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inactive levers. The same schedule allowed the establishment of ketamine self-administration on a weekly basis. During the extinction phase, rate of responding significantly dropped in both weekly and daily groups although it was twofold longer in the former, which showed a lack of reacquisition.

Both pre-session ketamine priming and a conditioned stimulus paired to the ketamine infusions are required for the acquisition of ketamine self-administration. The longer extinction and the lack of reacquisition in the weekly group could be due to changes in temporal context that might affect the conditioning process.

Both pre-session ketamine priming and a conditioned stimulus paired to the ketamine infusions are required for the acquisition of ketamine self-administration. The longer extinction and the lack of reacquisition in the weekly group could be due to changes in temporal context that might affect the conditioning process.

Herpes simplex encephalitis (HSE) is a rare disease with a poor prognosis. No recent evaluation of hospital incidence, acute mortality and morbidity is available. In particular, decompressive craniectomy has rarely been proposed in cases of life-threatening HSE with temporal herniation, in the absence of evidence. This study aimed to assess the hospital incidence and mortality of HSE, and to evaluate the characteristics, management, the potential value of decompressive craniectomy and the outcome of patients with HSE admitted to intensive care units (ICUs).

Epidemiological study we used the hospital medical and administrative discharge database to identify hospital stays, deaths and ICU admissions relating to HSE in 39 hospitals, from 2010 to 2013. Retrospective monocentric cohort all patients with HSE admitted to the ICU of the university hospital during the study were included. The use of decompressive craniectomy and long-term outcome were analyzed. The initial brain images were analyzed blind to outcomaging is not useful for identifying high-risk patients. Decompressive craniectomy may be a useful salvage procedure in cases of intractable high ICP.

HSE appears to be more frequent than historically reported. The high incidence we observed probably reflects improvements in diagnostic performance (routine use of PCR). Mortality during the acute phase and long-term disability appear to be stable. High ICP and brain herniation are rare, but must be monitored carefully, as initial brain imaging is not useful for identifying high-risk patients. Decompressive craniectomy may be a useful salvage procedure in cases of intractable high ICP.Porous poly(glycerol sebacate) (PGS) scaffolds were prepared using a salt leaching technique and subsequently surface modified by a low oxygen plasma treatment prior to the use in the in vitro culture of human chondrocytes. Condensation polymerization of glycerol and sebacic acid used at various mole ratios, i.e. 11, 11.25, and 11.5, was initially conducted to prepare PGS prepolymers. Porous elastomeric PGS scaffolds were directly fabricated from the mixtures of each prepolymer and 90% (w/w) NaCl particles and then subjected to the plasma treatment to enhance the surface hydrophilicity of the materials. The properties of both untreated and plasma-treated PGS scaffolds were comparatively evaluated, in terms of surface morphology, surface chemical composition, porosity, and storage modulus using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy, micro-computed tomography, and dynamic mechanical analysis, respectively. The responses of chondrocytes cultured on individual PGS scaffolds were assessed, in terms of cell proliferation and ECM production. The results revealed that average pore sizes and porosity of the scaffolds were increased with an increasing sebacic acid concentration used. The storage moduli of the scaffolds were raised after the plasma treatment, possibly due to the further crosslinking of PGS upon treatment. Moreover, the scaffold prepared with a higher sebacic acid content demonstrated a greater capability of promoting cell infiltration, proliferation, and ECM production, especially when it was plasma-treated; the greatest HA, sGAG, uronic acid, and collagen contents were detected in matrix of this scaffold. The H & E and safranin O staining results also strongly supported this finding. The storage modulus of the scaffold was intensified after incubation with the chondrocytes for 21 days, indicating the accretion and retention of matrix ECM on the cell-cultured scaffold.The first controllable, regioselective radical amination of allenes with N-fluoroarylsulfonimide is described to proceed under very mild reaction conditions. With this methodology, a general and straightforward route for the synthesis of both allenamides and fluorinated tetrasubstituted alkenes was realized from a wide range of terminal and internal allenes.We report the synthesis of [n]manganoarenophanes (n=1, 2) featuring boron, silicon, germanium, and tin as ansa-bridging elements. Their preparation was achieved by salt-elimination reactions of the dilithiated precursor [Mn(η(5) -C5 H4 Li)(η(6) -C6 H5 Li)]⋅pmdta (pmdta=N,N,N',N',N-pentamethyldiethylenetriamine) with corresponding element dichlorides. Besides characterization by multinuclear NMR spectroscopy and elemental analysis, the identity of two single-atom-bridged derivatives, [Mn(η(5) -C5 H4 )(η(6) -C6 H5 )SntBu2 ] and [Mn(η(5) -C5 H4 )(η(6) -C6 H5 )SiPh2 ], could also be determined by X-ray structural analysis. We investigated for the first time the reactivity of these ansa-cyclopentadienyl-benzene manganese compounds. The reaction of the distannyl-bridged complex [Mn(η(5) -C5 H4 )(η(6) -C6 H5 )Sn2 tBu4 ] with elemental sulfur was shown to proceed through the expected oxidative addition of the Sn-Sn bond to give a triatomic ansa-bridge. The investigation of the ring-opening polymerization (ROP) capability of [Mn(η(5) -C5 H4 )(η(6) -C6 H5 )SntBu2 ] with [Pt(PEt3 )3 ] showed that an unexpected, unselective insertion into the Cipso -Sn bonds of [Mn(η(5) -C5 H4 )(η(6) -C6 H5 )SntBu2 ] had occurred.Rapid, large-scale manufacture of medical countermeasures can be uniquely met by the plant-made-pharmaceutical platform technology. As a participant in the Defense Advanced Research Projects Agency (DARPA) Blue Angel project, the Caliber Biotherapeutics facility was designed, constructed, commissioned and released a therapeutic target (H1N1 influenza subunit vaccine) in less then 18 months from groundbreaking. As of 2015, this facility was one of the world's largest plant-based manufacturing facilities, with the capacity to process over 3500 kg of plant biomass per week in an automated multilevel growing environment using proprietary LED lighting. The facility can commission additional plant grow rooms that are already built to double this capacity. In addition to the commercial-scale manufacturing facility, a pilot production facility was designed based on the large-scale manufacturing specifications as a way to integrate product development and technology transfer. The primary research, development and manufacturing system employs vacuum-infiltrated Nicotiana benthamiana plants grown in a fully contained, hydroponic system for transient expression of recombinant proteins. This expression platform has been linked to a downstream process system, analytical characterization, and assessment of biological activity. This integrated approach has demonstrated rapid, high-quality production of therapeutic monoclonal antibody targets, including a panel of rituximab biosimilar/biobetter molecules and antiviral antibodies against influenza and dengue fever.Despite progress in the prevention and treatment of infectious diseases, they continue to present a major threat to public health. The frequency of emerging and reemerging infections and the risk of bioterrorism warrant significant efforts towards the development of prophylactic and therapeutic countermeasures. Vaccines are the mainstay of infectious disease prophylaxis. Traditional vaccines, however, are failing to satisfy the global demand because of limited scalability of production systems, long production timelines and product safety concerns. Subunit vaccines are a highly promising alternative to traditional vaccines. Subunit vaccines, as well as monoclonal antibodies and other therapeutic proteins, can be produced in heterologous expression systems based on bacteria, yeast, insect cells or mammalian cells, in shorter times and at higher quantities, and are efficacious and safe. However, current recombinant systems have certain limitations associated with production capacity and cost. Plants are emerging as a promising platform for recombinant protein production due to time and cost efficiency, scalability, lack of harboured mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modification. So far, a variety of subunit vaccines, monoclonal antibodies and therapeutic proteins (antivirals) have been produced in plants as candidate countermeasures against emerging, reemerging and bioterrorism-related infections. Many of these have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, we overview ongoing efforts to producing such plant-based countermeasures.Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches.We describe herein the case of an adolescent girl with anemia non-responsive to oral iron, associated with low-grade fever, diminished appetite and fatigue. A palpable mass below the xiphoid was noted. Laboratory findings were consistent with anemia of inflammation. click here Direct antiglobulin test was positive without any other evidence of autoimmune anemia. Other autoantibodies, such as anti-thyroid and anti-nuclear antibodies, were also positive. After thorough investigation, Castleman disease was the most likely diagnosis on the basis of high serum interleukin (IL)-6 and the magnetic resonance imaging findings. (18)F-FDG positron emission tomography-computed tomography showed a localized hypermetabolic mass, which was resected. Castleman disease of plasma type was identified on histology. Hemogloblin and IL-6 gradually returned to normal, whereas positive autoantibodies became negative. This case emphasizes the need to investigate thoroughly for the underlying cause of anemia of inflammation and to include Castleman disease in the differential diagnosis, on the measurement of IL-6.

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