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OBJECTIVES: One Key Question (OKQ) is a clinical screening tool to assess pregnancy desire in the next year. We aimed to 1) describe the effect of OKQ implementation on contraceptive counseling rates at preventive health visits and 2) evaluate primary care providers’ perception of OKQ implementation on their contraceptive counseling practices. STUDY DESIGN: We performed a quantitative retrospective chart review of preventive health visits at eight federally qualified health centers in Utah between 2014 and 2017. Implementation of OKQ included a brief training and inclusion of OKQ in the electronic medical record. Providers received OKQ training in August 2015 and re-training in March 2017. We assessed OKQ and contraceptive counseling documentation rates using interrupted-time-series analysis. We then conducted semi-structured interviews with providers and queried them about the impact of OKQ. We identified dominant themes using modified grounded theory to create an explanatory framework. RESULTS: Abstracting 6634 charts yielded 9840 visits with 56 unique providers (51% physician assistant, 34% physician, 14% nurse practitioner). Interrupted-time-series analysis showed a documentation increase of OKQ in late 2015 (2.6%) and again in spring 2017 (9%), however rates remained low. Contraceptive counseling rates (39.7%) did not change after OKQ implementation. Charts with evidence of a current contraceptive method were less likely to have a OKQ response documented. Interviewees reported OKQ’s algorithm did not alter their contraceptive counseling. CONCLUSIONS: OKQ did not change documented rates of contraceptive counseling and uptake was low in quantitative and qualitative analyses. Our study suggests limited usefulness of OKQ in the primary care setting. IMPLICATIONS: Implementation of the One Key Question tool through training and optional EHR field did not increase documented rates of contraceptive counseling in a large federally qualified health center or affect provider contraceptive counseling. Our study suggests limited usefulness of OKQ as a robust screening tool in this primary care setting.

Recent evidence demonstrates the effectiveness of the levonorgestrel 52mg intrauterine device (IUD) for emergency contraception compared to the copper (Cu T380A) IUD. One-year pregnancy and continuation rates after IUD placement for emergency contraception remain understudied.(s): We compared one-year pregnancy and IUD continuation rates and reasons for discontinuation among emergency contraception users randomized to the levonorgestrel 52mg IUD or a copper IUD.This participant-masked, randomized noninferiority trial recruited emergency contraception clients desiring an IUD from six Utah family planning clinics between August 2016 and December 2019. We randomized participants 1:1 to the levonorgestrel 52 mg IUD or copper T380A IUD. Treatment allocation was revealed to participants at the one-month follow up. Trained personnel followed participants by phone, text, or email at five timepoints over one year and reviewed electronic health records for pregnancy and IUD continuation outcomes for both confirmation and for non-responders. We assessed reasons for discontinuation and used Cox Proportional Hazard Models, Kaplan-Meier estimates, and log-rank tests to assess differences in continuation and pregnancy rates between groups.The levonorgestrel and copper IUD groups included 327 and 328 participants receiving the respective interventions. By intention-to-treat analysis at one year, pregnancy rates were similar between IUD types (9/327 (2.8%) levonorgestrel 52mg IUD vs 10/328 (3.0%) copper IUD (RR 0.9, 95% CI 0.4-2.2, p=0.82)). The majority of pregnancies occurred in participants after IUD removal, with only 1 device failure in each group. One-year continuation rates did not differ between groups with 204/327 (62.4%) of levonorgestrel 52mg IUD users and 183/328 (55.8%) of Cu T380A IUD users continuing IUD use at one year (RR 1.1, 95% CI 1.0-1.2, p=0.09). There were differences with regards for reasons for discontinuation between IUD types, with more bleeding and cramping cited among copper IUD users.(s): Pregnancy rates were low and similar between IUD types. Six in ten IUD emergency contraception users continued use at one year. One-year continuation rates were similar between IUD types.

Examine intrauterine device (IUD) switching or discontinuation up to 6 months after participant-masked randomization to different IUDs.Participants were randomized 1:1 to the copper T380A or levonorgestrel 52 mg IUD for emergency contraception and informed they could switch IUD type without cost at any time.Of the 327 subjects allocated to the levonorgestrel IUD, 7 (2.1%) switched their IUD type by 6 months versus 18 (5.5%) of the 328 copper IUD users (RR: 0.4 [95% CI: 0.2, 0.9], p = 0.03). Six-month IUD discontinuation occurred in 34 (10.4%) levonorgestrel and 35 (10.7%) copper IUD users.Individuals randomly assigned to IUD type at presentation for emergency contraception continue their assigned IUDs at high rates over 6 months.While many recruited individuals declined enrollment, those who accepted randomization had high continuation rates; the high continuation and low cross-over supports using IUD randomization as a tool for future investigation. Participants' similar rates of and reasons for switching and discontinuation by IUD type over the study period may impact clinical counseling.

In a 6 × 3 × 3 factorial design, the effect of three sulfur fertilization rates (0, 8.4 and 16.8 kg/ha) on the properties of six spring wheat varieties grown in three locations in the US Midwest was evaluated. Dough properties were assessed via the Farinograph and GlutoPeak; contents of free amino acids and sugars in flour were determined by high-performance anion exchange chromatography. Bread volume and crust color were assessed as well. Overall, the main influence on flour, dough and bread properties was exerted by the growing location. However, sulfur fertilization rates significantly affected bread volume and the content of several free amino acids; the main ones being asparagine, glutamine, aspartate, glutamate, and alanine. At a fertilization rate of 0, 8.4 and 16.8 kg/ha, values ranged from 8.39 to 22.42, 7,92–22.563 and 6.67–25.05 mmol/kg, respectively, for asparagine, the precursor to the probable carcinogen acrylamide. GlutoPeak parameters appeared to be unaffected by sulfur fertilizer rate. Specific bread volumes ranged from 2.21 to 4.71 cm3/g. Across locations, the specific bread volume tended to be highest when samples had been grown at a sulfur fertilization rate of 8.4 kg/ha. Thus, the asparagine reductions achieved with the highest sulfur fertilization rate partially came at the expense of volume reduction.

Objective Research has called for more exploration into how reproductive autonomy (which includes agency over pregnancy decisions) is related to structural, relational, and individual elements. Thus, we use surveys to investigate how one potential indicator of reproductive autonomy—feelings of control over pregnancy—may relate to structural, relational, and individual factors in emerging adults’ (age 18–24) lives. Methods Using survey data from 2594 emerging adult women participating in a contraceptive initiative in Utah (USA), we analyzed level of agreement with the statement: “I feel that I have control over whether or not I get pregnant,” exploring relationships between sociodemographic characteristics and agreement with the statement. We used chi-square tests and multinomial logistic regression to investigate relationships between individual, relational, and structural factors and feelings of control. Results Most participants (86%) agreed with the statement (n = 2231), while the remainder were neutral or disagreed. Participants reporting poverty-level incomes (RRR: 1.80; 95 %CI 1.25–2.59) and previous unwanted pregnancies (RRR: 2.74; 95 %CI: 1.56–4.81) were more likely to describe “neutral” feelings of control. Conclusion Findings indicate a relationship between feelings of control over pregnancy and several factors, and these results may help identify reproductive autonomy access gaps among emerging adults. More work should investigate these relationships as well as the meaning of “neutral” responses when it comes to assessments of control over pregnancy. Trial Registration: Clinicaltrials.gov identifier NCT02734199, Registered 12 April 2016.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

Background In this observational study, we analyzed the feasibility and early results of a perioperative, video-based educational program and tele-health home monitoring model on postoperative care management and readmissions for patients undergoing liver transplantation. Methods Twenty consecutive liver transplantation recipients were provided with tele-health home monitoring and an educational video program during the perioperative period. Vital statistics were tracked and monitored daily with emphasis placed on readings outside of the normal range (threshold violations). Additionally, responses to effectiveness questionnaires were collected retrospectively for analysis. Results In the study, 19 of the 20 patients responded to the effectiveness questionnaire, with 95% reporting having watched all 10 videos, 68% watching some more than once, and 100% finding them effective in improving their preparedness for understanding their postoperative care. Among these 20 patients, there was an observed 19% threshold violation rate for systolic blood pressure, 6% threshold violation rate for mean blood glucose concentrations, and 8% threshold violation rate for mean weights. This subset of patients had a 90-day readmission rate of 30%. Conclusion This observational study demonstrates that tele-health home monitoring and video-based educational programs are feasible in liver transplantation recipients and seem to be effective in enhancing the monitoring of vital statistics postoperatively. These data suggest that smart technology is effective in creating a greater awareness and understanding of how to manage postoperative care after liver transplantation.

Modeling coupled social and biophysical dynamics of water resources systems is increasingly important due to population growth and changes in the water cycle driven by climate change. Models that explicitly represent these coupled dynamics are challenging to design and implement, particularly given the complicated and cross-scale nature of water governance. Agent-based models (ABMs) can capture human decision-making and nested social hierarchies, however, transferability is made difficult by location-specific details. A consistent description of water resources decision-makers (individuals, groups, agencies) would advance the rate of model development and increase synthesis across systems. Reviewing water resources ABMs, we propose eight agent types and associated operational roles that modify the storage, redistribution, and water use in a system. Application of the proposed typologies and use of best practices in model documentation, will support systematic design and development of transferable, scalable, water resources ABMs and facilitate the dynamic coupling of social and biophysical process modeling.

Integration of pharmacists into multidisciplinary transplant patient care has advanced in recent years, with limited data available to evaluate the current status of the profession. This was a national survey developed as an AST Pharmacy COP initiative. Responses were solicited from pharmacists practicing at U.S. transplant programs based on UNOS listing; 176 participants from 113 centers (41%) responded, with 79% practicing ≤10 years. There is a median of 1.4 pharmacist full-time equivalents (FTEs) (range 0.1-7.1) for every 100 transplants. The predominant activities performed by pharmacists during the transplant phase include medication review (95%), lab review (92%), allergy review (88%), medication therapy management (92%), bedside rounds (87%), medication education (79%), documentation (71%), and coordinating discharge medications (58%). Similar activities were reported during the other phases, but participation was less common. The involvement of dedicated transplant pharmacists within multidisciplinary care has become standard at a large number of centers, although expansion is still needed to ensure core pharmaceutical care components are provided to all transplant recipients across all centers. These results inform on the typical responsibilities of pharmacists practicing within the field of transplantation and illustrate that the level of pharmacist involvement significantly varies across transplant centers and the phases of transplantation.

Background Rivaroxaban has become an alternative to vitamin-K antagonists (VKA) for stroke prevention in non-valvular atrial fibrillation (AF) patients due to its favourable risk–benefit profile in the restrictive setting of a large randomized trial. However in the primary care setting, physician's motivation to begin with rivaroxaban, treatment satisfaction and the clinical event rate after the initiation of rivaroxaban are not known. Methods Prospective data collection by 115 primary care physicians in Switzerland on consecutive nonvalvular AF patients with newly established rivaroxaban anticoagulation with 3-month follow-up. Results We enrolled 537 patients (73 ± 11 years, 57% men) with mean CHADS2 and HAS-BLED-scores of 2.2 ± 1.3 and 2.4 ± 1.1, respectively: 301(56%) were switched from VKA to rivaroxaban (STR-group) and 236(44%) were VKA-naive (VN-group). Absence of routine coagulation monitoring (68%) and fixed-dose once-daily treatment (58%) were the most frequent criteria for physicians to initiate rivaroxaban. In the STR-group, patient's satisfaction increased from 3.6 ± 1.4 under VKA to 5.5 ± 0.8 points (P Conclusion Initiation of rivaroxaban for patients with nonvalvular AF by primary care physicians was associated with a low clinical event rate and with high overall patient's and physician's satisfaction.

Resume Introduction L’arthroplastie du genou occasionne d’importantes pertes sanguines. Differentes techniques d’epargne transfusionnelle existent dont la retransfusion de sang epanche de redon. Certaines etudes remettent en cause la qualite de ce sang et notamment sa capacite a coaguler. Elles utilisent des tests d’hemostase « statiques » qui refletent de maniere tres incomplete la realite, contrairement aux methodes viscoelastiques. L’objectif principal de cette etude etait d’evaluer le profil thromboelastometrique par ROTEM ® du sang epanche en le comparant au sang veineux du patient. Patients et methodes Il s’agissait d’une etude observationnelle, prospective et monocentrique effectuee sur 3 mois en 2013. L’accord du CPP et le consentement des patients ont ete obtenus au prealable. Tous les patients majeurs ayant beneficie d’une arthroplastie totale primaire du genou avec mise en place d’un redon recuperateur ont ete inclus. Un profil thromboelastometrique et un bilan biologique standard (hemoglobine, plaquette, TP, TCA, fibrinogene) ont ete realises sur le sang veineux du patient et sur le sang epanche du redon recuperateur en SSPI. Resultats Vingt patients ont ete inclus. La duree mediane de chirurgie etait de 93 minutes. Treize patients (65 %) ont recu de l’acide tranexamique en peroperatoire. Le volume median de sang epanche a ete de 225 mL. Deux patients (10 %) ont beneficie d’une retransfusion. L’analyse du sang epanche a montre un deficit majeur en facteurs de coagulation en biologie standard (TP ® , Ex-tem ® , Fib-tem ® ou Ap-tem ® ). Par rapport au sang veineux, le sang du redon avait un taux d’hemoglobine significativement plus bas : 8,8 vs 13,5 g/dL ( p Discussion Dans ce travail, nous avons confirme que le sang de redon etait incoagulable probablement en relation avec un mecanisme multifactoriel associant un deficit en facteur et une activation de la fibrinolyse.

A Python package, “EONR”, was developed for computing the economic optimum nitrogen rate (EONR) and its profile-likelihood confidence intervals (CIs) under economic conditions defined by the user. This work was motivated by the need to improve nitrogen fertilizer recommendations using the maximum return to nitrogen approach, specifically to make it easier for researchers and other practitioners to calculate uncertainty and consider externalities to the cost function while computing the EONR. The “EONR” package fits yield response data to a re-parameterized quadratic-plateau model, which is generally accepted as the most appropriate model for describing yield response to nitrogen in maize (the package also supports the quadratic model). Although grain price and fertilizer cost are typically the only economic factors producers consider for determining the EONR, this package allows the user to also consider variable costs and/or externalities. A general cost function may be desired if the user wishes to consider costs to the farm operation (e.g., equipment, technology, labor, etc.) or environmental costs/penalties that may result from excess fertilizer application (e.g., water treatment or health costs that result from pollution) in addition to the traditional fertilizer to grain price ratio. In addition to the development of the “EONR” Python package, the objectives of this work were to: (i) design an algorithm that utilizes a general cost function for computing the EONR and its profile-likelihood CIs for any crop and (ii) clearly document the methodology and algorithms used. The “EONR” Python package can be downloaded from the Python Package Index ( https://pypi.org/ ), and installation instructions, tutorials, and supplementary background information can be found in the online documentation ( https://eonr.readthedocs.io ).

Objective Twenty-four hour ambulatory blood pressure (ABP) is superior to office blood pressure (BP) in predicting cardiovascular events. However, its use to optimise BP control in treated hypertensive patients is less well examined. Design and method In this observational study conducted in 899 general practitioners' offices, 4078 hypertensive patients with uncontrolled office BP were included. Antihypertensive therapy was intensified and after 1year office BP and 24-hour ABP were measured to categorise patients according to the ESC/ESH 2007 guidelines. Results In this cohort (mean office BP 156/90mmHg, mean ABP 146/85mmHg), 2059 out of 4078 patients (50.5%) had controlled office BP ( Conclusion In hypertensive patients on therapy, 2 out of 3 with apparently controlled office BP had masked hypertension, suggesting a more aggressive therapy, and 1 out of 8 with elevated office BP had white coat hypertension potentially falsely forcing physicians to intensify therapy. The 3A Registry is listed under clinicaltrials.gov, NCT01454583.

Anesthetic management of burnsKey points Patients with burn injury can and will present to any hospital. Many of those hospitalized for burn injury will require surgical treatment of theirinjuries. Patients undergoing surgical treatment for major thermal burn injury often exhibitpreexisting medical issues and/or burn-related pathophysiology that must beconsidered in the anesthetic plan. Performing a focused preoperative assessment of a patient with burn injury isparamount, particularly with respect to airway abnormalities, gas exchange,and hemodynamic status. Smoke-inhalation injury largely influences the clinical course of patients withmajor burn injury. Recognizing and managing intraoperative blood loss and volume replacement iscritical.Continued

The diversity of ubiquitin (Ub)-dependent signaling is attributed to the ability of this small protein to form different types of covalently linked polyUb chains and to the existence of Ub binding proteins that interpret this molecular syntax. We used affinity capture/mass spectrometry to identify ALIX, a component of the ESCRT pathway, that has not been previously reported to possess a Ub binding domain. We report that the V domain of ALIX binds directly and selectively to K63-linked polyUb chains, exhibiting a strong preference for chains composed of more than three Ub. Sequence analysis identified two potential Ub binding sites on a single α-helical surface within the coiled-coil region of the V domain. Mutation of these putative Ub binding sites inhibited polyUb binding to the isolated V domain in vitro and impaired budding of lentiviruses. These data reveal an important role for K63 polyUb binding by ALIX in retroviral release.

In order to improve the discovery and development of new drugs, a broad effort is being made to assess the 'drug-like' properties of molecules in early stages of the discovery-research process. Although there are numerous approaches to this problem, perhaps the simplest and most widespread one is that developed by Chris Lipinski and his co-workers at Pfizer, which is generally referred either as the Lipinski Rules or the Rule of Five (ROF). The ROF is based on four properties of molecules, namely, molecular weight (MW), log P, number of hydrogen bond donors (HBD), and the number of hydrogen bond acceptors (HBA). A 'flag' is set if the value of a given property exceeds the chosen threshold value for that property-MW 500 Da, log P 5, the number of HBDs 5, and the number of HBAs 10. Each flag corresponds to an ROF violation. The total number of violations is the ROF-Score, which lies between '0' and '4'. Molecules with ROF-Scores greater than one are considered to be marginal for further development. The difficulty with this approach is that two molecules with nearly identical property values can, nonetheless, possess ROF-Scores that can differ by two or more. Thus, one molecule could be considered for further studies while the other, nearly identical molecule (in terms of its four ROF properties), would most likely not be. This problem arises because of the sharp thresholds imposed by the present formulation of the ROF, which is based upon classical sets. In the current work an alternative approach based on the use of utility functions, within the framework of the analytic hierarchy process (AHP), are employed to 'soften' the sharp boundaries inherent in classical sets. This provides a more realistic assessment of compounds in terms of their potential suitability in drug-discovery research programs.

A two-step strategy for the synthesis of arrays of tricyclic tetrazolo-fused benzodiazepines and benzodiazepinones has been investigated. The protocol uses ortho-N-Boc phenylisocyanides and phenylglyoxaldehydes or ethyl glyoxylate in the four-component Ugi-azide reaction to afford MCR (MultiComponent Reactions) derived adducts equipped with the desired diversity inputs. A subsequent acidic treatment (TFA/DCE) allows a simultaneous deprotectionecyclization leading to the final products. 2012 Elsevier Ltd. All rights reserved.

Summary Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7 NTD ) recruits a unique "flexible region" from Atg3 (Atg3 FR ). The structure of an Atg7 NTD -Atg3 FR complex reveals hydrophobic residues from Atg3 engaging a conserved groove in Atg7, important for Atg8 conjugation. We also report the structure of the homodimeric Atg7 C-terminal domain, which is homologous to canonical E1s and bacterial antecedents. The structures, SAXS, and crosslinking data allow modeling of a full-length, dimeric (Atg7∼Atg8-Atg3) 2 complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. The studies reveal a distinctive E1∼UBL-E2 architecture for enzymes mediating autophagy.

Novel two-step solution phase protocols for the synthesis of dihydroquinazolines and fused dihydroquinazoline-benzodiazepine tetracycles are reported. The methodology employs the Ugi reaction to assemble the desired diversity and acid treatment enables ring-closing transformations. The protocols are further facilitated by the use of microwave irradiation and n-butyl isocyanide to control the rate of each ring-forming transformation.

Resume Objectif Definir la place de l’anesthesie locoregionale (ALR) dans la prise en charge des plaies de la face dans un service d’accueil des urgences (SAU). Type d’etude Etude prospective observationnelle realisee dans le SAU d’un centre hospitalier regional. Patients et methodes Deux cent quarante-six patients successifs presentant une ou plusieurs plaies de la face ont ete inclus du 1 er aout 2004 au 31 decembre 2004. Les donnees concernant le patient, l’operateur, la plaie (evaluee par le nombre de points de suture), la methode anesthesique (ALR, anesthesie locale [AL] ou pas d’anesthesie), la methode de reparation cutanee, la duree de l’intervention, le confort de l’operateur (echelle verbale numerique [EVN] de zero a dix) et la douleur ressentie par le patient (echelle visuelle analogique [EVA] de 0 a 10) aux differents stades de la prise en charge ont ete recueillies. Resultats Par rapport a l’AL, l’ALR de la face a diminue le nombre de ponctions (1,36 vs 4,38 ponctions, p p p Conclusion Quand l’ALR de la face est realisable, elle est plus performante que l’AL pour le traitement des plaies du visage.

Propofol infusion syndrome (PRIS) is a new clinical entity reported in critically ill patients. Lactic acidosis, cardiac failure and rhabdomyolysis are the features. Lactic acidosis related to short-term propofol administration has been described during general anaesthesia. Lactic acidosis could be an early marker of PRIS. We report here a case of very early lactic acidosis in a 66-year-old-man receiving propofol during a neurosurgery. The outcome was good after discontinuation of propofol.

SNARE proteins form a complex that leads to membrane fusion between vesicles, organelles, and plasma membrane in all eukaryotic cells. We report the 1.7A resolution structure of the SNARE complex that mediates exocytosis at the plasma membrane in the yeast Saccharomyces cerevisiae. Similar to its neuronal and endosomal homologues, the S. cerevisiae SNARE complex forms a parallel four-helix bundle in the center of which is an ionic layer. The S. cerevisiae SNARE complex exhibits increased helix bending near the ionic layer, contains water-filled cavities in the complex core, and exhibits reduced thermal stability relative to mammalian SNARE complexes. Mutagenesis experiments suggest that the water-filled cavities contribute to the lower stability of the S. cerevisiae complex.

Proper hand hygiene has long been recognized as a primary tool in reducing transmission of health care-acquired infections. Compliance with recommended practices and an increase in the frequency of hand hygiene can have a negative impact on skin condition. Poor skin condition can result in reduced compliance with hand hygiene guidelines. In addition to reduced compliance with proper hand hygiene, deterioration in skin condition leads to reduced barrier function of the skin, changes in skin microflora, and increased shedding of skin squames. Thus, poor skin condition can increase the risk of infection, increase costs to the facility, and reduce the quality of life for the health care worker. To address the problem of skin irritation and its link to low compliance to hand hygiene practices, the Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene for Health Care Settings recommends that hand hygiene agents should be well accepted, well tolerated, and formulated to minimize irritancy. Sophisticated formulation technologies and the proper selection of ingredients can provide products that encourage hand hygiene compliance through pleasing aesthetic properties and by overcoming the damaging effects of hand hygiene practices.

We report a case of transient acquired and isolated factor VII deficiency associated with severe head trauma. A 16-year-old boy was involved in a motor vehicle accident. CT scan showed frontal brain contusion and a cerebral haematoma (5 cm). First prothrombine time (PT) was normal. Rapidly, a severe coagulopathy developed, unresponsiving to fresh frozen plasma and vitamin K. Haemostatic markers analysis showed an isolated deficiency of factor VII at 15%. No inhibitory activity against factor VII could be detected. We successfully treated the deficiency with intermittent intravenous human factor VII (factor VII-LFB) during 10 days. Factor VII return to normal at 84%. Physiopathological and therapeutic aspects of this rare pathology are presented.

Interleukin (IL)-6 mRNA expression in general is low in normal, adenomatous and cancerous human colon mucosa, except in rather undifferentiated lesions, in which IL-6 is overexpressed. Cytokeratin (CK) 8-positive carcinoma cells were identified by double immunostaining as almost exclusive source of IL-6. Likewise, in five (sub)clones of primary culture COGA-1 and COGA-13 human colon carcinoma cells, and in three established cell lines (Caco-2/AQ, Caco-2/15 and HT-29), efficient translation of IL-6 mRNA into protein was observed only in the least differentiated COGA-13 cells. Notably, IL-1beta (5 ng/ml) enhanced IL-6 release in COGA-13 cultures by three orders of magnitude. Although all cell clones studied expressed the IL-6 receptor (IL-6R), rhIL-6 (1-100 ng/ml) had a significant effect on cellular proliferation only in highly differentiated Caco-2 cells. Our data imply that IL-6, when released from rather undifferentiated carcinoma cells, particularly in response to IL-1beta, can advance tumour progression through paracrine growth stimulation of normal or highly differentiated colon tumour cells with intact STAT-3-mediated IL-6 signalling.

We report a case of intracranial dural arteriovenous (DAVF) draining into the spinal medullary veins. A 49-year-old woman presented a rapidly progressive ascending myelopathy resulting in a C3-C4 tetraplegia associated with acute respiratory failure at the twelfth hour. MRI revealed swelling of the cervical spinal cord, hyperintensity on T2 and enhancement of enlarged veins on MR angiography. A conventional angiography showed the DAVF with venous drainage into the spinal vein extending to the conus medullaris. After embolization, neurological recovery occurred during the first week, allowing tracheal extubation on day 2. Clinical, radiological and therapeutic aspects of this uncommon pathology are presented.

Resume Le LTV 1000™ (BREAS medical®) est un ventilateur de transport dote d’une turbine qui comprime l’air ambiant et assure la ventilation du patient independamment d’une source d’oxygene hyperbare. Objectifs Evaluer la fraction d’oxygene reellement delivree par le LTV 1000™ alimente par de l’oxygene normobare delivre au moyen d’un extracteur d’oxygene et/ou d’un debitmetre de bouteille d’oxygene. Methodes Les fractions d’oxygene delivrees par le LTV 1000™ alimente par un extracteur d’oxygene (debit 5 l.mn-1) et des debits croissants d’oxygene pur normobare ont ete mesurees a differents niveaux de PEP (ventilation minute 10 l.mn-1). Les fractions d’oxygene ont egalement ete mesurees avec alimentation du ventilateur par oxygene pur issu d’un debitmetre de bouteille seul, ainsi qu’avec alimentation par extracteur seul et des ventilations minutes elevees. Resultats Les fractions d’oxygene delivrees allaient de 43 % a 75 % en fonction du debit d’oxygene normobare. La consommation maximale d’oxygene en bouteille etait de 5 l.mn-1. Le niveau de PEP n’a pas influence ces resultats. Alimente par oxygene pur issu d’un debitmetre, le LTV 1000™ a delivre des fractions d’oxygene concordant avec les abaques fournies par le constructeur. L’augmentation importante du volume minute a reduit notablement la fraction d’oxygene delivree quand le ventilateur etait alimente par un extracteur d’oxygene seul. Conclusion Le LTV 1000TM en mode basse pression utilise avec un extracteur d’oxygene et/ou un debitmetre peut permettre d’economiser l’oxygene hyperbare.

SummaryThe FFAT motif is a targeting signal responsible for localizing a number of proteins to the cytosolic surface of the endoplasmic reticulum (ER) and to the nuclear membrane. FFAT motifs bind to members of the highly conserved VAP protein family, which are tethered to the cytoplasmic face of the ER by a C-terminal transmembrane domain. We have solved crystal structures of the rat VAP-A MSP homology domain alone and in complex with an FFAT motif. The co-crystal structure was used to design a VAP mutant that disrupts rat and yeast VAP-FFAT interactions in vitro. The FFAT binding-defective mutant also blocked function of the VAP homolog Scs2p in yeast. Finally, overexpression of the FFAT binding-defective VAP in COS7 cells dramatically altered ER morphology. Our data establish the structural basis of FFAT-mediated ER targeting and suggest that FFAT-targeted proteins play an important role in determining ER morphology.

Rapid advances in information technology have dramatically transformed the world during the past several decades. Access to computers and the World Wide Web is increasingly required for education and employment, as well as for many activities of daily living. Although these changes have improved society in many respects, they present an obstacle for visually disabled patients who may have significant difficulty processing the visual cues presented by modern graphical user interfaces. This article reviews the specific barriers to computer and Web access faced by visually disabled patients, describes clinical evaluation methods, summarizes traditional low vision methods as well as newer assistive computer technologies for universal accessibility, and discusses emerging technologies and future directions in this area.

Resume La pyelonephrite emphysemateuse est une infection necrotique du rein caracterisee par la presence de gaz au sein du parenchyme renal, des cavites excretrices ou des espaces perirenaux. C'est une affection rare, survenant preferentiellement chez le diabetique et liee au developpement de bacteries gazogenes non anaerobies. C'est aussi une affection grave, engageant rapidement le pronostic vital par etat de choc septique et syndrome de dysfonction multiviscerale. Le diagnostic est suspecte devant une pyelonephrite repondant mal au traitement ou presentant des signes de gravite, surtout chez un patient diabetique. La tomodensitometrie est l'examen de reference qui permet le diagnostic positif de la presence de gaz et une classification radiologique ayant une valeur pronostique. L'attitude therapeutique est basee sur une analyse repetee de l'etat clinique du patient et de la tomodensitometrie. L'antibiotherapie precoce est systematique. Le drainage percutane est probablement la premiere etape therapeutique dans la majorite des cas, mais ne doit pas retarder une eventuelle nephrectomie de sauvetage.

Resume Les hemorragies faciales massives au cours des traumatismes crânio-faciaux sont considerees comme rares. La richesse de la circulation collaterale entre les carotides internes et externes explique les difficultes d’hemostase. Nous rapportons 4 cas d’hemorragies faciales massives associees a des traumatismes crâniens graves. Differentes methodes d’hemostase ont ete utilisees (tamponnement nasal, reduction des fractures, traitement endovasculaire, ligature des carotides externes). La ligature d’une ou des deux carotides externes est un moyen efficace, et sa simplicite peut en faire une technique de choix dans certaines situations.

La pielonefritis enfisematosa es una infeccion necrotica del rinon caracterizada por la presencia de gas en el interior del parenquima renal, en estructuras excretoras o en los espacios perirrenales. Es un proceso poco frecuente, que afecta sobre todo a las personas diabeticas, y que se asocia a la proliferacion de bacterias no anaerobias formadoras de gas. Tambien es un proceso grave, capaz de provocar la muerte con rapidez, como consecuencia del estado de shock septico y del sindrome de disfuncion multiorganica que origina. El diagnostico debe sospecharse ante una pielonefritis que no responde bien al tratamiento o que muestra signos de gravedad, sobre todo en los pacientes diabeticos. La exploracion de eleccion es la tomografia computarizada, pues permite tanto el diagnostico de certeza, basado en la presencia del gas, como la clasificacion radiologica, que posee valor pronostico. La actitud terapeutica depende del analisis repetido del estado clinico del paciente y de las imagenes de tomografia computarizada. Requiere un tratamiento antibiotico precoz. En la mayor parte de los casos, el primer paso del tratamiento es, casi siempre, la evacuacion mediante drenaje percutaneo, pero no conviene retrasar una eventual nefrectomia de salvamento.

Resume Les plaies penetrantes cervicales sont aussi souvent « seches » que cause d’hemorragies ou de lesions des zones adjacentes. Le diagnostic lesionnel repose sur l’etat des fonctions vitales, la region du cou concernee, l’examen clinique et la tomodensitometrie du cou. L’arteriographie des quatre axes cervicaux et l’œsophagoscopie ne sont pas systematiques, mais decidees en fonction de la clinique ou de l’angioscanner. Laryngoscopie et fibroscopie tracheobronchique dependent de la clinique. Les risques vitaux sont l’obstruction des voies aeriennes superieures (VAS), l’hemorragie brutale, l’ischemie cerebrale ou medullaire et l’infection. Une hemorragie franche, un hematome pulsatile en expansion, une lesion manifeste des VAS doivent conduire le malade au bloc sans delai et sans intermediaire. L’hemorragie et l’obstruction des VAS sont possibles a tout moment, sous l’effet du remplissage, de l’agitation ou du retrait d’un corps etranger fiche dans la plaie. L’intubation orotracheale est souvent realisable ; la cricothyroidotomie est la meilleure alternative. A l’hopital, ce controle des VAS est plus sur en salle d’operation, chirurgien present. Des qu’un malade est ventile, on doit craindre la decompensation d’un eventuel pneumothorax. Les lesions carotidiennes minimes sans consequences cerebrales n’imposent pas une reparation systematique. Les lesions carotidiennes compliquees de deficit neurologique central doivent etre reparees, sauf coma profond sans autre origine. Les lesions arterielles vertebrales sont plus accessibles par voie endovasculaire.

This paper investigates the wall effects on the settling velocity of a falling ball in concentrated suspensions. The model suspensions consist of uniform neutrally buoyant spheres in a viscous Newtonian suspending fluid under conditions such that only hydrodynamic forces exert an appreciable effect. A number of previous studies have focused on determining the average velocity of the settling particle along the centerline or axis of the containing cylinders. The objective of this study is to determine the wall effects experienced by the falling balls as they settle off-center or eccentrically at a radial distance b from the centerline in a cylinder of radius R. We find that in the dilute suspensions (volume concentration of solids, φ=10%), off-center wall effects are indistinguishable from those in pure Newtonian fluids. For the moderately concentrated suspensions (φ=30%), off-center wall effects begin to deviate from Newtonian behavior as the ball approaches the wall (b/R>0.5) and the ball settles slower than it would in a Newtonian fluid with the same apparent viscosity. In a highly concentrated suspension (φ=50%), the Newtonian region in the center of the cylinder is much smaller (b/R

This study shows that endocrine and vascular etiologies of erectile dysfunction are more common in the older age group, whereas depression and marital discord are more common in the younger age group. There is considerable overlap between various factors pointing to the multifactorial nature of erectile dysfunction. Review of the treatment option chosen reveals that the invasive modalities were least common as compared with the popular vacuum tumescence device (although cumbersome) and testosterone replacement. Persons with low testosterone have an improved efficacy of sildenafil when hypogonadism is treated. Sildenafil with its ease of administration and high efficacy seems to be the logical first choice for most of the patients. If contraindications exist or treatment failures occur, other treatment options should be offered to patients.

Vitamin A and its metabolites are known to be involved in patterning the vertebrate embryo. Study of the effect of vitamin A on axial skeletal patterning has been hindered by the fact that deficient embryos do not survive past midgestation. In this study, pregnant vitamin A-deficient rats were maintained on a purified diet containing limiting amounts of all-trans retinoic acid (12 microg atRA/g diet) and given a daily oral bolus dose of retinol starting at embryonic day 0.5, 8.25, 8.5, 8.75, 9.25, 9.5, 9.75, or 10.5. Embryos were recovered at E21.5 for analysis of the skeleton and at earlier times for analysis of select mRNAs. Normal axial skeletal development and patterning were observed in embryos from pregnant animals receiving retinol starting on or before E8.75. Delay of retinol supplementation to E9.5 or later resulted in a marked increase in both occurrence and severity of skeletal malformations, extending from the craniocervical to sacral regions. Embryos from the groups receiving retinol starting at E9.5 and E9.75 had one-vertebral anterior transformations of the cervical, thoracic, lumbar, and sacral vertebrae. Few embryos survived in the E10.5 group, but these embryos yielded the most severe and extensive anteriorization events. The skeletal alterations seen in vitamin A deficiency are associated with posterior shifts in the mesodermal expression of Hoxa-4, Hoxb-3, Hoxd-3, Hoxd-4, and Hoxa-9 mRNAs, whereas the anterior domains of Hoxb-4 and Cdx2 expression are unaltered. This work defines a critical window of development in the late gastrula-stage embryo when vitamin A is essential for normal axial skeletal patterning and shows that vitamin A deficiency causes anterior homeotic transformations extending from the cervical to lumbosacral regions.

During systematic cell-surface antigen expression profile analyses of 76 primary childhood brain tumors [34 medulloblastomas (MED)/primitive neuroectodermal tumors (PNETs) and 42 astrocytomas (ASTR)], a library of monoclonal antibodies (MoABs) directed against various leukocyte-associated, lymphocyte cell-line differentiation antigens in childhood brain tumors was utilized. The antigens were detected employing an indirect, biotin-streptavidin conjugated alkaline phosphatase (AP) immunocytochemical technique. Major histocompatibility complex (MHC) class I restricted, tumor-associated antigen (TAA) specific, CD8(+) cytotoxic T lymphocytes (CTL) were identified in 58/76 (76.32%) brain tumors, and usually represented 1-10% of all cells, but in some cases 30-44% of the cells were CD8(+). CD4(+), MHC class II restricted helper lymphocytes were present in 65/76 (85.53%) brain tumors, and accounted for 1-10% of the observed cells. Macrophages were present in 74/76 (97.37%) brain tumors, and their number also represented 1-10% of all observed cells in the brain tumor frozen sections. Leukocyte common antigen (LCA) expression was detected in all 76 (100%) brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 (78.95%) brain tumors. Natural killer (NK) cells were not defined in the observed brain tumors. The great majority of childhood glial tumors, particularly ASTRs express Fas (APO-1/CD95) receptor whereas normal cells in the central nervous system (CNS) do not. FasR is a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. As part of our screening, the 42 childhood ASTRs were also investigated for expression of CD95. We detected strong expression (strong intensity of staining, number of stained cells 50-100%) of FasR, employing formalin fixed, paraffin-wax embedded tissue slides. Brain tumors and melanomas have been shown to produce their autocrine FasL, and are even capable of switching CD95-related signal transduction from the PCD pathway to a proliferative pathway. In view of our results, we conclude that: (1) the tumor infiltrating leukocytes in MEDs/PNETs and ASTRs represent a very diverse population and are present in a great majority of the cases studied; (2) the strong expression of FasR in ASTRs provides a manner in which T lymphocytes may exert their anti-tumor effects, but may also represent yet another way that tumors may evade the immune response; and (3) further observations of the expression of various antigens involved in juxtacrine, in situ growth control are necessary for the refinement of cellular immunotherapeutical approaches in the treatment of human malignancies.

The developing nervous system is particularly vulnerable to vitamin A deficiency. Retinoid has been proposed to be a posteriorizing factor during hindbrain development, although direct evidence in the mammalian embryo is lacking. In the present study, pregnant vitamin A-deficient (VAD) rats were fed purified diets containing varying levels of all-trans-retinoic acid (atRA; 0, 0.5, 1.5, 6, 12, 25, 50, 125, or 250 microg/g diet) or were supplemented with retinol. Hindbrain development was studied from embryonic day 10 to 12.5 ( approximately 6 to 40 somites). Normal morphogenesis was observed in all embryos from groups fed 250 microg atRA/g diet or retinol. The most caudal region of the hindbrain was the most sensitive to retinoid insufficiency, as evidenced by a loss of the hypoglossal nerve (cranial nerve XII) in embryos from the 125 microg atRA/g diet group. Further reduction of atRA to 50 microg/g diet led to the loss of cranial nerves IX, X, XI, and XII and associated sensory ganglia IX and X in all embryos as well as the loss of hindbrain segmentation caudal to the rhombomere (r) 3/4 border in a subset of embryos. Dysmorphic orthotopic otic vesicles or immature otic-like vesicles in both orthotopic and caudally ectopic locations were also observed. As the level of atRA was reduced, a loss of caudal hindbrain segmentation was observed in all embryos and the incidence of otic vesicle abnormalities increased. Perturbations in hindbrain segmentation, cranial nerve formation, and otic vesicle development were associated with abnormal patterning of the posterior hindbrain. Embryos from VAD dams fed between 0.5 and 50 microg atRA/g diet exhibited Hoxb-1 protein expression along the entire neural tube caudal to the r3/r4 border at a time when it should be restricted to r4. Krox-20 protein expression was expanded in r3 but absent or reduced in presumptive r5. Hoxd-4 mRNA expression was absent in the posterior hindbrain, and the rostral limit of Hoxb-5 protein expression in the neural tube was anteriorized, suggesting that the most posterior hindbrain region (r7/r8) had been deleted and/or improperly patterned. Thus, when limiting amounts of atRA are provided to VAD dams, the caudal portion of the hindbrain is shortened and possesses r4/r5-like characteristics, with this region finally exhibiting r4-like gene expression when retinoid is restricted even more severely. Thus, regions of the anterior hindbrain (i.e., r3 and r4) appear to be greatly expanded, whereas the posterior hindbrain (r5-r8) is reduced or absent. This work shows that retinoid plays a critical role in patterning, segmentation, and neurogenesis of the caudal hindbrain and serves as an essential posteriorizing signal for this region of the central nervous system in the mammal.

The tracheo-innominate artery fistula is a rare but life-threatening complication of the tracheotomy. Its care management requires a rapid airway control to allow haemostasis by compression and ventilation. The haemostasis must be immediate and two techniques exist: surgery opencast (sternotomy) or interventional radiology. The choice between the two depends largely on the technical platform available. Our case report describes a tracheo-innomninate artery fistula surgically managed with success. The patient carried an anatomic variant, the two carotids come from innominate artery.