Anomalous Diffusion and Lévy Walks Distinguish Active from Inertial Turbulence.

Bacterial swarms display intriguing dynamical states like active turbulence. Now, using a hydrodynamic model, we show that such dense active suspensions manifest superdiffusion, via Lévy walks, which masquerades as a crossover from ballistic to diffusive scaling in measurements of mean-squared displacements, and is tied to the emergence of hitherto undetected oscillatory streaks in the flow. Thus, while laying the theoretical framework of an emergent advantageous strategy in the collective behavior of microorganisms, our Letter underlines the essential differences between active and inertial turbulence.

Characterization of the crosslinking kinetics of multi-arm poly(ethylene glycol) hydrogels formed via Michael-type addition.

Tunable properties of multi-arm poly(ethylene glycol) (PEG) hydrogel, crosslinked by Michael-type addition, support diverse applications in tissue engineering. Bioactive modification of PEG is achieved by incorporating integrin binding sequences, like RGD, and crosslinking with tri-functional protease sensitive crosslinking peptide (GCYKNRGCYKNRCG), which compete for the same reactive groups in PEG. This competition leads to a narrow range of conditions that support sufficient crosslinking density to provide structural control. Kinetics of hydrogel formation plays an important role in defining the conditions to form hydrogels with desired mechanical and biological properties, which have not been fully characterized. In this study, we explored how increasing PEG functionality from 4 to 8-arms and the concentration of biological moieties, ranging from 0.5 mM to 3.75 mM, affected the kinetics of hydrogel formation, storage modulus, and swelling after the hydrogels were allowed to form for 15 or 60 minutes. Next, human bone marrow stromal cells were encapsulated and cultured in these modified hydrogels to investigate the combined effect of mechano-biological properties on phenotypes of encapsulated cells. While the molar concentration of the reactive functional groups (-vinyl sulfone) was identical in the conditions comparing 4 and 8-arm PEG, the 8-arm PEG formed faster, allowed a greater degree of modification, and was superior in three-dimensional culture. The degrees of swelling and storage modulus of 8-arm PEG were less affected by the modification compared to 4-arm PEG. These findings suggest that 8-arm PEG allows a more precise control of mechanical properties that could lead to a larger spectrum of tissue engineering applications.

Intermittency in the not-so-smooth elastic turbulence.

Elastic turbulence is the chaotic fluid motion resulting from elastic instabilities due to the addition of polymers in small concentrations at very small Reynolds ( Re ) numbers. Our direct numerical simulations show that elastic turbulence, though a low Re phenomenon, has more in common with classical, Newtonian turbulence than previously thought. In particular, we find power-law spectra for kinetic energy E(k) ~ k-4 and polymeric energy Ep(k) ~ k-3/2, independent of the Deborah (De) number. This is further supported by calculation of scale-by-scale energy budget which shows a balance between the viscous term and the polymeric term in the momentum equation. In real space, as expected, the velocity field is smooth, i.e., the velocity difference across a length scale r, δu ~ r but, crucially, with a non-trivial sub-leading contribution r3/2 which we extract by using the second difference of velocity. The structure functions of second difference of velocity up to order 6 show clear evidence of intermittency/multifractality. We provide additional evidence in support of this intermittent nature by calculating moments of rate of dissipation of kinetic energy averaged over a ball of radius r, εr, from which we compute the multifractal spectrum.

Emerging role of miR-320a in lung cancer: a comprehensive review.

A specialized biomarker(s) for lung cancer is imperative owing to its high mortality. Continuing our earlier work demonstrating the role of miR-320a as a tumor suppressor, here we discuss the most recent updates on miR-320a in lung cancer pathogenesis. We found that miR-320a modulates levels of diverse cancer-associated molecules and signaling pathways, and is also involved in modulating the immune microenvironment of lung cancer during its pathogenesis. We also discuss how miR-320a encapsulated in exosomes inhibits invasive phenotypes of lung cancer. Therefore, based on the multimodal role of miR-320a in lung cancer development and progression, we believe that miR-320a may be utilized as a potential diagnostic/prognostic marker and therapeutic target for lung cancer patients.

Estrogen regulation of brain vasotocin secretion in the catfish Heteropneustes fossilis: an interaction with catecholaminergic system.

Vasotocin (VT) is a basic neurohypophysial nonapeptide in non-mammalian vertebrates and is involved in diverse functions like osmoregulation, reproduction, metabolism and behavior. In this study, we report that estradiol-17ß (E(2)) regulates brain and plasma VT secretion through the involvement of the catecholaminergic (CA) system. To demonstrate this, E(2) level was altered through ovariectomy (OVX, 3 weeks) and replacement study with low and high E(2) doses (0.1 and 0.5 µg/g body weight). CA activity was inhibited by treatment with α-methylparatyrosine (α-MPT; 250 µg/g body weight), a competitive inhibitor of tyrosine hydroxylase. VT was assayed by an enzyme immunoassay method. In the sham group, the low E(2) dose produced 82% and 104% increase, respectively, in brain and plasma VT levels. The high E(2) dose decreased the VT levels significantly. The low E(2) dose decreased brain E(2) but elevated plasma E(2). In the high E(2) group, the E(2) level increased further in both brain and plasma. OVX resulted in a significant inhibition (69% and 25%, respectively) of both brain and plasma VT, which was correlated with low E(2) levels. The low E(2) dose not only reversed the inhibition, but increased the VT level in both brain and plasma in comparison to the sham groups. The high E(2) replacement inhibited VT levels further low in both brain and plasma. The α-MPT treatment inhibited VT levels significantly in both sham and OVX groups. The drug treatment abolished partially the restorative effect of the low E(2) dose in the ovariectomized fish. In the high E(2) dose group, α-MPT decreased brain and plasma VT levels further low compared to the sham + 0. 5 µg E(2) group or OVX + 0.5 µg E(2) group except the brain VT level, which increased in the OVX+0.5 µg E(2) group. It is inferred that E(2) may exert biphasic effects on VT through the mediation of the CA system.

VIBe Scale: Validation of the Intraoperative Bleeding Severity Scale by Spine Surgeons.

BACKGROUND: The Validated Intraoperative Bleeding Scale (VIBe Scale) was initially validated with surgeons who operate on cardiothoracic, abdominal, and pelvic cavities and fulfilled criteria for a clinician-reported scale. However, there is a need for a tool to aid in intraoperative blood management during spine surgeries. The purpose of the present study was to establish the reliability and consistency of the VIBe Scale as a tool for spine surgeons to assess intraoperative bleeding. METHODS: Orthopedic (n = 16) and neurological (n = 9) spine surgeons scored videos depicting surgical bleeding and assessed the VIBe Scale's relevance and clarity. Inter- and intraobserver agreement (Kendall's W) were calculated for all surgeons and pooled with responses from the original study to establish agreement across specialties. RESULTS: All of the spine surgeons indicated that the scale was clinically relevant for evaluating hemostasis and could be implemented in a clinical study. Twenty-two spine surgeons (88%) reported that the scale represents the range of bleeding site sizes and severities expected in their practice. Twenty-four spine surgeons (96%) indicated that the scale would be useful in communicating bleeding severity with other members of the surgical team. Interobserver agreement was acceptable (0.79) for orthopedic specialists, appreciable (0.88) for neurological specialists, and appreciable (0.88) for the combined specialists. Intraobserver agreement was excellent for orthopedic (0.91) and neurological (0.91) spine surgeons and excellent (0.96) for the combined specialists. CONCLUSIONS: The results highlight the reliability of the VIBe Scale and potential utility for quantifying intraoperative blood loss in spine surgery. CLINICAL RELEVANCE: The VIBe Scale may be useful for evaluating the efficacy of untested intraoperative hemostatic agents and for comparing the relative efficacy of 2 or more analogous agents. It may also prove useful for intraoperative staff by quantifying ongoing intraoperative blood loss and correlating losses with the potential transfusion and intraoperative hemostatic agent requirements.

Toxicopathological impact of sub-lethal concentrations of lead nitrate on the gill of the catfish Heteropneustes fossilis.

In recent studies, fish are heavily used as biomarkers of aquatic pollution, and heavy metals are among the main contributors to water pollution. In the present study, we investigated histopathological changes along with alterations in localization and activity of enzymes alkaline phosphatase (ALP), acid phosphatase (ACP), catalase (CAT), peroxidase (PER) and Na+/K+-ATPase in the gill tissues of Indian stinging catfish Heteropneustes fossilis exposed to two different concentrations (0.4 and 4 mg/L) of lead nitrate for 15 days. Histopathological examination of gill tissues revealed hypertrophy and swelling of epithelial cells, the fusion of epithelium of gill filaments and secondary lamellae, and alteration of secondary lamellae structure. Biochemical assays and histochemical localization show a pronounced effect on enzyme alkaline phosphatase activity and acid phosphatase in the gills of both groups of treated groups. In contrast, a significant decrease was noticed in the enzymatic response including catalase and peroxidase activity. Being a vital organ gill reflects the fish's physiological condition and the severity of the contamination in the surrounding environment. Gill is also the prime organ of osmoregulation in teleosts. Decreased activity of Na+/K+-ATPase suggests lead as a potent inhibitor of Na+/K+-ATPase that causes sodium hyperregulation. Alteration in the activity of metabolic enzymes reflects the level of tissue damage and metabolic disruption. At the same time, the increased activity of antioxidant enzymes states the condition of oxidative stress. Haematological parameters also altered with the lead nitrate exposure, reflecting metal toxicity and immune response against it. Meanwhile, this study also provides a potential use of H. fossilis as a biomarker for aquatic pollution.

Double glassy states and large spontaneous and conventional exchange bias in La1.5Ca0.5CoFeO6ferrimagnetic double perovskite.

The structural and magnetic properties of hole doped double perovskite La1.5Ca0.5CoFeO6have been investigated by measuring x-ray photoemission spectroscopy, neutron powder diffraction and magnetization. A ferrimagnetic transition is observed atTC∼ 167 K. The presence of anti-site disorder (ASD) in La1.5Ca0.5CoFeO6has also been demonstrated. Double re-entrant cluster glass transitions (T1∼ 11 K andTS∼ 35 K) were observed which has been attributed to the ASD effect. The presence of both large spontaneous exchange biasHSEB∼ 2.106 kOe and giant conventional exchange biasHCEB∼ 1.56 T at 5 K has also been observed which can be attributed to the coexistence of long range magnetic ordering and glassy state. The experimental observations were explained with the results obtained by the density functional theory calculation. The presence of double glassy states, large exchange-bias effect and different magnetic phases make this system a potential candidate for spintronic applications.

In search of an ideal test for diagnosis and prognosis of kala-azar.

The latex agglutination test (KAtex), direct agglutination test (DAT), and the rK39 immuno-chromatographic strip test (dipstick test) were evaluated for their role in the diagnosis and prognosis of visceral leishmaniasis (kala-azar) in India. Sera and urine samples from 455 subjects--150 confirmed visceral leishmaniasis cases, 160 endemic controls, 100 non-endemic controls, and 45 other febrile diseases--were included in the study. The sensitivity of the KAtex, DAT, and rK39 strip test was 87% [95% confidence interval (CI) 80-96], 93.3% (95% CI 88-100), and 98% (95% CI 93-100) respectively. The specificity of these tests was 98% (95% CI 93-100), 93% (95% CI 87-100), and 89% (95% CI 82-97) for the KAtex, DAT, and rK39 strip test respectively. Fifty cases were followed up and subjected to the KAtex, DAT, and rK39 strip test after 30 days of successful treatment. The DAT and rK39 strip test showed positive results in all the 50 cases whereas the KAtex showed no positive reaction in any case. Based on the results, it is concluded that the sensitivity and specificity of the DAT and rK39 strip test are comparable but the greater convenience of use of the strip test makes it a better tool for the diagnosis of visceral leishmaniasis in the peripheral areas of endemic regions whereas the sensitivity of the KAtex needs to be improved to promote its use as a first-line diagnostic test in the field-setting. It may be used for the prognosis of the disease as antigen becomes undetectable in urine after 30 days of the completion of the treatment. Alternatively, it can be used as an adjunct with rK39 for sero-epidemiological surveys.

Immunomodulatory effect of Moringa oleifera Lam. extract on cyclophosphamide induced toxicity in mice.

Immunomodulatory effect of ethanolic extract (50%) of M. oleifera leaves (MOE) has been studied in normal and immunosuppressed mice models. Different doses of MOE i.e. 125, 250 and 500 mg/kg body weight of mice were administered orally for 15 days. Cyclophosphamide at a dose of 30 mg/kg body weight was administered orally for the next 3 days. On day 16 and 19, hematological parameters like white blood cell (WBC) count, red blood cell (RBC) count, haemoglobin level (Hb), percent neutrophils and organ weight were recorded. Effect of MOE on phagocytic activity of mice macrophages was determined by carbon clearance test. MOE showed significant dose dependent increase in WBC, percent neutrophils, weight of thymus and spleen along with phagocytic index in normal and immunosuppressed mice. The results indicate that MOE significantly reduced cyclophosphamide induced immunosuppression by stimulating both cellular and humoral immunity.

Hemostatic Comparison of a Polysaccharide Powder and a Gelatin Powder.

Purpose/Aim: Powdered hemostats have been widely adopted for their ease-of-use; however, their efficacy has been limited resulting in applications restricted to low-level bleeds. This study investigates the use of bovine-derived gelatin particles (BGP) as a standalone hemostatic powder and compare BGP to commercially available microporous polysaccharide hemospheres (MPH). Materials and Methods: The powders were investigated for their hemostatic efficacy in a heparinized pre-clinical bleeding model limited to grade 1 and 2 bleeds on a validated intraoperative bleeding scale, which represents the accepted, clinical use of hemostatic powders. Results: At 10 minutes, the hemostatic success of lesions treated with BGP were 78% while MPH were 22%. The odds ratio for hemostatic success of BGP relative to MPH was 15.18 (95% CI: 7.37, 31.27). The 95% lower limit of the odds ratio was greater than 1. This indicates that BGP are superior to MPH (p < 0.001). The median time to hemostasis for BGP was 1.6 minutes and MPH was 14.5 minutes. The ratio for time to hemostasis of MPH relative to BGP was 9.23 (95% CI: 6.99, 12.19). This indicates that BGP achieve significantly faster time to hemostasis (p < 0.001). Conclusions: Characterization of tissue explant ultrastructure, particle size, and swelling revealed differences in the materials. BGP, in addition to absorbing fluid and concentrating clotting factors and platelets, integrate into the clot and stabilize the fibrin matrix. BGP have advantages over MPH in terms of speed and efficacy. BGP are a favorable biomaterial for further research that greatly improve the limited efficacy of powdered hemostats.

Automatic tuberculosis screening using chest radiographs.

Tuberculosis is a major health threat in many regions of the world. Opportunistic infections in immunocompromised HIV/AIDS patients and multi-drug-resistant bacterial strains have exacerbated the problem, while diagnosing tuberculosis still remains a challenge. When left undiagnosed and thus untreated, mortality rates of patients with tuberculosis are high. Standard diagnostics still rely on methods developed in the last century. They are slow and often unreliable. In an effort to reduce the burden of the disease, this paper presents our automated approach for detecting tuberculosis in conventional posteroanterior chest radiographs. We first extract the lung region using a graph cut segmentation method. For this lung region, we compute a set of texture and shape features, which enable the X-rays to be classified as normal or abnormal using a binary classifier. We measure the performance of our system on two datasets: a set collected by the tuberculosis control program of our local county's health department in the United States, and a set collected by Shenzhen Hospital, China. The proposed computer-aided diagnostic system for TB screening, which is ready for field deployment, achieves a performance that approaches the performance of human experts. We achieve an area under the ROC curve (AUC) of 87% (78.3% accuracy) for the first set, and an AUC of 90% (84% accuracy) for the second set. For the first set, we compare our system performance with the performance of radiologists. When trying not to miss any positive cases, radiologists achieve an accuracy of about 82% on this set, and their false positive rate is about half of our system's rate.

Lung segmentation in chest radiographs using anatomical atlases with nonrigid registration.

The National Library of Medicine (NLM) is developing a digital chest X-ray (CXR) screening system for deployment in resource constrained communities and developing countries worldwide with a focus on early detection of tuberculosis. A critical component in the computer-aided diagnosis of digital CXRs is the automatic detection of the lung regions. In this paper, we present a nonrigid registration-driven robust lung segmentation method using image retrieval-based patient specific adaptive lung models that detects lung boundaries, surpassing state-of-the-art performance. The method consists of three main stages: 1) a content-based image retrieval approach for identifying training images (with masks) most similar to the patient CXR using a partial Radon transform and Bhattacharyya shape similarity measure, 2) creating the initial patient-specific anatomical model of lung shape using SIFT-flow for deformable registration of training masks to the patient CXR, and 3) extracting refined lung boundaries using a graph cuts optimization approach with a customized energy function. Our average accuracy of 95.4% on the public JSRT database is the highest among published results. A similar degree of accuracy of 94.1% and 91.7% on two new CXR datasets from Montgomery County, MD, USA, and India, respectively, demonstrates the robustness of our lung segmentation approach.

Capillary morphogenesis in PEG-collagen hydrogels.

A wide variety of hydrogels have been explored as 3D culture platforms and for applications in tissue engineering. Hydrogels formed from natural extracellular matrix (ECM) proteins readily support the formation of vasculature in vitro, but only a handful of hydrogels composed of synthetic materials have shown anything comparable. This relative lack of synthetic material options has hindered efforts to better understand how ECM cues direct vascularization. We developed a biosynthetic hydrogel consisting of polyethylene glycol diacrylamide conjugated to macromolecular type-I collagen. Through their acrylamide-based crosslinks, these materials allow for independent control of physical properties and bulk ligand concentration. These hydrogels exhibited hydrolytic stability, but the collagen component retained its susceptibility to enzymatic remodeling. Photoencapsulation of endothelial cells and fibroblasts within this hydrogel material and their subsequent co-culture led to the formation of capillary vessel-like networks with well-defined hollow lumens. Capillary formation was prevented by inhibiting matrix metalloproteinase (MMP) activity, recapitulating the MMP-dependence of vascularization observed in natural hydrogels. These findings validate the utility of this material platform to decipher how the ECM regulates capillary morphogenesis and to support the formation of vascularized tissue constructs for potential applications in regenerative medicine.

Matrix identity and tractional forces influence indirect cardiac reprogramming.

Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming.

In vitro effects of lead nitrate on steroid profiles in the post-vitellogenic ovary of the catfish Heteropneustes fossilis.

Heavy metals are endocrine disruptors with the ability to cause hormonal imbalances, affecting various physiological processes such as reproduction. In this study, in vitro effects of exposure (12 or 24h) of lead nitrate [Pb(NO(3))(2)] (0, 0.01, 0.1, 1, 3 and 10 µg/ml) on steroid levels in post-vitellogenic catfish (Heteropneustes fossilis) ovary was investigated. Steroids were assayed by HPLC/ELISA. Lead (Pb) elicited biphasic effects on estradiol-17ß, testosterone and cortisol: stimulatory at lower concentrations and inhibitory at higher concentrations. In contrast, progesterone, 17-hydroxyprogesterone, 17,20ß-dihydroxyprogesterone, corticosterone, 21-deoxycortisol and deoxycorticosterone were inhibited in a dose-dependent manner. Thus, the present results suggest that short-term Pb response can be a potent endocrine disruptor of normal follicular steroidogenesis. The stimulatory effect on E(2) suggests that Pb in trace amounts may be beneficial. The cortisol elevation may be indicative of the metal/stress insult. Nevertheless, further studies are required to understand the mechanism of action of lead toxicity.