Amitriptyline, minocycline and maropitant reduce the sevoflurane minimum alveolar concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat: a randomised laboratory study.

Background: The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance.

Objectives: To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane minimum alveolar concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia.

Design: A randomised, laboratory study.

Dynamic self-assembly of polycationic clusters based on cyclodextrins for pH-sensitive DNA nanocondensation and delivery by component design.

The ability of cyclodextrin-based polycationic cluster to undergo reversible DNA condensation and release in a physiologically useful pH window has been finely tuned by the installation of a capping xylylene moiety at the secondary face of the cyclooligosaccharide. This strategy can be exploited advantageously in the design of self-assembling nonviral gene-delivery systems from molecular entities.

Use of a gentamicin-impregnated collagen sheet (Collatamp(®)) in the management of major soft tissue complications in pediatric cochlear implants.

Objective And Importance: The objective was to report the effectiveness of salvage treatment in soft tissue infection around cochlear implants with an absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps.

Clinical Presentation: Three patients with cochlear implant and persistent surrounding soft tissue infection are included. All of them underwent antibiotic treatment prior to surgery without any response.

SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome.

Aberrant expression of the secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) gene, which encodes a matricellular protein that participates in normal tissue remodeling, is associated with a variety of diseases including cancer, but the contribution of SPARC to malignant growth remains controversial. We previously reported that SPARC was among the most upregulated genes in cytogenetically normal acute myeloid leukemia (CN-AML) patients with gene-expression profiles predictive of unfavorable outcome, such as mutations in isocitrate dehydrogenase 2 (IDH2-R172) and overexpression of the oncogenes brain and acute leukemia, cytoplasmic (BAALC) and v-ets erythroblastosis virus E26 oncogene homolog (ERG). In contrast, SPARC was downregulated in CN-AML patients harboring mutations in nucleophosmin (NPM1) that are associated with favorable prognosis.

Targeted delivery of pharmacological chaperones for Gaucher disease to macrophages by a mannosylated cyclodextrin carrier.

Gaucher disease (GD) is a rare monogenetic disorder leading to dysfunction of acid β-glucosidase (β-glucocerebrosidase; GCase) and accumulation of glucosylceramide in lysosomes, especially in macrophages (Gaucher cells). Many of the mutations at the origin of GD do not impair the catalytic activity of GCase, but cause misfolding and subsequent degradation by the quality control system at the endoplasmic reticulum. Pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the endogenous mutant enzyme represent promising alternatives to the currently available enzyme replacement and substrate reduction therapies (ERT and SRT, respectively), but unfavorable biodistribution and potential side-effects remain important issues.

European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients.

Objectives: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV).

Targeting hypoxia in the leukemia microenvironment.

The bone marrow (BM) microenvironment regulates survival and maintenance of normal hematopoietic stem cells. Within the endosteal niche, hypoxia has an essential role in maintenance of the primitive quiescent hematopoietic stem cell. We and others have demonstrated that in the context of hematologic malignancies the BM is highly hypoxic, and that progression of the disease is associated with expansion of hypoxic niches and stabilization of the oncogenic HIF-1α.

A novel fluorometric assay for aldo-keto reductase 1C3 predicts metabolic activation of the nitrogen mustard prodrug PR-104A in human leukaemia cells.

Aldo-keto reductase 1C3 (AKR1C3, EC 1.1.1.

Immunological function restoration with lopinavir/ritonavir versus efavirenz containing regimens in HIV-infected patients: a randomized clinical trial.

CD4(+) count increase has been reported to be different with lopinavir/r (LPV/r) and efavirenz (EFV)-containing regimens. The different effect of these two regimens on other immune function parameters and the relationship with the gain of CD4(+) count have not been assessed in a randomized clinical trial. Fifty antiretroviral treatment (cART) naïve HIV-infected individuals were randomized to receive LPV/r or EFV both with tenofovir/emtricitabine for 48 weeks.

From cradle to adolescence: the development of Research in European Pediatric Emergency Medicine.

Pediatric emergency medicine (PEM) has been developing rapidly but heterogeneously in many European countries in recent years, and many national PEM societies have been founded to improve the quality of care of ill and injured children and adolescents. Key facets of any such improvement are the development, delivery and translation of high-quality research. Research in European Pediatric Emergency Medicine (REPEM) has developed a robust international structure involving clinicians, academics and national PEM research networks.

Reappearance of sympathetic skin response below a thoracic level-9 complete spinal cord injury.

Reappearance of sympathetic skin response (SSR) below lesion is reported in a patient with a complete thoracic-9 spinal cord injury 6 months following injury. SSR was elicited by electrical stimulation of supraorbital nerve (SON) and pudendal nerve (PN). SON stimulation induced SSRs only in the hand.

Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia.

B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199.

Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx--part I: how.

Objectives/hypothesis: To revisit the surgical technique of lateral pharyngotomy in patients with selected, isolated, and untreated invasive squamous cell carcinoma of the lateral oropharynx. To describe postoperative management, complications, and functional outcomes.

Study Design: Retrospective review from a French university teaching hospital.

Feasibility and repeatability of thermal quantitative sensory testing in normal dogs and dogs with hind limb osteoarthritis-associated pain.

The objectives of this study were to determine whether thermal quantitative sensory testing (QST) can be performed in client-owned dogs, is repeatable and whether QST differs between normal dogs and dogs with hind limb osteoarthritis (OA). This clinical, prospective, observational study used clinically normal dogs (n=23) and dogs with OA-associated hind limb pain (n=9). Thermal QST was performed in standing dogs using a high-powered light source delivered by a previously validated system.

A modified Delphi survey on the signs and symptoms of low back pain: indicators for an interventional management approach.

Background: Low back pain (LBP) symptoms and signs are nonspecific. If required, diagnostic blocks may find the source of pain, but indicators of suspect diagnosis must be defined to identify anatomical targets.

Objective: To reach a consensus from an expert panel on the indicators for the most common causes of LBP.

Suspension of the gluteal region with silhouette sutures.

The authors present their minimally invasive gluteopexy technique, using polypropylene 2-0 sutures with 10 absorbable polylactic cones in their distal section (Silhouette Lift, Irvine, California) to improve the anteroposterior projection of the gluteal region. Histological study of the reaction of adipose tissue surrounding the cones previously has shown that, 3 months after insertion of the sutures, fibrous scar tissue is sufficiently developed to resist the weight of the tissues. On the basis of this finding, the authors decided to perform the gluteopexy with sutures, in 2 surgical steps.

Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic Huntington's disease monkeys.

Background: Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling.

PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML cells in the hypoxic bone marrow microenvironment.

Unlabelled: Both phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling and antiapoptotic Bcl-2 family members are critical for survival of acute myeloid leukemia (AML) cells. Here, we demonstrate the antileukemic effects of simultaneous inhibition of PI3K by the selective class I PI3K inhibitor GDC-0941 and of Bcl-2 family members by the BH3 mimetic ABT-737 in the context of the bone marrow microenvironment, where hypoxia and interactions with bone marrow stromal cells promote AML cell survival and chemoresistance. The combination of GDC-0941 and ABT-737 profoundly downregulated antiapoptotic Mcl-1 expression levels, activated BAX, and induced mitochondrial apoptosis in AML cells co-cultured with bone marrow stromal cells under hypoxic conditions.

HIV exposed seronegative individuals show antibodies specifically recognizing native HIV envelope glycoprotein.

Background: Susceptibility to HIV transmission by sexual intercourse has been associated with cellular anti-HIV responses. We aimed to also evaluate potential systemic humoral responses against HIV in a group of HIV-exposed seronegative individuals (HESN) in stable relationship with HIV-infected partners.

Methods: We recruited 27 serodiscordant couples.

Recent developments on synthetic tools towards structural and functional glycodiversity.

Despite being the most abundant type of biopolymers in Nature, the biological relevance of carbohydrates has systematically been underrated for decades, associating them far less sophisticated functions (structural or energy sourcing) than those unraveled for polynucleotides and proteins. The inherently large and complex diversity of carbohydrates and glycoconjugates, together with the lack of efficient technologies to either isolate them from natural sources or produce them synthetically in useful amounts, have burdened the appreciation of their utmost importance in the most fundamental biological processes. For these reasons, carbohydrate-mediated transmission of biological information was largely unexplored.

Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection.

Introduction: Much effort has been put in the past years to create and assess accurate tools for the management of febrile infants. However, no optimal strategy has been so far identified. A sequential approach evaluating, first, the appearance of the infant, second, the age and result of the urinanalysis and, finally, the results of the blood biomarkers, including procalcitonin, may better identify low risk febrile infants suitable for outpatient management.

Descending mediastinitis with mediastinal abscess after supracricoid partial laryngectomy.

We document a rare and not-yet-reported condition after supracricoid partial laryngectomy: the development of descending mediastinitis with mediastinal abscess. We present a case in which early diagnosis and team management allowed for a successful outcome. The pathophysiology of this severe complication, as well as its diagnosis, management, and prevention, is discussed, together with a review of the medical scientific literature.

Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

Objectives: It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls.

Methods: Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls.

HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.

Objectives: To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients.

Design: Retrospective follow-up study.

Methods: We studied 321 naive patients who started HCV treatment.