Connexins in lymphatic vessel physiology and disease.

Connexins are transmembrane proteins that form gap junction- and hemi-channels. Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of ions and small molecules (<1kDa) between the extracellular space and the cytosol. Gap junction channels allow diffusion of similar molecules between the cytoplasms of adjacent cells. The expression and function of connexins in blood vessels has been intensely studied in the last few decades. In contrast, only a few studies paid attention to lymphatic vessels; convincing in vivo data with respect to expression patterns of lymphatic connexins and their functional roles have only recently begun to emerge. Interestingly, mutations in connexin genes have been linked to diseases of lymphatic vasculature, most notably primary and secondary lymphedema. This review summarizes the available data regarding lymphatic connexins. More specifically it addresses (i) early studies aimed at presence of gap junction-like structures in lymphatic vessels, (ii) more recent studies focusing on lymphatic connexins using genetically engineered mice, and (iii) results of clinical studies that have reported lymphedema-linked mutations in connexin genes.

Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers.

MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.

Multi-parametric evaluation of sit-to-stand and stand-to-sit transitions in elderly people.

The aim of this study was to extract multi-parametric measures characterizing different features of sit-to-stand (Si-St) and stand-to-sit (St-Si) transitions in older persons, using a single inertial sensor attached to the chest. Investigated parameters were transition's duration, range of trunk tilt, smoothness of transition pattern assessed by its fractal dimension, and trunk movement's dynamic described by local wavelet energy. A measurement protocol with a Si-St followed by a St-Si postural transition was performed by two groups of participants: the first group (N=79) included Frail Elderly subjects admitted to a post-acute rehabilitation facility and the second group (N=27) were healthy community-dwelling elderly persons. Subjects were also evaluated with Tinetti's POMA scale. Compared to Healthy Elderly persons, frail group at baseline had significantly longer Si-St (3.85±1.04 vs. 2.60±0.32, p=0.001) and St-Si (4.08±1.21 vs. 2.81±0.36, p=0.001) transition's duration. Frail older persons also had significantly decreased smoothness of Si-St transition pattern (1.36±0.07 vs. 1.21±0.05, p=0.001) and dynamic of trunk movement. Measurements after three weeks of rehabilitation in frail older persons showed that smoothness of transition pattern had the highest improvement effect size (0.4) and discriminative performance. These results demonstrate the potential interest of such parameters to distinguish older subjects with different functional and health conditions.

IVA in addition to BMD can change the osteoporosis management in 25% of clinical routine patients

Introduction Vertebral fracture is one of the major osteoporoticfractures which are unfortunately very often undetected. In addition,it is well known that prevalent vertebral fracture increases dramaticallythe risk of future additional fracture. Instant Vertebral Assessment(IVA) has been introduced in DXA device a couple of years ago toease the detection of such fracture when routine DXA are performed.To correctly use such tool, ISCD provided clinical recommendationon when and how to use it. The aim of our study was to evaluate theISCD guidelines in clinical routine patients and see how often itmay change of patient management.Methods During two months (March and April 2010), a medicalquestionnaire was systematically given to our clinical routine patientto check the validity of ISCD IVA recommendations in our population.In addition, all women had BMD measurement at AP spine,femur and 1/3 radius using a Discovery A System (Hologic, Waltham,USA). When appropriate, IVA measurement had been performedon the same DXA system and had been centrally evaluated by twotrained doctors for fracture status according to the semi-quantitativemethod of Genant. The reading had been performed when possiblebetween L5 and T4.Results Out of 210 women seen in the consultation, 109 (52 %)of them (mean age 68.2 ± 11.5 years) fulfilled the necessary criteriato have an IVA measurement. Out of these 109 women, 43 (incidence39.4 %) had osteoporosis at one of the three skeletal sitesand 31 (incidence 28.4 %) had at least one vertebral fracture. 14.7 %of women had both osteoporosis and at least one vertebral fractureclassifying them as "severe osteoporosis" while 46.8 % did not haveosteoporosis and no vertebral fracture. 24.8 % of the women hadosteoporosis but no vertebral fracture while 13.8 % of women didhave osteoporosis but vertebral fracture (clinical osteoporosis).Conclusions In 52 % of our patients, IVA was needed accordingto ISCD criteria. In half of them the IVA test influenced of patientmanagement either may changing the type of treatment of simplyby classifying patient as "clinical osteoporosis". IVA appears to bean important tool in clinical routine but unfortunately is not yetvery often use in most of the centers.

How robust are global conservation priorities to climate change?

International conservation organisations have identified priority areas for biodiversity conservation. These global-scale prioritisations affect the distribution of funds for conservation interventions. As each organisation has a different focus, each prioritisation scheme is determined by different decision criteria and the resultant priority areas vary considerably. However, little is known about how the priority areas will respond to the impacts of climate change. In this paper, we examined the robustness of eight global-scale prioritisations to climate change under various climate predictions from seven global circulation models. We developed a novel metric of the climate stability for 803 ecoregions based on a recently introduced method to estimate the overlap of climate envelopes. The relationships between the decision criteria and the robustness of the global prioritisation schemes were statistically examined. We found that decision criteria related to level of endemism and landscape fragmentation were strongly correlated with areas predicted to be robust to a changing climate. Hence, policies that prioritise intact areas due to the likely cost efficiency, and assumptions related to the potential to mitigate the impacts of climate change, require further examination. Our findings will help determine where additional management is required to enable biodiversity to adapt to the impacts of climate change

NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?

The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and IL-18. The NLRP3 inflammasome is activated by a wide range of danger signals that derive not only from microorganisms but also from metabolic dysregulation. It is unclear how these highly varied stress signals can be detected by a single inflammasome. In this Opinion article, we review the different signalling pathways that have been proposed to engage the NLRP3 inflammasome and suggest a model in which one of the crucial elements for NLRP3 activation is the generation of reactive oxygen species (ROS).

Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes.

NOD2 functions as an intracellular sensor for microbial pathogen and plays an important role in epithelial defense. The loss-of-function mutation of NOD2 is strongly associated with human Crohn's disease (CD). However, the mechanisms of how NOD2 maintains the intestinal homeostasis and regulates the susceptibility of CD are still unclear. Here we found that the numbers of intestinal intraepithelial lymphocytes (IELs) were reduced significantly in Nod2(-/-) mice and the residual IELs displayed reduced proliferation and increased apoptosis. Further study showed that NOD2 signaling maintained IELs via recognition of gut microbiota and IL-15 production. Notably, recovery of IELs by adoptive transfer could reduce the susceptibility of Nod2(-/-) mice to the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Our results demonstrate that recognition of gut microbiota by NOD2 is important to maintain the homeostasis of IELs and provide a clue that may link NOD2 variation to the impaired innate immunity and higher susceptibility in CD.

15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer.

PURPOSE: We have investigated the expression and regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer. EXPERIMENTAL DESIGN: Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines. RESULTS: In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E(2) production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues (n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210). CONCLUSIONS: 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.

Can neurally adjusted ventilatory assist (NAVA) improve patient-ventilator interaction? A preliminary study

INTRODUCTION. NAVA is a new spontaneous-assisted ventilatory mode based on thedetection of diaphragmatic electrical activity (Eadi) and its feedback to adjust ventilatorsettings. NAVA uses the Eadi, an expression of the respiratory center's activity, to initiatepressurization, set the level of pressure support and cycle the ventilator into exhalation.Therefore, NAVA should theoretically allow near-perfect synchronization between the patientand the ventilator. However there are few data documenting these effects in intensive carepatients.OBJECTIVES. To determine whether NAVA can improve patient-ventilator synchronycompared to standard pressure support (PS) in intubated intensive care patients.METHODS. Comparative study of patient-ventilator interaction during PS with cliniciandetermined ventilator settings and NAVA with NAVA gain (proportionality factor betweenEadi and the amount of delivered inspiratory pressure) set as to obtain the same peak airwaypressure as the total pressure obtained in PS. A 20 min continuous recording with eachventilatory mode was performed allowing determination of trigger delay (Td), patient neuralinspiratory time (Tin), duration of pressurization by the ventilator (Tiv), excess durationof pressurization (Ti excess = Tiv - Tin/Tin 9 100) and number of asynchrony events byminute: non-triggering breaths, auto-triggering, double triggering, premature and delayedcycling.Results are given in mean ± SD. p is considered significant if\0.05.RESULTS. Preliminary results (mean ± SD): five patients (age 75 ± 12 years, 1 M/4F,BMI 25.7 ± 4.1 kg m-2), two pts with COPD, 1 with restrictive disease, initial settings: PS14.6 ± 1.7 cm H2O, PEEP 6.4 ± 1.5 cm H2O, NAVA gain 2.8 ± 1.3PS NAVA % reduction NAVAversus PSTd (ms) 210.4 ± 63.0 51.8 ± 12.1* 74.5 ± 5.0Ti excess (%) 12.9 ± 19.6 2.2 ± 0.6 70.8 ± 37.8n asynchrony/minute 7.6 ± 6.4 4.1 ± 3.7* 47.5 ± 17.0Respiratory rate (min-1) 16.8 ± 2.6 20.4 ± 4.7 NA* p\0.05CONCLUSION. Compared to standard PS, NAVA improves patient ventilator interaction byreducing Td and the overall incidence of asynchrony events. There is also a strong trend inreducing delayed cycling. This ongoing trial should provide evidence that NAVA can indeedimprove patient-ventilator synchrony in intubated patients undergoing PS.REFERENCE(S). 1. Sinderby C, Navalesi P et al (1995) Neural control of mechanicalventilation in respiratory failure. Nat Med 5(12):1433-1436.2. Colombo D, Cammarota G et al (2008) Physiologic response to varying levels of pressuresupport and neurally adjusted ventilator assist in patients with acute respiratory failure.Intensive Care Med 34(11):2010-2018.

Colour-polymorphic snake species are older

Many characteristics, for example life-history traits, physiological tolerance to heat and cold, and energy requirements, contribute to a population's ability to persist in the face of climatic variation. Recent studies have suggested that the presence of intraspecific colour polymorphism could be another potential contributor to population resilience (e.g. to climate change) in ectothermic vertebrates such as reptiles. In the present study, we tested for a relationship between the presence of intraspecific colour polymorphism and the age of snake species. Using phylogenetic comparative methods, we demonstrate that the presence of intraspecific colour polymorphism is correlated with the age of a species, with polymorphic snake species being significantly older than monomorphic species. Understanding how species have dealt with past environmental modifications, such as climate change, can provide important insights into how they are likely to respond in the future to ongoing climate warming.

Marked increase of the astrocytic marker S100B in the cerebrospinal fluid of HIV-infected patients on LPV/r-monotherapy.

OBJECTIVE: To determine changes of cerebrospinal fluid (CSF) biomarkers of patients on monotherapy with lopinavir/ritonavir. DESIGN: The Monotherapy Switzerland/Thailand study (MOST) trial compared monotherapy with ritonavir-boosted lopinavir with continued therapy. The trial was prematurely stopped due to virological failure in six patients on monotherapy. It, thus, offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. METHODS: : Sixty-five CSF samples (34 on continued therapy and 31 on monotherapy) from 49 HIV-positive patients enrolled in MOST. Using enzyme-linked immunosorbent assay, we determined the CSF concentration of S100B (astrocytosis), neopterin (inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-β 1-42 (Aβ), the latter three indicating neuronal damage. Controls were CSF samples of 29 HIV-negative patients with Alzheimer dementia. RESULTS: In the CSF of monotherapy, concentrations of S100B and neopterin were significantly higher than in continued therapy (P = 0.006 and P = 0.013, respectively) and Alzheimer dementia patients (P < 0.0001 and P = 0.0005, respectively). In Alzheimer dementia, concentration of Aβ was lower than in monotherapy (P = 0.005) and continued therapy (P = 0.016) and concentrations of tTau were higher than in monotherapy (P = 0.019) and continued therapy (P = 0.001). There was no difference in pTau among the three groups. After removal of the 16 CSF with detectable viral load in the blood and/or CSF, only S100B remained significantly higher in monotherapy than in the two other groups. CONCLUSION: Despite full viral load-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

2q34-qter duplication and 4q34.2-qter deletion in a patient with developmental delay.

The 2q3 duplication and 4q3 deletion syndromes are two conditions with variable phenotypes including Pierre-Robin sequence (PRS), limb anomalies, congenital heart defects (CHD), developmental delays and intellectual disabilities. We describe a patient born to a mother with a balanced t(2; 4) translocation who combines both a 2q34-qter duplication and a 4q34.2-qter deletion through inheritance of the derivative chromosome 4 (der(4)). He showed developmental delay, growth retardation, hearing problems, minor facial and non-facial anomalies, such as bilateral fifth finger shortness and clinodactyly, but no PRS or CHD. The comparison of his features with those of 46 and 65 published cases of 2q3 duplication and 4q3 deletion, respectively, allows us to further restrict the size of the proposed critical intervals for PRS and CHD on chromosome 4.

Chirurgie [Trends in surgery]

More than the number of real novelties, trends and preliminary results characterise the annual development in surgery. The wealth and diversity of topics to be covered require arbitrary choices, therefore not necessarily complete. The constant development of choledocolithiasis management, dominated by minimal invasive technology, treatments of unusual nature of two frequent proctological conditions, fistulae and haemorrhoids, the increasing importance of metabolic bariatric surgery, as well as the strict rules of effective melanoma treatment, represent as many directions in which the operating procedure, although unseen, continue to gain quality and security.

What is the relationship between fear of falling and gait in well-functioning older persons aged 65 to 70 years?

OBJECTIVE: To investigate the association between fear of falling and gait performance in well-functioning older persons. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Subjects (N=860, aged 65-70y) were a subsample of participants enrolled in a cohort study who underwent gait measurements. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fear of falling and its severity were assessed by 2 questions about fear and related activity restriction. Gait performance, including gait variability, was measured using body-fixed sensors. RESULTS: Overall, 29.6% (210/860) of the participants reported fear of falling, with 5.2% (45/860) reporting activity restriction. Fear of falling was associated with reduced gait performance, including increased gait variability. A gradient in gait performance was observed from participants without fear to those reporting fear without activity restriction and those reporting both fear and activity restriction. For instance, stride velocity decreased from 1.15+/-.15 to 1.11+/-.17 to 1.00+/-.19 m/s (P<.001) in participants without fear, with fear but no activity restriction and with fear and activity restriction, respectively. In multivariate analysis, fear of falling with activity restriction remained associated with reduced gait performance, independent of sex, comorbidity, functional status, falls history, and depressive symptoms. CONCLUSIONS: In these well-functioning older people, those reporting fear of falling with activity restriction had reduced gait performance and increased gait variability, independent of health and functional status. These relationships suggest that early interventions targeting fear of falling might potentially help to prevent its adverse consequences on mobility and function in similar populations.

Fractures dorsales du triquetrum : avulsion ou conflit ulno-carpien? Aspects IRM 3T et lésions associées.

Objectifs: Déterminer les caractéristiques en IRM 3T et discuter l'étiologie des fractures dorsales du triquetrum. Evaluer les lésions associées, notamment des ligamentsextrinsèques dorsaux.Matériels et méthodes: Etude rétrospective (septembre 2007 - décembre 2010) incluant 18 patients avec radiographies conventionnelles et IRM du poignet à 3T présentant une fracturedorsale du triquetrum. Protocole IRM comprenant une séquence T1-VIBE coronale haute résolution (0,3mm) isotropique avec suppression de graisse et aprèsinjection intraveineuse de Gadolinium. Lecture consensuelle par 2 radiologues évaluant les caractéristiques suivantes : taille et déplacement du fragment osseux,localisation de l'oedème médullaire, lésion des ligaments extrinsèques dorsaux (radio-triquetral, scapho-triquetral et ulno-triquetral), autres lésions associées.Inclusion d'un groupe contrôle de 20 patients, afin d'évaluer localisation et visibilité des enthèses ligamentaires extrinsèques dorsales .Résultats: Identification de 14 lésions ligamentaires scapho-triquetrales, 12 ulno-triquetrales et 8 radio-triquetrales, corrélées à la localisation de l'oedème osseux. Absenced'oedème de la styloïde ulnaire évocatrice de conflit. Volume moyen des fragments de 210 mm3, avec déplacement le plus fréquemment distal. Dans le groupecontrôle, visibilité des ligaments scapho-triquetral, radio-triquetral et ulno-triquetral dans respectivement 100% (20/20), 90% (18/20) et 70% (14/20) des cas.Conclusion: L'IRM 3T permet d'évaluer précisément les fractures dorsales du triquetrum et leurs lésions associées , y compris la distribution des oedèmes osseux. Cesfractures auraient donc une étiologie mixte.