Penetratin translocation mechanism through asymmetric droplet interface bilayers.

Penetratin is a cell penetrating peptide (CPP) that can enter cells by direct translocation through the plasma membrane. The molecular mechanism of this translocation still remains poorly understood. Here we provide insights on this mechanism by studying the direct translocation of the peptide across model membranes based on Droplet Interface Bilayers (DIBs), which are bilayers at the interface between two adhering aqueous-in-oil droplets. We first showed with symmetric bilayers made of a mix of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (POPC) that the translocation of penetratin required the presence of at least 40% of POPG on both leaflets. Interestingly when replacing POPG with another anionic lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), translocation was inefficient. To elucidate the lipid partners required at each step of the CPP translocation process, we then investigated the crossing of asymmetric bilayers. We found that POPG on the proximal leaflet and POPS on the distal leaflet allowed penetratin translocation. Translocation was not observed when POPS was on the proximal leaflet and POPG on the distal leaflet or if POPS on the distal leaflet was replaced with POPC. These observations led us to propose a three-step translocation mechanism: (i) peptide recruitment by anionic lipids, (ii) formation of a transient peptide-lipid structure leading to the initiation of translocation which required specifically POPG on the proximal leaflet, (iii) termination of the translocation process favored by a driving force provided by anionic lipids in the distal leaflet.

Combinations of non-invasive indicators to detect dairy cows submitted to high-starch-diet challenge.

High-starch diets (HSDs) fed to high-producing ruminants are often responsible for rumen dysfunction and could impair animal health and production. Feeding HSDs are often characterized by transient rumen pH depression, accurate monitoring of which requires costly or invasive methods. Numerous clinical signs can be followed to monitor such diet changes but no specific indicator is able to make a statement at animal level on-farm. The aim of this pilot study was to assess a combination of non-invasive indicators in dairy cows able to monitor a HSD in experimental conditions. A longitudinal study was conducted in 11 primiparous dairy cows fed with two different diets during three successive periods: a 4-week control period (P1) with a low-starch diet (LSD; 13% starch), a 4-week period with an HSD (P2, 35% starch) and a 3-week recovery period (P3) again with the LSD. Animal behaviour was monitored throughout the experiment, and faeces, urine, saliva, milk and blood were sampled simultaneously in each animal at least once a week for analysis. A total of 136 variables were screened by successive statistical approaches including: partial least squares-discriminant analysis, multivariate analysis and mixed-effect models. Finally, 16 indicators were selected as the most representative of a HSD challenge. A generalized linear mixed model analysis was applied to highlight parsimonious combinations of indicators able to identify animals under our experimental conditions. Eighteen models were established and the combination of milk urea nitrogen, blood bicarbonate and feed intake was the best to detect the different periods of the challenge with both 100% of specificity and sensitivity. Other indicators such as the number of drinking acts, fat:protein ratio in milk, urine, and faecal pH, were the most frequently used in the proposed models. Finally, the established models highlight the necessity for animals to have more than 1 week of recovery diet to return to their initial control state after a HSD challenge. This pilot study demonstrates the interest of using combinations of non-invasive indicators to monitor feed changes from a LSD to a HSD to dairy cows in order to improve prevention of rumen dysfunction on-farm. However, the adjustment and robustness of the proposed combinations of indicators need to be challenged using a greater number of animals as well as different acidogenic conditions before being applied on-farm.

Relative reticulo-rumen pH indicators for subacute ruminal acidosis detection in dairy cows.

Subacute ruminal acidosis (SARA) is usually characterized by abnormal and intermittent drops in rumen pH. Nevertheless, high individual animal variability in rumen pH and the difference in measurement methods for pH data acquisition decrease the sensitivity and accuracy of pH indicators for detecting SARA in ruminants. The aim of this study was to refine rumen pH indicators in long-term SARA based on individual dairy cow reticulo-rumen pH kinetics. Animal performances and rumen parameters were studied weekly in order to validate SARA syndrome and rumen pH was continuously measured using reticulo-rumen sensors. In total, 11 primiparous dairy cows were consecutively fed two different diets for 12 successive weeks: a control diet as low-starch diet (LSD; 13% starch for 4 weeks in period 1), an acidotic diet as high-starch diet (HSD; 32% starch for 4 weeks in period 2), and again the LSD diet (3 weeks in period 3). There was a 1-week dietary transition between LSD and HSD. Commonly used absolute SARA pH indicators such as daily average, area under the curve (AUC) and time spent below pH<5.8 and pH<6 were processed from absolute (raw) daily kinetics. Then signal processing was applied to raw pH values in order to calculate relative pH indicators by filtering and normalizing data to remove inter-individual variability, sensor drift and sensor noise. Normalized AUC, times spent below NpH<-0.3 and NpH<-0.5, NpH range and NpH standard deviation were calculated. Those relative pH indicators were compared with commonly used pH indicators to assess their ability to detect SARA. This syndrome induced by HSD was confirmed by consistent expected changes in milk quality, dry matter intake and acetate : propionate ratio in the rumen, whereas the ruminal concentration of lipopolysaccharide was increased. Commonly used pH SARA indicators were not able to discriminate SARA syndrome due to high animal variability and sensor drift and noise, whereas relative pH indicators developed in this study appeared more relevant for SARA detection as assessed by receiver operating characteristic tests. This work shows that absolute pH kinetics should be corrected for drift, noise and animal variability to produce relative pH indicators that are more robust for SARA detection. These relative pH indicators could be more relevant for identifying affected animals in a herd and also for comparing SARA risk among studies.

Impact of a direct-admission stroke pathway on delays of admission, care, and rates of intravenous thrombolysis.

INTRODUCTION: This study examined the impact of a "direct potential thrombolysis" pathway with direct admission to a neurological stroke unit (SU) on delays of admission, stroke care and proportion of patients with ischemic stroke (IS) treated with intravenous (IV) rtPA. METHODS: This prospective study included all patients admitted in the intensive SU for potential thrombolysis over a 2-month period. Data collected included the time of symptom onset, mode of transport, National Institutes of Health Stroke Scale (NIHSS) score on arrival, delays of care, delays of imaging and modalities, diagnosis and therapeutic data. RESULTS: During the 2-month study period, 81 patients (mean age of 65 years) were included in the study. The Emergency Medical Services (EMS) were involved in 86% of admissions, with a median delay of admission of 1h48 and access within 4.5h in 84% of cases. Every patient underwent immediate neurovascular assessment and imaging examination, which was a MRI in 80% of cases. Only 70% of patients had a final diagnosis of stroke. Intravenous rtPA therapy was administered to 26 patients (32%), and 58% of patients with IS. The median door-to-needle time delay was 63min. CONCLUSION: A direct 'potential thrombolysis' pathway, based on EMS and located in the SU, can result in earlier admission, reaching the recommended care delay, and a large proportion (58%) of IS patients receiving rtPA therapy. On the other hand, the proportion of patients with stroke mimics is high, thereby increasing the chances of intermittent periods of saturation of this specific pathway.

Evolution of psychosocial factors at work in a French region.

BACKGROUND: Psychosocial factors at work (PFW) can be defined as all non-physicochemical occupational risks. Several epidemiological models have been proposed to measure PFW, but one of the most widely used is Karasek's model. AIMS: To determine whether psychosocial factors, evaluated by Karasek's questionnaire, had increased in a cohort of workers. METHODS: A random sample of workers in the Pays de la Loire region of France, who could be considered representative of the region's population of salaried workers, filled in a self-administered questionnaire, including Karasek's self-administered questionnaire, in 2002-05 and 2007-09. Karasek's questionnaire can be used to study three psychosocial dimensions (psychological demand, decision latitude and social support in the workplace) in workers in order to define two high-risk situations for their health: 'Job Strain' and 'Iso Strain'. Changes in job strain and iso strain among workers were studied according to the workers' sociodemographic characteristics and their working conditions. RESULTS: In this sample of 2049 workers, the proportion with iso strain increased between the two periods from 12 to 16%, P < 0.001, mainly among manual workers. Deterioration of Karasek indicators was mainly explained by an increase of the 'low social support' dimension (38 versus 49%, P < 0.001). Working conditions such as temporary employment of colleagues and high perceived physical exertion were associated with higher PFW. CONCLUSIONS: This study, based on a quantitative and collective model, showed deterioration of working team environments and increased risk for individual mental health in this cohort of French workers in recent years.

Carpal tunnel syndrome and computer exposure at work in two large complementary cohorts.

OBJECTIVES: The boom in computer use and concurrent high rates in musculoskeletal complaints and carpal tunnel syndrome (CTS) among users have led to a controversy about a possible link. Most studies have used cross-sectional designs and shown no association. The present study used longitudinal data from two large complementary cohorts to evaluate a possible relationship between CTS and the performance of computer work. SETTINGS AND PARTICIPANTS: The Cosali cohort is a representative sample of a French working population that evaluated CTS using standardised clinical examinations and assessed self-reported computer use. The PrediCTS cohort study enrolled newly hired clerical, service and construction workers in several industries in the USA, evaluated CTS using symptoms and nerve conduction studies (NCS), and estimated exposures to computer work using a job exposure matrix. PRIMARY AND SECONDARY OUTCOME MEASURES: During a follow-up of 3-5 years, the association between new cases of CTS and computer work was calculated using logistic regression models adjusting for sex, age, obesity and relevant associated disorders. RESULTS: In the Cosali study, 1551 workers (41.8%) completed follow-up physical examinations; 36 (2.3%) participants were diagnosed with CTS. In the PrediCTS study, 711 workers (64.2%) completed follow-up evaluations, whereas 31 (4.3%) had new cases of CTS. The adjusted OR for the group with the highest exposure to computer use was 0.39 (0.17; 0.89) in the Cosali cohort and 0.16 (0.05; 0.59) in the PrediCTS cohort. CONCLUSIONS: Data from two large cohorts in two different countries showed no association between computer work and new cases of CTS among workers in diverse jobs with varying job exposures. CTS is far more common among workers in non-computer related jobs; prevention efforts and work-related compensation programmes should focus on workers performing forceful hand exertion.

Interest of the Ergo-Kit(®) for the clinical practice of the occupational physician. A study of 149 patients recruited in a rehabilitation program.

OBJECTIVE: Functional capacity evaluation is commonly used to assess the abilities of patients to perform some tasks. Ergo-Kit(®) is a validated tool assessing both functional capacities of patients and workplace demands. The objective of this study was to evaluate the relevance of the Ergo-Kit(®) data for occupational physicians during the return-to-work process. METHODS: A retrospective and monocenter study was conducted on all patients included in a rehabilitation program and assessed with the Ergo-Kit(®) tool between 2005 and 2014. Workplace demands and patients' functional capacities were evaluated and confronted. Self-beliefs and perceived disability were also assessed and compared to the functional capacity evaluation. RESULTS: One hundred and forty-nine working-age patients (85 men, 64 women; 39±12 years) suffering from musculoskeletal disorders or other diseases were included. Main causes of mismatch between workplace demands and functional capacities were manual handling of loads, postures with arms away from the body and repetitive motions at work; sitting posture was correlated with a lesser physical workload; and Oswestry score was correlated with functional capacities evaluated by the Ergo-Kit(®). CONCLUSION: Ergo-Kit(®) is a relevant tool to assess the multidimensional aspects of workplace demands and functional capacities. It could be very helpful for occupational physicians to manage return-to-work.

Prevalence of thoracic spine pain in a surveillance network.

BACKGROUND: Back pain has long been identified as a major occupational health issue, but there are few prevalence studies on thoracic spine pain (TSP). The epidemiological surveillance of musculoskeletal disorders implemented in 2002 by the French Institute for Public Health Surveillance in the Pays de la Loire region provided the opportunity to study the prevalence of TSP in a large, representative sample of workers. AIMS: To assess the prevalence of TSP across a week in a regional workforce according to age, occupational category and industry sector in men and women separately. METHODS: A random sample of workers aged 20-59 years, representative of the regional workforce, was constituted between 2002 and 2005. Medical and occupational data were gathered by questionnaire. RESULTS: The sample consisted of 3710 workers (58% men). The prevalence of TSP was higher in women (17%) than in men (9%). Lower grade male white-collar workers were more likely to report TSP (17%) than male workers in other occupational categories, whereas upper grade female white-collar and professional workers were more likely to report TSP. No significant difference in the prevalence of TSP was noted in either men or women according to industry sector. CONCLUSIONS: Although TSP is less frequent than low back and neck pain, the results of this study indicate that 1 in 10 men and 1 in 5 women suffer from TSP.

Working in temporary employment and exposure to musculoskeletal constraints.

BACKGROUND: In recent years, temporary work (TW) has increased in European countries due to the greater uncertainty in the economy. AIMS: To compare the prevalence of non-specific musculoskeletal symptoms of the upper extremities (UEMSDs) and their main risk factors in blue-collar workers employed through temporary agencies (TW) and in those in permanent employment (PE). METHODS: UEMSDs occurring during the preceding 7 days were assessed using a Nordic questionnaire completed by 1493 blue-collar workers randomly included in a surveillance programme for UEMSDs (171 in TW and 1322 in PE) in a large French region. Personal factors and work-related risk factors for UEMSDs were assessed by self-administered questionnaires. RESULTS: The prevalence of UEMSDs during the preceding 7 days did not significantly differ between workers in TW or PE. However, after adjustment for age and gender, TW had a higher risk of symptoms of the wrist/hand region (OR = 1.6, 95% CI 1.04-2.6). TW was characterized by higher exposure to paced work (OR = 2.0, 95% CI 1.4-3.0), repetitive work (OR = 2.3, 95% CI 1.6-3.4), awkward postures of the wrist (OR = 1.6, 95% CI 1.2-2.4) and intensive use of vibrating hand tools (OR = 1.7, 95% CI 1.1-2.3). Workers in TW suffered from a lack of autonomy (OR = 2.5, 95% CI 1.7-3.6) and skill discretion at work (OR = 2.0, 95% CI 1.3-3.1) more frequently, but there was no difference in relation to psychological demands of the task or social support. CONCLUSIONS: Temporary workers were more frequently exposed to working time constraints, repetitive work and biomechanical constraints of the wrist/hand region when compared to permanent workers and may represent a subpopulation at particularly high risk of UEMSDs.

Adult-to-adult living related liver transplantation: preliminary results of the Hepatic Transplantation Group in Algiers.

INTRODUCTION: In the absence of cadaveric grafts, a living donor liver transplant program was started in Algeria in February 2003. The aim of this study is to report the preliminary results. PATIENTS AND METHODS: From February 2003 to September 2004, eight adult-to-adult living related liver transplantations were performed. The donors were six women and two men of mean age of 25 years (range, 18 to 48 years). Right hepatectomy was performed in seven patients and left hepatectomy in one patient. The recipients were four women and four men of mean age 33 years (range, 16 to 56 years). Follow-up ranged from 1 month to 18 months (median 7 months). RESULTS: All donors survived the procedure. In the immediate postoperative period, two donors experienced complications. One donor underwent reoperation for hemorrhage and one suffered partial portal vein thrombosis, which was treated medically. The eight donors are alive at home without any late complications. One recipient died on postoperative day 43 due to sepsis. Among the seven other recipients, two experienced complications: one bilioma in relation to a biliary-intestinal fistula and one thrombosis of the splenic vein with a left portal embolus. At present the seven recipients are alive with normal liver function and without complications. CONCLUSION: Our results are comparable to other reports suggesting that adult-to-adult living related liver transplantation is feasible with no mortality and low morbidity in donors. However, it is important to develop a cadaveric liver transplant program.

[Pneumonitis caused by hydrocarbon inhalation]. / Pneumopathies par inhalation d'hydrocarbures volatiles.

INTRODUCTION: Kerosene pneumonitis is rare. It most commonly occurs in children who have ingested a hydrocarbon by accident. In adults, pneumonitis caused by aspiration of incompletely vaporized kerosene may be seen in fire-eaters can cause pneumonitis. CASE REPORTS: We report six cases of fire-eater's pneumonitis, from our region, due to hydrocarbon inhalation. CONCLUSIONS: This inhalational pulmonary insult has classical clinical manifestations. The frequency of cases, particularly in tourist areas that host street festivals, is probably underestimated. Its tendency to spontaneously resolve questions the need for antibiotics and corticosteroids.

[Acute toxic accident following lumbar plexus block with bupivacaine]. / Accident aigu toxique après bloc du plexus lombaire à la bupivacaïne.

We report the case of a patient who experienced ventricular dysrhythmias and seizure five minutes after the injection of 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine, during a lumbar plexus block performed via the posterior approach described by Winnie. The patient who underwent his total hip arthroplasty was still anaesthetised and under controlled ventilation at the time of bupivacaine administration. Aspiration test performed before injection was negative. Normal cardiac activity and stable haemodynamic condition were restored after one hour of resuscitation including 15 electric shocks and administration of epinephrine (40 mg) and clonidine (300 micrograms). The patient was discharged without neurologic sequelae after four days in the ICU.

[Sciatic nerve block: an new lateral mediofemoral approach. The value of its combination with a "3 in 1" block for invasive surgery of the knee]. / Bloc du nerf sciatique: une nouvelle voie d'abord latérale médiofémoral. Intérêt de son association à un bloc "3 en 1" pour la chirurgie invasive du genou.

OBJECTIVE: To describe a new midfemoral lateral approach for the sciatic nerve block. Its combination with the "3 in 1" block was tested for postoperative analgesia following major surgery of the knee. STUDY DESIGN: Descriptive, anatomical and clinical study prospective. PATIENTS: After testing in four unembalmed corpses the new approach was applied to 42 ASA 1-2 patients, in combination with a continuous "3 in 1" block. METHODS: The new approach was analysed for reliability of the surface landmarks (a line drawn from the posterior margin of the greater trochanter towards the knee and parallel to the femur) and block extent assessed on the foot. Its combination with the "3 in 1" block was evaluated with a visual analogue scale (VAS) scoring, for postoperative analgesia after total knee arthroplasty. RESULTS: The sciatic nerve was located in less than 10 min. A block of the sciatic nerve was fully achieved in all patients. Its median duration was 16 h. The median VAS score at rest was 0 mm (sciatic bloc + continuous block "3 in 1"), but increased to 40 mm (block "3 in 1" alone). CONCLUSION: The new lateral midfemoral sciatic block is easy to master. Combined with a continuous "3 in 1" block, it provides excellent analgesia during the early postoperative period after major surgery of the knee.

[Pulmonary metastasis of a uterine epithelioid leiomyosarcoma]. / Métastase pulmonaire d'un léiomyosarcome épithélioïde utérin.

We report a case of patient presenting with a very large pulmonary metastasis which revealed a previously unrecognised uterine epithelioid leiomyosarcoma. This is a rare tumour with a poor prognosis. The treatment of both the primary tumour and the metastasis was surgical.

[Meningococcal pneumonia]. / La pneumonie à méningocoque.

Meningococci can cause primary bacterial pneumonia. The clinical picture is non-specific and the clinical course leads to meningeal infection. Diagnosis is based on isolation of Neisseria meningitidis in lung samples. Outcome is usually favourable.