateralization of mu activity in both Full and Free conditions indicated effective external and internal motor preparation. In older subjects, external motor preparation was associated with lateralization of low beta in addition with mu activity, compatible with an increase of motor-related resources. In contrast, absence of mu and limited low beta lateralization in internal motor preparation was concomitant with reaction time slowing and suggested less efficient cerebral processes subtending free movement selection in older adults, indicating reduced capacity for internally driven action with age.

Teaching cardiac auscultation to trainees in internal medicine and family practice: does it work?

BACKGROUND: The general proficiency in physical diagnostic skills seems to be declining in relation to the development of new technologies. The few studies that have examined this question have invariably used recordings of cardiac events obtained from patients. However, this type of evaluation may not correlate particularly well with bedside skills. Our objectives were 1) To compare the cardiac auscultatory skills of physicians in training with those of experienced cardiologists by using real patients to test bedside diagnostic skills. 2) To evaluate the impact of a five-month bedside cardiac auscultation training program. METHODS: 1) In an academic primary care center, 20 physicians (trainees in internal medicine and family practice) and two skilled academic cardiologists listened to 33 cardiac events in 13 patients directly at bedside and identified the cardiac events by completing an open questionnaire. Heart sounds, murmurs and diagnosis were determined beforehand by an independent skilled cardiologist and were validated by echocardiography. Thirteen primary cardiologic diagnoses were possible.2) Ten of the physicians agreed to participate in a course of 45-minute sessions once a week for 5 months. After the course they listened again to the same patients (pre/post-interventional study). RESULTS: 1) The experts were the most skillful, achieving 69% recognition of heart sounds and murmurs and correct diagnoses in 62% of cases. They also heard all of the diastolic murmurs. The residents heard only 40% of the extra heart sounds and made a correct diagnosis in 24% of cases. 2) After the weekly training sessions, their mean percentage for correct diagnosis was 35% [an increase of 66% (p < 0.05)]. CONCLUSIONS: The level of bedside diagnostic skills in this relatively small group of physicians in training is indeed low, but can be improved by a course focusing on realistic bedside teaching.