Vasodilators in the treatment of acute heart failure: what we know, what we don’t

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients’ outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1–2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic signal. Furthermore, we have shown that inhibition of Fas mediated apoptosis is an early event in DU 145 cells, occurring upstream of Caspase 8 cleavage. It is hoped that identifying the target of JNK will allow novel therapies to be developed for the treatment of hormone refractory prostate cancer. Such therapies are especially important because no single or combined treatment to date has significantly prolonged survival in patients with hormone refractory prostate cancer

Visual Acuity Measures Do Not Reliably Detect Childhood Refractive Error - an Epidemiological Study

PURPOSE: To investigate the utility of uncorrected visual acuity measures in screening for refractive error in white school children aged 6-7-years and 12-13-years. METHODS: The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit children from schools in Northern Ireland. Detailed eye examinations included assessment of logMAR visual acuity and cycloplegic autorefraction. Spherical equivalent refractive data from the right eye were used to classify significant refractive error as myopia of at least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than 1.50DC, whether it occurred in isolation or in association with myopia or hyperopia. RESULTS: Results are presented from 661 white 12-13-year-old and 392 white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12-13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had a sensitivity of 92% and a specificity of 91% in detecting myopia and a sensitivity of 41% and a specificity of 84% in detecting hyperopia. CONCLUSIONS: Vision screening using logMAR acuity can reliably detect myopia, but not hyperopia or astigmatism in school-age children. Providers of vision screening programs should be cognisant that where detection of uncorrected hyperopic and/or astigmatic refractive error is an aspiration, current UK protocols will not effectively deliver

From bore-soliton-splash to a new wave-to-wire wave-energy model

We explore extreme nonlinear water-wave amplification in a contraction or, analogously, wave amplification in crossing seas. The latter case can lead to extreme or rogue-wave formation at sea. First, amplification of a solitary-water-wave compound running into a contraction is disseminated experimentally in a wave tank. Maximum amplification in our bore–soliton–splash observed is circa tenfold. Subsequently, we summarise some nonlinear and numerical modelling approaches, validated for amplifying, contracting waves. These amplification phenomena observed have led us to develop a novel wave-energy device with wave amplification in a contraction used to enhance wave-activated buoy motion and magnetically induced energy generation. An experimental proof-of-principle shows that our wave-energy device works. Most importantly, we develop a novel wave-to-wire mathematical model of the combined wave hydrodynamics, wave-activated buoy motion and electric power generation by magnetic induction, from first principles, satisfying one grand variational principle in its conservative limit. Wave and buoy dynamics are coupled via a Lagrange multiplier, which boundary value at the waterline is in a subtle way solved explicitly by imposing incompressibility in a weak sense. Dissipative features, such as electrical wire resistance and nonlinear LED loads, are added a posteriori. New is also the intricate and compatible finite-element space–time discretisation of the linearised dynamics, guaranteeing numerical stability and the correct energy transfer between the three subsystems. Preliminary simulations of our simplified and linearised wave-energy model are encouraging and involve a first study of the resonant behaviour and parameter dependence of the device

Cooling athletes with a spinal cord injury

Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport

A Morphometric Assessment of the Intended Function of Cached Clovis Points

A number of functions have been proposed for cached Clovis points. The least complicated hypothesis is that they were intended to arm hunting weapons. It has also been argued that they were produced for use in rituals or in connection with costly signaling displays. Lastly, it has been suggested that some cached Clovis points may have been used as saws. Here we report a study in which we morphometrically compared Clovis points from caches with Clovis points recovered from kill and camp sites to test two predictions of the hypothesis that cached Clovis points were intended to arm hunting weapons: 1) cached points should be the same shape as, but generally larger than, points from kill/camp sites, and 2) cached points and points from kill/camp sites should follow the same allometric trajectory. The results of the analyses are consistent with both predictions and therefore support the hypothesis. A follow-up review of the fit between the results of the analyses and the predictions of the other hypotheses indicates that the analyses support only the hunting equipment hypothesis. We conclude from this that cached Clovis points were likely produced with the intention of using them to arm hunting weapons