Inhibition of bacterial growth through LED (light-emitting diode) 465 and 630 nm: in vitro

Lasers in Medical Science - Photobiomodulation has been used to inactivate bacterial growth, in different laser or LED protocols. Thus, the aim of this study was to verify the inhibition of...     

Form,function, and evolution of living organisms

Despite the vast diversity of sizes and shapes of living organisms, life’s organization across scales exhibits remarkable commonalities, most notably through the approximate validity of Kleiber’s law, the power law scaling of metabolic rates with the mass of an organism. Here, we present a derivation of Kleiber’s law that is independent of the specificity of the myriads of organism species. Specifically, we account for the distinct geometries of trees and mammals as well as deviations from the pure power law behavior of Kleiber’s law, and predict the possibility of life forms with geometries intermediate between trees and mammals. We also make several predictions in excellent accord with empirical data. Our theory relates the separate evolutionary histories of plants and animals through the fundamental physics underlying their distinct overall forms and physiologies.Understanding the origin and evolution of the geometries of living forms is a formidable challenge (1, 2). The geometry of an object can be characterized by its surface−volume relationship—the surface area S of an object of volume V can scale at most as and at least as (3). These geometries have been used by nature in space-filling trees and animals, respectively. Here, our principal goal is to explore how it is that both geometries of life coexist on Earth, whether intermediate geometries are possible, and what all this implies for evolution of life on Earth.Living organisms span an impressive range of body mass, shapes, and scales. They are inherently complex, they have been shaped by history through evolution and natural section, and they continually extract, transform, and use energy from their environment. The most prevalent large multicellular organisms on Earth, namely plants and animals, exhibit distinct shapes, as determined by the distribution of mass over the volume. Animals are able to move and are approximately homogeneous in their mass distribution—yet they have beautiful fractal transportation networks. Plants are rooted organisms with a heterogeneous self-similar (fractal) geometry—the mass of the tree is more concentrated in the stem and branches than in the leaves.The approximate power law dependence of the metabolic rate, the rate at which an organism burns energy, on organism mass has been carefully studied for nearly two centuries and is known as allometric scaling (4–32). From the power law behavior, with an exponent around 3/4, one can deduce the scaling of characteristic quantities with mass and, through dimensional analysis, obtain wide-ranging predictions often in accord with empirical data. However, what underlies this ubiquitous quarter-power scaling, and with a dominant exponent of 3/4?In an influential series of papers, West and coworkers (11, 12, 14–16) suggested that fractality was at the heart of allometric scaling. Inspired by these papers, a contrasting view was presented (13), which argued that, although fractal circulatory networks may have advantages, quarter-power scaling came built in with the directed transport of nutrients. However, this latter paper was necessarily incomplete because it did not address the distinct geometries of animals and trees. More recently, members of both groups joined together to construct explicit models for animals, which showed (24) that “quarter-power scaling can arise even when there is no underlying fractality.” Here, we take a fresh look at the problem and derive quarter-power scaling quite generally for all living organisms. We then turn to a consideration of the sharp differences in the geometries of animals and trees and argue that the evolution of organismal forms follows from a rich interplay of geometry, evolutionary history, developmental symmetry, and efficient nutrient acquisition.Despite their independent evolution and different metabolisms, vascular plants and bilaterian animals share major design features, namely, an internal mass comprising organized cells capable of metabolic and bioenergetic activities, a transport mechanism for distributing molecules and energy within itself, and a surface capable of exchanging matter and energy with the environment. Regardless of the shape differences observed between these two groups, the physics associated with the transformation, transport, and exchange of matter and energy must unavoidably impose physical constraints on their designs. An organism is akin to an engine—part of the energy obtained from nourishment is used for organism function, growth, reproduction, while the rest is dissipated through its surface. We consider the hypothesis of the survival of the fittest in terms of energy metabolism and postulate that an organism with a higher energy intake would have a competitive advantage over another organism of similar mass performing energetically suboptimally, and explore its consequences.Consider an isotropic 3D organism of spatial extent h whose volume V scales as . Generalization to organisms with distinct scaling along the three different directions is straightforward. We make the simplifying assumption that the consumption and metabolic activity is distributed uniformly in space and in time or suitable averaging is used. We denote the basal metabolic rate of the organism by B and its mass by M. B is a measure of the energy being delivered to the organism per unit time and ought to be proportional to the energy dissipated through its surface. There is no evidence of size selection in empirical data, and this lends support to the assumption that the efficiency of the engine is independent of the organism’s size. We will derive Kleiber’s law based on energy intake considerations and study the role of geometry, as captured in the surface−volume relationship, on considering the expelled energy.Our goal is to understand the ideal dependence of B on M in the scaling regime. The characteristic time scale associated with the organism is known to scale as —it is a measure of how long it would take for energy proportional to M to be dissipated at a rate of B. Henceforth, proportionality constants, which serve to fix the correct units of various quantities related through scaling relations, will be omitted for the sake of simplicity.The number of metabolites, N, consumed in the organism per unit time is proportional to B. Let us define , so that a single metabolite is consumed per unit time in the local region surrounding each site of an grid. Each of these sites can be thought of as being within a service volume, in which one metabolite is consumed per unit time, of linear spatial extent . At the local level, the metabolites need to be transported this distance over unit time, and one immediately finds (24) that the transport velocity . Another measure of the transport velocity is obtained by noting that it is a characteristic length scale of the organism divided by the corresponding characteristic time scale and therefore scales as . Setting the two measures to be proportional to each other, one obtains Kleiber’s law .An alternative way of deriving the same result in a more rigorous manner is through the consideration of the properties of efficient transportation networks. The goal is to determine the minimum number of metabolites in transit, a measure of the organism mass, to ensure that metabolites are delivered in unit time within the organism volume. One can prove that the mass scales at least as with the optimality arising for efficient directed networks with no large-scale backtracking (13). This again leads to Kleiber’s law.Remarkably, the idealized metabolic rate−mass relationship is predicted to be algebraic with a exponent independent of the geometry of the organism. Such competitive equivalence explains the coexistence of animals with a homogeneous tissue density and fractal plants on Earth. The mass-specific metabolic rate, , scales as , whereas the transit time scales as . Indeed, characteristic biological rates (such as the heart beat and mutation rates) and characteristic biological times (such as circulation times or lifetimes) scale as and , respectively (6, 7, 9–12, 14–16).     

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.     

The 17-year single-center experience with the use of azathioprine to maintain remission in ulcerative colitis

Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2 mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1–201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate = 38%). The figures were 32 and 15 at the first year. The majority of the patients had 1–2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.     

Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Na_v1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.     

Acute renal failure in the critically I11: Management by continuous veno-venous hemodiafiltration

The consequences of newer techniques of continuous renal replacement therapy in critically ill patients are not yet fully known. The clinical and biochemical impact of continuous veno-venous hemodiafiltration (CVVHD) was, therefore, prospectively studied in 60 critically ill patients with acute renal failure. Prospective clinical, biochemical, and hematological data were collected from patients receiving CVVHD. Over the initial 24 hours of therapy, CVVHD resulted in a decrease in mean plasma urea from 34.5 mmol/L (95% confidence interval [CI], 29.4 to 39.6) to 25 mmol/L (95% CI, 21.8 to 28.2). With continued CVVHD, the mean plasma urea reached a plateau level of 17.6 mmol/L (95% CI, 15.8 to 19.4) at 72 hours. This degree of azotemia control was achieved with ease and essentially without complications during 8,360 hours of therapy despite the presence of multi-organ failure and the aggressive administration of protein nitrogen (0.25 to 0.35 g/kg/day). No abnormalities of serum electrolytes developed during treatment. Survival to intensive care discharge was 46.6% and to hospital discharge 41.6%, despite a mean Acute Physiology and Chronic Health Evaluation (APACHE) Il score at presentation of 27.7. Continuous veno-venous hemodiafiltration offers superior azotemia control and a safe approach to renal replacement therapy in critically ill patients. Its use is associated with a comparatively favorable outcome. CVVHD may be regarded as the treatment of choice in such patients.