Isoform-and cell-state-specific APOE homeostasis and function

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

Why people should run after positive affective experiences instead of health benefits

Over time,physical activity(PA)has shifted from being a necessity to being an alternative.As a result,levels of PA have sharply decreased.1 Today,we are facing a worldwide pandemic of physical inactivity,with one death every 6 s attributed to insufficient PA.2 To counteract this trend,a tremendous effort is being made to promote regular PA across the lifespan,mainly through the dissemination of knowledge about the health benefits of accumulating sufficient PA.

Schisming as an Interactional Resource for Learning at the Frontiers of Work and Vocational Training-A Secondary Publication

This paper examines the sorts of interactional competencies and institutional demands required from students as they engage in complex forms of participation combining work and training purposes.It focuses on a series of empirical cases,recorded through video data and analyzed from a conversation analytic perspective,in which mentors make the decision to intervene during work sessions moderated by students.Such interventions do not interrupt the student’s activity and lead to the emergence of two distinct but not impermeable interactional spaces.This complex participation framework,known as“schisming,”contributes to overcoming practical issues within multiparty settings.Our study shows how schisming constitutes a particular sequential phenomenon where participants reorganize the interaction and co-construct a social and cognitive interactional space,thus enabling a shared understanding of the specific training context.Empirical data from the practical training of medical radiographers are used to illustrate how schisming may contribute to learning in the conditions of guided practice.

Persistence and growth of faecal culturable bacterial indicators in water column and sediments of Vidy Bay,Lake Geneva,Switzerland

The aims of this study was to investigate the persistence and the growth of culturable bacterial indicators （CBI） including total coliforms （TC） and faecal coliforms represented by Escherichia coli, enterococcus （ENT）, and aerobic mesophilic bacteria （AMB） in the surface sediments and the water column of Vidy Bay fLake Geneva, City of Lausanne, Switzerland）. The study was carded out for 60 d using microcosms containing Sewage Treatment Plant （STP） effluent and nonsterile water without CBI, as well as contaminated and non-contaminated sediments. The effects of water temperature and of organic matter associated with sediments on the survival of CBI in the sediments and the water column were observed. The number of CBI colonies in the contaminated sediments of Vidy Bay and in the STP effluent was almost identical in the order of 10^5-10^7, 10^4-10^6, 10^5-10^5, and 10^4-10^7 CFU/100 g sediment or/100 mL water for TC, E. coli, ENT, and AMB respectively. A degradation of CBI was observed in the sediments where organic mater content was low and in the water column at a temperature of 10℃ after 5 d of experimentation. In addition, a growth of CBI was observed in the sediment which is rich in organic matter at 20℃. The results of this study indicate： （1） the higher concentrations of the CBI observed in different points in the water column of Vidy Bay may not be explained only by the recent contribution of the three potential sources of the Bay contamination including STP and the Chamberonne and Flon Rivers, but also by the persistence, removal from sediment and multiplication of CBI in the sediment and water column; （2） the sediment of Vidy Bay constitute a reservoir of CBI and can even support their growth; and （3） the CBI not only survive in sediments, but also can be remobilized and increased in the water column, therefore, it become a permanent microbiological pollution in Vidy Bay.

Survival of a Patient with Amniotic Fluid Embolism Based on Multidisciplinary Team Training: A Case Report of a Swiss University Hospital

Amniotic fluid embolism (AFE) is a rare, unpredictable and unpreventable event with high maternal and fetal morbidity and mortality. Its clinical presentation is nonspecific ranging from moderate organ dysfunction to cardiovascular collapse with disseminated intravascular coagulation (DIC), which can lead to death. In a situation of severe systemic disease, maternal survival is largely dependent on the combined efficacy of gynecological and anesthetic teams. We report a case of AFE in a healthy woman admitted to the delivery room for labor induction. Due to a loss of consciousness soon after epidural anesthesia associated to fetal bradycardia, an emergency caesarean section was performed which was complicated by uterine atony and DIC requiring hysterectomy. The outcome was favorable due to fast and efficient multidisciplinary care, emphasizing the benefit of having been trained for such situations through simulation and team training programs for obstetrical emergency management.

Introducing a HPV Vaccination Program: the Experience in the State of Geneva, Switzerland (2007-2009)

Objective: The objective of this study is to assess the HPV vaccination coverage of 11 to 19 year-old girls during a state coordinated HPV vaccination program in Geneva, Switzerland, from September 2007 to December 2009. Methods: The HPV vaccination program was coordinated by the State Medical Office. It relied on practitioners in private practice, on the School Health Service and on a temporary vaccination structure at the Geneva University Hospital. Each service provider transmitted quarterly to the State Medical Office the nominal list of the persons who had received their first, second or third shot. The data were processed through the Téléform ? software and analyzed to assess the HPV cover-age of the target population. Results: The global coverage rates on December 31st 2009, 2 years after the program had been launched, were 48.1% for one dose, 43.7% for two doses and 41.6% for three doses of the HPV vaccine. These rates were quite different from one cohort to another: for girls born in 1995 (14 year-old), cover rates were 70% for the first, 68.1% for second and 65.1% for the third dose. Conclusion: This study shows that it is possible to obtain a high coverage rates after two years of a state coordinated HPV vaccination program.

Humanization for neurological disease modeling:A roadmap to increase the potential of Drosophila model systems

Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.

Unveil the Redox Evolution of Ore-forming Fluids using Sulfur Isotope:A Case Study of the Zhengguang Intermediate Sulfidation Epithermal Au-Zn Deposit,NE China

Oxygen fugacity(fO_(2))is a key intensity variable during the entire magmatic-hydrothermal mineralization courses.The redox state and its variations between different stages of the ore-forming fluids of intermediate sulfidation epithermal deposits are rarely deciphered due to the lack of appropriate approaches to determine fO_(2)of the fluids.Here,we reported theδ^(34)S of the sulfides from three different stages(stageⅠ,Ⅱ,Ⅲ)of Zhengguang,an Early Ordovician Au-rich intermediate sulfidation(IS)epithermal deposit,to decipher the redox evolution of the ore-forming fluids.The increasingδ^(34)S values from stageⅠpyrite(pyl,average-2.6‰)through py2(average-1.9‰)to py3(average-0.2‰)indicates a decrease of the oxygen fugacity of the ore-forming fluids.A compilation ofδ^(34)S values of sulfides from two subtypes of IS deposits(Au-rich and Ag-rich)from NE China shows that theδ^(34)S values of sulfides from Au-rich IS deposits are systematically lighter than those of Ag-rich IS Ag-Pb-Zn deposit,indicating the ore-forming fluids of the former are more oxidized than the latter.We highlight that sulfur isotopic composition of hypogene sulfides is an efficacious proxy to fingerprint the oxygen fugacity fluctuations of epithermal deposits and could potentially be used to distinguish the subtypes of IS deposits.

Validation of the Chinese Version of the Affective Exercise Experiences Questionnaire (AFFEXX-C)

Despite the well-established benefits of regular physical activity(PA)on health,a large proportion of the world population does not achieve the recommended level of regular PA.Although affective experiences toward PA may play a key role to foster a sustained engagement in PA,they have been largely overlooked and crudely measured in the existing studies.To address this shortcoming,the Affective Exercise Experiences(AFFEXX)questionnaire has been developed to measure such experiences.Specifically,this questionnaire was developped to assess the following three domains:antecedent appraisals(e.g.,liking vs.disliking exercise in groups),core affective exercise experiences(i.e.,pleasure vs.displeasure,energy vs.tiredness,and calmness vs.tension),and exercise motivation(i.e.,attraction vs.antipathy toward exercise).The current study aimed to validate a Chinese version of the AFFEXX questionnaire(AFFEXX-C).In study 1,722 Chinese college students provided data for analyses of factorial,convergent,discriminant,criterion validity,and test-retest reliability of the AFFEXX-C.In addition,1,300 college students were recruited in study 2 to further validate its structural model.Results showed that the AFFEXX-C demonstrates a goodfit and reliability.Additionally,results further supported the hypothesized model based on previous research:antecedent appraisals predicted core affective exercise experiences,which in turn predicted attraction-antipathy toward physical exercise.The AFFEXX-C was found to be a reliable and valid measure of affective exercise experiences in a population of Chinese college students.

Pediatric GNAO1 encephalopathies:from molecular etiology of the disease to drug discovery

Gao is the major G protein in neurons,where it transduces signals from numerous G proteincoupled receptors(GPCRs)such as D2 dopamine,μ-opioid,M2 muscarinic,or α2-adrenergic receptors.In 2013,the first mutations in GNAO1,the gene encoding Gao,were described in pediatric patients with encephalopathies(Nakamura et al.,2013),suffering from movementdisorders,epileptic seizures。

Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial risk.Nwaedozie et al brought to the body of evidence electrocardiogram and clinical findings.However,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing rate.In this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: a review article

Emerging data have highlighted the co-existence of nonalcoholic fatty liver disease(NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease,largely due to differences in disease definition and diagnostic tools utilised in the studies. Age,obesity,insulin resistance and other metabolic conditions are common risks factors in observational studies. However,other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity,duration,steroid use and prior surgical intervention,in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability,gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity,however no definitive evidence exist linking them to the development of hepatic steatosis,nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification,intervention and improve patient outcomes.

Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis

AIM: To study the safety of epidural anesthesia(EA),its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis(AP).METHODS: From 2005 to August 2010,patients with predicted severe AP [Ranson score ≥ 2,C-reactive protein > 100 or necrosis on computed tomography(CT)] were prospectively randomized to either a group receiving EA or a control group treated by patientcontrolled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale(VAS). Parameters for clinical severity such as length of hospital stay,use of antibiotics,admission to the intensive care unit,radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head,body and tail of the pancreas.RESULTS: We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group(mean score 4.15 ± 2.54 vs 3.38 ± 1.75,respectively,P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively(P = NS). The median duration of EA was 5.7 d,and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30(43%) of measurements in the EA group vs 2/27(7%) in the control group(P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group(P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group(0.2 vs 2.33,P = 0.034 at 10 d). Length of stay and mortality were not statistically different between the 2 groups(26 d vs 30 d,P = 0.65,and 0% for both respectively).CONCLUSION: Our study demonstrates that EA increases arterial perfusion of the pancreas and improves the clinical outcome of patients with AP.

A Parametric Genetic Algorithm Approach to Assess Complementary Options of Large Scale Wind-solar Coupling

The transitional path towards a highly renewable power system based on wind and solar energy sources is investigated considering their intermittent and spatially distributed characteristics. Using an extensive weather-driven simulation of hourly power mismatches between generation and load, we explore the interplay between geographical resource complementarity and energy storage strategies. Solar and wind resources are considered at variable spatial scales across Europe and related to the Swiss load curve, which serve as a typical demand side reference. The optimal spatial distribution of renewable units is further assessed through a parameterized optimization method based on a genetic algorithm. It allows us to explore systematically the effective potential of combined integration strategies depending on the sizing of the system, with a focus on how overall performance is affected by the definition of network boundaries. Upper bounds on integration schemes are provided considering both renewable penetration and needed reserve power capacity. The quantitative trade-off between grid extension, storage and optimal wind-solar mix is highlighted.This paper also brings insights on how optimal geographical distribution of renewable units evolves as a function of renewable penetration and grid extent.

Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease

AIM To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease.METHODS Systematic searches were performed( January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high(> 3 L) or low-volume(2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-torepeat the procedure and side effects/complications.RESULTS Out of 439 citations, 4 trials fulfilled our inclusion criteria(n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol(PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84(0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11(1.31-20.0). CONCLUSION In inflammatory bowel disease population, PEG lowvolume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-torepeat. Further additional research is urgently required to compare contemporary products in this population.

Biological mesh reconstruction of the pelvic floor following abdominoperineal excision for cancer:A review

Extralevator abdominoperineal excision and pelvic exenteration are mutilating operations that leave wide perineal wounds.Such large wounds are prone to infection and perineal herniation,and their closure is a major concern to most surgeons.Different approaches to the perineal repair exist,varying from primary or mesh closure to myocutaneous flaps.Each technique has its own associated advantages and potential complications and the ideal approach is still debated.In the present study,we reviewed the current literature and our own local data regarding the use of biological mesh for perineal wound closure.Current evidence suggests that the use of biological mesh carries an acceptable risk of wound complications compared to primary closure and is similar to flap reconstruction.In addition,the rate of perineal hernia is lower in early follow-up,while long-term hernia occurrence appears to be similar between the different techniques.Finally,it is an easy and quick reconstruction method.Although more expensive than primary closure,the cost associated with the use of a biological mesh is at least equal,if not less,than flap reconstruction.

Characteristics of Photosystem Ⅱ Behavior in Cotton(Gossypium hirsutum L.) Bract and Capsule Wall

Though bract and capsule wall of boll in cotton （Gossypium hirsutum L.） have different photosynthetic capacities, the features of photosystem II （PS II） in these organs are scarce. In this paper, chlorophyll a lfuorescence emission was measured to investigate the difference in the photosynthetic apparatus of dark-acclimated （JIP-test） and light-acclimated （light-saturation pulse method） bract and capsule wall. Compared with leaves, the oxygen evolving system of non-foliar organs had lower efifciency. The pool size of PS II electron acceptor of non-foliar organs was small, and the photochemical activity of leaves was higher than that of the bract and capsule wall. In regard to the photosystem I （PS I） electron acceptor side, the pool size of end electron acceptors of leaves was larger, and the quantum yield of electron transport from QA （PS II primary plastoquinone acceptor） further than the PS I electron acceptors of leaves was higher than that of bract and capsule wall. In all green organs, the actual quantum yield of photochemistry decreased with light. The thermal dissipation fraction of light absorbed by the PS II antennae was the highest in bract and the lowest in capsule wall relative to leaves. Compared with leaves, capsule wall was characterized by less constitutive thermal dissipation and via dissipation as lfuorescence emission. These results suggested that lower PS II photochemical activity in non-foliar organs may be result from limitations at the donor side of PS II and the acceptor sides of both photosystems.

Health-related quality of life outcomes after cholecystectomy

Gallbladder diseases are very common in developed countries. Complicated gallstone disease represents the most frequent of biliary disorders for which surgery is regularly advocated. As regards, cholecystectomy represents a common abdominal surgical intervention; it can be performed as either an elective intervention or emergency surgery, in the case of gangrene, perforation, peritonitis or sepsis. Nowadays, the laparoscopic approach is preferred over open laparotomy. Globally, numerous cholecystectomies are performed daily; however, little evidence exists regarding assessment of post-surgical quality of life (QOL) following these interventions. To assess post-cholecystectomy QOL, in fact, documentation of high quality care has been subject to extended discussions, and the use of patientreported outcome satisfaction for quality improvement has been advocated for several years. However, there has been little research published regarding QOL out-comes following cholecystectomy; in addition, much of the current literature lacks systematic data on patientcentered outcomes. Then, although several tools have been used to measure QOL after cholecystectomy, diffi culty remains in selecting meaningful parameters in order to obtain reproducible data to reflect postoperative QOL. The aim of this study was to review the impact of surgery for gallbladder diseases on QOL. This review includes Medline searches of current literature on QOL following cholecystectomy. Most studies demonstrated that symptomatic patients profi ted more from surgery than patients receiving an elective intervention. Thus, the gain in QOL depends on the general conditions before surgery, and patients without symptoms profi t less or may even have a reduction in QOL.

Reconstruction of debris-flow activity in a temperate mountain forest catchment of central Mexico

The use of dendrochronology to study and date geomorphic processes in volcanic environments is still incipient, even more so on the volcanic slopes covered by temperate forests in central Mexico. Mass movements, such as debris flows, often impact forest stands where they cause damage to individual trees, thereby generating growth disturbances(GD) in the tree-ring records. The identification and dating of GD enables reconstruction of the age of trees colonizing bare surfaces after major events, but also allows the assessment of the frequency or spatial distribution of past geomorphic process activity. Here we used increment cores from 65 Pinus leiophylla, Abies religiosa, and Alnus jorullensis trees growing in the Axal gorge, on the southern slopes of La Malinche volcano, to unravel past debris-flow activity both temporally and spatially. Based on the combination of GD records, a weighted tree response index(Wit), field evidence and hydrometeorological records, we reconstructed 23 debris flows since 1933.Interestingly, almost two-thirds of the reconstructed years with debris-flow activity in Axal gorge match with events recorded in Axaltzintle gorge located on the NE slopes of La Malinche. These findings suggest a regional triggering mechanism, most likely related to the occurrence of hurricanes. This research could be useful for disaster risk management of the La Malinche National Park.

Perforated duodenal diverticulum, a rare complication of a common pathology: A seven-patient case series

Duodenal diverticula (DD) are frequently encountered and are usually asymptomatic, with an incidence at autopsy of 22%. Perforation of DD is a rare complication (around 160 cases reported) with potentially dramatic consequences. However, little evidence regarding its treatment is available in the literature. The aim of this study was to review our experience of perforated DD, with a focus on surgical management. Between January 2001 and June 2011, all perforated DD were retrospectively reviewed at a single centre. Seven cases (5 women and 2 men; median age: 72.4 years old, rang: 48-91 years) were found. The median American Society of Anesthesiologists' score in this population was 3 (range: 3-4). The perforation was located in the second portion of duodenum (D2) in six patients and in the third portion (D3) in one patient. Six of these patients were treated surgically: five patients underwent DD resection with direct closure and one was treated by surgical drainage and laparostomy. One patient was treated conservatively. One patient died and one patient presented a leak that was successfully treated conservatively. The median hospital stay was 21.1 d (range: 15-30 d). Perforated DD is an uncommon presentation of a common pathology. Diverticular excision with direct closure seems to offer the best chance of survival and was associated with a low morbidity, even in fragile patients.