Force measurements with optical tweezers inside living cells

The force exerted by optical tweezers can be measured by tracking the momentum changes of the trapping beam, a method which is more general and powerful than traditional calibration techniques as it is based on first principles, but which has not been brought to its full potential yet, probably due to practical difficulties when combined with high-NA optical traps, such as the necessity to capture a large fraction of the scattered light. We show that it is possible to measure forces on arbitrary biological objects inside cells without an in situ calibration, using this approach. The instrument can be calibrated by measuring three scaling parameters that are exclusively determined by the design of the system, thus obtaining a conversion factor from volts to piconewtons that is theoretically independent of the physical properties of the sample and its environment. We prove that this factor keeps valid inside cells as it shows good agreement with other calibration methods developed in recent years for viscoelastic media. Finally, we apply the method to measuring the stall forces of kinesin and dynein in living A549 cells.Publisher PD

Are we there yet?:An update on transitional care in rheumatology

Abstract Significant progress has been made in the understanding of transitional care in rheumatology over the last few decades, yet universal implementation has not been realised and unmet needs continue to be reported. Possible explanations for this include lack of evidence as to which model is most effective; lack of attention to the multiple dimensions, stakeholders and systems involved in health transitions; and lack of consideration of the developmental appropriateness of transition interventions and the services/organisations/systems where such interventions are delivered. Successful transition has major implications to both the young people with juvenile-onset rheumatic disease and their families. Future research in this area will need to reflect both the multidimensional (biopsychosocial) and the multisystemic (multiple systems and stakeholders across personal/social/family support networks and health/social care/education systems). Only then will we be able to determine which aspects of transition readiness and service components influence which dimension. It is therefore imperative we continue to research and develop this area, involving both paediatric and adult rheumatology clinicians and researchers, remembering to look beyond both the condition and our discipline. Neither should we forget to tap into the exciting potential associated with digital technology to ensure further advances in transitional care are brought about in and beyond rheumatology

Predictive significance of the six-minute walk distance for long-term survival in chronic hypercapnic respiratory failure

Background: The 6-min walk distance ( 6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease ( COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure ( CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation ( NIV) comprising COPD ( n = 197), restrictive diseases ( RD; n = 112) and obesity-hypoventilation- syndrome ( OHS; n = 115), the prognostic value of 6-MWD for long- term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD ( median 280 m; quartiles 204/350 m) and RD ( 290 m; 204/362 m) compared to OHS ( 360 m; 275/440 m; p <0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s ( p <0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median {[} p <0.001, hazard ratio ( HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long- term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF. Copyright (C) 2007 S. Karger AG, Basel

Telemonitoring in Chronic Obstructive Pulmonary Disease (CHROMED). A Randomized Clinical Trial

Rationale: Early detection of COPD exacerbations using tele-monitoring of physiological variables might reduce the frequency of hospitalisation. Objectives: To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique (FOT) and cardiac parameters in older COPD patients with co-morbidities. Methods: This multicentre, randomized clinical trial recruited 312 GOLD grade II-IV COPD patients (median age 71 years [IQR:66-76], 49.6% grade II, 50.4% grade III-IV), with a history of exacerbation in the previous year and at least one non-pulmonary co-morbidity. Patients were randomised to usual care (n=158) or tele-monitoring (n=154) and followed for 9 months. All tele-monitoring patients self-assessed lung mechanics daily and in a subgroup with congestive heart failure (n=37) cardiac parameters were also monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions. Measurements and Main results: Primary outcomes were time to first hospitalisation (TTFH) and change in EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescriptions, hospitalisation, CAT, PHQ-9 and MLHF questionnaire scores, quality-adjusted life years and healthcare costs. Tele-monitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate and questionnaire scores. In an exploratory analysis, tele-medicine was associated with fewer repeat hospitalizations (-54%, p=0.017). Conclusions: In older COPD patients with co-morbidities remote monitoring of lung function by FOT and cardiac parameters did not change TTFH and EQ-5D. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01960907

EP11.01: Incidence and complications of obstructive sleep apnea in high-risk pregnancies

To describe the incidence during gestation of Obstructive Sleep Apnea (OSA) in cardiometabolic-risk pregnancies and to evaluate pregnancy complications due to OSA in these high-risk pregnancies

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine

Gender Differences in Russian Colour Naming

In the present study we explored Russian colour naming in a web-based psycholinguistic experiment (http://www.colournaming.com). Colour singletons representing the Munsell Color Solid (N=600 in total) were presented on a computer monitor and named using an unconstrained colour-naming method. Respondents were Russian speakers (N=713). For gender-split equal-size samples (NF=333, NM=333) we estimated and compared (i) location of centroids of 12 Russian basic colour terms (BCTs); (ii) the number of words in colour descriptors; (iii) occurrences of BCTs most frequent non-BCTs. We found a close correspondence between females’ and males’ BCT centroids. Among individual BCTs, the highest inter-gender agreement was for seryj ‘grey’ and goluboj ‘light blue’, while the lowest was for sinij ‘dark blue’ and krasnyj ‘red’. Females revealed a significantly richer repertory of distinct colour descriptors, with great variety of monolexemic non-BCTs and “fancy” colour names; in comparison, males offered relatively more BCTs or their compounds. Along with these measures, we gauged denotata of most frequent CTs, reflected by linguistic segmentation of colour space, by employing a synthetic observer trained by gender-specific responses. This psycholinguistic representation revealed females’ more refined linguistic segmentation, compared to males, with higher linguistic density predominantly along the redgreen axis of colour space

Limpet Shells from the Aterian Level 8 of El Harhoura 2 Cave (Témara, Morocco): Preservation State of Crossed-Foliated Layers

International audienceThe exploitation of mollusks by the first anatomically modern humans is a central question for archaeologists. This paper focuses on level 8 (dated around * 100 ka BP) of El Har-houra 2 Cave, located along the coastline in the Rabat-Témara region (Morocco). The large quantity of Patella sp. shells found in this level highlights questions regarding their origin and preservation. This study presents an estimation of the preservation status of these shells. We focus here on the diagenetic evolution of both the microstructural patterns and organic components of crossed-foliated shell layers, in order to assess the viability of further investigations based on shell layer minor elements, isotopic or biochemical compositions. The results show that the shells seem to be well conserved, with microstructural patterns preserved down to sub-micrometric scales, and that some organic components are still present in situ. But faint taphonomic degradations affecting both mineral and organic components are nonetheless evidenced, such as the disappearance of organic envelopes surrounding crossed-foliated lamellae, combined with a partial recrystallization of the lamellae. Our results provide a solid case-study of the early stages of the diagenetic evolution of crossed-foliated shell layers. Moreover, they highlight the fact that extreme caution must be taken before using fossil shells for palaeoenvironmental or geochronological reconstructions. Without thorough investigation, the alteration patterns illustrated here would easily have gone unnoticed. However, these degradations are liable to bias any proxy based on the elemental, isotopic or biochemical composition of the shells. This study also provides significant data concerning human subsistence behavior: the presence of notches and the good preservation state of limpet shells (no dissolution/recrystallization, no bioerosion and no abrasion/fragmentation aspects) would attest that limpets were gathered alive with tools by Middle Palaeolithic (Aterian) populations in North Africa for consumption