Dissociated representations of irritation and valence in human primary olfactory cortex

Irritation and negative valence are closely associated in perception. However, these perceptual aspects can be dissociated in olfaction where irritation can accompany both pleasant and unpleasant odorants. Whereas the sensation of odor reflects transduction at olfactory receptors, irritation reflects concurrent transduction of the odorant at trigeminal receptors. Thus a stimulus can be either a pure olfactant activating the olfactory receptors only or a bimodal odorant activating both types of receptors. Using event-related functional magnetic resonance imaging and a 2 x 2 experimental design contrasting odorant valence (pleasant/unpleasant) and odorant type (pure olfactant/bimodal) we found activity in piriform cortex to be associated with valence, and not type, of odors. In contrast, activity in the olfactory tubercle was associated with type, and not valence, of odors. Importantly, this was found when perceived intensity was held equal across odorants. These findings suggest that dissociable neural substrates subserve the encoding of irritation and valence in olfaction.     

Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation

Heme oxygenase-1 (HO-1, encoded by HMOX1) dampens inflammatory reactions via the catabolism of heme into CO, Fe, and biliverdin. We report that expression of HO-1 dictates the pathologic outcome of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Induction of EAE in Hmox1(-/- )C57BL/6 mice led to enhanced CNS demyelination, paralysis, and mortality, as compared with Hmox1(+/+) mice. Induction of HO-1 by cobalt protoporphyrin IX (CoPPIX) administration after EAE onset reversed paralysis in C57BL/6 and SJL/J mice and disease relapse in SJL/J mice. These effects were not observed using zinc protoporphyrin IX, which does not induce HO-1. CoPPIX protection was abrogated in Hmox1(-/-) C57BL/6 mice, indicating that CoPPIX acts via HO-1 to suppress EAE progression. The protective effect of HO-1 was associated with inhibition of MHC class II expression by APCs and inhibition of Th and CD8 T cell accumulation, proliferation, and effector function within the CNS. Exogenous CO mimicked these effects, suggesting that CO contributes to the protective action of HO-1. In conclusion, HO-1 or exposure to its end product CO counters autoimmune neuroinflammation and thus might be used therapeutically to treat MS.     

Trans-peritoneal vs. retroperitoneal robotic assisted partial nephrectomy in posterior renal tumours: need for a risk-stratified patient individualised approach. A systematic review and meta-analysis

Journal of Robotic Surgery - To systematically review world literature and compare peri-operative outcome including operating time (OT), estimated blood loss (EBL), warm ischemia time (WIT), length...     

Proposition for new terminologies in PCNL: what does ‘ultra-mini-micro’ actually mean?

Ever smaller miniaturised techniques are being developed for percutaneous nephrolithotomy (PCNL), with access sheaths now as small as 4.8Fr being used in adults. With the ever expanding use of the terms “micro” “mini” or “ultra” techniques, the terminology can be somewhat confusing. We propose a simple classification system to standardise the terminology for PCNL, encapsulating technological and procedural advancements.     

Revealing the WEDM Process Parameters for the Machining of Pure and Heat-Treated Titanium (Ti-6Al-4V) Alloy

Ti-6Al-4V is an alloy that has a high strength-to-weight ratio. It is known as an alpha-beta titanium alloy with excellent corrosion resistance. This alloy has a wide range of applications, e.g., in the aerospace and biomedical industries. Examples of alpha stabilizers are aluminum, oxygen, nitrogen, and carbon, which are added to titanium. Examples of beta stabilizers are titanium–iron, titanium–chromium, and titanium–manganese. Despite the exceptional properties, the processing of this titanium alloy is challenging when using conventional methods as it is quite a hard and tough material. Nonconventional methods are required to create intricate and complex geometries, which are difficult with the traditional methods. The present study focused on machining Ti-6Al-4V using wire electrical discharge machining (WEDM) and conducting numerous experiments to establish the machining parameters. The optimal setting of the machining parameters was predicted using a multiresponse optimization technique. Experiments were planned using the response surface methodology (RSM) technique and analysis of variance (ANOVA) was used to determine the significance and contribution of the input parameters to changes in the output characteristics (cutting speed and surface roughness). The cutting speed obtained during the processing of the annealed titanium alloy using WEDM was quite large as compared to the cutting speed obtained in the case of processing the pure, quenched, and hardened titanium alloys using WEDM. The maximum cutting speed obtained while processing the annealed titanium alloy was 1.75 mm/min.     

Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis

To determine whether sustained plasma concentration of human tissue-type plasminogen activator (t-PA) can be induced promptly after intramuscular injection with enhancers of absorption devoid of deleterious local and systemic effects, we studied 250 rabbits and 13 dogs. In rabbits with t-PA injected directly into exposed muscle followed by local electrical stimulation at the site, early absorption was increased markedly by addition of 0.63M methylamine plus 0.079M hydroxylamine to the excipient. Elevations peaked within 5 min and increased with dose of t-PA, concentration of methylamine, and volume of injection medium. The enhancers were effective with percutaneous injections in the absence of local electrical stimulation as well. They did not elicit any obviously deleterious local or systemic effects. In separate experiments in rats, intramuscular injections of 0.63M methylamine plus 0.079M hydroxylamine induced local egress of intravascular radiolabeled albumin within the injection site and endothelial gaps in venules detected with colloidal carbon--changes consistent with direct effects on vascular permeability. In dogs, percutaneous intramuscular injection of t-PA in excipient without enhancers did not lead to early elevations of human t-PA in plasma, although late elevations were seen. When the enhancers were used, early elevations occurred as well, with functional activity documented by fibrin plate assays of serially obtained plasma samples and by sequential coronary angiography delineating thrombolysis after experimentally induced coronary thrombosis. The results indicate that intramuscular administration of t-PA with selected enhancers of absorption is a feasible approach for rapid induction of fibrinolysis.     

Candidiasis in the intensive care unit

In the last 2 decades, Candida species have progressed from infrequent pathogens to among the most important and frequent opportunistic microorganisms causing nosocomial infection in intensive care unit (ICU) patients. Medical and surgical ICUs have become the epicenter of the Candida epidemic. Superficial infections causing oropharyngeal and esophageal candidiasis are common, and, although non-life threatening, may be refractory to conventional antifungals. In contrast, invasive candidiasis, candidemia, and hematogenous disseminated infections are associated with considerable attributable mortality. Although blood isolates of C. albicans remain susceptible to fluconazole, the increasing incidence of non- albicans Candida species with intrinsic reduced susceptibility to azoles creates new therapeutic challenges. Fortunately, lipid formulations of amphotericin B and the recently introduced echinocandin group represent new and strategic treatment responses to the challenge of invasive candidiasis.     

Evolution of antifungal susceptibility among Candida species isolates recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis.

The effect of fluconazole on the susceptibility of Candida isolates recovered from women infected with human immunodeficiency virus (HIV) was evaluated in a randomized, double-blind, placebo-controlled trial. Women with CD4(+) cell counts of < or =300 cells/mm(3) received either fluconazole (200 mg/week) or placebo as prophylaxis. The antifungal susceptibility of specimens was evaluated. One patient who received fluconazole and 2 patients assigned to placebo had Candida albicans isolates recovered that were resistant to fluconazole (MIC, > or =64 microg/mL). Eleven patients assigned fluconazole and 4 patients assigned placebo had non-albicans Candida strains (all Candida glabrata) recovered that were resistant to fluconazole. There was significant azole cross-resistance among the non-albicans Candida species isolates. Although the rate of azole resistance did not significantly increase after fluconazole prophylaxis, there was a trend toward more in vitro azole resistance in C. glabrata isolates from patients assigned fluconazole. Moreover, the majority of resistant vaginal isolates of Candida species were recovered after initiation of open-label fluconazole use.