Second-order optimization strategies for neural network quantum states.

The Variational Monte Carlo (VMC) method has recently seen important advances through the use of neural network quantum states. While more and more sophisticated ansatze have been designed to tackle a wide variety of quantum many-body problems, modest progress has been made on the associated optimization algorithms. In this work, we revisit the Kronecker-Factored Approximate Curvature (KFAC), an optimizer that has been used extensively in a variety of simulations. We suggest improvements in the scaling and the direction of this optimizer and find that they substantially increase its performance at a negligible additional cost. We also reformulate the VMC approach in a game theory framework, to propose a novel optimizer based on decision geometry. We find that on a practical test case for continuous systems, this new optimizer consistently outperforms any of the KFAC improvements in terms of stability, accuracy and speed of convergence. Beyond VMC, the versatility of this approach suggests that decision geometry could provide a solid foundation for accelerating a broad class of machine learning algorithms. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.

New Delhi Metallo-beta-lactamase around the world: an eReview using Google Maps.

Gram-negative carbapenem-resistant bacteria, in particular those producing New Delhi Metallo-betalactamase-1 (NDM-1), are a major global health problem. To inform the scientific and medical community in real time about worldwide dissemination of isolates of NDM-1-producing bacteria, we used the PubMed database to review all available publications from the first description in 2009 up to 31 December 2012, and created a regularly updated worldwide dissemination map using a web-based mapping application. We retrieved 33 reviews, and 136 case reports describing 950 isolates of NDM-1-producing bacteria. Klebsiella pneumoniae (n= 359) and Escherichia coli (n=268) were the most commonly reported bacteria producing NDM-1 enzyme. Several case reports of infections due to imported NDM-1 producing bacteria have been reported in a number of countries, including the United Kingdom, Italy, and Oman. In most cases (132/153, 86.3%), patients had connections with the Indian subcontinent or Balkan countries. Those infected were originally from these areas, had either spent time and/or been hospitalised there, or were potentially linked to other patients who had been hospitalised in these regions. By using Google Maps, we were able to trace spread of NDM-1-producing bacteria. We strongly encourage epidemiologists to use these types of interactive tools for surveillance purposes and use the information to prevent the spread and outbreaks of such bacteria.

The quality monitoring of paracetamol medicament using a noninvasive microwave sensor.

Environmental conditions, including temperature, humidity, and light, can impact the quality of drugs. Microwave-based approaches offer a fast and cost-effective way to detect quality variations, providing an alternative to traditional techniques in the pharmaceutical and cosmetic industries. This article proposes the use of a microwave sensor for monitoring the quality of pharmaceutical drugs at distinct temperature levels. A small planar sensor based on three hexagonal split ring resonators (TH-SRR) is fabricated. The design is manufactured on an FR-4 dielectric substrate. The sensor is tested on a 1000 mg paracetamol tablet, at temperatures ranging from 40 to 80 [Formula: see text]C. The Variation in the permittivity that characterizes product degradation is translated into a shift in the frequency of the scattering matrix elements. To validate the microwave approach, drug quality is examined with the laser-induced breakdown spectroscopy (LIBS) technique, an optical emission laser used for both qualitative and quantitative investigations of elements contained in a sample. The existing elements are classified using the National Institute of Standards and Technology (NIST) database and categorized according to their spectral line wavelengths. The experiments show the presence of optimal wavelength values for carbon (C), hydrogen (H), nitrogen (N), and oxygen (O) at 247.92 nm, 656.49 nm, 244.23 nm, and 777.48 nm, respectively. The microwave experimental results show a shift frequency of approximately 1 MHz on average when the tablet is heated at 80 [Formula: see text]C for 15 min. Meanwhile, the LIBS measurement shows a remarkable shift in terms of intensity of approximately 8884 and 812 for carbon and hydrogen, respectively. Understanding how paracetamol dries under high temperatures and improving the process settings of the microwave sensor are investigated and assessed in this work.

CTX-M-15 extended-spectrum beta-lactamases in Enterobacteriaceae in the intensive care unit of Tlemcen Hospital, Algeria.

The aim of this study was to detect extended-spectrum beta-lactamases (ESBL) in Enterobacteriaceae isolates in the intensive care unit (ICU) of Tlemcen hospital in north-western Algeria. Antimicrobial susceptibility testing, molecular typing, characterization of ESBL-encoding genes and the genetic environment, conjugation experiments and plasmid analysis were carried out. In all, 28 Enterobacteriaceae isolates were isolated from specimens recovered from patients in the ICU and 2 from surfaces of the unit. Of these, 11 isolates (4 Escherichia coli, 5 Klebsiella pneumoniae and 2 Enterobacter cloacae) produced ESBL of the CT-X-M-15 type. Molecular typing of the isolates showed the clonal nature of 4 K. pneumoniae isolates. The bla(CTXM-15) gene was genetically linked to insertion sequence lSEcp1B and was transferable by conjugation from 3 isolates. Regular monitoring of resistance mechanisms, the establishment of a prevention strategy, and more rational and appropriate use of antibiotics are needed.

Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway.

Although genetic evidence has demonstrated a role for Wnt5b during cartilage and limb development, little is known about the mechanisms underlying Wnt5b-regulated chondrocyte differentiation. We observed that Wnt5b inhibited chondrocyte hypertrophy and expression of type X collagen. In addition, Wnt5b regulated the overall size of chondrogenic cultures, suggesting that Wnt5b regulates other processes involved in cartilage development. We therefore investigated the signaling pathways by which Wnt5b influences differentiation. Wnt5b activated known calcium-dependent signaling pathways and JNK, a component of the planar cell polarity pathway. Since the planar cell polarity pathway regulates process such as cell migration and cell aggregation that are involved in limb development, we assayed for effects of Wnt5b on these processes. We observed a marked increase chondroprogenitor cell migration with Wnt5b expression. This effect was blocked by inhibition of JNK, but not by inhibition of other Wnt5b-responsive factors. Expression of Wnt5b also disrupted the cellular aggregation associated with mesenchymal condensation. Decreased aggregation was associated with reduced cadherin expression as well as increased cadherin receptor turnover. This increase in cadherin receptor turnover was associated with an increase in Src-dependent beta-catenin phosphorylation downstream of Wnt5b. Our data demonstrate that not only does Wnt5b inhibit chondrocyte hypertrophy, but document a novel role for Wnt5b in modulating cellular migration through the JNK-dependent and cell adhesion through an activation of Src and subsequent cadherin receptor turnover.

Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery.

Tendon reconstruction using grafts often results in adhesions that limit joint flexion. These adhesions are precipitated by inflammation, fibrosis, and the paucity of tendon differentiation signals during healing. In order to study this problem, we developed a mouse model in which the flexor digitorum longus (FDL) tendon is reconstructed using a live autograft or a freeze-dried allograft, and identified growth and differentiation factor 5 (Gdf5) as a therapeutic target. In this study we have investigated the potential of rAAV-Gdf5 -loaded freeze-dried tendon allografts as "therapeutically endowed" tissue-engineering scaffolds to reduce adhesions. In reporter gene studies we have demonstrated that recombinant adeno-associated virus (rAAV)-loaded tendon allografts mediate efficient transduction of adjacent soft tissues, with expression peaking at 7 days. We have also demonstrated that the rAAV-Gdf5 vector significantly accelerates wound healing in an in vitro fibroblast scratch model and, when loaded onto freeze-dried FDL tendon allografts, improves the metatarsophalangeal (MTP) joint flexion to a significantly greater extent than the rAAV-lacZ controls do. Collectively, our data demonstrate the feasibility and efficacy of therapeutic tendon allograft processing as a novel paradigm in tissue engineering in order to address difficult clinical problems such as tendon adhesions.

[Effects of skin infiltration with ropivacaine 0,75% on postoperative pain after caesarean section]. / Effet d'une infiltration sous-cutanée de ropivacaïne 0,75 % sur l'analgésie postopératoire après césarienne.

OBJECTIVE: Evaluate the effects of skin infiltration with ropivacaine 0,75% on postoperative pain after caesarean section in the first 24h. PATIENTS AND METHODS: A prospective randomized double blind study was realized during three months in Auxerre Hospital. All ASA 1-2 patients presenting for elective caesarean section under spinal anesthesia were enrolled in the study. Drug addicts and patients with chronic pain were excluded from the study. The patients were randomly divided into two groups to receive skin infiltration 20 ml of ropivacaine 0,75% (Gr R) or skin infiltration of 20 ml of 0,9% saline solution. All patients received systematically propacetamol 1g per six hours and ketoprofen 50mg per six hours. Intravenous morphine titration was delivered to patients with a simple numerical scale greater or equal to three (SNS> or =3). Postoperative pain (SNS), morphine consumption and adverse reactions were compared. RESULTS: From July to September 2005, 42 patients were enrolled in the study. The SNS was lower in the Gr R. Total morphine consumption was reduced in the Gr R. The incidence of the adverse effects were higher in the Gr P. One case of parietal haematoma was detected in the Gr P, the evolution of which was favorable. DISCUSSION AND CONCLUSION: Skin infiltration of ropivacaine 0,75% is a simple technique able to reduce postoperative pain score and morphine consumption after caesarean section.

[Middle aortic syndrome: a case report]. / Middle aortic syndrome: à propos d'un cas.

Middle aortic syndrome (MAS) results from a diffuse narrowing of the distal thoracic or abdominal aorta commonly involving both the visceral and renal arteries. Congenital, acquired, inflammatory, and infectious etiologies have been described. Symptoms typically occur within the first three decades of life and include hypertension, lower extremity claudication, and mesenteric ischemia. The condition is considered a life-threatening emergency as a result of the complications associated with severe hypertension. Diagnosis is made with magnetic resonance and computed tomography angiography. Surgical bypass grafting is the optimal method of treatment and must be tailored depending on the distribution of disease. We report one case of MAS treated with thoracic aorta to abdominal aorta bypass and reimplantation of the right renal artery.

Antibiotic susceptibility and mechanisms of beta-lactam resistance among clinical strains of Pseudomonas aeruginosa: first report in Algeria.

OBJECTIVE: Pseudomonas aeruginosa is a major causative agent of hospital infections. Studies on this subject being rare in Algeria, we determined the antibiotic susceptibility of P. aeruginosa and investigated the mechanisms of beta-lactam resistance and the spread of multidrug resistant strains in the university affiliated Hospital of Tlemcen (Algeria). DESIGN: One hundred and ninety-nine consecutive strains of P. aeruginosa were collected between November 2005 and February 2007. MICs of antibiotics were measured by the agar dilution method. The resistance mechanisms to beta-lactams were identified phenotypically or by molecular methods (isoelectrofocusing, PCR and sequencing). Strains expressing a secondary beta-lactamase were serotyped and genotyped (Random Amplified Polymorphic DNA). RESULTS: The proportion of susceptible isolates were: ticarcillin (56%), piperacillin-tazobactam (81%), ceftazidime (88%), cefepime (80%), aztreonam (64%), imipenem (65%), amikacin (83%), tobramycin (81%) and ciprofloxacin (97%) according to the French CASFM breakpoints. Resistance to beta-lactams was linked to the production of transferable beta-lactamases (16%), overproduction of cephalosporinase AmpC (12%) and/or non-enzymatic mechanisms such as the loss of porin OprD (35%) and overproduction of the active efflux system MexAB-OprM (24%). High level resistance to ticarcillin was due to the expression of beta- lactamase OXA-10 alone or associated with TEM-110. A genotypic analysis revealed the spread of a multidrug resistant epidemic clone expressing these two acquired beta-lactamases in the surgical ICU. CONCLUSIONS: This study shows that resistance to antibiotics, in particular to imipenem of P. aeruginosa, is becoming a cause of concern in the Hospital of Tlemcen.

[Vesicouterine fistulas: an experience of 17 years]. / Les fistules vésico-utérines: une expérience de 17 ans.

OBJECTIVE: To discuss the diagnostic and the prognostic problems of vesicouterine fistulas (VUF) emphasizing on the therapeutic characteristics that lead to successful treatment. MATERIALS AND METHODS: The authors retrieve retrospective series of 16 cases, collected between 1989 and June 2006, and they analyze the clinical, diagnostic and therapeutic aspects. RESULTS: The patients were young (29-40 years) with an average having three children. Cesarean was the most frequent etiology. The presentation symptoms were hematuria (in five cases), a urinary incontinence through the vagina (in eight cases) and both of them (in three cases). The diagnosis was suspected from the history and confirmed by the additional analyses. The treatment was surgical (excision of the fistulas) in 15 cases with an average follow-up of 2.5 years, the results on the functional aspect were satisfactory hence they were marked by the absence of urinary incontinence as well as the hematuria. On the obstetric aspect, the occurrence of pregnancy was noted in a patient at four years post-VUF repair. CONCLUSION: Vesicouterine fistulas are not very frequent and most often secondary to a cesarean or to consequences of difficult delivery. The treatment is essentially preventive by improving the obstetrical techniques through avoiding the bladder injuries during the cesareans.

[Antifibrinolytic agents and repeat open-heart surgery: a comparison of tranexamic acid and low dose aprotinin]. / Antifibrinolytiques et réinterventions chirurgicales à coeur ouvert: comparaison de l'acide tranexamique aux faibles doses d'aprotinine.

PURPOSE: This retrospective study has for objective to compare the effect of tranexamic acid with low-dose of aprotinin therapy on blood loss in reoperative cardiac surgery. METHODS: Ninety-one adult patients underwent repeated open-heart surgery. Two groups of patients were collected. The aprotinin group AP (N=60) has received an intravenous full low dose of 500000 UIK of aprotinin. The tranexamic group TA (N=31) has received 30 mg/kg of tranexamic acid. Criteria for assessment included: cumulative blood loss at 4 hours and 20 hours after operation, need for transfusion and parameters of coagulation (platelet, fibrinogen count). RESULTS: Demographics characteristics and echocardiographic data were similar between the tow groups. Postoperative blood loss at 4th hour and at 20th hour were reduced in tranexamic group compared with aprotinin group (P=0,009, P=0,001). The transfusion requirement was frequent in the AP group 39% vs 19.4% in TA group. The TA group received fewer total unit of red blood (0.38 unit RBC/patient vs 1.06 in AP group) [RBC=red blood cells]. There was no statistically significant difference in platelet and fibrinogen profiles. CONCLUSION: This study concludes that tranexamic acid and low dose aprotinin effectively reduces postoperative bleeding in repeat open-heart surgery. However, the marked difference in superiority between these tow drug therapies needs the randomized and controlled study.

[Upper digestive bleedings after cardiac surgery]. / Hémorragies digestives hautes après chirurgie cardiaque.

INTRODUCTION: Upper gastrointestinal haemorrhage (UGH) following cardiac surgery is infrequent with high mortality. The aim of this study is to compare the frequency and outcome of UGH in patients who had undergone open heart surgery at our institution. PATIENTS AND METHODS: From January 1994 to December 2005, 1278 cardiac operations were performed. A systematic prophylaxis antiacid was used by antagonists of histaminic receptor (anti-H2, ranitidine 150 mg/12 h) in all patients. The diagnosis was based on clinical symptoms (haematemesis and/or melaena) in the postoperative period and confirmed by fibroscopy. We conducted a retrospective study of these patients. RESULTS: Only 8 of the 1278 (0,6%) cardiac operations were complicated by UGH. Demographic data were reported in Table 1. The mean interval between surgery and UGH was 10+/-3,7 days (range 5,15 days). Gastro-duodenal ulcer was the most common cause of UGH in 5 patients (62%), ulcero-hemorrhagic eosophagitis was developed in one patient (12,5%), candidosic eosophagitis in one and multiple gastric ulcer in one patient (12,5%). Medical treatment was applied in 6 patients (72%) with successful result. Surgical intervention was necessary in 2 patients (25%). 2 patients had repeat gastrointestinal bleeding. One patient was died; he was recorded as having severe sepsis and multiple organ failure in addition to UGH. CONCLUSION: UGH in patients undergoing heart operation is rare but associated with poor prognosis despite antiacid prophylaxis. These complications occurred in patients who had in postoperative bad hemodynamic conditions.

[Predictors of prolonged ICU stay following elective adult cardiac surgery: Monocentric retrospective study on 5 and half years]. / Facteurs prédictifs de long séjour en réanimation après chirurgie cardiaque programmée de l'adulte : étude rétrospective monocentrique sur 5 ans et demi.

AIM: The aim of our study was to identify predictors for prolonged ICU stay following elective adult cardiac surgery under cardiopulmonary bypass. PATIENTS AND METHODS: A retrospective study was conducted during 5 years and a half period. Were included, patients age≥18 years old, underwent elective cardiac surgery under cardiopulmonary bypass. Patients who died within 48hours of surgery were excluded. Prolonged ICU stay was defined as stay in the ICU for 48hours or more. RESULTS: During the review period, 610 patients were included. One hundred and sixty-four patients have required a prolonged ICU stay (26.9 %). In multivariate analysis, 5 predictors were identified: ejection fraction<30 % (OR 19.991, IC 95 % [1.382-289.1], P=0.028], pulmonary hypertension (OR 2.293, IC 95 % [1.058-4.973], P=0.036), prolonged ventilation (≥12hours) (OR 4.026, IC 95 % [2.407-6.733], P<0.001). Number of blood units transfused (OR 1.568, IC 95 % [1.073-2.291], and postoperative acute renal failure (OR 2.620, IC 95 % [1.026-6.690], P=0.044]. Prolonged ICU stay is significantly associated with prolonged hospital stay (17 days vs 13 days ; P<0.001) and higher in hospital mortality (22 % vs. 3 %, P<0.001). CONCLUSION: The identification of these patients at risk of prolonged ICU stay is crucial. It will aid to plan prophylactic measures to optimize their support.

Autoimmunity and bone.

Focal erosions of cartilage and bone, which occur in the joints of patients with autoimmune inflammatory arthritis (i.e., rheumatoid arthritis (RA) and psoriatic arthritis [PsA]), represent the most debilitating and irreversible components of the disease. Over the last decade, seminal breakthroughs in our understanding of the cells and signal transduction pathways central to this process have been elucidated. From this information an established paradigm has been developed to explain focal erosions in which osteoclasts responsible for erosions are derived from bone marrow-derived myeloid precursors. Using the tumor necrosis factor (TNF) transgenic mouse model of erosive arthritis and anti-TNF clinical trials with PsA patients, we have demonstrated that systemic TNF induces the migration of CD11b+ osteoclast precursors (OCP) from the bone marrow into peripheral blood. These OCP can then enter the joints in blood vessels, translocate across the receptor activator of NF-kappaB ligand (RANKL) rich inflamed synovium, and differentiate into active osteoclasts. In direct contrast to this, systemic lupus erythematosus (SLE) patients appear to have an innate resistance to bone resorption. Our hypothesis to explain this phenomenon is that systemic interferon-alpha (IFN-alpha) diverts the bone marrow-derived myeloid precursors away from the osteoclast lineage and stimulates their differentiation into dendritic cells (DC). In support of this model, several labs have used microarray analyses to define the IFN-induced transcriptome in peripheral blood mononuclear cells (PBMC) from SLE patients. Here we propose the hypothesis that systemic TNF induces osteoclastic differentiation of PBMC in PsA patients that correlates with their erosive disease, and that the innate immune TNF/IFN axis in patients with autoimmune disease dictates their erosive phenotype. To demonstrate this, we injected wild-type C57B/6 and TNF-Tg mice with poly I:C, which is known to induce systemic IFN responses, and show its dominant effects on increasing the number of circulating CD11b+/CD11c+ precursor dendritic cells (pDC), concomitant with a dramatic reduction in CD11b+/CD11c- OCP. Thus, systemic factors produced by autoimmunity have a dramatic impact on active myelopoiesis and bone homeostasis.

Safety and efficacy of ultraviolet-a light-activated gene transduction for gene therapy of articular cartilage defects.

BACKGROUND: Gene therapies for articular cartilage defects are limited by the absence of an in vivo delivery system that can mediate site-specific transduction restricted to within the margins of the defect during routine arthroscopy. We have proposed the use of ultraviolet light to stimulate gene expression following infection by recombinant adeno-associated virus (rAAV). However, research has demonstrated that short-wavelength ultraviolet light (ultraviolet C), while effective, is neither safe nor practical for this purpose. We evaluated the safety and efficacy of long-wavelength ultraviolet light (ultraviolet A) from a laser to induce light-activated gene transduction in articular chondrocytes in vitro and in vivo. METHODS: The effects of ultraviolet A from a 325-nm helium-cadmium laser, delivered through a fiberoptic cable, on cytotoxicity, mutagenesis, intracellular reactive oxygen species, and light-activated gene transduction of human articular chondrocytes were evaluated in dose-response experiments of primary cultures. Cytotoxicity was determined by trypan blue exclusion. The presence of pyrimidine dimers in purified genomic DNA was determined by enzyme-linked immunosorbent assays. Intracellular reactive oxygen species levels were determined by flow cytometry at one hour and twenty-four hours. In vitro light-activated gene transduction with rAAV vectors expressing the green fluorescent protein (eGFP) or beta-galactosidase (LacZ) was determined by fluorescence microscopy and bioluminescence assays, respectively. In vivo light-activated gene transduction was quantified by stereotactic immunohistochemistry for beta-galactosidase in rabbit articular cartilage defects in the patellar groove that had been irradiated with +/-6000 J/m2 of ultraviolet A one week after direct injection of 10(7) transducing units of rAAV-eGFP. RESULTS: Ultraviolet A failed to induce significant cytotoxicity at all fluencies below 6000 J/m2. Dose-dependent cytotoxicity was observed at greater fluencies. In contrast to ultraviolet C, which induced significant (p < 0.05) pyrimidine dimer formation at all fluencies in a dose-dependent manner, ultraviolet A failed to induce DNA modifications. Conversely, ultraviolet C proved to be a poor inducer of intracellular reactive oxygen species, while ultraviolet A immediately induced high levels of intracellular reactive oxygen species, which were completely resolved twenty-four hours later. Ultraviolet A demonstrated significant light-activated gene transduction effects in vitro, which were dose-dependent (p < 0.05). In vivo, ultraviolet A mediated a tenfold increase in transduction in which 40.8% of the superficial chondrocytes adjacent to the defect stained positive for green fluorescent protein compared with 5.2% in the knees treated with no ultraviolet A (p < 0.006). CONCLUSIONS: These results provide what we believe is the first formal demonstration of an agent that can induce rAAV transduction in the complete absence of cytotoxicity and DNA modification. They also suggest that the mechanism by which long-wavelength ultraviolet light mediates site-specific gene expression is by means of the induction of intracellular reactive oxygen species. Finally, laser-derived ultraviolet A can be readily transferred through a fiberoptic cable to mediate light-activated gene transduction in vivo.

Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles.

UNLABELLED: Synovial fibroblasts are possible mediators of osteolysis. Fibroblasts respond directly to titanium particles and increase RANKL expression through a COX-2/PGE2/EP4/PKA signaling pathway. Fibroblasts pretreated with titanium or PGE2 stimulated osteoclast formation, showing the functional importance of RANKL induction. Synovial fibroblasts and their activation pathways are potential targets to prevent osteolysis. INTRODUCTION: Bone loss adjacent to the implant is a major cause of joint arthroplasty failure. Although the cellular and molecular response to microscopic wear debris particles is recognized as causative, little is known concerning role of synovial fibroblasts in these events. MATERIALS AND METHODS: Murine embryonic fibroblasts and knee synovial fibroblasts in culture stimulated with titanium particles were examined by FACS, real time RT-PCR, Northern blot, and Western blot for expressions of vascular cell adhesion molecule (VCAM)1, RANKL, cyclooxygenase (COX)-1, and COX-2, and the four prostaglandin E2 (PGE2) receptor isoforms. Experiments were performed in the presence and absence of COX inhibitors, protein kinase A (PKA) and protein kinase C (PKC) inhibitors, and various EP receptor agonists. Osteoclast formation was examined in co-cultures of pretreated glutaraldehyde-fixed fibroblasts and primary murine spleen cells treated with macrophage-colony stimulating factor (M-CSF) for 7-days. RESULTS: TNF-alpha stimulated VCAM1 expression, consistent with a synovial fibroblast phenotype. Titanium particles stimulated RANKL gene and protein expressions in fibroblasts in a dose-dependent manner. Gene expression was increased 5-fold by 4 h, and protein levels reached a maximum after 48 h. Within 1 h, titanium particles also induced COX-2 mRNA and protein levels, whereas both indomethacin and celecoxib blocked the stimulation of RANKL, suggesting a COX-2-mediated event. Furthermore, PGE2 induced RANKL gene and protein expression and rescued RANKL expression in titanium-treated cultures containing COX-2 inhibitors. Fibroblast cultures pretreated with either PGE2 or titanium particles enhanced osteoclast formation, indicating the functional importance of RANKL induction. EP4 was the most abundant PGE2 receptor isoform, EP1 and EP2 were expressed at low levels, and EP3 was absent. The EP1 selective agonist iloprost and the EP2 selective agonist butaprost minimally stimulated RANKL. In contrast, the EP2 and EP4 agonist misoprostol induced RANKL to a magnitude similar to PGE2. Finally, PKA antagonism strongly repressed RANKL stimulation by PGE2. CONCLUSION: Fibroblasts respond directly to titanium particles and increase RANKL expression through a COX-2/PGE2/EP4/PKA signaling pathway. Thus, the synovial fibroblast is important mediator of osteolysis and target for therapeutic strategies.

Nutrition care in patients with cancer: A retrospective multicenter analysis of current practice - Indications for further studies?

BACKGROUND & AIMS: Weight loss and malnutrition are frequent problems in oncology patients. The aim of this study was to get a perspective of the current practice of parenteral nutrition (PN) care in an outpatient setting and to improve patient-centered nutritional care. METHODS: Fifty-three outpatient oncology centers participated in this observational study performed between July 2010 and March 2011. All participating centers entered data online into a web-based documentation form, containing a number of oncology patients, diagnoses, and detailed data about oncology patients receiving PN. RESULTS: Two cohorts were analyzed. First cohort consisted of all oncology patients in quarter 04/2010. Second cohort consisted of patients with PN during the whole studying period. In the first cohort 2.46% (n = 626) of 25,424 oncology patients received PN. Most frequent diagnoses of patients receiving PN were gastric cancer (n = 119) and colorectal cancer (n = 104), however most stated diagnosis was "other" (n = 163). In the second cohort (n = 1137), a common indication for PN was impaired gastrointestinal passage (n = 177), although here again most stated reason was "other" (n = 924). In the course of the PN treatment, patients (n = 1137) showed a stable or slowly increasing body mass index (from 21.6 ± 3.8 kg/m(2) to 21.8 ± 3.5 kg/m(2)). CONCLUSION: This is the largest study outlining the characteristics of oncology patients in the context of PN in German ambulatory centers. They confirm the important role of PN in the care of gastrointestinal cancer. Further studies have to be performed to identify if other indications than those mentioned in relevant guidelines can trigger initiation of PN.

[The aneurysms of digestive system arteries: three cases]. / Les anévrysmes des artères digestives. À propos de trois cas.

The aneurysms of digestive arteries are a rare pathological entity, with a risk of rupture associated to a high mortality rate, often asymptomatic, then they are discovered incidentally during a exam for other diagnostic purposes. We report three cases of digestive aneurysms, one of celiac trunk, one of mesenteric artery on behçet disease, and one of splenic artery, which were treated surgically with success.

Small abnormal echos after mitral valve replacement with bileaflet mechanical prostheses: predisposing factors and effect on thromboembolism.

Early transesophageal echocardiography (TEE) after mitral valve replacement can detect symptomless, non-obstructive thrombus on prosthetic valves and also small filamentous abnormal echoes (SAE). The object of this study is to evaluate their respective frequency and predisposing factors. Between October 1988 and June 1992, 129 consecutive patients underwent mitral valve replacement with a bileaflet prosthesis and had transesophageal echocardiography at an average of 15 +/- 7 days (range: 6-35 days) after surgery. Details of postoperative anticoagulation were analyzed in 99 patients from five surgical centers having comparable postoperative anticoagulation protocols. Among those patients presenting with SAE, 76% had a second transesophageal echocardiography at an average of 145 +/- 166 days after the first examination. Mean age was 56 +/- 13 years. Small filamentous echoes were found in 55 patients (43%). In univariate analysis, independent predictors were age, absence of systolic regurgitation across the mitral prosthesis as observed with continuous Doppler, and the presence of spontaneous echo contrast (SC) in the left atrium: 54 +/- 14 years in the absence vs. 59 +/- 10 in the presence of SAE (p < 0.05); 54% of systolic leak vs. 36% (p < 0.05); 43% of SC vs. 75% (p < 0.00001). In multivariate analysis, spontaneous echo contrast was the only independent predictor for SAE (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)