Effect of lymphokines on 35sulfate uptake by the glomerular basement membrane.
We have previously shown that lymphocytes from idiopathic minimal-lesion nephrotic patients produce a lymphokine (supernatant factor) that increases the 35sulfate uptake in the glomerular basement membrane (GBM). The purpose of this report was to further characterize the supernatant factor by studying the effects of interleukins (IL) 2-4, 6, and 8, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor on the 35sulfate incorporation by rat glomeruli in vitro. A significant increase in GBM 35sulfate uptake was only seen when the glomeruli were cultured with the addition of IL-8 as compared with control cultures: 10.8 +/- (SEM) 1.7 and 7.9 +/- 1.4 cpm/micrograms GBM protein, respectively (p < 0.005). IL-8 reproduces the effect of the reported supernatant factor on the GBM 35sulfate uptake. Because IL-8 was detected in the supernatant of peripheral mononuclear cell cultures from idiopathic minimal-lesion nephrotic syndrome patients in relapse and because the increased GBM 35sulfate incorporation induced by the supernatant factor has been abolished by the addition to the culture media of anti-IL-8 neutralizing antibodies, we postulate that IL-8 is the previously described supernatant factor.


Integration, effectiveness and costs of different models of primary health care provision for people who are homeless: an evaluation study.
There is a high prevalence of health problems among single people who are homeless. Specialist primary health care services for this population have been developed in several locations across England; however, there have been very few evaluations of these services. This study evaluated the work of different models of primary health care provision in England to determine their effectiveness in engaging people who are homeless in health care and in providing continuity of care for long-term conditions. It concerned single people (not families or couples with dependent children) staying in hostels, other temporary accommodation or on the streets. The influence on outcomes of contextual factors and mechanisms (service delivery factors), including integration with other services, were examined. Data from medical records were collated on participants' use of health care and social care services over 12 months, and costs were calculated. The evaluation involved four existing Health Service Models: (1) health centres primarily for people who are homeless (Dedicated Centres), (2) Mobile Teams providing health care in hostels and day centres, (3) Specialist GPs providing some services exclusively for patients who are homeless and (4) Usual Care GPs providing no special services for people who are homeless (as a comparison). Two Case Study Sites were recruited for each of the specialist models, and four for the Usual Care GP model. People who had been homeless during the previous 12 months were recruited as 'case study participants'; they were interviewed at baseline and at 4 and 8 months, and information was collected about their circumstances and their health and service use in the preceding 4 months. Overall, 363 participants were recruited; medical records were obtained for 349 participants. Interviews were conducted with 65 Case Study Site staff and sessional workers, and 81 service providers and stakeholders. The primary outcome was the extent of health screening for body mass index, mental health, alcohol use, tuberculosis, smoking and hepatitis A among participants, and evidence of an intervention if a problem was identified. There were no overall differences in screening between the models apart from Mobile Teams, which scored considerably lower. Dedicated Centres and Specialist GPs were more successful in providing continuity of care for participants with depression and alcohol and drug problems. Service use and costs were significantly higher for Dedicated Centre participants and lower for Usual Care GP participants. Participants and staff welcomed flexible and tailored approaches to care, and related services being available in the same building. Across all models, dental needs were unaddressed and staff reported poor availability of mental health services. There were difficulties recruiting mainstream general practices for the Usual Care GP model. Medical records could not be accessed for 14 participants of this model. Participant characteristics, contextual factors and mechanisms were influential in determining outcomes. Overall, outcomes for Dedicated Centres and for one of the Specialist GP sites were relatively favourable. They had dedicated staff for patients who were homeless, 'drop-in' services, on-site mental health and substance misuse services, and worked closely with hospitals and homelessness sector services. This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (HSDR 13/156/03) and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 16. See the NIHR Journals Library website for further project information.


Hemoglobin S target of <50% as compared to 30% in chronic red cell exchange for secondary stroke prevention in sickle cell disease.
Sickle cell disease (SCD) patients with a history of stroke are encouraged to receive chronic red blood cell exchange (RBCx) for stroke prevention. The American Society of Hematology guideline published in 2020 recommends an HbS target of <30%. However, this approach necessitates more frequent RBCx and more RBC units. UT Southwestern has devised a chronic exchange protocol that elevates the HbS target to <50% in patients with a low risk of stroke. This retrospective chart review study reviewed the medical records of patients receiving chronic RBCx with a target of HbS <50% over the past 10-year period to assess the safety of maintaining higher HbS targets in SCD patients with a low risk of cerebrovascular accidents (CVA). Among 49 SCD patients in the chronic RBCx program for secondary stroke prevention, 33 patients were maintained on an HbS target of <50% (average measured: 35.4%) for the duration of RBCx program enrollment (median 93.0 months, 95% CI, 83-99). Stroke or transient ischemic attack (TIA) clearly attributable to changing target HbS had not been identified among the 33 study subjects. Seven patients experienced conversion between the HbS targets of <50% and <30% HbS target. Significant reductions were observed in the frequency of RBCx and usage of blood volume in four of them. The findings suggest that liberalizing the HbS target could confer clinical flexibility without increasing the risk of CVA in a selective population. Further studies to fully evaluate the potential benefits of this approach are indicated.


Promise and peril-defining ethical telehealth practice from the clinician and patient perspective: A qualitative study.
We undertook a qualitative study to examine and compare the experience of ethical principles by telehealth practitioners and patients in relation to service delivery theory. The study was conducted prior to and during the recent global increase in the use of telehealth services due to the COVID-19 pandemic. We conducted semi-structured interviews with 20 telehealth practitioners and patients using constructionist grounded theory methods to collect and analyse data. Twenty-five axial coded data categories were then unified and aligned through selective coding with the Beauchamp and Childress (2013) framework of biomedical ethics. The groups were then compared. Thirteen categories aligned to the ethical framework were identified for practitioners and 12 for patients. Variance existed between the groups. Practitioner results were non-maleficence 4/13 or (31%), beneficence 4/13 (31%), professional-patient relationships 3/12 (22%), autonomy 1/13 (8%) and justice 1/13 (8%). Patient data results were non-maleficence 4/12 (33%), professional-patient relationships 3/12 (33%), autonomy 2/12 (18%), beneficence 1/12 (8%) and justice 1/12 (8%). Ethical principles are experienced differently between telehealth practitioners and patients. These differences can impact the quality and safety of care. Practitioners feel telehealth provides better care overall than patients do. Patients felt telehealth may force a greater share of costs and burdens onto them and reduce equity. Both patients and practitioners felt telehealth can be more harmful than face-to-face service delivery when it creates new or increased risk of harms. Building sufficient trust and mutual understanding are equally important to patients as privacy and confidentiality.


Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis.
To report the incidence of postoperative nausea and vomiting (PONV), to describe the use of anti-emetics both for the prophylaxis and treatment of PONV, and to assess resource utilization and duration of post-anesthesia care unit (PACU) stay. We retrieved data from the Duke Anesthesia Peri-operative database. We included adult patients, who underwent inpatient surgery under general anesthesia with inhaled agents between January 2004 and February 2005, and had two or more risk factors for PONV documented preoperatively (female, previous history of PONV or motion sickness, non-smoker or use of postoperative opioid). Data on the use of prophylactic anti-emetics, the incidence of PONV, nausea scores, pain scores, and the use of rescue anti-emetics in PACU and in the period between PACU discharge and 24 h after surgery were recorded. Resource utilization and cost assessment was performed from the perspective of the hospital and included length and direct cost of PACU stay, as well as the acquisition costs of rescue anti-emetics in PACU. Descriptive statistics were used to summarize the demographic characteristics of patients. For group comparisons, data were analyzed with the t-test for continuous data, and the Chi-square test for categorical data. Multiple linear regression models were used to evaluate the association between PONV and PACU length of stay adjusting for confounding factors. A total of 3641 patients were included in the analysis. Of those, 2869 (79%) received prophylactic anti-emetics. In the PACU, nausea and vomiting were reported in 16% and 3% of the patients, respectively. Rescue anti-emetics were given to 26% of all patients. The incidence of vomiting was significantly less in patients who received PONV prophylaxis (p = 0.03). In multiple linear regression models, the duration of PACU stay was longer by a mean of 25 min in patients who experienced PONV or received rescue anti-emetics in PACU (p < 0.0001) despite the fact that the duration of surgery was shorter by a mean of 24 min in this group of patients (p < 0.0001). Following PACU discharge, 40% of patients reported nausea, vomiting or needed rescue anti-emetics. PONV was associated with significantly increased resource utilization and costs of PACU stay (p < 0.0001). Emesis was associated with greater incremental cost (138 US dollars) than nausea (85 US dollars), mainly from the longer duration of PACU stay. PONV remain a significant problem postoperatively and often persists beyond PACU discharge. The presence of PONV is associated with increased length of PACU stay and greater resource utilization and costs.


Genetic components of vocal learning.
Vocal learning is a rare trait. Humans depend on vocal learning to acquire spoken language, but most species that communicate acoustically have an innate repertoire of sounds that they use for information exchange. Among the few non-human species that also rely on vocal learning, songbirds have provided by far the most information for understanding this process. This article concentrates on the genetic components of vocal learning in humans and birds. We summarize the existing evidence for a genetic predisposition towards acquiring the species-specific human and avian vocal repertoires. We describe the approaches used for finding genes involved in shaping the neural circuitry required for vocal learning or in mediating the learning process itself. Special attention is given to a particular gene, FOXP2, which has been implicated in a human speech and language disorder. We have studied FoxP2 in avian vocal learners and non-learners and review evidence that links both the molecule and its close homologue FoxP1 to the development of brain regions implicated in vocal learning and to their function. FoxP2 has a characteristic expression pattern in a brain structure uniquely associated with learned vocal communication, Area X in songbirds, or its analogue in parrots and hummingbirds. In both avian song learners and non-learners FoxP2 expression predominates in sensory and sensory-motor circuits. These latter regions also express FoxP2 in mammals and reptiles. We conclude that FoxP2 is important for the building and function of brain pathways including, but not limited to, those essential for learned vocal communication.


[Analysis of the growth system of Candida albicans in a host and the development of new antifungal material].
Hyphal cells of Candida albicans bind to human hemoglobin, but not yeast cells. The amount of hemoglobin receptor is significantly higher in hyphal cells than on yeast cells. Only the hyphal cells of C. albicans use hemoglobin as a source of iron. The culture supernatant of C. albicans promoted the disruption of human red blood cells (RBC). Hemolytic activity was detected in a sugar-rich fraction (about 200 kDa) purified by Sephacryl S-100 chromatography. As the hemolytic activity was adsorbed by concanavalin A (Con A)-Sepharose, the hemolytic factor might be a mannoprotein. The activity was inactivated by periodate oxidation, indicating that the sugar moiety of the mannoprotein plays an important role in hemolysis. The structure of the sugar moiety of the mannoprotein was identified as a cell wall mannan by 1H-NMR analysis, and purified C. albicans mannan promoted the disruption of RBC. The binding of mannan to RBC was demonstrated by flow cytometric analysis and was inhibited by the addition of the band 3 protein inhibitor, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS). The hemolysis caused by mannan is inhibited by DIDS, 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid, and Bis (sulfosuccinimidyl) suberate, but not by pyridoxal-5'-phosphate. A new platinum derivative of the form H[Pt(IV) (Hdigly)Cl2(OH)2] (Hdigly = glycylglycine) has candidacidal activity 10-fold lower than that of cisplatin.


Demonstration of 3D computed tomography of chemiluminescence with a restricted field of view.
Three-dimensional imaging techniques have experienced a surge in research interest during the past few years due to advancements in both hardware, i.e., the sensor arrays and data acquisition systems, and new imaging concepts, such as light field imaging and compressed sensing. Computed tomography of chemiluminescence (CTC) is an intriguing technique for combustion diagnostics due to its ease of implementation, as no excitation source is required in measurements. It has been applied extensively for the retrieval of intermediate species such as CH*/OH*, from which the flame topology can be obtained. However, all previous demonstrations or applications were performed under the assumption that a complete field of view is available for all projections. However, this prerequisite cannot be guaranteed for some practical scenarios, such as engine measurements, in which optical access is extremely limited and a portion of the field of view is unavoidably blocked, especially when a considerable number of projections are required. This work aims to develop an improved CTC modality that can handle projections with a restricted field of view, and to suggest the best strategy for tomographic reconstruction under such experimental conditions. Although this technique is discussed under the context of combustion diagnostics, it can also be useful and adapted for other tomographic areas, such as biomedical imaging.


Structure of the Reduced TiO2(110) Surface Determined by Scanning Tunneling Microscopy.
The scanning tunneling microscope has been used to image a reduced TiO(2)(110) surface in ultrahigh vacuum. Structural units with periodicities rangng from 21 to 3.4 angstroms have been clearly imaged, demonstrating that atomic resolution imaging of an ionic, wide band gap (3.2 electron volts) semiconductor is possible. The observed surface structures can be explained by a model involving ordered arrangements of two-dimensional defects known as crystallographic shear planes and indicate that the topography of nonstoichiometric oxide surfaces can be complex.


Laparoscopy decreases the disparity in postoperative complications between black and white women after hysterectomy for endometrial cancer.
Black race has been associated with increased 30-day morbidity and mortality following surgery for endometrial cancer. Black women are also less likely to undergo laparoscopy when compared to white women. With the development of improved laparoscopic techniques and equipment, including the robotic platform, we sought to evaluate whether there has been a change in surgical approach for black women, and in turn, improvement in perioperative outcomes. Using the American College of Surgeons' National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2010 to 2015 were identified. Comparative analyses stratified by race and hysterectomy approach were performed to assess the relationship between race and perioperative outcomes. A total of 17,692 patients were identified: of these, 13,720 (77.5%) were white and 1553 (8.8%) were black. Black women were less likely to undergo laparoscopic hysterectomy compared to white women (49.3% vs 71.3%, p<0.0001). Rates of laparoscopy in both races increased over the 6-year period; however these consistently remained lower in black women each year. Black women had higher 30-day postoperative complication rates compared to white women (22.5% vs 13.6%, p<0.0001). When laparoscopic hysterectomies were isolated, there was no difference in postoperative complication rates between black and white women (9.2% vs 7.5%, p=0.1). Overall black women incur more postoperative complications compared to white women undergoing hysterectomy for endometrial cancer. However, laparoscopy may mitigate this disparity. Efforts should be made to maximize the utilization of minimally invasive surgery for the surgical management of endometrial cancer.


The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD Prediction.
Effective biomarkers are urgently needed to facilitate early diagnosis of autism spectrum disorder (ASD), permitting early intervention, and consequently improving prognosis. In this study, we evaluate the usefulness of nine biomarkers and their association (combination) in predicting ASD onset and development. Data were analyzed using multiple independent mathematical and statistical approaches to verify the suitability of obtained results as predictive parameters. All biomarkers tested appeared useful in predicting ASD, particularly vitamin E, glutathione-S-transferase, and dopamine. Combining biomarkers into profiles improved the accuracy of ASD prediction but still failed to distinguish between participants with severe versus mild or moderate ASD. Library-based identification was effective in predicting the occurrence of disease. Due to the small sample size and wide participant age variation in this study, we conclude that the use of multi-parametric biomarker profiles directly related to autism phenotype may help predict the disease occurrence more accurately, but studies using larger, more age-homogeneous populations are needed to corroborate our findings.


Incidentally detection of non-palpable testicular nodules at scrotal ultrasound: what is new?
The increased use of ultrasound in patients with urological and andrological symptoms has given an higher detection of intra-testicular nodules. Most of these lesions are hypoechoic and their interpretation is often equivocal. Recently, new ultrasound techniques have been developed alongside of B-mode and color-Doppler ultrasound. Although not completely standardized, contrast-enhanced ultrasound (CEUS) and tissue elastography (TE), added to traditional ultrasonography, can provide useful information about the correct interpretation of incidentally detected non-palpable testicular nodules. The purpose of this review article is to illustrate these new techniques in the patient management.


Sorghum Malt Extract as a Growth Medium for Lactic Acid Bacteria Cultures: A Case of Lactobacillus plantarum MNC 21.
Cultivation of lactic acid bacteria cultures is vital for research and commercial production of fermented foods. However, the conventional growth media used are generally costly. Malt extracts from four sorghum varieties (SESO 1, SESO 3, Epuripur, and Eyera) were evaluated as alternative low-cost growth media for Lactobacillus plantarum MNC 21. Saccharified sorghum malt extracts were inoculated with 4 log cfu/mL MNC 21 and incubated at 30°C for 24 h. MRS broth was the reference medium. Microbial counts, pH, titratable acidity (TA), free amino nitrogen (FAN), and total sugars were measured. Maximum microbial counts in the extracts and MRS broth were 9 and 10 log cfu/mL, respectively. Maximum growth rate in the extracts was 0.7-0.9 log cfu/mL/h and 0.8 log cfu/mL/h in MRS broth. The final pH of the extracts was 3.5-3.6, with an overall increase in TA of 1.2% in Epuripur and 0.2% in other varieties. Final pH and TA of MRS broth were 4.1 and 1.3%, respectively. Total sugars dropped by 95.2% and FAN by 2.1% in MRS broth. In contrast, total sugars and FAN dropped by 5.6-9.1% and 24.9-32.7% respectively, in the extracts. Sorghum malt extracts can be adopted as alternative low-cost growth media for lactic acid bacteria cultures.


Utilization by Escherichia coli of a high-molecular-weight, linear polyphosphate: roles of phosphatases and pore proteins.
We observed that wild-type Escherichia coli utilized a linear polyphosphate with a chain length of 100 phosphate residues (poly-P100) as the sole source of phosphate in growth medium. A mutation in the gene phoA of alkaline phosphatase or phoB, the positive regulatory gene, prevented growth in this medium. Since no alkaline phosphatase activity was detected outside the wild-type cells, the periplasmic presence of the enzyme was necessary for the degradation of polyphosphate. A 90% reduction in the activity of periplasmic acid phosphatase with a pH optimum of 2.5 (delta appA mutants) did not affect polyphosphate utilization. Of the porins analyzed (OmpC, OmpF, and PhoE), the phoB-inducible porin PhoE was not essential since its absence did not prevent growth. To study how poly-P100 diffused into the cells, we used high-resolution 31P nuclear magnetic resonance (31P NMR) spectroscopy. The results suggest that poly-P100 entered the periplasm and remained in equilibrium between the periplasm and the medium. When present individually, porins PhoE and OmpF facilitated a higher permeability for poly-P100 than porin OmpC did. The degradation of polyphosphate by intact cells of E. coli observed by 31P NMR showed a time-dependent increase in cellular phosphate and a decrease in polyphosphate concentration.


Cognitive assessment of patients with nonalcoholic fatty liver disease.
The aim of this study was to investigate cognitive performance for the first time in participants with nonalcoholic fatty liver disease (NAFLD) using the Montreal Cognitive Assessment (MoCA). In total, 70 participants with NAFLD and 73 age-matched and sex-matched healthy participants were enrolled in this prospective cross-sectional study. The diagnosis of NAFLD was made on the basis of abdominal ultrasonography findings. Anthropometric indices were calculated, and routine laboratory analyses were carried out for each participant. All participants provided sociodemographic data and completed the Beck Depression Inventory-II. Cognitive functions were evaluated using the Turkish version of the MoCA, with a cut-off score for mild cognitive impairment of less than 21 points. The MoCA scores were significantly lower in participants with NAFLD than in the healthy group (P<0.05). In addition, more NAFLD participants than healthy participants presented with deficits in the visuospatial (P<0.05) and executive function domains (P<0.05). In the multivariate model, education level [2.79 (1.12-6.96); P<0.05] and area of residence [5.68 (2.24-14.38); P<0.001] were associated independently with cognitive dysfunction in both the NAFLD and the healthy groups. The MoCA scores were correlated negatively with fibrosis 4 scores in NAFLD participants (r=-0.359; P<0.05). However, hepatosteatosis grade and the presence of metabolic syndrome were not correlated with MoCA scores in the NAFLD group (P>0.05). Our results show that NAFLD patients may have early or subtle cognitive dysfunction, including in the visuospatial and executive function domains, as indexed by scores on the MoCA test. Further targeted psychometric testing will be required to confirm the presence of cognitive impairment in this population.


Interactive nervous system development: control of cell survival in Drosophila.
The non-autonomous control of cell survival has long been thought to be a mechanism of adjusting cell populations in the vertebrate nervous system, enabling connectivity and myelination to produce a functional brain. Despite cellular evidence that analogous mechanisms occur in invertebrates, scepticism has long reigned over whether they operate in model organisms such as Drosophila. This has led to speculation that there are inherent differences between the development and evolution of simple brains and the brains of vertebrates. The great paradox has, until recently, been the absence of molecular evidence of trophic factors in Drosophila. Recent data have finally shown that EGFR (epidermal-growth-factor receptor) ligands function in the Drosophila CNS to maintain glial survival. Trophic interactions are, thus, a general mechanism of nervous system development.


Joint crisis plans and psychiatric advance directives in German psychiatric practice.
This study explores the attitude of German psychiatrists in leading positions towards joint crisis plans and psychiatric advance directives. This topic was examined by contacting 473 medical directors of German psychiatric hospitals and departments. They were asked to complete a questionnaire developed by us. That form contained questions about the incidence and acceptance of joint crisis plans and psychiatric advance directives and previous experiences with them. 108 medical directors of psychiatric hospitals and departments responded (response rate: 22.8%). Their answers demonstrate that in their hospitals these documents are rarely used. Among the respondents, joint crisis plans are more accepted than psychiatric advance directives. There is a certain uncertainty when dealing with these instruments. Our main conclusion is that German psychiatry needs an intensified discussion on the use of instruments for patients to constitute procedures for future critical psychiatric events. For this purpose it will be helpful to collect more empirical data. Furthermore, the proposal of joint crisis plans in psychiatric hospitals and departments should be discussed as well as the possibility of consulting an expert during the preparation of a psychiatric advance directive.


Relation between feeding behaviour and energy metabolism in pigs fed diets enriched in dietary fibre and wheat aleurone.
Feed intake and its daily pattern are regulated both at a short and a long term by several control pathways, including energy balance regulation. This trial aimed to determine the effect of dietary fibre (DB) (mix of wheat, soy and sugar beet pulp fibres) and aleurone supplementation and their interaction on energy and nitrogen balances in growing pigs with ad libitum access to feed. Forty pigs (BW: 35 kg) were fed diets differing by fibre concentration (NDF concentration: 10% or 14% DM) and aleurone supplementation (0, 2 or 4 g/kg) during 3 weeks. Pigs were housed individually in a respiration chamber during the last week to record feeding behaviour and measure energy and nitrogen balances (n = 36). Glucose oxidation was studied on the 6th day with an injection of [U-13C] glucose and measurement of 13CO2 production. There was no significant interaction between DB inclusion and aleurone supplementation on any variables characterizing feeding behaviour. Pigs had less but longer meals with high level of DB, with an increased interval between two meals without effect on daily feed intake. The meal frequency significantly decreased when aleurone supplementation increased. Total tract apparent digestibility coefficient of DM, organic matter, ash, nitrogen and gross energy decreased when pigs received high DB level. Dietary fibre level increased significantly faecal excreted nitrogen. Aleurone supplementation decreased nitrogen retention. Free access to the feed induced a great individual variability not only in feed intake level (from 784 to 2290 g/day) but also in feeding behaviour (from 5.5 to 21.5 meals per day). This variability can be linked with the importance of underlying feed intake regulation pathways and difference in energy balance and metabolism efficiency. Several profiles of metabolism efficiency can be discriminate, thanks to a clustering based on feeding behaviour and pre-prandial concentrations of metabolites and hormones. In conclusion, DB inclusion decreased meal frequency, increased average meal size, decreased total tract apparent faecal digestibility coefficient of nitrogen and gross energy. Supplementation of aleurone decreased average daily feed intake with a reduction of the meal number per day, without modification of average meal size. Aleurone supplementation decreased nitrogen retention and nutrient deposition. Independently of experimental diets, the high individual variability permitted discriminating different profiles with different metabolic strategies. Efficient pigs with a high energy retention as protein and lipid seem to be able to adapt their metabolism according to energy sources.


The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load.
Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d') in a retroactive cue (retro-cue) pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners' attention to one, to-be-probed syllable in memory. Participants' overall memory performance (i.e., perceptual sensitivity d') was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners' overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029). Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners' optimal use of informative cues depends on their overall memory abilities.


Ubiquitous Emergency Medical Service System Based on Wireless Biosensors, Traffic Information, and Wireless Communication Technologies: Development and Evaluation.
This study presents a new ubiquitous emergency medical service system (UEMS) that consists of a ubiquitous tele-diagnosis interface and a traffic guiding subsystem. The UEMS addresses unresolved issues of emergency medical services by managing the sensor wires for eliminating inconvenience for both patients and paramedics in an ambulance, providing ubiquitous accessibility of patients' biosignals in remote areas where the ambulance cannot arrive directly, and offering availability of real-time traffic information which can make the ambulance reach the destination within the shortest time. In the proposed system, patient's biosignals and real-time video, acquired by wireless biosensors and a webcam, can be simultaneously transmitted to an emergency room for pre-hospital treatment via WiMax/3.5 G networks. Performances of WiMax and 3.5 G, in terms of initialization time, data rate, and average end-to-end delay are evaluated and compared. A driver can choose the route of the shortest time among the suggested routes by Google Maps after inspecting the current traffic conditions based on real-time CCTV camera streams and traffic information. The destination address can be inputted vocally for easiness and safety in driving. A series of field test results validates the feasibility of the proposed system for application in real-life scenarios.


Improved nitrogen removal in upflow anaerobic sludge blanket (UASB) reactors by incorporation of Anammox bacteria into the granular sludge.
Upflow anaerobic sludge blanket reactors may offer a number of advantages over conventional mixed-tank, SBR, and biofilm reactors, including high space-loading, low footprint, and resistance to shocks and toxins. In this study, we assessed the use of upflow anaerobic sludge blanket (UASB) reactor technology as applied to anaerobic ammonia removal, or Anammox. Four 200 ml UASB reactors were inoculated with 50% (by volume) anaerobic granular sludge and 50% flocular sludge from different sources (all with the potential for containing Anammox organisms). Tools used to assess the reactors included basic analyses, fluorescent in-situ hybridisation, and mathematical modelling, with statistical non-linear parameter estimation. Two of the reactors showed statistically identical Anammox activity (i.e., identical kinetic parameters), with good ammonia and nitrite removal (0.14 kgNHx m(-3) reactor day(-1), with 99% ammonia removal). The third reactor also demonstrated significant Anammox activity, but with poor identifiability of parameters. The fourth reactor had no statistical Anammox activity. Modelling indicated that poor identifiability and performance in the third and fourth reactors were related to an excess of reduced carbon, probably originating in the inoculum. Accumulation of Anammox organisms was confirmed both by a volume loading much lower than the growth rate, and response to a probe specific for organisms previously reported to mediate Anammox processes. Overall, the UASB reactors were effective as Anammox systems, and identifiability of the systems was good, and repeatable (even compared to a previous study in a rotating biological contactor). This indicates that operation, design, and analysis of Anammox UASB reactors specifically, and Anammox systems in general, are reliable and portable, and that UASB systems are an appropriate technology for this process.


Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity.
The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics. Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke). During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (P=0.002 and P=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69. These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.


[Oxidation of n-alkanes by Pseudomonas aeruginosa strain carrying the plasmid pBS251].
Pseudomonas aeruginosa PAO8 cannot use n-alkanes or their respective alcohols as a sole carbon source. However, it can grow on n-alkanes when plasmid pBS251 is transferred into its cells. The hybrid plasmid pBS251 is a plasmid RP4 containing genes which control the capability to grow on n-alkanes of the C6-C12 series. Studies of n-alkane oxidation by P. aeruginosa PAO8 carrying pBS251 have shown that this plasmid controls the inducible alkane and alcohol oxidizing activities; the subsequent steps of n-alkane oxidation controlled by chromosomal genes are constitutive.


Duration of Care Trajectories in Persons With Dementia Differs According to Demographic and Clinical Characteristics.
To estimate (1) the duration of no formal care, home care, and institutional care after dementia diagnosis, and (2) the effect of age, sex, living situation, dementia medication, migration background, and income on this dementia care duration. Longitudinal retrospective study using routinely recorded general practice electronic health records linked with population-based healthcare and mortality data. In total, 11,012 community-dwelling persons who received an incident dementia diagnosis and were listed in a Dutch general practitioner database from 448 general practices in the Netherlands. Using multistate modeling analyses, we estimated the mean duration of care types (no/home/institutional care) for different ages based on simulations of transition rates and examined the influence of demographic and clinical factors on these durations. From dementia diagnosis onward in 85-year-old men, the mean duration without formal care was 0.7 years, of home care 1.7, and institutional care 1.1 years. In 85-year-old women, the duration without formal care was 0.8 years, of home care 2.3, and institutional care 2.3 years. Total care duration was 3.5 years in 85-year-old men and 5.4 years in 85-year-old women. In men, the duration of home care was longer compared with no formal care and institutional care. The duration of no formal care was longer in persons not living alone, without prescribed dementia medication, with a non‒Western migration background, or with a higher income. The duration of home or institutional care was longer in women, persons without polypharmacy, in those living alone, or those with a Western background. Our findings help to increase understanding of long-term dementia care trajectories and show that demographic and clinical factors determine the duration of care types. Our results can contribute to the organization of healthcare resource planning and monitoring of the effects of healthcare policy and interventions.


Variational filtering.
This note presents a simple Bayesian filtering scheme, using variational calculus, for inference on the hidden states of dynamic systems. Variational filtering is a stochastic scheme that propagates particles over a changing variational energy landscape, such that their sample density approximates the conditional density of hidden and states and inputs. The key innovation, on which variational filtering rests, is a formulation in generalised coordinates of motion. This renders the scheme much simpler and more versatile than existing approaches, such as those based on particle filtering. We demonstrate variational filtering using simulated and real data from hemodynamic systems studied in neuroimaging and provide comparative evaluations using particle filtering and the fixed-form homologue of variational filtering, namely dynamic expectation maximisation.


Biomarkers for risk assessment and prevention of breast cancer.
Breast carcinogenesis is a multistep and multipath disease process which occurs in the epithelium lining of the ductal system in the vast majority of cases. Several studies have shown that the relative risk of breast cancer is increased in every step of this progression and many tumour associated antigens or biomarkers appear during each phase of carcinogenesis. However, their ability to predict for a substantial likelihood of developing breast cancer remains unclear. The acquisition of breast tissue samples, representative of an individual's cellular stability and subcellular biochemical and molecular state could lead to definition of surrogates for risk, early detection, pharmacodynamic determination and finally chemopreventive intervention. The intraductal approach includes nipple aspiration fluid (NAF), ductal lavage (DL) and mammary ductoscopy (MD). These techniques together with random periareolar fine needle aspiration (RPFNA) represent the available techniques for the sampling of breast fluid and exfoliated epithelial cells. At the moment, these procedures are not considered a screening procedure for early breast cancer detection but might provide a powerful research tool for studying breast carcinogenesis in vivo. We summarize the current knowledge regarding the vast array of molecules involved at all stages of carcinogenesis, which can be studied by intraductal approach, and the possibility to utilize them as candidate biomarkers to refine risk assessment, and their possible use in prevention strategies.


Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial.
Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homoeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that daily oral CGMP intake would reduce high-sensitive C-reactive protein (hsCRP) in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a 4-week intervention of either 25 g of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, with regard to either hsCRP or faecal calprotectin level, faecal microbiota composition or faecal SCFA content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable, and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 g of CGMP during 4 weeks was safe, well tolerated, had acceptable palatability and was without any effects on body weight.


A puzzle of hemolytic anemia, iron and vitamin B12 deficiencies in a 52-year-old male.
A 52-year-old male with no significant past medical history reports increasing generalized fatigue and weakness for the past 2 weeks. Physical examination reveals jaundice and pallor without organomegaly or lymphadenopathy. His hemoglobin was 5.9 g/dL with a mean corpuscular volume of 87.1 fL and elevated red blood cell distribution width of 30.7%. His liver function test was normal except for elevated total bilirubin of 3.7 mg/dL. Serum LDH was 701 IU/L, and serum haptoglobin was undetectable. Further investigation revealed serum vitamin B12 of <30 pg/mL with elevated methylmalonic acid and homocysteine level. In addition, serum ferritin and transferrin saturation were low. The patient was diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with concomitant iron deficiency anemia.


Compressive shear strength of core materials and restoring techniques.
In this study, ninety extracted endodontically treated mandibular molars were mounted in acrylic resin blocks. Five groups of eighteen extracted teeth were prepared by two different techniques. A peripheral shelf 2 mm deep and 1.4 mm wide was prepared as a first technique, while TMS pins were used in the second group. The teeth were then restored with five different core materials: silver-reinforced glass-ionomer, resin-modified glass-ionomer, self-cured glass-ionomer, polyacid-modified composite resin, and titanium-reinforced composite resin. An Instron testing machine was used to apply shear force at a crosshead speed of 2 mm/min until fracture occurred. The results were obtained statistically using analysis of variance and least significant difference tests. According to the results of this study, Ti-core and composite resin were the strongest core materials when subjected to shear forces, and the most retentive preparation design was the vertical-pin design. The fractures of these materials with a vertical-pin design were mostly seen at the core and the tooth.


Hypoxia and HIF-1alpha in chondrogenesis.
In endochondral bone development chondrocytes undergo proliferation, hypertrophic differentiation, mineralization of the surrounding matrix, death, blood vessel invasion, and finally replacement of cartilage with bone. The chondrocytic growth plate is a unique mesenchymal tissue, as it is avascular but it requires blood vessel invasion in order to be replaced by bone. We have recently provided evidence that the growth plate is hypoxic during fetal development. Adaptation to hypoxia is a critical event in numerous pathological settings, such as tumor progression and survival of tissues in which blood flow has been suddenly interrupted. One of the hallmarks of the response to hypoxia is activation of the transcription factor HIF-1alpha. The von Hippel-Lindau (VHL) tumor suppressor protein is a component of a ubiquitin ligase promoting proteolysis of HIF-1alpha. By using a genetic approach, we have demonstrated that VHL and HIF-1alpha are critical regulators of endochondral bone development.


Temporalis muscle flap for craniofacial reconstruction after tumor resection.
Temporalis muscle flap provides a good solution for the reconstruction of craniofacial defects after tumor resection. Nine patients with complicated defects located at the upper two thirds of the face, anterior cranial base, or mastoid region are presented. Five patients had orbital exenteration, two with total maxillectomy and two with anterior craniofacial resection. Temporalis muscle flap provided profuse well-vascularized tissue for the obliteration of orbital exenteration and total maxillectomy cavities and coverage of surface defects. Cranial, oral, and nasal spaces were separated successfully in all patients. Temporalis muscle flap is a very reliable technique with low complication rates and few donor site problems. This safe and technically easy flap can be preferred for the reconstruction of craniofacial defects after ablative tumor surgery, especially in older and debilitated patients.


Analysis of fMRI data using improved self-organizing mapping and spatio-temporal metric hierarchical clustering.
The self-organizing mapping (SOM) and hierarchical clustering (HC) methods are integrated to detect brain functional activation; functional magnetic resonance imaging (fMRI) data are first processed by SOM to obtain a primary merged neural nodes image, and then by HC to obtain further brain activation patterns. The conventional Euclidean distance metric was replaced by the correlation distance metric in SOM to improve clustering and merging of neural nodes. To improve the use of spatial and temporal information in fMRI data, a new spatial distance (node coordinates in the 2-D lattice) and temporal correlation (correlation degree of each time course in the exemplar matrix) are introduced in HC to merge the primary SOM results. Two simulation studies and two in vivo fMRI data that both contained block-design and event-related experiments revealed that brain functional activation can be effectively detected and that different response patterns can be distinguished using these methods. Our results demonstrate that the improved SOM and HC methods are clearly superior to the statistical parametric mapping (SPM), independent component analysis (ICA), and conventional SOM methods in the block-design, especially in the event-related experiment, as revealed by their performance measured by receiver operating characteristic (ROC) analysis. Our results also suggest that the proposed new integrated approach could be useful in detecting block-design and event-related fMRI data.


Trophic cascades from wolves to grizzly bears or changing abundance of bears and alternate foods?
This is a Forum article commenting on: Ripple, W. J., Beschta, R. L., Fortin, J. K., & Robbins, C. T. (2014) Trophic cascades from wolves to grizzly bears in Yellowstone. Journal of Animal Ecology, 83, 223-233. Comparisons Ripple et al. (2014) used to demonstrate increased fruit availability and consumption by grizzly bears post-wolf reintroduction are flawed and tenuous at best. Importantly, a more parsimonious (than trophic cascades) hypothesis, not sufficiently considered by Ripple et al., exists and is better supported by available data I review.


Higher internality of health locus of control is associated with the use of complementary and alternative medicine providers among patients seeking care for acute low-back pain.
Given that persons with a stronger belief in internal health locus of control (HLC) have been shown to comply well with medical advice, HLC internality may play an important role in low-back pain (LBP) prevention and management because it requires the patient's own commitment. Previous studies in conditions other than LBP have shown that the use of complementary and alternative medicine (CAM) is associated with high HLC internality. Here, we examined the relationship between CAM facility visits and internality of HLC in persons with LBP. We analyzed the data from the Health Diary Study, which surveyed the health-related behavior of 3477 persons sampled from the general population of Japan. Among 2377 participants aged 18 to 75 years, 673 reported LBP during the study period. We examined CAM facility visits and HLC among 81 previously untreated LBP patients who sought care from western medical doctors or CAM providers during the 1-month study period. Of the 81 patients, 40 reported at least 1 CAM visit, whereas 41 visited western medical doctors only. Participants who visited CAM facilities had a higher internality score than those who visited western medical doctors after controlling for age, sex, size of residential city, and bodily pain score of the Short Form-8 Health Survey scale. Visitors to CAM facilities had a stronger belief in internal HLC. This finding suggests that visitors to CAM facilities are more sensitive to educational intervention for the self-management of LBP than those who visit western medicine. In order not to miss the opportunity of reaching these patients, the education should be more emphasized on CAM facilities.


The relationship between serum zinc level and preeclampsia.
Preeclampsia is one of the commonest causes of prenatal and maternity related death in the world. Preeclampsia is caused by multiple factors and finding any factor related to this disorder can help on time prevention of this disease, which reduces the mortality of mothers and infants. Zinc deficiency is a possible risk factor for risky pregnancies and the results of studies on this subject are controversial. This study investigated the relationship between mothers' serum zinc and risky pregnancies. This was a case-control study on 48 normal pregnancies as controls and 48 preeclamptic pregnancies as case group. The women were studied in their third month of pregnancy. Simple random sampling was done based on inclusion and exclusion criteria. The two groups were matched in mothers' age, pregnancy age, number of childbirth, and socioeconomic status. Data were collected by blood sampling and a questionnaire. Serum zinc level was assessed by atomic absorption spectrometry method. Data were analyzed using SPSS Software. The level of serum zinc in most women in both groups was under 50 mg/dl (62.5% in normal pregnancy group and 79.2% in preeclamptic group). There was no significant difference between the mean (SD) serum zinc concentration of the two groups (47.83 (12.72) for normal pregnancy and 43.66 (11.98) for preeclampsia). There was an association between serum zinc concentration and the severity of preeclampsia (p = 0.04, r = -0.12). We did not find any significant relation between serum zinc level and the following variables: mothers' age (p = 0.15, r = -0.11), pregnancy age (p = 0.07, r = -0.24), and parity (p = 0.02, r = -0.39). The findings of this study showed that the assessment of serum zinc level does not have any clinical values for managing preeclampsia. However, based on the relationship between serum zinc concentration and the severity of preeclampsia in this study, we recommend assessment of serum zinc concentration as an index for predicting the severity of preeclampsia.


Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site.
Local anaesthetics are often used as part of multimodal pain management techniques to manage postsurgical pain and lessen the need for opioid analgesics; however, the duration of action of traditional formulations of local anaesthetics is short. Liposome bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound. This article provides a summary of the pharmacokinetic profile of liposome bupivacaine compared with bupivacaine HCl based on data compiled from four randomized, active- and placebo-controlled trials that included pharmacokinetic assessments following single administrations of study drug. Each study evaluated the safety, efficacy and pharmacokinetic profile of liposome bupivacaine in separate surgical populations (patients undergoing inguinal hernia repair, total knee arthroplasty, haemorrhoidectomy or bunionectomy). Pharmacokinetic parameters included maximum plasma drug concentration (C(max)), area under the curve (AUC) for plasma bupivacaine concentration over time extrapolated to infinity (AUC(∞)), time to observed C(max) (t(max)) and terminal elimination half-life of bupivacaine (t(½)). The studies assessed single administrations of liposome bupivacaine at dose levels ranging from 106 to 532 mg or bupivacaine HCl 100 to 150 mg or placebo (0.9 % sodium chloride) given locally via wound infiltration at the end of surgery prior to wound closure. Male and non-pregnant female patients (n = 253) aged ≥18 years, scheduled to undergo surgery as per the specific protocol for each study, were enrolled. Patient characteristics were stratified by liposome bupivacaine doses ≤266 mg and >266 mg, and bupivacaine HCl treatment arms. Pharmacokinetic parameters for liposome bupivacaine doses of 106, 266, 399 and 532 mg were compared. Plasma concentration versus time profiles were quantitatively similar across these four dose levels of liposome bupivacaine, with an initial peak occurring within 1 h after administration followed by a second peak about 12-36 h later. The overall incidence of adverse events was lower in the liposome bupivacaine ≤266-mg group than the liposome bupivacaine >266-mg and bupivacaine HCl groups (100- or 150-mg doses). In summary, liposome bupivacaine was well tolerated across the four studies and varied surgical models, and exhibited bimodal kinetics with rapid uptake observed during the first few hours and prolonged release through 96 h after administration.


A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels.
To evaluate the impact of a focused preconceptional and early pregnancy program specializing in the care of women with Type 1 diabetes on perinatal mortality and congenital malformations. This clinical study included women with Type 1 diabetes in an interdisciplinary Diabetes in Pregnancy Program Project Grant (PPG) funded by the NIH (1978-1993); these women were enrolled preconceptionally or during the first trimester (up to 14 weeks) and had pregnancies continuing beyond 20 weeks gestation. Strict glucose control was implemented and adherence assessed. Antepartum fetal surveillance was started at 32 weeks gestation. All live-born infants and stillbirths were examined. A retrospective comparison analysis of the period before PPG I (1973-1978) and after cessation of funding (1993-1999) was performed, specifically evaluating perinatal mortality and congenital malformation rates. Data were analyzed using analysis of variance, chi2, and Fisher's exact test. Three hundred and six women were enrolled in three 5-year periods: PPG I (1978-1983) n = 111, PPG II (1983-1988) n = 103, and PPG III (1988-1993) n = 92. Entry and interval glycohemoglobin A1 concentrations obtained decreased with each consecutive PPG. An emphasis on preconception care began in 1984, with preconception enrollment reaching 23% for PPG II and increasing in PPG III to 37%. As preconception enrollment increased, perinatal mortality rate decreased from 3% for PPG I and 2% for PPG II, to 0% in PPG III, and the congenital malformation rate decreased to a low 2.2% by PPG III. Comparison data collected for the period before PPG 1 (1973-1978) n = 79 revealed a perinatal mortality rate of 7% and a congenital malformation rate of 14%. Also, a postprogram retrospective analysis of the period 1993-1999 (n = 82) revealed an increase in perinatal mortality, with one death compared to none in PPG III, and a congenital malformation rate of 3.65% compared to 2.2% during PPG III. The preconception enrollment for this period decreased (19.5%). A program emphasizing preconceptional care, strict glycemic control preconceptionally and throughout gestation, and the use of antepartum fetal surveillance was associated with a significant decrease in the rate of perinatal mortality and congenital malformations in infants of women with Type 1 diabetes. However, ongoing improved outcome appears to depend on the availability of funding for a specialized preconception program.


Attitudes of Students at Sultan Qaboos University towards the Nursing Profession.
The aim of this study was to explore the attitudes of Sultan Qaboos University (SQU) students towards the nursing profession. A sample of 377 students (male = 130; female = 247) were selected from different colleges of SQU, including the College of Nursing. A questionnaire was constructed and validated to assess the attitudes of SQU students towards the nursing profession. Findings revealed that both male and female students in all academic years and colleges had positive attitudes toward the nursing profession. The findings also revealed that gender and academic year created no significant differences (P <0.05) among the study participants, but that the students' college affiliation did have a significant effect on their attitudes. In particular, nursing students had more positive attitudes than students of other colleges. Findings indicated that the attitudes of SQU students towards the nursing profession were positive, especially those of the nursing students. This means that serious efforts should be made to continue to promote the nursing profession and so ensure that it remains positively regarded by all concerned.


Total hip arthroplasty in rapidly progressive osteoarthritis of the hip: clinical and radiological outcome of a consecutive series of patients.
Rapidly progressive osteoarthritis (RPOA) is an uncommon subset of osteoarthritis (OA) characterized by rapid joint degeneration and destruction. The treatment of choice for these patients has traditionally been total hip arthroplasty (THA) because nonoperative treatments modalities are not effective. RPOA can lead to acetabular bone loss and consequently intraoperative technical difficulties making joint reconstruction in such patients a challenge for the surgeon. The purpose of this study was to determine the clinical and radiological results of patients suffering from RPOA and treated with hybrid or cementless THA at a single institution. We retrospectively review of all patients who underwent THA for RPOA from January 2011 to December 2016. Twenty-three hips in twenty-one patients were included in this study, with a mean age at surgery of 74 years (range, 41-82) and a mean follow-up of 30 months (range, 24-60). In all patients an uncemented cup, either plasma-spray or trabecular titanium, was implanted. In eighteen cases a cemented femoral stem was used. In eight cases autologous bone graft was used to replace the acetabular defect. Radiographic and clinical follow-up was performed at six months postoperatively, twelve months and yearly thereafter. At radiographic follow-up, no signs of prosthetic loosening or migration were seen. Harris Hip Score improved from 65.3 preoperatively to 89.2 at latest follow-up. The use of both hybrid and uncemented THA in the treatment of RPOA was found to be successful in our patients with a mean 30 months follow-up. Hemispherical cementless cups with both plasma spray and high porosity outer surface (used in the worse cases) were effective in getting primary stability and bone ingrowth.


High permeability sub-nanometre sieve composite MoS2 membranes.
Two-dimensional membranes have gained enormous interest due to their potential to deliver precision filtration of species with performance that can challenge current desalination membrane platforms. Molybdenum disulfide (MoS2) laminar membranes have recently demonstrated superior stability in aqueous environment to their extensively-studied analogs graphene-based membranes; however, challenges such as low ion rejection for high salinity water, low water flux, and low stability over time delay their potential adoption as a viable technology. Here, we report composite laminate multilayer MoS2 membranes with stacked heterodimensional one- to two-layer-thick porous nanosheets and nanodisks. These membranes have a multimodal porous network structure with tunable surface charge, pore size, and interlayer spacing. In forward osmosis, our membranes reject more than 99% of salts at high salinities and, in reverse osmosis, small-molecule organic dyes and salts are efficiently filtered. Finally, our membranes stably operate for over a month, implying their potential for use in commercial water purification applications.


Pressure effects in laser-induced plasmas of trinitrotoluene and pyrene by laser-induced breakdown spectroscopy (LIBS).
The influence of the ambient atmosphere on the dynamics of plasma expansion, besides the interaction between excited plasma and gas molecules, has been studied for specific organic aromatic compounds. To analyze the influence of air on the formation pathways of atomic and molecular species inside the plasma plume, the spectral emissions in laser-induced breakdown spectroscopy (LIBS) of 2,4,6-trinitrotoluene (TNT) and pyrene were compared at different pressure environments, from high vacuum to atmospheric pressure. Pelletized samples of the compounds were introduced in a vacuum chamber for excitation with the fourth harmonic output of an Nd : YAG laser (266 nm). The optical emission signal was collected with an optical fiber connected to a spectrograph fitted with a intensified charge-coupled device detector. Results from LIBS spectra indicate that changes in pressure level affect the kinetics of the characteristic excited species and their spatial distribution inside the plasma plume.


How the speed of word finding depends on ventral tract integrity in primary progressive aphasia.
Primary progressive aphasia (PPA) is a clinical neurodegenerative syndrome with word finding problems as a core clinical symptom. Many aspects of word finding have been clarified in psycholinguistics using picture naming and a picture-word interference (PWI) paradigm, which emulates naming under contextual noise. However, little is known about how word finding depends on white-matter tract integrity, in particular, the atrophy of tracts located ventrally to the Sylvian fissure. To elucidate this question, we examined word finding in individuals with PPA and healthy controls employing PWI, tractography, and computer simulations using the WEAVER++ model of word finding. Twenty-three individuals with PPA and twenty healthy controls named pictures in two noise conditions. Mixed-effects modelling was performed on naming accuracy and reaction time (RT) and fixel-based tractography analyses were conducted to assess the relation between ventral white-matter integrity and naming performance. Naming RTs were longer for individuals with PPA compared to controls and, critically, individuals with PPA showed a larger noise effect compared to controls. Moreover, this difference in noise effect was differentially related to tract integrity. Whereas the noise effect did not depend much on tract integrity in controls, a lower tract integrity was related to a smaller noise effect in individuals with PPA. Computer simulations supported an explanation of this paradoxical finding in terms of reduced propagation of noise when tract integrity is low. By using multimodal analyses, our study indicates the significance of the ventral pathway for naming and the importance of RT measurement in the clinical assessment of PPA.


Effects of marijuana on visuospatial working memory: an fMRI study in young adults.
The effects of marijuana use on visuospatial working memory were investigated in 19-21-year-olds using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood including: prenatal drug history, detailed cognitive/behavioral performance, and current and past drug usage. This information allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana, nicotine, alcohol, and caffeine exposure and offspring alcohol, marijuana, and nicotine use. Ten marijuana users and 14 nonusing controls performed a visuospatial 2-back task while fMRI blood oxygen level-dependent response was examined. Despite similar task performance, marijuana users had significantly greater activation in the inferior and middle frontal gyri, regions of the brain normally associated with visuospatial working memory. Marijuana users also had greater activation in the right superior temporal gyrus, a region of the brain not typically associated with visuospatial working memory tasks. These results suggest that marijuana use leads to altered neural functioning during visuospatial working memory after controlling for other prenatal and current drug use. This alteration appears to be compensated for by the recruitment of blood flow in additional brain regions. It is possible that this compensation may not be sufficient in more real-life situations where this type of processing is required and thus deficits may be observed. Awareness of these neural physiological effects of marijuana in youth is critical.


Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic.
Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs). The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs) with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with rituximab in the treatment of patients with B-cell malignancies.


The interrelation of the two c-type cytochromes in Rhodopseudomonas sphaeroides photosynthesis.
Photosynthetic electron flow in the bacterium Rhodopseudomonas sphaeroides involves two c-type cytochromes, one membrane-bound and the other a soluble protein, cytochrome c2. Membranes deficient in cytochrome c2 were used for photo-oxidation studies, with and without the addition of purified cytochrome c2. The results favour a series interrelation, membrane cytochrome c-cytochrome c2-reaction centre.


Peritoneal fluid values and collection technique in young, normal calves.
Peritoneal fluid from 10 healthy young male Holstein calves was analyzed three times (2 to 3 days, 12 to 15 days and 27 to 30 days) during the first month of life. A new technique for collection of peritoneal fluid from calves positioned in left lateral recumbency was developed. The technique was found to be reliable and without noticeable complications. Mean peritoneal fluid nucleated cell counts, red blood cell counts, and absolute counts for mononuclear cells, lymphocytes and eosinophils did not change significantly (P </= 0.05) over the first month of life. Mean peritoneal fluid protein concentrations were significantly (P </= 0.05) higher at the earliest sampling period compared to the latter two sampling times. The mean absolute neutrophil count in peritoneal fluid at the final sampling time was significantly (P </= 0.05) higher than in the earlier two sampling times. These changes were considered to be of equivocal importance. There was no significant (P </= 0.05) correlation between the calves' white blood cell counts and peritoneal fluid nucleated cell counts, or between absolute counts of similar cell types in peripheral blood and peritoneal fluid. Peritoneal fluid from the young calves in the present study had higher mean total nucleated cell counts and lower protein concentrations when compared non-statistically to peritoneal fluid values reported in the literature for older calves and mature pregnant cattle. The young calves also had lower mean absolute eosinophil counts and higher mean absolute neutrophil cell counts than those previously reported for older calves and mature cattle. It was concluded that use of data for peritoneal fluid values in older calves or mature cattle may be inappropriate for evaluating peritoneal fluid from younger calves.


Successful implementation of remote video consultations for patients receiving home parenteral nutrition in a national UK Centre.
Our intestinal failure unit provides care for patients from a wide geographical area. Patients dependent on home parenteral nutrition (HPN) are routinely reviewed in the clinic at 3-6 monthly intervals. Between March 2008 and 2015, we noted a significant rise in the number of patients under our care, with an associated 51% increase in clinic appointments offered. We evaluated whether telemedicine would provide a strategy to reduce patients' need to travel while maintaining safe clinical standards. Implementation began in December 2015 via patient consultation and small tests of change. Clinical data were obtained from a prospectively maintained database. Remote video consultation discussions were carried out via internet video call service (Skype). An anonymous satisfaction questionnaire was offered to patients for completion following consultation. The number of miles saved by obviating the need to attend hospital was calculated for each patient. During the study period, patients receiving HPN rose by 18% to 288. Twenty-five patients used telemedicine for HPN follow-up, three of these for follow-up with the psychologist. By avoiding hospital attendance, this saved a mean travel distance of 56.7 miles with a total of 18 346.6 cumulative miles saved. Sixty-three per cent of patients rated their satisfaction with the system at ≥90%, with a mean satisfaction of 85%. Eight per cent of the telemedicine cohort was admitted with an HPN complication, compared with an admission rate of 24% for the whole HPN cohort. One emergency admission was avoided. Telemedicine can obviate the need for clinic attendance in HPN-dependent patients, so reducing the need of individuals with chronic illness to travel while maintaining standards for follow-up.


Rhythmic and spatial abnormalities of gastric slow waves in patients with functional dyspepsia.
The objectives of this study were to assess differences in gastric slow waves measured by a newly approved multichannel electrogastrogram (EGG) device between patients with functional dyspepsia (FD) and healthy controls. Gastric myoelectrical activity was measured by multichannel EGG for 1 hour preprandially and for 2 hours postprandially in 72 FD patients and 16 healthy volunteers. Computerized spectral analysis methods were used to compute various EGG parameters. (1) Multichannel EGG was abnormal in 83.3% of patients. (2) The regularity of the gastric slow wave was significantly lower in the FD patients in both fasting and fed states; the lowest regularity was seen in channel 3. (3) There was a significantly higher incidence of arrhythmia and tachygastria in FD patients. The highest percentage of arrhythmia and tachygastria were both seen in channel 3. (4) The FD patients showed a significantly lower percentage of slow wave coupling among the 4-channel EGGs in the fed state. (5) The postprandial-preprandial power ratio was significantly less in FD patients. (6) These patients had high symptom scores particularly to nausea, upper abdominal pain, and bloating. However, no significant correlation was noted between the EGG parameters and the symptoms. Gastric myoelectrical activity is impaired in most patients with FD. The impairment is reflected as a decreased percentage of normal slow waves and an excessive amount of arrhythmia as well as an abnormal spatial distribution of EGG parameters among the 4 channels, suggesting an impaired coordination of gastric slow waves.


[The use of non-Euclidean metrics in epidemiological classifications].
A non-Euclidean metric, stable to pollutions in sample data, for hierarchical cluster analysis in epidemiology is proposed. The simplicity of calculations permits its easy use in practice. On the basis of this metric the towns of Tula Province have been grouped according to morbidity rates in the shigellosis of Flexner and Sonne with the conjugated value of parameters.


Penicillin-resistant pneumococcal meningitis: high antibiotic exposure impedes new vaccine protection.
The frequency of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRP) has increased in recent years, making treatment failure more likely. It is currently expected that pneumococcal conjugate vaccines might curb this trend. We investigated this issue using a mathematical model applied to the current prevalence of resistance and antibiotic exposure in the United States and in France. Our main finding was that the level of antibiotic exposure may limit the effect of the vaccine. In relatively low antibiotic exposure environments such as the United States, large-scale vaccination prevents a large part of PRP meningitis cases, whereas in high antibiotic-exposure environments such as France, vaccination alone does not lead to a substantial reduction in PRP meningitis incidence. Our results suggest that antibiotic exposure reduction will remain of primary importance for the control of PRP meningitis despite wide scale use of pneumococcal conjugate vaccines.


Elevated Fe(II) and dissolved Fe in hypoxic shelf waters off Oregon and Washington: an enhanced source of iron to coastal upwelling regimes.
There has been a growing interest in the cause and impact of hypoxic regions known as "dead zones" that have increasingly appeared along the west coast of the United States and have caused widespread destruction to the crab and fishing industry in this upwelling region. Here, we present results that demonstrate that the hypoxic conditions in the water column over the continental shelf result in a marked increase in iron(II) concentrations, which contribute to elevated dissolved and labile particulate iron concentrations. These elevated dissolved iron(II) concentrations result from two factors: (1) the hypoxic water column allows extremely elevated iron(II) concentrations in reducing porewaters to exist close to the sediment water interface, leading to an increased flux of iron(II) from the sediments; (2) the low oxygen, low pH, and low temperatures within the bottom boundary layer act in concert to markedly slow down the oxidation rate of Fe(ll). During upwelling conditions, this process can result in a greatly enhanced source of Fe available to upwell to surface waters, potentially increasing phytoplankton productivity, which can, in turn, lead to enhanced export flux, driving the system further into hypoxic or suboxic conditions.


Protein metabolism in pregnancy.
Adaptation to pregnancy involves major changes in maternal metabolism to provide for the growing demands of the conceptus. Although changes in glucose metabolism, and possibly in fatty acid metabolism, occur in parallel with the increasing energy demands of the mother and the fetus, adaptation of protein metabolism appears to be in anticipation of maternal and fetal needs. During pregnancy, there is an excess of maternal nitrogen in the form of lean body mass over that deposited in the fetus and the products of conception; there is also a pregnancy-induced hypoaminoacidemia and a diminished amino acid response to protein intake, suggesting an increased uptake of amino acids in the splanchnic compartment. With the use of stable-isotope-labeled tracers, it was shown that there is a decreased rate of urea synthesis during pregnancy that is evident early in gestation. Kinetic studies of leucine metabolism showed no significant change in leucine carbon turnover but a significantly lower rate of leucine nitrogen turnover, suggesting a lower rate of leucine transamination. These data suggest an integral regulation of whole-body protein and nitrogen metabolism starting early in gestation and aimed at conservation and accretion of nitrogen by the mother and the fetus.


Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration.
Diabetic retinopathy (DR) has been classically considered a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is also an early event in the pathogenesis of DR. Citicoline has been successfully used as a neuroprotective agent in the treatment of glaucoma but their effects on DR remain to be elucidated. On this basis, the main aim of the present study was to evaluate the effect of topical administration of citicoline in liposomal formulation on retinal neurodegeneration in db/db mouse and to investigate the underlying mechanisms of action. The treatment (citicoline or vehicle) was topically administered twice daily for 15 days. Retinal analyses were performed in vivo by electroretinography and ex vivo by using Western blot and immunofluorescence measurements. We found that the liposomal formulation of citicoline prevented glial activation and neural apoptosis in the diabetic retina. The main mechanism implicated in these beneficial effects were the inhibition of the downregulation of synaptophysin and its anti-inflammatory properties by means of preventing the upregulation of NF-κB and TNF-α (Tumor Necrosis Factor α) induced by diabetes. Overall, these results suggest that topical administration of citicoline in liposomal formulation could be considered as a new strategy for treating the early stages of DR.


Long-term safety of aromatase inhibitors in the treatment of breast cancer.
Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond the choice of clinical strategy, the long duration of exposure to AI in adjuvant setting required a full determination of the long-term toxicity profile of these agents. While all three AIs have either favorable (decreased incidence of hot flashes, gynecologic and thromboembolic side-effects) or unfavorable (skeletal complications, arthralgia, musculoskeletal pain, sexual dysfunction) class adverse events, some variability between AIs has been reported in side-effects as well as gastrointestinal, urogenital, neurologic, and visual disturbances, confirming the lack of interchangeability between the three AIs. The overall therapeutic index of AIs appears today superior to that of tamoxifen with proven improved efficacy and better toxicity profile. This review will explore the results from the available adjuvant AIs trials with a particular emphasis on safety profiles, quality of life, and therapeutic index, helping to define the present role of AIs in the adjuvant management of postmenopausal patients with breast cancer.


Modifier 22 on perioperative outcomes of robotic assisted laparoscopic prostatectomy.
Robotic assisted laparoscopic prostatectomy (RALP) is a mainstay in the treatment of prostate cancer. Current procedure terminology (CPT) identifies a case that requires substantially greater effort than usual by using the modifier 22 code (M22). Our objective was to identify the most common etiologies leading to M22 at our institution and determine the effect on perioperative outcomes. We retrospectively reviewed our prostatectomy database from 2009-2012 to identify patients who underwent RALP with and without M22. Reasons for M22 were determined by review of operative reports. Comparisons were made using Chi-square analysis and independent t-tests for continuous data. Of 579 patients identified from our database, 208 (36%) had a M22. Eighty-six (41%) patients had ≥ 2 documented reasons for M22. Adhesiolysis was the most common reason for M22 followed by large prostate and previous hernia mesh. Body mass index (BMI) (29.8 versus 28), prostate volume (53 g versus 44 g), operative time (259 minutes versus 234 minutes), and discharge from hospital with pelvic drain in place (6.7% versus 3%) were all significantly higher in the M22 group. Final pathological stage and positive margin rate were not increased in those with a M22. Complications were not different between those with and without M22. The M22 code is associated with longer operative times, larger prostates, and higher BMI. Adverse effects on final pathological stage, margin status and complications were not found in those with M22. Many patients with a M22 have more than one reason documented as for the explanation of the modifier.


Oral drug suitability parameters.
Assessing the oral drug suitability of compounds as early as possible within drug discovery is an important objective. This study describes a methodology that attempts to simplify the evaluation of compounds based on their in vivo quantity levels within a mammalian body, represented using a mathematical model that imposes a time limitation on oral absorption and assumes non-instantaneous drug distribution between plasma and tissue. This simplification results in two new oral drug suitability parameters that can quantitatively relate oral dose to in vivo exposure for compounds with vastly different tendencies in terms of absorption into, and elimination from, the body. Consequently, the complexities associated with evaluating a compound's oral drug suitability are simplified to an assessment of these two new parameters. Application of this methodology at the virtual design stage is discussed, along with functionality that accounts for uncertainty related to a compound's distribution kinetics and errors associated to in silico QSAR predictions for the required input data.


Coronavirus IBV: further evidence that the surface projections are associated with two glycopolypeptides.
The surface projections (peplomers) of avian infectious bronchitis virus (IBV) strain M41 have been separated from the nucleocapsid (N) and matrix (M) proteins by sedimentation in a sucrose gradient after virus disruption by the non-ionic detergent Nonidet P40. The peplomers comprised two glycopolypeptides of mol. wt. 90 X 10(3) (90K; S1) and 84K (S2), shown by analysis of differentially radiolabelled virus to be present in equimolar proportions. Polypeptides of 75K and 110K, which were detected by Coomassie Brilliant Blue staining in similar amounts to S1 and S2 in some unlabelled virus preparations, were absent from peplomer preparations and are probably host cell polypeptides. The S1:S2:N:M polypeptide molar ratio for IBV-M41 was approximately 1:1:6:15.


Web services in the life sciences.
Web services provide a standard way of publishing applications and data sources over the internet, enabling mass dissemination of knowledge. In the life sciences, the web-service approach is seen as being a road to standardizing the multitude of tools available from different providers. In this article, we present an overview of the technology (focusing on life-science applications), we list the currently available service providers and we discuss advanced issues raised by the concept.


In vivo calpain/caspase cross-talk during 3-nitropropionic acid-induced striatal degeneration: implication of a calpain-mediated cleavage of active caspase-3.
The role of caspases and calpains in neurodegeneration remains unclear. In this study, we focused on these proteases in a rat model of Huntington's disease using the mitochondrial toxin 3-nitropropionic acid (3NP). Results showed that 3NP-induced death of striatal neurons was preceded by cytochrome c redistribution, transient caspase-9 processing, and activation of calpain, whereas levels of the active/processed form of caspase-3 remained low and were even reduced as compared with control animals. We evidenced here that this decrease in active caspase-3 levels could be attributed to calpain activation. Several observations supported this conclusion. 1) Pharmacological blockade of calpain in 3NP-treated rats increased the levels of endogenous processed caspase-9 and caspase-3. 2) Cell-free extracts prepared from the striatum of 3NP-treated rats degraded in vitro the p34 and p20 subunits of active recombinant caspase-9 and caspase-3, respectively. 3) This degradation of p34 and p20 could be mimicked by purified mu-calpain and was prevented by calpain inhibitors. 4) mu-Calpain produced a loss of the DEVDase (Asp-Glu-Val-Asp) activity of active caspase-3. 5) Western blot analysis and experiments with 35S-radiolabeled caspase-3 showed that mu-calpain cleaved the p20 subunit of active caspase-3 near its catalytic site. 6) mu-Calpain activity was selectively inhibited (IC50 of 100 mum) by a 12 amino acid peptide corresponding to the C terminus of p20. Our results showed that calpain can down-regulate the caspase-9/caspase-3 cell death pathway during neurodegeneration due to chronic mitochondrial defects in vivo and that this effect may involve, at least in part, direct cleavage of the caspase-3 p20 subunit.


Leukocytapheresis in the treatment of inflammatory bowel disease: Current position and perspectives.
Therapeutic apheresis, a novel approach for immunodisorders, has been used in the last decade for the treatment of ulcerative colitis with promising result, and represents an alternative to conventional pharmacological therapy. Selective apheresis is aimed at reducing the number of circulating lymphocytes, interfering with recruitment and activation of mucosal granulocytes and macrophages, reducing cytokine and chemokine production which are thought to contribute to induction and perpetuation of inflammation. The article briefly reports indications, treatment schedule and clinical results of leukocytapheresis in ulcerative colitis. Available data for the two selective adsorption devices so far approved for clinical use (granulocyte-monocyte apheresis- Adacolumn- and leukocytapheresis-Cellsorba) are partially conflicting, and the number of controlled studies too small to draw definitive conclusions. Nonetheless apheresis definitely appears to be an effective non-conventional tool for the treatment of steroid refractory and steroid dependent UC patients with moderately active disease. The excellent safety profile of the procedure makes this approach attractive, both in adult and in pediatric patients, more so in those refractory to conventional drug therapy, who are presently treated with immunosuppressive and biological therapies.


Mechanisms of enhanced vasoconstriction in the mouse model of atherosclerosis: the beneficial effects of sildenafil.
Sildenafil ameliorates aortic relaxations in apolipoprotein E knockout (apoE) mice. Now, we tested the hypothesis that endothelial dysfunction (ED) in this model is characterized by contractile hyperresponsiveness to phenylephrine (PE) and that this abnormality may be repaired using sildenafil. The aortic rings were evaluated in apoE mice treated with sildenafil (apoE-sil, 40 mg/kg/day) and compared with apoE and wild-type (WT) mice administered with vehicle (veh). The apoE-veh mice exhibited an imbalance of nitric oxide and reactive oxygen species (NO/ROS) levels and an increased maximum response (Rmax, 20%) and sensitivity (7%) to PE, which were not modified by endothelial removal. Under the prostanoids blockade, vasocontraction was decreased more in apoE-veh (-37%) than in WT (-27%) and apoE-sil (-30%) mice. NADPH-oxidase blockade abolished the enhanced contractile responsiveness in apoE-veh (-33%), without effects in WT and apoE-sil groups. The atherosclerotic lesions and the imbalance of NO/ROS were reduced (40%) in apoE-sil mice. In conclusion, ED in apoE mice was characterized by decreased NO-bioavailability and contractile hyperresponsiveness, due to thromboxane and oxidative stress, and was normalized by sildenafil. The beneficial effects of this phosphodiesterase-5 inhibitor on ED and lipid deposition provide new insights for its use as adjuvant in the treatment of atherosclerosis.


Galectin-1 regulates initial axonal growth in peripheral nerves after axotomy.
The signals that prompt the axons to send out processes in peripheral nerves after axotomy are not well understood. Here, we report that galectin-1 can play an important role in this initial stage. We developed an in vitro nerve regeneration model that allows us to monitor the initial axon and support cell outgrowth from the proximal nerve stump, which is comparable to the initial stages of nerve repair. We isolated a factor secreted from COS1 cells that enhanced axonal regeneration, and we identified the factor as galectin-1. Recombinant human galectin-1 (rhGAL-1) showed the same activity at low concentrations (50 pg/ml) that are two orders of magnitude lower than those of lectin activity. A similarly low concentration was also effective in in vivo experiments of axonal regeneration with migrating reactive Schwann cells to a grafted silicone tube after transection of adult rat peripheral nerve. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited the regeneration in vivo as well as in vitro. The same effect of rhGAL-1 was confirmed in crush/freeze experiments of the adult mouse sciatic nerve. Because galectin-1 is expressed in the regenerating sciatic nerves as well as in both sensory neurons and motor neurons, we suggest that galectin-1 may regulate initial repair after axotomy. This high activity of the factor applied under nonreducing conditions suggests that galectin-1 may work as a cytokine, not as a lectin.


Identical genetic changes in different histologic components of Wilms' tumors.
In young children and infants, Wilms' tumor is the most common cancer of the kidney. Wilms' tumor exhibits heterogeneous histopathologic features, consisting of rapidly proliferating blastemal and epithelial cells and a stromal component that has heterologous elements (e.g., cartilage, bone, and striated muscle). It is unclear whether the stromal and heterologous components of sporadic Wilms' tumor are neoplastic or should be considered non-neoplastic. Our purpose was twofold: 1) to selectively analyze the different histologic tissue components of sporadic Wilms' tumors, including blastemal, epithelial, stromal, and heterologous elements, for loss of heterozygosity (LOH) of the WT1 gene and for expression of the WT1 gene and 2) to determine the role of WT1 gene expression in the development of these tissues. By use of tissue microdissection techniques, various histologic elements (blastema, stroma, epithelium, and striated muscle) of sporadic Wilms' tumor were obtained from specimens taken from 18 patients. DNA was extracted from the dissected tissue fragments, and DNA solutions were amplified by use of the polymerase chain reaction and the polymorphic genomic markers D11S1392 and D11S904 to detect LOH at the WT1 gene locus (11p13). Three selected specimens with heterologous elements and LOH at 11p13 were analyzed for expression of the WT1 gene by means of the in situ reverse transcription-polymerase chain reaction. Nine (50%) of the 18 specimens showed LOH at the WT1 locus. Although identical WT1 gene deletion was consistently observed in all of the various histologic components of these nine specimens, WT1 gene expression was high in the blastemal and epithelial elements and low in the stromal and heterologous elements. Identical allelic deletion at 11p13 in all components of the sporadic Wilms' tumors examined suggests that the stromal tissue components are neoplastic rather than non-neoplastic. In conjunction with variable WT1 gene expression in the different histologic components, the results raise the possibility that undifferentiated blastemal cells are the precursors of the stromal and heterologous elements. Morphologically benign stromal and heterologous elements may therefore be derived from neoplastic cells. The developmental state of the various tissue components of Wilms' tumor may be attributed to an altered residual WT1 gene that is required for the maturation of blastemal and epithelial cells but that is not required for the maturation of stromal and heterologous elements.


[Ischemic stroke: the cardiac workup].
The cardiac workup of stroke often includes a 24 hours Holter and an echocardiography looking for cardiac sources of emboli (atrial fibrillation (AF), intracardiac thrombus, mitral stenosis, recent myocardial infarction, endocarditis, dilated cardiomyopathy...) which would lead to a change of treatment (secondary prevention) aiming at decreasing the risk of recurrence. In case of a stroke with AF, the secondary prevention strategy is well defined (anticoagulants). It is less clear for the other causes. The diagnostic yield of these examinations is limited and there is a lack of consensus in their utility. This systematic review tries to sum up current guidelines. It appears that these examinations should rather be targeted than performed systematically.


Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition.
Epithelium-to-mesenchyme transitions (EMTs) are characterized by morphological and behavioral changes in cells. During an EMT, E-cadherin is downregulated while N-cadherin is upregulated. The goal of this study was to understand the role cadherin switching plays in EMT using a classical model system: transforming growth factor beta1 (TGF-beta1)-mediated EMT in mammary epithelial cells. We showed that stress fibers and focal adhesions are increased, and cell-cell junctions are decreased in response to TGF-beta1. Moreover, these changes were reversible upon removal of TGF-beta1. Downregulation of E-cadherin and upregulation of N-cadherin were both transcriptional. Neither experimental knockdown nor experimental overexpression of N-cadherin interfered with the morphological changes. In addition, the morphological changes associated with EMT preceded the downregulation of E-cadherin. Interestingly, TGF-beta1-induced motility in N-cadherin-knockdown cells was significantly reduced. Together, these data suggest that cadherin switching is necessary for increased motility but is not required for the morphological changes that accompany EMT.