There are two main types of fungal infections in the oncology patient: primary cutaneous fungal infections and cutaneous manifestations of fungemia. The main risk factor for all types of fungal ...infections in the oncology patient is prolonged and severe neutropenia; this is especially true for disseminated fungal infections. Severe neutropenia occurs most often in leukemia and lymphoma patients exposed to high-dose chemotherapy. Fungal infections in cancer patients can be further divided into five groups: (i) superficial dermatophyte infections with little potential for dissemination; (ii) superficial candidiasis; (iii) opportunistic fungal skin infections with distinct potential for dissemination; (iv) fungal sinusitis with cutaneous extension; and (v) cutaneous manifestations of disseminated fungal infections. In the oncology population, dermatophyte infections (i) and superficial candidiasis (ii) have similar presentations to those seen in the immunocompetent host. Primary cutaneous mold infections (iii) are especially caused by Aspergillus, Fusarium, Mucor, and Rhizopus spp. These infections may invade deeper tissues and cause disseminated fungal infections in the neutropenic host. Primary cutaneous mold infections are treated with systemic antifungal therapy and sometimes with debridement. The role of debridement in the severely neutropenic patient is unclear. In some patients with an invasive fungal sinusitis (iv) there may be direct extension to the overlying skin, causing a fungal cellulitis of the face. Aspergillus, Rhizopus, and Mucor spp. are the most common causes. We also describe the cutaneous manifestations of disseminated fungal infections (v). These infections usually occur in the setting of prolonged neutropenia. The most common causes are Candida, Aspergillus, and Fusarium spp. Therapy is with systemic antifungal therapy. The relative efficacies of amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin are discussed. Recovery from disseminated fungal infections is unlikely, however, unless the patient's neutropenia resolves.
Aim
Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been ...considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this doubleblind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).
Methods and results
A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6–8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6–8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size −0.7% 95% CI: −2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6–8 days and at 6 months and final infarct size (FIS) measured at 6 months.
Conclusions
Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.
Cysteine-rich knob domains found in the ultralong complementarity determining regions of a subset of bovine antibodies are capable of functioning autonomously as 3–6 kDa peptides. While they can be ...expressed recombinantly in cellular systems, in this paper we show that knob domains are also readily amenable to a chemical synthesis, with a co-crystal structure of a chemically synthesized knob domain in complex with an antigen showing structural equivalence to the biological product. For drug discovery, following the immunization of cattle, knob domain peptides can be synthesized directly from antibody sequence data, combining the power and diversity of the bovine immune repertoire with the ability to rapidly incorporate nonbiological modifications. We demonstrate that, through rational design with non-natural amino acids, a paratope diversity can be massively expanded, in this case improving the efficacy of an allosteric peptide. As a potential route to further improve stability, we also performed head-to-tail cyclizations, exploiting the proximity of the N and C termini to synthesize functional, fully cyclic antibody fragments. Lastly, we highlight the stability of knob domains in plasma and, through pharmacokinetic studies, use palmitoylation as a route to extend the plasma half-life of knob domains in vivo. This study presents an antibody-derived medicinal chemistry platform, with protocols for solid-phase synthesis of knob domains, together with the characterization of their molecular structures, in vitro pharmacology, and pharmacokinetics.
1
The effects of intracisternal (i.c.) application of putative 5‐hydroxytryptamine (5‐HT)1A antagonists on the reflex bradycardia evoked by injection of phenylbiguanide (i.v.) were investigated in ...anaesthetized, atenolol‐pretreated rats.
2
Intracisternal application of spiperone (100 μg kg−1) reversibly attenuated the reflex bradycardia whilst the same dose given i.v. had no effect. The bradycardia was also attenuated by i.e. methiothepin (200 μg kg−1), (±)‐pindolol (100 μg kg−1) and buspirone (200 μ kg−1) but was not attenuated by antagonists selective for α1‐adrenoceptors (alfuzosin; 100 μg kg−1), 5‐HT2‐receptors (BW 501C67; 100 μg kg−1) or dopamine D2‐receptors ((−)−sulpiride; 100 μg kg−1) given i.e.
3
It is concluded that the 5‐HT1A‐receptor antagonist action of intracisternally applied spiperone, methiothepin, (±)‐pindolol and buspirone is responsible for the ability of these drugs to attenuate reversibly the excitation of cardiac vagal motoneurones caused by activation of the von Bezold‐Jarisch reflex.
l-Threonine single crystals have been irradiated by 6
MeV electrons. Irradiated crystals at various electron fluences were subjected to various techniques such as UV–vis–NIR, atomic force microscopy ...(AFM) and thermomechanical analyses. Thermal strength of the irradiated crystals has also been studied through differential scanning calorimetry (DSC) measurements. The results have been discussed in detail.
Online distance education continues to grow at a fast pace, even outpacing the overall growth of U.S. higher education. Demands for quality are coming from all shareholders involved. As if caught by ...surprise, a patchwork response to quality is often the typical organizational response. The result can be inconsistent and uncoordinated levels of value to those invested in online learning. This often promotes negative images of the educational experience and institution. Comprised of highly regarded experts in the field, this edited volume provides a comprehensive overview of quality assurance, a snapshot of current practices and proven recommendations for raising standards of quality in online education. Topics discussed include:
Improving practices for teaching online
Using educational analytics for quality assurance and improvement
Accessibility: An important dimension of quality assurance
Assuring quality in online course design
Assuring quality in learner support, academic resources, advising and counseling
The role and realities of accreditation This text clearly answers the call for addressing quality from a broad, deep and coordinated understanding. It addresses the complexities of quality assurance in higher education and offers professionals top-shelf advice and support.
This text is also appropriate for students enrolled in Educational Technology and Higher Education Administration Masters and PhD programs
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