A comparison between joint coordinate system and attitude vector for multi-segment foot kinematics.

The joint angles of multi-segment foot models have been primarily described using two mathematical methods: the joint coordinate system and the attitude vector. This study aimed to determine whether the angles obtained through these two descriptors are comparable, and whether these descriptors have similar sensitivity to experimental errors. Six subjects walked eight times on an instrumented walkway while the joint angles among shank, hindfoot, medial forefoot, and lateral forefoot were measured. The angles obtained using both descriptors and their sensitivity to experimental errors were compared. There was no overall significant difference between the ranges of motion obtained using both descriptors. However, median differences of more than 6° were noticed for the medial-lateral forefoot joint. For all joints and rotation planes, both descriptors provided highly similar angle patterns (median correlation coefficient: R>0.90), except for the medial-lateral forefoot angle in the transverse plane (median R=0.77). The joint coordinate system was significantly more sensitive to anatomical landmarks misplacement errors. However, the absolute differences of sensitivity were small relative to the joints ranges of motion. In conclusion, the angles obtained using these two descriptors were not identical, but were similar for at least the shank-hindfoot and hindfoot-medial forefoot joints. Therefore, the angle comparison across descriptors is possible for these two joints. Comparison should be done more carefully for the medial-lateral forefoot joint. Moreover, despite different sensitivities to experimental errors, the effects of the experimental errors on the angles were small for both descriptors suggesting that both descriptors can be considered for multi-segment foot models.

Creatine, central nervous system and creatine deficiency syndromes

It was long thought that most of brain creatine was of peripheral origin. However, recentworks have demonstrated that creatine crosses blood-brain barrier only with poor efficiency, and thatCNS must ensure parts of its creatine needs by its own creatine synthesis pathway, thank to the brainexpression of AGAT and GAMT (creatine synthesis) and SLC6A8 (creatine transporter). This newunderstanding of creatine metabolism and transport in CNS allows a better comprehension of creatinedeficiency syndromes, which are due to deficiencies in AGAT, GAMT and SLC6A8 and mainly affectthe brain of patients who show severe neurodevelopmental delay and present neurological symptomsin early infancy.

Accès à la thrombolyse lors d'AVC: rôle des secours préhospitaliers et des médecins de premier recours [Access to thrombolysis in stroke: place of the rescue system and of the primary care physician].

Thrombolysis is the most effective treatment improving the outcome of patients suffering from acute stroke. Moreover, its effectiveness increases when administrated as quick as possible after the onset of the first symptoms. Prehospital selection of patients and their immediate transfer to stroke center are the principal factors allowing the practice of thrombolysis within the authorized time frame. On the basis of regional Swiss French data, it seems that patients evaluated by emergency physician and their direct transfer in an acute stroke unit reduces delays and allows for a higher thrombolysis rate.

Performance comparison of an active matrix flat panel imager, computed radiography system, and a screen-film system at four standard radiation qualities.

Four standard radiation qualities (from RQA 3 to RQA 9) were used to compare the imaging performance of a computed radiography (CR) system (general purpose and high resolution phosphor plates of a Kodak CR 9000 system), a selenium-based direct flat panel detector (Kodak Direct View DR 9000), and a conventional screen-film system (Kodak T-MAT L/RA film with a 3M Trimax Regular screen of speed 400) in conventional radiography. Reference exposure levels were chosen according to the manufacturer's recommendations to be representative of clinical practice (exposure index of 1700 for digital systems and a film optical density of 1.4). With the exception of the RQA 3 beam quality, the exposure levels needed to produce a mean digital signal of 1700 were higher than those needed to obtain a mean film optical density of 1.4. In spite of intense developments in the field of digital detectors, screen-film systems are still very efficient detectors for most of the beam qualities used in radiology. An important outcome of this study is the behavior of the detective quantum efficiency of the digital radiography (DR) system as a function of beam energy. The practice of users to increase beam energy when switching from a screen-film system to a CR system, in order to improve the compromise between patient dose and image quality, might not be appropriate when switching from screen-film to selenium-based DR systems.

The TetR-type MfsR protein of the integrative and conjugative element (ICE) ICEclc controls both a putative efflux system and initiation of ICE transfer.

Integrative and conjugating elements (ICE) are self-transferable DNAs widely present in bacterial genomes, which often carry a variety of auxiliary genes of potential adaptive benefit. One of the model ICE is ICEclc, an element originally found in Pseudomonas knackmussii B13 and known for its propensity to provide its host with the capacity to metabolize chlorocatechols and 2-aminophenol. In this work, we studied the mechanism and target of regulation of MfsR, a TetR-type repressor previously found to exert global control on ICEclc horizontal transfer. By using a combination of ICEclc mutant and transcriptome analysis, gene reporter fusions, and DNA binding assays, we found that MfsR is a repressor of both its own expression and that of a gene cluster putatively coding for a major facilitator superfamily efflux system on ICEclc (named mfsABC). Phylogenetic analysis suggests that mfsR was originally located immediately adjacent to the efflux pump genes but became displaced from its original cis target DNA by a gene insertion. This resulted in divergence of the original bidirectional promoters into two separated individual regulatory units. Deletion of mfsABC did not result in a strong phenotype, and despite screening a large number of compounds and conditions, we were unable to define the precise current function or target of the putative efflux pump. Our data reconstruct how the separation of an ancestor mfsR-mfsABC system led to global control of ICEclc transfer by MfsR.

Uric acid transport and disease.

Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.

Breeding system and genetic variance in the monogamous, semi-social shrew, Crocidura russula

The population-genetic consequences of monogamy and male philopatry (a rare breeding system in mammals) were investigated using microsatellite markers in the semisocial and anthropophilic shrew Crocidura russula. A hierarchical sampling design over a 16-km geographical transect revealed a large genetic diversity (h = 0.813) with significant differentiation among subpopulations (F-ST = 5-6%), which suggests an exchange of 4.4 migrants per generation. Demic effective-size estimates were very high, due both to this limited gene inflow and to the inner structure of subpopulations. These were made of 13-20 smaller units (breeding groups), comprising an estimate of four breeding pairs each. Members of the same breeding groups displayed significant coancestries (F-LS = 9-10%), which was essentially due to strong male kinship: syntopic males were on average related at the half-sib level. Female dispersal among breeding groups was not complete (similar to 39%), and insufficient to prevent inbreeding. From our results, the breeding strategy of C. russula seems less efficient than classical mammalian systems (polygyny and male dispersal) in disentangling coancestry from inbreeding, but more so in retaining genetic variance.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

Epithelial to mesenchymal transition in the pathogenesis of uterine malignant mixed Müllerian tumours: the role of ubiquitin proteasome system and therapeutic opportunities.

Malignant mixed Müllerian tumours (malignant mixed mesodermal tumours, MMMT) of the uterus are metaplastic carcinomas with a sarcomatous component and thus they are also called carcinosarcomas. It has now been accepted that the sarcomatous component is derived from epithelial elements that have undergone metaplasia. The process that produces this metaplasia is epithelial to mesenchymal transition (EMT), which has recently been described as a neoplasia-associated programme shared with embryonic development and enabling neoplastic cells to move and metastasise. The ubiquitin proteasome system (UPS) regulates the turnover and functions of hundreds of cellular proteins. It plays important roles in EMT by being involved in the regulation of several pathways participating in the execution of this metastasis-associated programme. In this review the specifi c role of UPS in EMT of MMMT is discussed and therapeutic opportunities from UPS manipulations are proposed.

Roles of PPARs in health and disease.

In developed societies, chronic diseases such as diabetes, obesity, atherosclerosis and cancer are responsible for most deaths. These ailments have complex causes involving genetic, environmental and nutritional factors. There is evidence that a group of closely related nuclear receptors, called peroxisome proliferator-activated receptors (PPARs), may be involved in these diseases. This, together with the fact that PPAR activity can be modulated by drugs such as thiazolidinediones and fibrates, has instigated a huge research effort into PPARs. Here we present the latest developments in the PPAR field, with particular emphasis on the physiological function of PPARs during various nutritional states, and the possible role of PPARs in several chronic diseases.

PPAR modulation of kinase-linked receptor signaling in physiology and disease.

Kinase-linked receptors and nuclear receptors connect external cues to gene transcription. Among nuclear receptors, peroxisome proliferator-activated receptors (PPARs) are of special interest in relation to widespread human diseases. Mapping out connections between PPARs and kinase-linked receptor signaling is central to better understand physiological and pathophysiological processes and to better define therapeutic strategies. This is the aim of the present review.

Measures of health and disease in Africa: are current methods giving us useful information about trends in cardiovascular diseases?

An enormous burst of interest in the public health burden from chronic disease in Africa has emerged as a consequence of efforts to estimate global population health. Detailed estimates are now published for Africa as a whole and each country on the continent. These data have formed the basis for warnings about sharp increases in cardiovascular disease (CVD) in the coming decades. In this essay we briefly examine the trajectory of social development on the continent and its consequences for the epidemiology of CVD and potential control strategies. Since full vital registration has only been implemented in segments of South Africa and the island nations of Seychelles and Mauritius - formally part of WHO-AFRO - mortality data are extremely limited. Numerous sample surveys have been conducted but they often lack standardization or objective measures of health status. Trend data are even less informative. However, using the best quality data available, age-standardized trends in CVD are downward, and in the case of stroke, sharply so. While acknowledging that the extremely limited available data cannot be used as the basis for inference to the continent, we raise the concern that general estimates based on imputation to fill in the missing mortality tables may be even more misleading. No immediate remedies to this problem can be identified, however bilateral collaborative efforts to strength local educational institutions and governmental agencies rank as the highest priority for near term development.